Textbook Hemodiafiltration Theory Technology and Clinical Practice 1St Edition Menso J Nube Ebook All Chapter PDF

Hemodiafiltration: Theory, Technology
and Clinical Practice 1st Edition Menso

J. Nubé
Visit to download the full and correct content document:
https://textbookfull.com/product/hemodiafiltration-theory-technology-and-clinical-practi
ce-1st-edition-menso-j-nube/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...
Biota Grow 2C gather 2C cook Loucas
https://textbookfull.com/product/biota-grow-2c-gather-2c-cook-
loucas/
Web Technology Theory and Practice 1st Edition Akshi

Kumar (Author)
https://textbookfull.com/product/web-technology-theory-and-
practice-1st-edition-akshi-kumar-author/
Randomization in clinical trials : theory and practice

2nd Edition Lachin
https://textbookfull.com/product/randomization-in-clinical-
trials-theory-and-practice-2nd-edition-lachin/
Microforming Technology Theory Simulation and Practice

Zhengyi Jiang
https://textbookfull.com/product/microforming-technology-theory-
simulation-and-practice-zhengyi-jiang/
Critical Schooling: Transformative Theory and Practice
Francisco J. Villegas
https://textbookfull.com/product/critical-schooling-
transformative-theory-and-practice-francisco-j-villegas/
Juvenile Delinquency: Theory, Practice, and Law Larry

J. Siegel
https://textbookfull.com/product/juvenile-delinquency-theory-
practice-and-law-larry-j-siegel/
Advanced MR Neuroimaging: From Theory to Clinical

Practice 1st Edition Ioannis Tsougos
https://textbookfull.com/product/advanced-mr-neuroimaging-from-
theory-to-clinical-practice-1st-edition-ioannis-tsougos/
Psychoanalytic Theory and Clinical Relevance What Makes

a Theory Consequential for Practice Louis S. Berger
https://textbookfull.com/product/psychoanalytic-theory-and-
clinical-relevance-what-makes-a-theory-consequential-for-
practice-louis-s-berger/
Dementia in Clinical Practice A Neurological

Perspective A. J. Larner
https://textbookfull.com/product/dementia-in-clinical-practice-a-
neurological-perspective-a-j-larner/
Menso J. Nubé
Muriel P.C. Grooteman
Peter J. Blankestijn
Editors
Hemodiafiltration
Theory, Technology
and Clinical Practice
123
Hemodiafiltration
Menso J. Nubé • Muriel P.C. Grooteman
Peter J. Blankestijn
Editors
Hemodiafiltration
Theory, Technology and Clinical Practice
Editors
Menso J. Nubé Peter J. Blankestijn
VU Medical Center University Medical Center Utrecht
Amsterdam Utrecht
The Netherlands The Netherlands
Muriel P.C. Grooteman

VU Medical Center
Amsterdam
The Netherlands
ISBN 978-3-319-23331-4 ISBN 978-3-319-23332-1 (eBook)

DOI 10.1007/978-3-319-23332-1
Library of Congress Control Number: 2015956130
Springer Cham Heidelberg New York Dordrecht London

© Springer International Publishing Switzerland 2016
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, express or implied, with respect to the material contained herein or for any errors
or omissions that may have been made.
Printed on acid-free paper
Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.

springer.com)
Preface
Hemodialysis (HD) has become the standard renal replacement therapy for patients
with end-stage kidney disease, with more than two million patients now treated
worldwide. However, despite prominent technological improvements over the last
decades, the overall 5-year survival for HD patients remains less than that for some
of the more common solid organ malignancies, such as colon cancer.
HD is an effective treatment for removing small water-soluble solutes, such as
urea by diffusion, but simply increasing urea clearance has not been shown to
improve survival. Standard HD with low-flux membranes is not effective in clearing
larger middle molecules, such as beta-2-microglobulin, which then accumulates
over time, leading to dialysis amyloid deposition. To improve the clearance of these
larger uremic toxins, large pore dialyzer membranes (high-flux) were developed,
but trials comparing high-flux HD with low-flux HD did not show improved patient
survival. The clearance of these larger molecules is much more efficient using con-
vection rather than diffusion, and this led to the introduction of hemodiafiltration
(HDF) which provides both efficient diffusive and convective clearances of water-
soluble substances.
Technological developments in dialysis machines and water treatment systems
have made it possible to treat a significant number of patients with HDF and to
analyze various clinical outcome parameters, including overall and cardiovascular
mortality. After several observational studies in the past, more recently, three large
randomized clinical trials and five meta-analyses have been published. Altogether,
results suggest that online postdilution HDF is at least as safe and useful as HD and
considerably better when high volumes are applied.
As online HDF has become an established treatment nowadays, and comprehen-
sive information on a diversity of clinical and scientific aspects is available, the time
has come to collect and structure this information in a textbook for professionals
interested in and/or working with patients with end stage kidney disease. This hand-
book on hemodiafiltration is divided into five parts. While Part I includes technical
and essential aspects of convective techniques, water treatment systems, quality
control, and safety requirements (Chaps. 2, 3, and 4), Part II deals with hemodiafil-
tration equipment. In this part, several machines that can be used for hemodiafiltration
v
vi Preface
are described, with their general and specific features. The manufacturers are listed
in an alphabetic order (Chaps. 5, 6, 7, 8, 9, and 10).
In Part III, the effects of HDF treatment on various biomarkers, such as electro-
lytes and mineral metabolism, anemia control, inflammation and oxidative stress,
uremic toxins, and effects on platelets and coagulation are described (Chaps. 11, 12,
13, 14, and 15). In Part IV, the results of recent large RCTs and meta-analyses on
HDF treatment are extensively described and discussed. In addition, in this part
attention is paid to the possible mechanisms behind the beneficial effect of high
volume HDF on clinical outcome and also to some possible side effects of HDF
treatment. Finally, this part also deals with the beneficial effects of HDF on growth
in children and nutrition and effects of more intensified HDF strategies (Chaps. 16,
17, 18, 19, 20, 21, and 22). Practical issues, such as how to achieve high volume
HDF and how to adapt medication when large convection volumes are applied, are
discussed in Part V (Chaps. 23 and 24). Finally, in Part VI the current status of HDF
is discussed (Chap. 25). As such, we hope that this handbook on hemodialfiltration
has the potential to be of great and global relevance for professionals, the health
regulatory authorities and insurance companies, the dialysis industries, and last but
not least for the two million or so patients for whom dialysis therapy is a life-saving
treatment.
Amsterdam, The Netherlands Menso J. Nubé

Amsterdam, The Netherlands Muriel P.C. Grooteman
Utrecht, The Netherlands Peter J. Blankestijn
Contents
1 History and Current Status of Online Haemodiafiltration . . . . . . . . 1

Bernard Canaud and Ingrid Ledebo
Part I Technical Aspects
2 Convective Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Luciano A. Pedrini and Simona Zerbi
3 Water Treatment and Safety Requirements . . . . . . . . . . . . . . . . . . . . 41
Richard A. Ward and James E. Tattersall
4 Dialyzers for Hemodiafiltraion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Claudio Ronco, Sara Samoni, and Silvia De Rosa
Part II Hemodiafiltration Equipment
5 Baxter Online Hemodiafiltration Systems . . . . . . . . . . . . . . . . . . . . . . 71

Jan Sternby, Anders Felding, and Lars-Göran Nilsson
6 Dialog+: B.Braun Hemodiafiltration System . . . . . . . . . . . . . . . . . . . . 79
Marten Kelm, Björn Bröker, and Claudia Barth
7 Online Hemodiafiltration Systems by Bellco: Flexya . . . . . . . . . . . . . 87
Andrea Fiorenzi
8 Online Hemodiafiltration by Fresenius Medical Care . . . . . . . . . . . . 95
Bernard Canaud, Pascal Kopperschmidt,
Reiner Spickermann, and Emanuele Gatti
9 Nikkiso Hemodiafiltration Equipment. . . . . . . . . . . . . . . . . . . . . . . . . 103
Daisuke Toshigami, Uwe Rogalla, and Yoshiro Ueda
10 Nipro Online Hemodiafiltration System: Surdial™-X. . . . . . . . . . . . 111
Matteo Lavezzini
vii
viii Contents
Part III Effects of Hemodiafiltration on Various Biomarkers
11 Effects of Convective Dialysis Techniques

on Electrolytes and Mineral Metabolism. . . . . . . . . . . . . . . . . . . . . . . 121
Andrew Davenport and Marc Vervloet
12 Effects of Haemodiafiltration of Anemia Control. . . . . . . . . . . . . . . . 137
Lucia Del Vecchio, Neelke C. van der Weerd, and Francesco Locatelli
13 Effects of Hemodiafiltration of Inflammation
and Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Andrew Davenport
14 Effects on the Removal of Uremic Toxins . . . . . . . . . . . . . . . . . . . . . . 165
Griet L.R.L. Glorieux and Detlef H. Krieter
15 Effects of Hemodiafiltration on Platelets
and Coagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Menso J. Nubé and Auguste Sturk
Part IV Clinical Aspects of Hemodiafiltration
16 Clinical Trials on Hemodiafiltration . . . . . . . . . . . . . . . . . . . . . . . . . . 199

Muriel P.C. Grooteman, Menso J. Nubé,
and Michiel L. Bots
17 Hemodynamic Stability and Cardiovascular
Effects of Convective Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Jeroen P. Kooman, Frank M. van der Sande,
and Karel M.L. Leunissen
18 Nutritional Aspects of On-Line Hemodiafiltration. . . . . . . . . . . . . . . 233
Pieter M. ter Wee and Denis Fouque
19 Why Is High Volume Online Post-dilution
Hemodiafiltration Associated with Improved Survival? . . . . . . . . . . 239
Menso J. Nubé
20 Hemodiafiltration in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Michel Fischbach, Ariane Zaloszyc,
and Rukshana Shroff
21 Intensified Hemodiafiltration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
Francisco Maduell, Raquel Ojeda,
and Marta Arias-Guillén
22 Are There Any Disadvantages of Hemodiafiltration? . . . . . . . . . . . . 279
Peter J. Blankestijn and Jeroen P. Kooman
Contents ix
Part V Practical Issues
23 Practical Guide to Performing High Volume

Hemodiafiltration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Muriel P.C. Grooteman, Isabelle Chapdelaine,
and Menso J. Nubé
24 Medication and Hemodiafiltration . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Anthe S. Zandvliet, Daniel J. Touw, and E. Lars Penne
Part VI Summary and Conclusions
25 Summary and Current Status of Hemodiafiltration. . . . . . . . . . . . . . 333

Menso J. Nubé, Muriel P.C. Grooteman,
and Peter J. Blankestijn
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
Contributors
Claudia Barth Department of Medical Scientific Affairs, B. Braun Avitum AG,

Melsungen, Germany
Peter J. Blankestijn, MD Department of Nephrology, University Medical
Center Utrecht, Utrecht, The Netherlands
Michiel L. Bots Julius Center for Health Sciences and Primary Care, University
Medical Center Utrecht, The Netherlands
Björn Bröker Department of Research & Development, B. Braun Avitum AG,
Melsungen, Germany
Bernard Canaud, PhD Emeritus Professor of Nephrology, Center of Excellence
Medical, Fresenius Medical Care Deutschland GmbH, Bad Homburg v.d.H.,
Germany
University of Montpellier, School of Medicine, Montpellier, France
Isabelle Chapdelaine, MD Department of Nephrology,
Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada
Andrew Davenport, MD UCL Centre for Nephrology, Royal Free Hospital,
London, UK
Lucia Del Vecchio, MD Department of Nephrology and Dialysis,
A. Manzoni Hospital, Lecco, Italy
Anders Felding, MScEE Technical Services, System Support,
Gambro Lundia AB, a subsidiary of Baxter International, Inc., Lund, Sweden
Andrea Fiorenzi, MBA Equipment Operations, Bellco Srl, Mirandola, Italy
Michel Fischbach, PhD Chef de Service Pédiarie 1, CHU Hautepierre,
Strasbourg, France
xi
xii Contributors
Denis Fouque, MD, PhD Department of Nephrology Nutrition Dialysis,

Centre Hospitalier Lyon Sud, Pierre Bénite, France
Emanuele Gatti Department of Health Sciences and Biomedicine,
Danube University Krems, Krems, Austria
Griet L.R.L. Glorieux, MSc, PhD Nephrology Division,
Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium
Muriel P.C. Grooteman, MD, PhD Department of Nephrology,
VU University Medical Center, Amsterdam, The Netherlands
Marta Arias-Guillén, MD Department of Nephrology, Hospital Clinic,
Barcelona, Catalonia, Spain
Marten Kelm, MBA Department of Medical Scientific Affairs,
B. Braun Avitum AG, Melsungen, Germany
Jeroen P. Kooman, MD, PhD Division of Nephrology, Department of Internal
Medicine, University Hospital Maastricht, Maastricht, Limburg, The Netherlands
Pascal Kopperschmidt, PhD Department of Global Research & Development,
Fresenius Medical Care Deutschland GmbH, Bad Homburg v.d.H., Germany
Detlef H. Krieter, PhD Division of Nephrology, Department of Medicine I,
University Hospital Würzburg, Würzburg, Germany
Matteo Lavezzini, PhD Department of Marketing, Nipro Europe N.V.,
Zaventem, Belgium
Ingrid Ledebo, PhD Director Scientific Support Gambro 1980–2012, Lund,
Sweden
Karel M.L. Leunissen, MD, PhD Division of Nephrology,
Department of Internal Medicine, University Hospital Maastricht, Maastricht,
Limburg, The Netherlands
Francesco Locatelli, MD Department of Nephrology and Dialysis,
A. Manzoni Hospital, Lecco, Italy
Raquel Ojeda López, MD Department of Nephrology, Hospital Clinic,
Barcelona, Catalonia, Spain
Francisco Maduell, MD, PhD Department of Nephrology,
Hospital Clínic Barcelona, Barcelona, Catalonia, Spain
Lars-Göran Nilsson, BSc Department of Baxter CSO, Renal Therapeutic Area,
Menso J. Nubé, MD, PhD Department of Nephrology,
Contributors xiii
Luciano A. Pedrini, MD Department of Nephrology and Dialysis,

Nephrocare – Bolognini Hospital, Seriate, Italy
E. Lars Penne, MD, PhD Department of Internal Medicine,
Medical Center Alkmaar, Alkmaar, The Netherlands
Uwe Rogalla Department of Sales & Marketing, NIKKISO Europe GmbH,
Langenhagen, Lower Saxony, Germany
Claudio Ronco, MD Department of Nephrology Dialysis & Transplantation,
International Renal Research Institute (IRRIV), San Bortolo Hospital,
Vicenza, Italy
Rukshana Shroff, MD, FRCPCH, PhD Nephrology Unit,
Great Ormond Street Hospital for Children NHS Foundation Trust,
London, UK
Reiner Spickermann Department of Global Research & Development,
Fresenius Medical Care Deutschland GmbH, Bad Homburg v.d.H., Germany
Jan Sternby, PhD Department of R&D, Treatment Systems Research,
Auguste Sturk, PhD Department of Clinical Chemistry,
Academic Medical Center, Amsterdam, The Netherlands
James E. Tattersall, MBBS, MD Department of Renal Medicine,
Leeds Teaching Hospitals, Leeds, West Yorkshire, UK
Pieter M. ter Wee, MD, PhD Department of Nephrology,
VU University Medical Center and ICaR-VU, Amsterdam, The Netherlands
Daisuke Toshigami Technical Department, NIKKISO Europe GmbH,
Langenhagen, Lower Saxony, Germany
Daniel J. Touw, PharmD, PhD Department of Clinical Pharmacy
and Pharmacology, University of Groningen, University Medical Center
Groningen, Groningen, The Netherlands
Yoshiro Ueda NIKKISO Europe GmbH, Langenhagen, Lower Saxony, Germany
Frank M. van der Sande, MD, PhD Division of Nephrology,
Department of Internal Medicine, Maastricht University Medical Center,
Maastricht, Limburg, The Netherlands
Neelke C. van der Weerd, MD, PhD Division of Nephrology,
Department of Internal Medicine, Academic Medical Center, Amsterdam,
The Netherlands
Marc Vervloet, MD, PhD Department of Nephrology,
xiv Contributors
Richard A. Ward, PhD Kidney Disease Program, University of Louisville,

Louisville, USA
Ariane Zaloszyc, PhD Children Dialysis Unit, University hospital Strasbourg,
Strasbourg, France
Anthe S. Zandvliet, PharmD, PhD Department of Clinical Pharmacology
and Pharmacy, VU Medical Center, Amsterdam, The Netherlands
Simona Zerbi, MD Nephrology and Dialysis Unit, NephroCare, Bolognini
Hospital, Seriate, Italy
Chapter 1
History and Current Status of Online
Haemodiafiltration
Bernard Canaud and Ingrid Ledebo
Abstract The genesis of hemodiafiltration (HDF) has followed the general

sequence of any new therapy passing through a conceptual phase, a development
phase and a long-term evaluation phase with adequate analysis in each step.
In the conceptual phase unmet needs of end stage kidney disease patients treated
by hemodialysis were identified, proof of concept was established and the necessary
technological development took place.
During the development phase short-term clinical studies demonstrated the
safety and efficacy of the online HDF and long-term clinical studies gave evidence
of benefits and risks of this new renal replacement modality.
After having satisfied these different steps, any remaining questions and/or
uncertainties can be formulated and the future of the therapy can be discussed. In
these entire phases one can identify key discoveries and applications that have con-
tributed to major steps forward, often in a new direction.
In this chapter, we have highlighted such events and discussed their importance.
Keywords End stage chronic kidney disease • Renal replacement therapy • Online
substitution fluid • Cold sterilization process • Convective dose
Introduction: Why Hemodiafiltration Was Needed?
The development of a new renal replacement therapy corresponds to a need

expressed by the nephrology community to correct for shortfalls and/or side effects
observed with the use of conventional dialysis. Looking back at the 1970s,
B. Canaud, PhD (*)

Emeritus Professor of Nephrology, Center of Excellence Medical, Fresenius Medical Care
Deutschland GmbH, Else-Kröner-Straße 1, Bad Homburg v.d.H. 61352, Germany
University of Montpellier, School of Medicine, Montpellier, France
e-mail: Bernard.Canaud@fmc-ag.com
I. Ledebo, PhD
Director Scientific Support Gambro 1980–2012, Lund, Sweden
© Springer International Publishing Switzerland 2016 1

M.J. Nubé et al. (eds.), Hemodiafiltration: Theory, Technology
and Clinical Practice, DOI 10.1007/978-3-319-23332-1_1
2 B. Canaud and I. Ledebo
conventional hemodialysis was performed with low-flux cuprophane membranes,

acetate as buffer source and simple pressure devices to control ultrafiltration. The
majority of patients were treated in 4–5 h sessions two to three times per week. As
a result, efficiency was limited to small water soluble uremic toxins, cardiovascular
tolerance was poor and problems with bioincompatibility and dialysis-related
pathology started to appear (amyloidosis, accelerated ageing and – atherosclerosis).
These factors were pointed out as limitations for long-term sustainability of this
supportive therapy. A need for improving hemodialysis treatment both on the short
term by improving efficacy and tolerability and on the long term by reducing side-
effects was the main focus of clinical research at the time.
The development of a new therapy follows the general sequence of any new
therapeutic agent and goes through a conceptual phase, a development phase and a
long-term evaluation phase with adequate analysis in each step. In the conceptual
phase unmet needs are identified, proof of concept is established and the necessary
technological development takes place. During the development phase short-term
clinical studies demonstrate the safety and efficacy of the therapy and long-term
clinical studies give evidence of benefits and risks. Major milestones achieved in
online HDF development over the last four decades has been summarized in Fig. 1.1.
When this is satisfactorily shown any remaining questions and uncertainties are
formulated and the future of the therapy can be discussed. In all these phases one can
identify key discoveries and applications that have contributed to major steps for-
ward, often in a new direction. For the therapy in focus in this handbook, hemodiafil-
tration (HDF), we would like to highlight such events and discuss their importance.
Conceptual Phase: How Did We Get There?
Unmet Needs
Renal replacement therapy (RRT) was successfully developed during the 1970s but
end stage kidney disease (ESKD) patients were still faced with a high morbidity and
mortality risk dominated by cardiovascular diseases [1, 2]. Although the exact
Fig. 1.1 Major milestones achieved in online HDF development over the last four decades
1 History and Current Status of Online Haemodiafiltration 3
reasons for these shortfalls were not clear, one can acknowledge that they were
multifactorial including patient and comorbid risk profile, past history of chronic
kidney disease (CKD) and care management before starting dialysis, and RRT effi-
cacy and tolerance.
Considering the pioneering work of Babb [3] and Bergstrom [4, 5], later updated
and completed by the Eutox group [6] and others, it becomes clear that uremic
toxins comprise a large spectrum of compounds characterized by molecular
weights, chemical characteristics, kinetics, protein and tissue binding capacities
that extends far beyond that of urea. Focusing on the ‘middle and larger molecule’
substances it is also obvious that these compounds can only be cleared by means of
large pore size membranes and the addition of a driving force such as convection to
solute fluxes.
Proof of Concept
In 1975 Henderson et al. using a synthetic ultrafiltration membrane (XM50, Amicon,

USA), reported the first clinical application of hemofiltration (HF), although at the
time referred to as “hemodiafiltration” [7, 8], see Fig. 1.2. The driving force for this
new therapy was the desire to remove “middle molecules”, i.e. uremic solutes that
were putatively held responsible for some pathophysiologic manifestations of ure-
mia and which could not be cleared in conventional low-flux HD because of their
size. Henderson could show that by using pure convective therapy (HF) it was pos-
sible to extend the blood purification to include a wide range of large solutes, nor-
mally removed by the kidneys. The clinical study also showed that the patients
tolerated the HF sessions much better than their regular HD. Fluid removal to reach
dry weight was better achieved without symptoms [9, 10]. Correction of hyperten-
sion and a high degree of clinical wellbeing was noted among the patients although
acetate was used as main buffer [11]. These results led to great expectations from
the nephrology community. HF was perceived as a superior dialysis therapy and
several groups started clinical trials.
In Europe, Quellhorst pioneered a large HF program using a new high-flux mem-
brane (AN69, Rhone-Poulenc) and conducted controlled crossover studies on
patients treated with HD and HF [12, 13]. He and others could show significant
improvement of vascular stability and reduced incidence of symptomatic hypoten-
sion when patients were treated with HF [14, 15]. These results were presented in
the late 1970s, at a time when the hopes of identifying the “middle molecules” were
dwindling [16, 17]. HF was still considered an attractive therapy, more because of
the improved hemodynamic stability than because of the capacity to remove large
solutes. In 1981, Shaldon predicted: “In at least 20–30 % of patients, progress from
classical diffusion dialysis will benefit the patient and at the same time improve
cost-effectiveness by shortening treatment time, reducing staff requirement and
offer better rehabilitation prospects” [18].
During the 1980s, based on urea kinetic modeling (UKM), Gotch and Sargent
[19, 20] introduced the concept of dialysis quantification and established Kt/V as
the dialysis dose index. Urea was used in this approach as an indicator of dialysis
Fig. 1.2 LW Henderson and the first hemo(dia)filtration machine (Reprinted from Henderson
et al. [7]. With permission from Elsevier)
efficacy, protein catabolic rate and dietary protein intake, and a surrogate of uremic
toxins derived from protein metabolism [21]. Dialysis dose (Kt/V) became a new
driving force and focus in the dialysis world for dialysis research and prescription
[22]. With the prospect of reducing treatment times and optimizing performances
all means were used to enhance the removal of urea. The determinants of diffusive
transport – blood flow rate, dialysis fluid flow rate, surface area and permeability
properties of the dialysis membrane (KoA) – were all adjusted upwards [23–25].
This meant that HF, which only applies convection and thus provides the same
clearance for urea as for larger solutes, was no longer interesting with the ultrafiltra-
tion volumes used at the time (20–25 L/session) [26, 27]. However, there were still
some pioneering groups in research-oriented hospitals who had experienced the
clinical benefits of HF therapy and explored larger ultrafiltration volume to match
performances with new standards [28].
During the late 1970s and early 1980s the dialysis industry thrived thanks to the
growing number of ESKD patients. Ambitious development projects were started in
collaboration with academia and resulted in new membranes and technical innova-
tions that were applied in experimental therapies. One such innovative therapy was
the combination of HD and HF, sometimes referred to as “simultaneous HF/HD”
and later renamed hemodiafiltration. The entrepreneur group in Giessen, having
worked with both HD and HF, felt that each therapy had something to offer [29].
Their goal was to achieve enhanced clearance for small as well as large solutes
while maintaining good hemodynamic stability. By combining regular high-flux
hemodialysis and forced ultrafiltration with substitution fluid provided in sterilized
bags, this group opened a new therapeutic avenue named hemodiafiltration [30, 31].
Technological Development
HDF is technically complex to perform because it requires components needed for

both HD and HF [32]. The membrane in the filter should have good diffusive prop-
erties, high hydraulic permeability for easy ultrafiltration and generous sieving pro-
file to allow passage of solutes up to the size of albumin. Because the fluid is used
for both diffusion and convection, it must meet the corresponding quality require-
ment, i.e. the dialysis fluid should be at least ultrapure and the substitution fluid be
sterile and non-pyrogenic. The fluid composition should be individualized within
physiological limits. Access to fluid must not be a limiting factor, which makes on-
line preparation integrated with the treatment the only option. This places special
hygienic and regulatory demands on the hardware, in addition to accurate volume
control and all other functions in modern dialysis equipment.
Technical limitations, mainly regarding membrane permeability and fluid com-
position and volume, have been the major determinants of the development of HDF
therapy during the course of the 35 years it has been applied. The membranes used
in the early days were suited for diffusive or convective transport respectively but
have been gradually developed and optimized for HDF. Modern membranes com-
bine high diffusive and hydraulic permeability with generous but controlled sieving
of solutes. To achieve these characteristics membranes are today made from various
synthetic polymers, which can be combined to provide optimal biocompatibility as
well as the desired performance.
The fluids have also undergone major changes. In the first HDF trials and for
many years the buffer source was acetate in the dialysis fluid, as in HD, and lactate
in the substitution fluid provided in autoclaved bags, as in HF. When bicarbonate
was introduced in the dialysis fluid, it still took many years until it was included in
the substitution fluid. Based on cold sterilization, as described earlier by Henderson
[33], Canaud et al. introduced and evaluated for the first time in clinic on-line HDF
with bicarbonate using a using a modified HD machine with fluid balancing cham-
bers to control ultrafiltration [34]. After this pilot trial, the feasibility of on-line
fluid preparation was recognized and the advantages became apparent. On-line
preparation of the sterile fluid used for substitution meant not only that bicarbonate
could be used and the electrolyte composition could be individualized. It also made
it possible to increase the dose of therapy by exchanging larger fluid volumes,
which for practical and economical reasons had been restricted to small research
studies when fluid in autoclaved bags were used. Different substitution modalities
have been developed to overcome patient barriers and/or to achieve targeted effi-
cacy of the method in peculiar conditions (pre-dilution, mid-dilution and mixed-
dilution) [35–38]. It was not until on-line fluid preparation became widely accepted,
which with some exceptions occurred in the new millennium, that the limitations
imposed by fluid issues were resolved [39–41].
Although described above as a technical limitation the general introduction of
on-line fluid preparation should probably be viewed as a regulatory limitation [42].
The ultrafilters required for stepwise removal of bacteria and pyrogens from dialysis
fluid were commercially available already in the mid-1980s and prototype systems
for on-line preparation of large volumes of sterile, non-pyrogenic fluid were origi-
nally used for HF. However, sterilization by on-line preparation is still not recog-
nized by the Pharmacopoeia and therefore not considered by regulatory authorities,
so the approval of dialysis machines with on-line capacity met with serious resis-
tance [43, 44].
In some countries, nephrologists managed to convince authorities to approve on-
line HF and HDF, but only with cumbersome safety measures attached to the appli-
cation, which increased labor and cost [45, 46]. Other countries lacked regulations
and practicing nephrologists hesitated to use the therapy. Alternative and/or hybrid
therapies have been developed to bypass those regulatory measures and/or to explore
additional benefits such as acetate-free biofiltration (AFB) and paired filtration dial-
ysis (PFD) or hemodiafiltration with endogenous reinfusion of substitution fluid
after regeneration on resin (HFR) [47–50]. Still, the accumulated European experi-
ence on the safety of performing on-line HDF and the potential of the promising
data from patients treated with on-line HDF finally broke the barrier and during the
new millennium on-line HDF is the only form of the therapy considered [51]. An
international guideline covering practical and safety aspects of on-line fluid prepa-
ration is now widely approved as standard [52].
While waiting for authorities to approve on-line fluid preparation some groups,
mainly in Japan and the US where on-line equipment was not commercially avail-
able, developed their own systems for performing diffusion and convection at the
same time, without using external fluid for substitution [53–56]. They designed
systems that increased ultrafiltration by various pressure manipulations and relied
on backfiltration of dialysis fluid to compensate for excess ultrafiltration. This can
increase the convective transport compared to HD but not to the extent of optimally
prescribed on-line HDF. In addition, the fluid quality may be a problem.
Representing the best of both extracorporeal therapies (HD and HF), hemodiafil-
tration (HDF) has attracted much interest throughout the western world, i.e. Europe,
Japan and the USA, from the early 1980s and it still does, although the therapeutic
application and the questions asked have undergone major changes [57]. Considering
these changes in the development of the therapy, clinical results from different time
periods reflect what could be achieved with the products available at that time, and
comparison with modern therapy should be avoided [58].
Clinical Implementation: What Are the Results?
Safety
Online preparation of substitution solution by cold sterilization process from fresh

dialysis fluid is a fundamental prerequisite for delivering high-volume HDF and HF
modalities. The potential of bacterial-derived products (endotoxin, peptidoglycans,
bacterial DNA) entering the bloodstream in case of cold sterilization failure or inad-
equate disinfection of HDF machine is an important consideration. By applying
strict hygienic rules of disinfection to the online HDF machine, stringent microbial
monitoring and periodical replacement of sterilizing ultrafilters, any risk may be
virtually abolished. Online blood purification modalities necessitate the use of ultra-
pure water and certified machines, and the compliance to strict hygienic rules that
have been detailed elsewhere [59]. For further reading, see Chap. 3. Several studies
have confirmed the safety of the online HDF provided the adequate HDF machines
are used and the best clinical practices are applied [60, 61]. The CONTRAST study
confirmed in 10 centers over more than 20,000 HDF sessions the reliability and
safety of the method [62]. As good clinical practice, it is advisable to monitor clini-
cal symptomatology of HDF treated patients and to ensure measurement of blood
sensitive CRP on a monthly basis [63].
HDF Versus HD in Short and Mid-term Studies
During the 1980s the dialysis industry was influenced by the interest in convective
therapies and introduced a number of associated technological innovations. New
membranes with increased hydraulic permeability, so called high-flux membranes,
were made from synthetic polymers and showed improved biocompatibility when
exposed to blood. Fluid removal during dialysis was simplified and made more
accurate by the incorporation of ultrafiltration control systems in the dialysis equip-
ment. New mixing devices facilitated the inclusion of bicarbonate in the dialysis
fluid and acetate was gradually replaced as buffer source.
Although the development of these innovations was triggered mainly by the
widespread interest in HF and HDF, they could all be used for HD. Performing
HD with high-flux membranes, ultrafiltration control and bicarbonate changed the
therapy significantly. The high-flux membrane allowed for increased ultrafiltra-
tion, which did not cause excess fluid removal because of the volume was con-
trolled. By means of ultrafiltration controller devices in the HD machine, the
excess ultrafiltration was compensated by backfiltration of dialysis fluid. This pro-
vided convective clearance, because the membrane was open and because the
ultrafiltration was increased [64, 65]. The presence of bicarbonate, and even more
so the absence of acetate, enhanced the hemodynamic stability and improved dial-
ysis symptomatology [66, 67]. When high-flux HD was compared with the form
of HDF used at the time, so called classical HDF with 9–10 L substitution fluid in
bags, which provided around 10–12 L of convective volume, the difference in
clearance and symptomatology could not always be detected [68, 69].
When the 1980s changed into the 1990s, urea kinetic monitoring still con-
trolled the prescription of dialysis. Classical HDF provided similar or only slightly
higher urea clearance than high-flux dialysis, but was considered more cumber-
some to perform and was definitely more expensive, so unless favored by reim-
bursement it was of little interest to the urea-believers [70, 71]. However, at this
time a large retention molecule, β2-microglobulin (β2m), appeared on the scene,
calling for convective removal [72–74]. Problems with β2m retention were taken
seriously, especially in Europe and Japan, where more effective and more biocom-
patible convective therapies were again discussed [75–78]. Both HF and HDF
were tested in clinical studies using on-line equipment and large convection vol-
umes [79–84]. Towards the end of the 1990s the flaws of urea kinetic modeling
and its consequence, reduced treatment times and poor outcome, became apparent
to the dialysis community and studies were designed to test new therapeutic alter-
natives [85, 86].
In 2002 the HEMO study could not show any difference in survival between
patients treated with either low or high urea dose or low-flux or high-flux membranes.
A subgroup analysis showed improved survival in long-term dialysis patients treated
with high-flux filters and the HEMO investigators made the reservation that “the
higher β2m clearances achievable with HDF might improve outcomes” [87].
HDF in Long-Term Studies: Patient Outcome
The ultimate benefits of HDF/HF therapies in terms of “hard clinical endpoint” such
as reduction of β2-M-amyloidosis risk, improved survival and reduced hospitalization
that were suggested by retrospective studies have been confirmed by recent prospec-
tive randomized controlled trials [88–91]. The Dialysis Outcomes and Practice
Patterns Study (DOPPS) first suggested that patients being treated with high-effi-
ciency HDF (15–25 L/session) had a 35 % lower mortality than those treated with
low-flux hemodialysis; comparison with high-flux hemodialysis and low-efficiency
HDF (<15 L/session), however, was not significantly different [92]. Two recent pro-
spective randomized trials (CONTRAST and Turkish HDF study) failed to show ben-
eficial effects on mortality (all-cause or CV mortality) as primary endpoint.
Interestingly, both studies showed, in post-hoc analysis, beneficial effects on all-cause
mortality when patients were stratified and allocated to high ultrafiltration volume
(>20 L/session), i.e. to high convective dose [93, 94]. The importance of best clinical
practices and weakness of these studies was identified since 50–66 % of patients
enrolled did not achieve the targeted ultrafiltration volume [95]. The most recent ran-
domized controlled trial, the Catalonian ESHOL study, complying with best clinical
practices and achieving targeted ultrafiltration volume in 90 % of patients proved that
mortality was reduced by 30 % (all-cause and CV cause) in high-volume HDF treated
patients. In addition, the Catalonian study found a reduction of hypotensive episodes
(28 %), stroke (61 %) and infection (55 %) [96]. For further reading, see Chap. 16.
Convective Dose Concept
The burning question in HDF today concerns the effective convection volume, i.e.
the total undiluted ultrafiltration volume [97–99]. How large should it be to make
a difference and how can we best obtain it? To answer this question, a group of
Dutch nephrologists designed the CONTRAST study aiming for 24 L of ultrafil-

tration, i.e. convection volume, per treatment but only achieved an average of
20.7 L [95, 100]. Post hoc analysis showed that the tertiles of patients treated with
the highest convection volume, >21.95 L, had significantly improved survival
[83]. In parallel a similar study was conducted in Turkey, the Turkish study com-
pared on-line HDF with high-flux HD, aimed for 15 L of infusion solution and
achieved an average of 17.2 L [94]. The result was similar to CONTRAST in that
no difference in survival could be shown for the total population, but again a post
hoc analysis of HDF patients treated with the highest convection volume, >21 L
(17.4 L substitution + 3.5 L weight loss), had significantly improved survival. The
secondary result from these two large, randomized, controlled studies was con-
firmed by the ESHOL study, which in the primary analysis showed that all patients
treated with HDF with convection volumes exceeding 22.9 L per session had sig-
nificantly improved survival compared with patients on high-flux HD [86]. Further
information on the pitfalls and reliability of RCTs and meta-analyses on this sub-
ject is provided in Chap. 16.
Remaining or Unsolved Questions Related to Online HDF:

Where Are We Today?
Online hemodiafiltration is no longer an experimental treatment, it is a mature renal

replacement therapy, used daily to sustain life of more than 160,000 ESKD patients
worldwide including 80,000 in the EMEA region [101]. This is presented in Fig. 1.3.
Online HDF represents the most advanced treatment modality for end stage kidney
disease patients [102]. Considering results of recent RCTs, the time has now come
for worldwide, including USA, acceptance of hemodiafiltration as the means to
improve ESKD patient outcomes [103].
The use of highly permeable membranes submitted to high transmembrane pres-
sure regime may lead to increased albumin loss, although improvement of mem-
brane manufacturing technology has reduced the sieving coefficient of albumin and
minimized losses [57]. For more porous or higher cut-off membranes that do leak
albumin, HDF modality exposes the patient to risk significant albumin loss and may
not be a good option. Nevertheless, clinical and biologic consequences of albumin
loss and hypoalbuminemia must be balanced with the putative beneficial effect of
increased removal of uremic toxin-bound substances.
Enhanced loss of nutrients is a theoretical risk associated with all modalities
using high-flux membranes and enhanced convective fluxes. Soluble vitamins, trace
elements, amino acids, small peptides, and proteins may be lost during high-flux
treatments. The total amount of nutrients lost per session is, however, sufficiently
low to be easily compensated for by adequate oral intake [104].
Electrolyte balance depends strongly on patient anthropometric characteristics,
electrolyte concentrations and convective volume achieved during HDF sessions.
Electrolyte prescription (Na, K, HCO3, Ca, Mg) needs to be customized to patient
180 000
online HDF
160 000 conventional HDF
total HDF
140 000
Number of HDF Patients
120 000
100 000
80 000
60 000
40 000
20 000
0
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Fig. 1.3 Development of HDF patients from 2004 to 2014 (Based on data from Ref. [103])
metabolic needs and convective volume. Higher ultrafiltration volumes will need to
reassess electrolyte mass balance and reset prescription accordingly, since all pres-
ent reported studies have been performed with restricted ultrafiltration volume
(<30 L/session in post-dilution HDF). For further reading, see Chap. 11.
Future Development of Online HDF
Modern online HDF equipment provides a unique technical platform that may be
used to facilitate the implementation of new dialysis options (nocturnal HDF, daily
HDF) or to revitilize home or self-care renal replacement therapies with automated
functions such as auto-priming, rinsing or flushing. With liberal access to sterile
apyrogenic fluid new applications can be developed without cost concern.
Conclusions
Online hemodiafiltration can today be considered a mature renal replacement ther-

apy, being used daily to sustain life of more than 80,000 ESKD patients in Europe
(18 % of all RRTs). By combining diffusive and convective clearances, online HDF
offers the most efficient solute removal capacity over the widest molecular weight
spectum of uremic toxins. With high-flux synthetic membrane and ultrapure dialy-
sis fluid, online HDF constitutes the most hemocompatible renal replacement ther-
apy. Safety and efficacy have been proven in numerous short and mid-term clinical
studies. Recent randomized controlled clinical trials tend to accredit the superiority
of online HDF over contemporary HD, i.e. high-flux HD, to the adequate convective
dose (or convective volume) being delivered. Further clinical trials should establish
the optimal convective dose in different clinical settings (patient characteristics and/
or ethnicity, substitution modalities) and to establish the cost-effectiveness of HDF
compared to contemporary HD.
Teaching Points
• The genesis of hemodiafiltration (HDF) has followed the general sequence
of any new therapy passing through a conceptual phase, a development
phase and a long-term evaluation phase with adequate analysis in each
step.
• In the conceptual phase:
– Unmet needs of end stage kidney disease patients treated by hemodialy-
sis were identified (high morbidity and mortality risk, retention of ure-
mic toxins in the middle molecular weight range)
– Proof of concept was established in 1975 (middle molecule removal by
hemofiltration)
– The necessary technological development took place (e.g. combination
of hemodialysis with hemofiltration, improvement of dialyzer mem-
branes, online preparation of substitution fluids).
• During the development phase:
– Short-term clinical studies demonstrated the safety and efficacy of the
online HDF.
– The ultimate benefits of HDF/HF therapies in terms of ‘hard clinical
endpoint’ (e.g. improved survival and reduced hospitalization) as sug-
gested by retrospective studies have been confirmed by randomized
controlled trials
• Finally, remaining questions and/or uncertainties can be formulated (e.g. the
most effective convection volume, the consequences of loss of albumin and
micro-nutrients, electrolyte balance).
References
1. Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged

maintenance hemodialysis. N Engl J Med. 1974;290(13):697–701.
2. Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal
disease. J Am Soc Nephrol. 1998;9(12 Suppl):S16–23.
3. Babb AL, Ahmad S, Bergström J, Scribner BH. The middle molecule hypothesis in perspec-
tive. Am J Kidney Dis. 1981;1(1):46–50.
4. Bergström J, Fürst P. Uremic toxins. Kidney Int Suppl. 1978;8:S9–12.
5. Asaba H, Fürst P, Oulés R, Yahiel V, Zimmerman L, Bergström J. The effect of hemodialysis
on endogenous middle molecules in uremic patients. Clin Nephrol. 1979;11(5):257–66.
6. Vanholder R, Baurmeister U, Brunet P, Cohen G, Glorieux G, Jankowski J, European Uremic

Toxin Work Group. A bench to bedside view of uremic toxins. J Am Soc Nephrol. 2008;19(5):
863–70.
7. Henderson LW, Colton CK, Ford CA. Kinetics of hemodiafiltration II. Clinical characteriza-
tion of a new blood cleansing modality. J Lab Clin Med. 1975;85(3):372–91.
8. Henderson LW, Silverstein ME, Ford CA, Lysaght MJ. Clinical response to maintenance
hemodiafiltration. Kidney Int Suppl. 1975;2:58–63.
9. Baldamus CA, Ernst W, Lysaght MJ, Shaldon S, Koch KM. Hemodynamics in hemofiltra-
tion. Int J Artif Organs. 1983;6(1):27–31.
10. Baldamus CA, Shaldon S, Koch KM. Cardiovascular stability in hemodialysis and hemofil-
tration. In: Cambi V, editor. ‘Short Dialysis’. Topics in renal medicine, vol. 3. Boston:
Martinus Nijhoff Publishing; 1987. p. 321–64. Chap 14.
11. Schünemann B, Girndt J, Quellhorst E. Hemofiltration as a treatment for “dialysis-resistant”
hypertension and hypotensive hyperhydration. J Dial. 1977;1(6):575–83.
12. Quellhorst EA, Schuenemann B, Hildebrand U. Morbidity and mortality in long-term hemo-
filtration. ASAIO J. 1983;6(4):185–91.
13. Quellhorst EA, Schuenemann B, Mietzsch G. Long-term hemofiltration in “poor risk”
patients. ASAIO Trans. 1987;33(3):758–64.
14. Baldamus CA, Quellhorst E. Outcome of long-term hemofiltration. Kidney Int Suppl.
1985;17:S41–6.
15. Quellhorst E, Hildebrand U, Solf A. Long-term morbidity: hemofiltration vs. hemodialysis.
Contrib Nephrol. 1995;113:110–9.
16. Fürst P, Zimmerman L, Bergström J. Determination of endogenous middle molecules in nor-
mal and uremic body fluids. Clin Nephrol. 1976;3(2):178–88.
17. Nolph KD. Short dialysis, middle molecules, and uremia. Ann Intern Med. 1977;86(1):
93–7.
18. Shaldon S. Progress from hemodialysis. Nephron. 1981;27:2–6.
19. Gotch FA, Sargent JA, Keen M, Lee M. Individualized quantified dialysis therapy of uremia.
Proc Clin Dial Transplant Forum. 1974;4:27–35.
20. Gotch FA, Sargent JA, Keen M, Lam M, Prowitt M, Grady M. Clinical results of intermittent
dialysis therapy (IDT) guided by ongoing kinetic analysis of urea metabolism. Trans Am Soc
Artif Intern Organs. 1976;22:175–88.
21. Gotch FA. Urea guided dialysis therapy. Current clinical results. Dial Transplant.
1976;5:15–8.
22. Gotch FA, Sargent JA. A mechanistic analysis of the National Cooperative Dialysis Study
(NCDS). Kidney Int. 1985;28:526–34.
23. Shaldon S, Florence P, Fontanier P, Polito C, Mion C. Comparison of two strategies for short
dialysis using 1m2 and 2m2 surface area dialysers. Proc Eur Dial Transplant Assoc.
1976;12:596–605.
24. Cambi V, Hampl H, Savazzi G, Arisi L, Bignardi L, Garini G, Rossi E, Paeprer P, Kessel M,
Migone L. Trans Am Soc Artif Intern Organs. 1978;24:443–7.
25. Trafford JAP, Sharpstone P, Evans R, Ireland R. Evaluation of ultra-short dialysis. Br Med J.
1979;1:518–9.
26. Shaldon S, Beau MC, Deschodt G, Mion C. Mixed hemofiltration (MHF): 18 months experi-
ence with ultrashort treatment time. Trans Am Soc Artif Intern Organs. 1981;27:610–2.
27. Quellhorst E, Scheunemann B, Hildebrand U. Hemofiltration: an improved method of treat-
ment for chronic renal failure. Contrib Nephrol. 1985;44:194–211.
28. Canaud B, Araujo A, Sany C, Farrell PC, Garred LJ, Shaldon S, Mion C. A urea kinetic
model for haemofiltration. Life Support Syst. 1985;3(1):15–25.
29. Leber HW, Wizemann V, Goubeaud G, Rawer P, Schütterle G. Hemodiafiltration: a new
alternative to hemofiltration and conventional hemodialysis. Artif Organs. 1978;2(2):150–3.
30. Wizemann V, Kramer W, Knopp G, Rawer P, Mueller K, Schütterle G. Ultrashort hemodiafil-
tration: efficiency and hemodynamic tolerance. Clin Nephrol. 1983;19(1):24–30.
31. Wizemann V. Hemodiafiltration: an avenue to shorter dialysis? Contrib Nephrol.
1985;44:49–56.
32. Ledebo I, Blankestijn PJ. Haemodiafiltration-optimal efficiency and safety. NDT Plus.
2010;3(1):8–16.
33. Henderson LW, Beans E. Successful production of sterile pyrogen-free electrolyte solution
by ultrafiltration. Kidney Int. 1978;14(5):522–5.
34. Canaud B, N’Guyen QV, Lagarde C, Stec F, Polaschegg HD, Mion C. Clinical evaluation of
a multipurpose dialysis system adequate for hemodialysis or for postdilution hemofiltration/
hemodiafiltration with on-line preparation of substitution fluid from dialysate. Contrib
Nephrol. 1985;46:184–6.
35. Fischbach M, Attal Y, Geisert J. Hemodiafiltration versus hemodialysis in children. Int J
Pediatr Nephrol. 1984;5(3):151–4.
36. Krieter DH, Falkenhain S, Chalabi L, Collins G, Lemke HD, Canaud B. Clinical cross-over
comparison of mid-dilution hemodiafiltration using a novel dialyzer concept and post-
dilution hemodiafiltration. Kidney Int. 2005;67(1):349–56.
37. Santoro A, Conz PA, De Cristofaro V, Acquistapace I, Gaggi R, Ferramosca E, Renaux JL,
Rizzioli E, Wratten ML. Mid-dilution: the perfect balance between convection and diffusion.
Contrib Nephrol. 2005;149:107–14.
38. Pedrini LA, De Cristofaro V, Pagliari B, Samà F. Mixed predilution and postdilution online hemo-
diafiltration compared with the traditional infusion modes. Kidney Int. 2000;58(5):2155–65.
39. Ledebo I. On-line hemodiafiltration: technique and therapy. Adv Ren Replace Ther.
1999;6(2):195–208.
40. Spalding E, Farrington K. Haemodiafiltration: current status. Nephron Clin Pract. 2003;93(3):
c87–96.
41. Canaud B. Online hemodiafiltration. Technical options and best clinical practices. Contrib
Nephrol. 2007;158:110–22.
42. Ledebo I. On-line preparation of solutions for dialysis: practical aspects versus safety and
regulations. J Am Soc Nephrol. 2002;13 Suppl 1:S78–83.
43. Pirovano D. Regulatory issues for on-line haemodiafiltration. Nephrol Dial Transplant.
1998;13 Suppl 5:21–3.
44. Pirovano D. Regulatory challenges of on-line hemodiafiltration. Contrib Nephrol. 2011;175:
69–73.
45. Martin K, Laydet E, Canaud B. Design and technical adjustment of a water treatment system:
15 years of experience. Adv Ren Replace Ther. 2003;10(2):122–32.
46. Canaud B, Bosc JY, Leray H, Morena M, Stec F. Microbiologic purity of dialysate: rationale
and technical aspects. Blood Purif. 2000;18(3):200–13.
47. Zucchelli P, Santoro A, Spongano M. Acetate-free biofiltration: acidosis correction and car-
diovascular stability. Contrib Nephrol. 1994;108:105–13.
48. Santoro A, Panzetta G, Tessitore N, Atti M, Mancini E, Esteban J, London G, Ara JM,
Miguel JL, Neumann KH, Opatrny K, Perez R, Perrone B, Wizemann V, Zucchelli P. A
prospective randomised European multicentre study of medium-long run mortality and mor-
bidity comparing acetate-free biofiltration and bicarbonate dialysis. J Nephrol. 1999;12(6):
375–82.
49. Ghezzi PM, Frigato G, Fantini GF, Dutto A, Meinero S, Cento G, Marazzi F, D’Andria V,
Grivet V. Theoretical model and first clinical results of the paired filtration-dialysis (PFD).
Life Support Syst. 1983;1 Suppl 1:271–4.
50. Ghezzi PM. Hemodiafiltration with endogenous reinfusion (HFR): evolution of the method.
G Ital Nefrol. 2005;22 Suppl 31:S105–10.
51. European best practice guidelines for haemodialysis (part 1). Section IV: dialysis fluid purity.
Nephrol Dial Transplant. 2002;17(Suppl 7):45–61.
52. Quality of dialysis fluid for haemodialysis and related therapies. ISO 11663:2009–2014.
53. Shinzato T, Sezaki R, Usuda M, Maeda K, Ohbayashi S, Toyota T. Infusion-free hemodiafil-
tration: simultaneous hemofiltration and dialysis with no need for infusion fluid. Artif Organs.
1982;6(4):453–6.
54. Shinzato T, Kobayakawa H, Maeda K. Comparison of various treatment modes in terms of
beta 2-microglobulin removal: hemodialysis, hemofiltration, and push/pull HDF. Artif
Organs. 1989;13(1):66–70.
55. Miller JH, von Albertini B, Gardner PW, Shinaberger JH. Technical aspects of high-flux
hemodiafiltration for adequate short (under 2 hours) treatment. Trans Am Soc Artif Intern
Organs. 1984;30:377–81.
56. von Albertini B, Miller JH, Gardner PW, Shinaberger JH. Performance characteristics of the
hemoflow F 60 in high-flux hemodiafiltration. Contrib Nephrol. 1985;46:169–73.
57. Blankestijn PJ, Ledebo I, Canaud B. Hemodiafiltration: clinical evidence and remaining
questions. Kidney Int. 2010;77(7):581–7.
58. Rabindranath KS, Strippoli GF, Roderick P, Wallace SA, MacLeod AM, Daly C. Comparison
of hemodialysis, hemofiltration, and acetate-free biofiltration for ESRD: systematic review.
Am J Kidney Dis. 2005;45(3):437–47.
59. Cappelli G, Perrone S, Ciuffreda A. Water quality for on-line haemodiafiltration. Nephrol
Dial Transplant. 1998;13 Suppl 5:12–6.
60. Di Felice A, Cappelli G, Facchini F, Tetta C, Cornia F, Aimo G, Lusvarghi E. Ultrafiltration
and endotoxin removal from dialysis fluids. Kidney Int Suppl. 1993;41:S201–4.
61. Vaslaki L, Karátson A, Vörös P, Major L, Pethö F, Ladányi E, Weber C, Mitteregger R,
Falkenhagen D. Can sterile and pyrogen-free on-line substitution fluid be routinely deliv-
ered? A multicentric study on the microbiological safety of on-line haemodiafiltration.
Nephrol Dial Transplant. 2000;15 Suppl 1:74–8.
62. Penne EL, Visser L, van den Dorpel MA, van der Weerd NC, Mazairac AH, van Jaarsveld
BC, Koopman MG, Vos P, Feith GW, Kremer Hovinga TK, van Hamersvelt HW, Wauters IM,
Bots ML, Nubé MJ, Ter Wee PM, Blankestijn PJ, Grooteman MP. Microbiological quality
and quality control of purified water and ultrapure dialysis fluids for online hemodiafiltration
in routine clinical practice. Kidney Int. 2009;76(6):665–72.
63. den Hoedt CH, Bots ML, Grooteman MP, van der Weerd NC, Mazairac AH, Penne EL,
Levesque R, ter Wee PM, Nubé MJ, Blankestijn PJ, van den Dorpel MA, CONTRAST
Investigators. Online hemodiafiltration reduces systemic inflammation compared to low-flux
hemodialysis. Kidney Int. 2014;86(2):423–32.
64. Ronco C, Brendolan A, Lupi A, Metry G, Levin NW. Effects of a reduced inner diameter of
hollow fibers in hemodialyzers. Kidney Int. 2000;58(2):809–17.
65. Lee K, Jeong JH, Mun CH, Lee SR, Yoo KJ, Park YW, Won YS, Min BG. Convection-
enhanced high-flux hemodialysis. Artif Organs. 2007;31(8):653–8.
66. Hakim RM, Pontzer MA, Tilton D, Lazarus JM, Gottlieb MN. Effects of acetate and bicar-
bonate dialysate in stable chronic dialysis patients. Kidney Int. 1985;28(3):535–40.
67. Leunissen KM, Hoorntje SJ, Fiers HA, Dekkers WT, Mulder AW. Acetate versus bicarbonate
hemodialysis in critically ill patients. Nephron. 1986;42(2):146–51.
68. Locatelli F, Mastrangelo F, Redaelli B, Ronco C, Marcelli D, La Greca G, Orlandini G. Effects
of different membranes and dialysis technologies on patient treatment tolerance and nutri-
tional parameters. The Italian Cooperative Dialysis Study Group. Kidney Int. 1996;50(4):
1293–302.
69. Locatelli F, Marcelli D, Conte F, Limido A, Malberti F, Spotti D. Comparison of mortality in
ESRD patients on convective and diffusive extracorporeal treatments. The Registro Lombardo
Dialisi E Trapianto. Kidney Int. 1999;55(1):286–93.
70. Dr Devil. Hemodialysis vs. Hemodiafiltration…the future..or another fad? http://ihatedialy-
sis.com/forum/index.php?PHPSESSID=fb10a0c1341ebd2ae0f07af65de46e94&topic=1502.
msg18977#msg18977.
71. Blankestijn PJ. Is hemodiafiltration medically superior to hemodialysis? Semin Dial.
2014;27(3):248–9.
72. Gejyo F, Yamada T, Odani S, Nakagawa Y, Arakawa M, Kunitomo T, Kataoka H, Suzuki M,
Hirasawa Y, Shirahama T, et al. A new form of amyloid protein associated with chronic hemo-
dialysis was identified as beta 2-microglobulin. Biochem Biophys Res Commun.
1985;129(3):701–6.
73. Gejyo F, Odani S, Yamada T, Honma N, Saito H, Suzuki Y, Nakagawa Y, Kobayashi H,
Maruyama Y, Hirasawa Y, et al. Beta 2-microglobulin: a new form of amyloid protein associ-
ated with chronic hemodialysis. Kidney Int. 1986;30(3):385–90.
Another random document with
no related content on Scribd:
Friends being to encourage a school in this [Sidenote: Friends
town, and in order hereunto they have agreed school set up
with George Keith to assure him a certain salary under Geo. Keith]
of 50 pounds per year to be paid quarterly, with
house rent, convenient for his family and school, with the
profit of his school for one year, and for two years more to
make his school worth to him 120 pounds per year, if he shall
think fit to stay in this place, the said George also promiseth
to teach the poor (which are not of ability to pay) for nothing.
The abovesaid Keith having heard the proposals of Friends,
readily assented and agreed thereto, his salary beginning
from the time school begins. It is agreed that it be also
mentioned to the next Quarterly Meeting for their concurrence
with the same, as also agreed that Anthony Morris give notice
to the several monthly meetings in this county.[149]
The number of children who attended this school [Sidenote: A

is not known, but it is clear that it grew rapidly. In larger school
January, succeeding the first establishment, the needed]
new master complained of the “inconvenience and [Sidenote: Makin
straitness” of his school and Anthony Morris and hired as usher]
Samuel Carpenter were appointed to consult with
Robert Turner for a more convenient situation.[150] The first
interpretation of “straitness” would undoubtedly be that it was
crowded, and that might well have been true without there having
been an increase in the size of the school; more conclusive proof of
the rapid increase in numbers is to be found in the fact that Thomas
Makin was hired as usher to assist Keith,[151] probably about
February, 1690.[152] A more convenient room for the school was
arranged for with John Fuller at thirteen pounds per year, three
pounds more than was paid for the first.[153]
In the 3rd month, 1691, Keith made known his [Sidenote:
intention of leaving the school,[154] whether Thomas Makin
recommended by
because of dissatisfaction with the school itself or Keith to be
the beginning of the feeling against the Quakers master]
which resulted in his rupture with them,[155] it is not [Sidenote: Makin
known, and recommended to the meeting the chosen]
appointment of his usher, Thomas Makin, to take
his place.[156] It was Keith’s desire to leave on 4th month, 10th and
he may have discontinued teaching at that time, but it appears that
his account against the meeting was not settled until the eleventh or
the twelfth month, 1691.[157] According to his suggestion concerning
Makin, the meeting appointed a committee to consult with him,[158]
the outcome of which was a satisfactory agreement. It would appear
from numerous references to the subject, that the matter of getting
the subscriptions and keeping them paid was a chief source of
trouble, which required their constant energies and attention.[159] In
1693 Thomas Makin brought in a bill against the meeting for
£12/15/7, which was still owing for his services as usher in 1690.[160]
The last four years of the century saw greater [Sidenote: Penn
strides made in the better establishment of said to have
education as a system. In 1696 it was agreed that written letter to
Lloyd about the
there should be established four meetings a year, school]
the chief function of which was the religious
education of the youth in the principles of Friends.[161] Steps were
shortly taken for the establishment of the so-called “free school.”
Penn had written to Thomas Lloyd, President of the Council, in 1689,
advising that a grammar school be set up (that of George Keith)[162]
and it was this same school which in 1697 the meeting desired to
make a “free school.” On 10th month, 31st, 1697:
A paper for the encouragement of a free school was this

day read, whereupon Samuel Carpenter and James Fox are
desired to treat with Daniel Pastorius and Thomas Makin
concerning the same, and—they desire the Friends of the
town to meet together this day week, about the 1st hour at
this meeting house to consider further of it, and that Daniel
Pastorius and Thomas Makin be present.[163]
In the month following (11th month) Samuel [Sidenote:
Carpenter reported to the assembly that the Pastorius and
committee had met with Daniel Pastorius and Makin in the
school]
Thomas Makin and agreed to pay each of them
forty pounds per year for keeping school.[164] The means of support
was the familiar subscription blank, Samuel Carpenter and James
Fox being the first appointed to take them. School was to begin the
first of the following month, in the room over the meeting house,
which had been prepared for that purpose.[165] In the 12th month a
petition was sent to the Governor and Council, requesting the
ordaining and establishment of the “Public School.” The text of the
petition is as follows:
[Sidenote: Petition
The humble petition of Samuel Carpenter ... to Council to
in behalf of themselves and the rest of the incorporate the
people called Quakers, who are members of the school]
Monthly Meeting, ... showeth that it has been and is much
desired by many that a school be set up and upheld in this
town of Philadelphia, where poor children may be freely
maintained, taught and educated in good literature, until they
are fit to be put out as apprentices, or capable to be masters
or ushers in the same schools. And forasmuch as in the laws
and constitution of this government it is provided and enacted
that the Governor and Council shall erect ... public schools ...
reward the authors of useful sciences and laudable inventions
... therefore, may it please the Governor and Council to ordain
and establish that in the said town of Philadelphia a public
school may be founded, where all children and servants, male
and female, whose parents, guardians and masters be willing
to subject them to the rules and orders of the said schools,
shall from time to time with the approbation of the overseers
thereof for the time being, be received and admitted, taught
and instructed; the rich at reasonable rates, and the poor to
be maintained and schooled for nothing. And to that end a
meet and convenient house or houses, buildings and rooms
may be erected for the keeping of the said school, and for the
entertainment and abode of such and so many masters,
ushers, mistresses and poor children, as by orders of said
meeting shall be limited and appointed from time to time. And
also that the members of the aforesaid Meetings ... make
choice and admit such and so many persons as they think fit,
to be masters, overseers, ushers, mistresses and poor
children of the said school, and the same persons ... to
remove or displace as often ... as they shall see fit. And that
the overseers and the school aforesaid, may ... be ... in name
and deed, a body politic and corporate, to have continuance
forever by the name of the Overseers of the Public School
founded in Philadelphia at the request of the people of God
called Quakers. And that they, the said overseers, may have
perfect succession, and by that name they and their
successors may hold and enjoy, all lands, tenements and
chattels, and receive and take all gifts and legacies as shall
be given, granted or devised for the use and maintenance of
the said school and poor scholars, without any further or other
license or authority from this Government in that behalf;
saving unto the chief Proprietary his quitrents of the said
lands. And that the said overseers by the same name shall
and may, with consent of said meeting, have power and
capacity to devise and grant by writing, under their hand and
seal and of said lands and tenements and to take and
purchase any other lands ... for ... advantage of said school.
And to prescribe such rules and ordinance for the good order
and government of the same school ... successively, and for
their and every of their stipends and allowances, as to
members of the said Meeting for the time being ... shall seem
meet; with power also to sue and to be sued, and to do and
perform and execute all and every other lawful act and thing,
good and profitable for the said school, in as full and ample
manner, as any other body politic or corporate more perfectly
founded or incorporated, may do.[166]
[Sidenote: The
petition granted
This request was immediately granted by the and charter
issued by Penn in
Council,[167] and the school thus incorporated in 1701]
1697.[168] In 1701 Penn confirmed its incorporation
by the following charter:
William Penn True and absolute Proprietary and Governor

in Chief of the Province of Pennsylvania and territories
thereunto belonging. To all to whom these presents shall
come sendeth greeting. Whereas Charles the Second, late
King of England by his letters patents bearing date the fourth
day of March in the three and thirtieth year of his reign did
grant unto me my heirs and assigns the said Province And
Absolute Proprietary thereof with full power to me by the
assent of the freemen there to make laws for the good and
happy government of the same with divers other powers
preheminsures jurisdictions, privileges and immunities therein
specified. And Whereas I with a great colony of the People of
God called Quakers for the free enjoyment of liberty of our
consciences in matters of religion as of other privileges and
advantages in the said patent granted as well to me the said
Proprietary and Governor as also to the said people did
transport ourselves unto the said Province and at our own risk
costs pains and charges settled and planted the same the soil
also of the said Province being first by me purchased of the
Indian Natives. And forasmuch as by the laws of the said
Province since enacted the Governor and Council have power
to erect and order all public schools of literature and science.
And Whereas Samuel Carpenter—Edward Shippen—Anthony
Morris—James Fox—David Lloyd—William Southby and John
Jones in behalf of themselves and the rest of the said people
called Quakers Members of their Monthly Meeting at
Philadelphia in the said Province by their petition to the
Governor and Council of the said Province and territories at
Philadelphia the tenth day of the twelfth month Anno Domini
one thousand six hundred ninety seven (eight) set forth that it
was the desire of many that a school should be set up and
upheld in the said town of Philadelphia where poor children
might be freely maintained taught and educated in good
literature until they should be fit to be put apprentices or
capable to be masters or Ushers in the said school requesting
the Governor and Council in the said petition to ordain that at
the said town of Philadelphia a Public School might be
founded where all children male and female whose parents
guardians or masters might be willing to subject them to the
rules and orders of the school should from time to time with
the approbation of the overseers thereof for the time being be
received or admitted taught and instructed the rich at
reasonable rates and the poor to be maintained and schooled
for nothing. And that to that end a meet and convenient house
or houses buildings or rooms might be erected for the keeping
of the said school and for the entertainment and abode of
such and so many Masters Ushers Mistresses and poor
children as by the order and direction of the said Monthly
Meeting should be free from time to time limited and
appointed and also that the members of the aforesaid
meeting for the time being might at their respective monthly
meeting from time to time make choice of and admit such and
so many persons as they should think fit to be Overseers
Masters Ushers Mistresses and poor children of the said
school and the same person or any of them to remove and
displace as often as the said meeting shall see occasion, and
that the overseers and school aforesaid might forever
thereafter stand and be established and founded in name and
in deed a body politic and corporate to have continuance
forever by the name of the Overseers of the Public School
grounded in Philadelphia at the request cost and charges of
the people of God called Quakers. And that the said
Overseers might have perpetual succession, and by that
name they and their successors forever, have hold and enjoy
all the lands tenements and chattels and receive and take all
gifts and legacies that should be given granted or devised for
the use and maintenance of said schools and poor scholars
without further or other license or authority from the
government on that behalf. Saving unto the Chief Proprietary
his quit rents out of the said lands and that the said Overseers
by the same name might with consent of the said Meeting
have power and capacity to demise and grant by writing
under their hand and common seal any of the said lands and
tenements and to take and purchase any other lands and
tenements and hereditaments for the best advantage of the
said schools and to prescribe such rules and ordinances for
the good order and government of the said school and of the
masters ushers mistresses and poor children successively
and for their and every of their stipends and allowances as to
them members of the said monthly meeting for the time or the
major part of them should seem meet, with power also to sue
and be used and to do perform and execute all and every
other lawful act and thing good and profitable for the said
school in as full and ample manner as any other body politic
and corporate more perfectly founded and incorporated might
do and by the said petition which I have seen may more fully
appear whereupon my then lieutenant Governor and Council
did grant and order that the said schools should be founded
and erected with the incorporation privileges and powers as
desired. Now forasmuch as those of the said petitioners that
are living have made fresh application to me in Council for
confirming the said lieutenant Governor and Councils order
and grant upon the said petition which being well weighed
and considered by me I greatly favor the good inclinations
and just and laudable desires and conscientious regards of
the said petitioners and people for the education instruction
and literature of their children and posterity and more
especially their care and concerns for the poor on that
behalf....
Therefore Know Ye that pursuant to the powers to me
granted as aforesaid and to the laws of the said Province
already enacted I have (by and with the consent of my
Provincial Council) granted and confirmed all and every
request matter and thing ... contained in the said petition and
do by these presents for me my heirs and assigns grant
ordain and establish that the said Public School shall be
erected and founded, and I do grant, ordain and found the
same to be kept forever hereafter in the said town of
Philadelphia or in some convenient place adjacent as the
overseers of the said school for the time being shall see meet
and I do likewise grant and ordain that in the said school all
children and servants as in the school petition requested shall
from time to time (with approbation of the said Overseers) be
received admitted taught and instructed as in the same
petition is mentioned and desired and to the end that all meet
and convenient houses, rooms, chambers and buildings may
be erected for keeping of the said schools and entertainment
of the masters ushers mistresses and poor children to be
therein admitted as hereinafter mentioned. I do by these
presents for me my heirs and successors grant and ordain
that from the day of the date of these presents forever
hereafter the members of the Monthly Meeting of the said
People called Quakers in the town of Philadelphia for the time
being shall have full and absolute power and authority and the
same power is hereby given unto them in their respective
monthly meetings from time to time to make choice of and
admit such and so many persons as they shall think fit to be
Overseers Masters Ushers Mistresses and poor children of
the said school and the same persons or any of them to
remove and displace as often as the said Meeting shall see
occasion and likewise that the said Overseers shall have like
powers and authority (with the direction and consent of the
said Meeting) from time to time to frame and erect or cause or
procure to be framed and erected such and so many houses
and buildings as they shall see meet for the use and service
of the said schools. And moreover I do by these presents for
me my heirs and successors grant and ordain that the
overseers and schools aforesaid shall forever hereafter stand
and be established and founded and are hereby founded
erected and established in name and in deed a body politic
and corporate to continue forever by the name of The
Overseers of the Public School founded in Philadelphia at the
request cost and charges of the People of God called
Quakers. And also that they the said overseers shall have
perpetual succession and by the said name they and their
successors shall forever have hold and enjoy (to the use of
the said school) all the messuages lands tenements
hereditaments goods and chattels and receive and take all
gifts and legacies already given granted and devised or that
shall be hereafter given granted or devised to the use and
maintenance of the said school and masters ushers
mistresses and poor scholars thereof without further or other
leave license authority or power whatsoever from me my heirs
or successors or from this government or any therein on that
behalf saving unto me my heirs and successors the
respective quit rents and other duties and payments out of the
said messuages lands tenements and hereditaments and
every of them reserved and payable in and by their several
original grants and patents and furthermore I do by these
presents for me my heirs and successors give and grant unto
the said Overseers by the name aforesaid full power license
and authority to give grant bargain sell alien enfeoff or demise
with the consent of the said meeting by writing under their
hands and common seal (or the hands and said seal of so
many of them as shall make a quorum) to such person or
persons his or her heirs or their heirs executors administrators
and assigns as shall be willing to purchase or rent the same
all or any of the aforesaid messuages lands tenements and
hereditaments goods and chattels and likewise to purchase
receive and enjoy all or any other messuages houses lands
tenements and hereditaments for the best advantage of the
said school. And also to frame make and prescribe such rules
orders and ordinances for the good order and government of
the said school and of the masters ushers mistresses and
poor children thereof successively and for their and every of
their stipends salaries and allowances as to the members of
the said Monthly Meeting for the time being or the major part
of them (in their respective meetings) shall seem meet with
power also to the said overseers by the name aforesaid to
sue and be sued and to do perform and execute and suffer to
be done all and every other lawful act and thing good and
profitable for the said school in as full and ample manner as
any other body politic or corporate more perfectly founded
and incorporated may and can do. And I do for me my heirs
and assigns ordain and grant that the said school and the
masters ushers members officers and scholars and all other
persons placed or to be placed in the said school shall forever
hereafter be accepted and freed from all visitation punishment
and connection to be had used or exercised by any person or
persons whatsoever other than the said Overseers for the
time being and their successors. In Witness whereof I have
hereunto set my hand cause the Great Seal to be affixed
dated at Philadelphia the five and twentieth day of the eighth
month in the thirteenth year of the reign of William the third
over England etc. King etc. and the one and twentieth of my
government Anno Domino one thousand seven hundred and
one 1701. Recorded the 5th 10th 1701.[169]
Wm. Penn.
For Aaron K. Dunkel, Sec’y of Internal Affairs,
W. B. Huston.
The charter of 1701 was confirmed and enlarged [Sidenote:

by another of 1708,[170] according to which the Rechartered in
1708, and 1711,
corporation was to consist of fifteen persons extended
(Quakers) by the name of “The Overseers of the privileges]
Public School, founded in Philadelphia, at the
request of, cost and charges of the people called [Sidenote: Made a
self-perpetuating
Quakers.” The charter of 1711[171] contained corporation]
extended privileges[172] and also provided that the
election of new members of the board of overseers should be the
right of the overseers themselves, thus constituting them a self-
perpetuating corporation.[173] From this the reader might expect that
the school at once became independent of the Friends’ meeting, but
this did not occur, since the original members or overseers were
Friends and continued to appoint Friends as their successors.
Reports on the various details of the business of the school
continued to come into the monthly meeting, but it is not to be
considered that we find there a complete story of its existence.[174]
In 1699 it was found that the affairs of the school took too much time
in meeting and therefore it was decided that Friends in the care of
schools and press should meet on sixth day before monthly meeting,
transact their business and keep a record thereof in books provided
for the purpose.[175]
The affairs of the school continued much the [Sidenote:
same as though no charter had been requested or Mistresses
granted. The records lead one to think that the employed
schools]
in
growth was very rapid. Pastorius and Makin had

become the masters in 1697 and by 1699 the indications are that
“mistresses” were also employed, money being turned over to
Anthony Morris to “pay the schoolmasters’ and the mistresses’
salaries.”[176] This is the first mention made of women as teachers.
Pastorius having severed his connections with the school in 1701
steps were taken to fill the vacancy, it being decided that the
newcomer should show his ability by competing with the one
remaining master, Thomas Makin.[177]
[Sidenote:
Griffith Owen ... recommended John Cadwalader to fill
Cadwalader as a person very fit for an assistant vacancy made by
Pastorius’ leaving]
in the school, and it being proposed a good
method for the better improvement of the scholars that they
be equally divided between them for trial to see which of them
best discharged their duty, there having been great complaint
of former neglect. The meeting approves thereof and desires
the said Griffith to acquaint John Cadwalader thereof, and
that he may have twenty pounds for a half year for a trial, as
the former master had, and Anthony Morris is desired to show
Thomas Makin this minute for his information in the matter.
[178]
MASTERS AND MISTRESSES FROM 1700 TO
1800
Nothing like a complete or connected story can [Sidenote: Makin
be given with reference to the masters and plans to leave
mistresses of this period, due to a lack of adequate school]
available records. In August, 1701, Thomas Makin [Sidenote:
announced his intention of leaving the school and Cadwalader
requested that his accounts be settled.[179] John becomes
headmaster]
Cadwalader, who had been his assistant since
1700, was interviewed as to his ability to undertake [Sidenote:
the headship of the school; intimating if he thought Salaries
increased]
himself fit, he would be further considered.[180]
There is no direct record of how Mr. Cadwalader rated himself as
teacher, but he was continued in the capacity of master. He found
the limited salary[181] almost too small for the support of his family
and upon his request it was soon raised to fifty pounds per year.[182]
At the same time the salary of a mistress, Olive Songhurst, whom we
meet for the first time and with scant introduction, was increased five
or ten pounds. The prospect of a higher salary does not appear to
have attracted him much for we learn of his intended separation from
the school in May, 1702. It is not clear that he did actually sever his
connection therewith at that time, for in June, 1703, it was desired
that John Cadwalader, schoolmaster, be paid ten pounds that was
left by Robert Jones for the use of the Public School.[183] This sum
may have been for other services such as copying, which he
frequently performed,[184] but it is more probable that he was
convinced of the advantages of remaining at a salary of fifty pounds
per year, with the additional sums paid for the copying work.[185]
John Every’s connection with the school as usher [Sidenote: John
is first announced in April, 1702, when he made Every, usher]
demands for an increase of salary to thirty pounds,
[Sidenote: Makin
which was agreed to.[186] He remained there nearly returns]
two years and then departed, making a place for
Thomas Makin, who returned at his request, [Sidenote: Jacob
agreeing to accept the salary previously paid to Naylor suggested
Every. These two masters, Makin and Cadwalader, for teacher]
appear to have been employed continuously until
1706, when they decided the school could not furnish a competent
living for both of them and Cadwalader accordingly left.[187] There
were further suggestions considered at that time and Friends
appointed to endeavor to secure a qualified master from England. So
far as the meeting’s minutes record, it seems that Thomas Makin
was the only master employed from 1706 to 1708, when it was
suggested that Jacob Naylor be employed as a teacher.[188]
The duties of the schoolmasters were by no [Sidenote: Extra
means limited to the routine of the schoolroom. school room
They were required to be careful of their several duties]
scholars and often had to do police duty among
them during the meetings on first day.[189] The master’s only hope
for any respite from the imposition of such duties was to stand firmly
for his rights, else he might have been given charge of all the
children in the meeting. John Walby, a master, when asked to
perform a similar service, made answer that “he would take care of
his own scholars, but did not care to undertake any further.”[190] His
objection was sustained and another Friend endeavored to perform
the task.
In 1711 William Robbins[191] came to wield the [Sidenote: William
rod in Friends School, having requested permission Robbins]
to keep school in a part of the Friends’ [Sidenote:
schoolhouse, which was “granted for the Richard Warden]
present.”[192] It cannot be determined how long he
remained in that capacity, but the following year it [Sidenote:
Thomas Makin]
was proposed that Richard Warden be allowed to
teach school in one end of the schoolhouse, and it [Sidenote:
is quite probable that he filled the place of Robbins. Richard
Brockden]
[193] On the other hand, if Robbins did leave at that
time he had returned again to the school in 1715.[194] Thomas Makin

had in the meantime severed his connection with the school, but not
permanently. Seven years after the employment of Richard Warden
(1719) a vacancy occurred and a committee was appointed to visit
the overseers requesting them to take action regarding the vacancy.
[195] From this it may be judged that the overseers were at times
remiss in their attention to their trust. The overseers were set in
action, and Thomas Makin was secured to fill the place, provided he
would agree to teach six children of the poor and give up the house
when Friends ordered him to do so.[196] He doubtless filled a minor
position at this time, though he was offered a better one, later in
1722, provided Richard Brockden were willing to leave it, which does
not appear to have met with the said Brockden’s approval.[197] Of
Richard Brockden little is known, save that he had been
schoolmaster at Byberry about 1710 or 1711.[198] In 1724 William
Robbins[199] mentioned above as a teacher some years earlier,
applied for a place as master. It was agreed that he be allowed to
teach on the condition that he would agree to teach at least four
children for the use of the house, if ordered to do so.[200]
It is quite probable that for most of the ten years [Sidenote: J.
preceding 1730 the school was under the charge of Walby]
three or four masters just mentioned, Robbins,
Brockden, Makin and Warden. They shifted quite [Sidenote: Death
of T. Makin]
often, that is certain. In 1730 mention is made of a
John Walby as master; but no further account of him is given.[201]
Thomas Makin’s career as teacher very likely came to an end in that
period, as he was getting aged, though he may have taught up to the
time of his death. An account of his death is given in the Weekly
Mercury of 1733.[202]
From 1730 there is only an occasional mention [Sidenote:
made of the masters employed at the public Anthony Benezet
school, until we come to the period about 1770 employed 1742]
when the names were occasionally given in [Sidenote: Robert
committee reports on the condition of the schools. Willian master in
However, with the fourth decade came a period of 1748]
real greatness, for in 1742[203] began the services
of Anthony Benezet, of whom considerable mention is made
elsewhere, who continued in the public school till 1782.[204] He had
throughout his life been interested in the Negroes and for several
years previous had cherished a desire to work in their schools. His
request, in that regard, was accordingly granted in 1782, after John
Houghton relinquished that position.[205] He continued to teach the
Negro school, until the time of his death two years later.[206] In 1748
Robert Willian came from England for the purpose of keeping
Friends school, and was accordingly accepted into their meeting,
having produced the customary certificate from his home meeting at
Scarborough in Yorkshire.[207] The next mention of a new master in
the ranks is concerned with Josai, who married in 1763.[208]
Encouragement was at all times given to women as teachers,
mention having already been made to their employment as early as
1699.[209] In 1764:
[Sidenote: Ann
The meeting being informed that Ann Brientnall
Brientnall is desirous of keeping a small school establishes small
for the instruction of Friends children only in school]
reading and sewing and not being at present able to hire a
place suitable for the purpose, requests the use of a vacant
lower room in one of the alms-houses, and Friends approving
her proposal, it is agreed that she may make use of one of
these rooms for that purpose until she can accommodate
herself elsewhere, or it may be wanted (for other purposes).
[210]
The recommendations of the Yearly Meeting of Philadelphia in

1778,[211] produced a very beneficial effect upon the school affairs in
all of its monthly meetings. Thereafter, reports were sent in, bad,
good and indifferent, which were much superior to anything that had
been done previously, though they were still too infrequent and
abbreviated in regard to information contained. A digest of the report
of 1779 follows, which shows the number of teachers in the several
schools at that time:[212]
1. The Grammar School was presided over [Sidenote:
by John Thompson who also taught writing and Schools reported
arithmetic. in 1779]
2. John Todd taught reading, English, writing, arithmetic

and some branches of mathematics.
3. Another master was Joseph Yerkes, who taught the
same branches as Todd.
4. George Smith taught reading, writing and arithmetic to
the children of Friends and others.
5. Anthony Benezet at this time was employed in teaching
the Girls’ School in which were received also the children of
other denominations besides Friends.
6. Sarah Lancaster taught the younger children of both
sexes the rudiments of learning, and other branches suitable
to girls.
7. Rebecca Jones and Hannah Cathrall taught together in
the same school, which was for girls, a large number of them
poor.
8. A school for younger boys and girls of various societies
was taught in Pine Street by Essex Flower.
9. Spelling and reading were taught the younger children by
Ann Rakestraw.
It appears from the meeting’s records that these masters and

mistresses were all Friends, and that the schools which they taught
were under the direction of the overseers of the public school.[213]
Five years later another report was prepared and presented on the
state of schools. At the later date several new names are found
among the teachers.[214]
[Sidenote:
1. The Latin and Greek Grammar School is Schools and
under the direction of Robert Proud, the teachers reported
in 1784]
historian.[215]
2. John Todd still continues in his old place.
3. Isaac Weaver teaches boys reading, writing, and
arithmetic.
4. Sarah Lancaster continues in her old position as teacher
of young children.
5. William Brown, engaged in teaching a girls’ school.
The five schools above mentioned were under the direction of the
school corporation of overseers, and poor children were taught there
free of expense. The committee also reported on five other schools,
whose masters and mistresses were either Friends or made the
professions of that religious society.[216]
[Sidenote: Other
1. Mary Harry, teaching in Charters Alley. schools reported]
2. Joseph Clarke, teaching in the girls school.

3. Mrs. Clarke (wife of Joseph).
4. Ann Marsh, teaching about fifty girls.
5. Mary McDonnell, teaching fifteen children.
This report of 1784 is the best during the century [Sidenote:

which gives a clew to the members in the teachers’ Richard
ranks. The growth from a school employing one Hartshorne
superintendent of
teacher to a system employing ten does not seem the new school
great when measured by our present standards of established at
increase, but for that century it is significant of rapid Westtown]
growth. Many of the teachers were people of no
great importance, whose names were probably never known outside
of Quaker circles; others were distinctly well known. In 1799 we find
one other Quaker schoolmaster mentioned, Richard Hartshorne. The
idea of a boarding school for Friends’ children had received quite an
impetus about 1791, due largely to the interest and influence of
Owen Biddle,[217] and by 1799 the school was ready to begin
operations.[218] Richard Hartshorne was chosen to serve as its first
superintendent and with the permission of the Monthly Meeting of
Philadelphia moved to Westtown in 1799.[219]
SUPPORT OF THE SCHOOLS

From the very beginning of the schools in [Sidenote: Three
Philadelphia their primary means of support lay in chief means of
voluntary subscriptions. We have already seen that support]
this was the accepted means of raising money to
maintain the poor and orphans,[220] and also to build their meeting
houses; it was quite the natural way, really about the only way then
familiar to them for maintaining their school system. As the meeting
grew and the schools also increased many members were led to
believe that it was advisable to endow them with legacies. This being
in accordance with the recommendations of the Yearly Meetings of
London and Philadelphia,[221] it became quite a common procedure
in Philadelphia, as also in the other monthly meetings. Their third
means of support was the rate which was paid by all children whose
parents were able to bear the expense of their education.
As has been stated, subscriptions were made [Sidenote:
voluntarily, though they might be rigorously Subscriptions
solicited, enough at least to make some feel urged, but not
compulsory]
uncomfortable who did not contribute when they
were able. There are instances which might be [Sidenote:
considered as mandatory though such cases are Subscription
method not
very rare. One such occurred in 1701 when, Tobias entirely
Dinnock desiring a certificate, the meeting reported satisfactory]
there was nothing to hinder it save that he had not
paid anything toward the school.[222] This does not mean that he had
to subscribe but it was doubtless unpleasant pressure to have
brought to bear on one. Subscriptions were usually made and paid at
the subscriber’s convenience, or on a date which he designated
when making the subscription. Though this was ideally satisfactory it
often failed to work out just at the right time, so it was necessary to
appoint a committee to go out after the subscriber and get that which
he had promised to pay. The first record of a committee appointed
on a service of this kind was in 1691. The work of such committees
was continued throughout the century, and the following extract will
indicate very well their function, without further explanation or
reference.
Whereas several of the subscriptions towards the school

are unpaid, the Meeting being engaged for the same, they
have requested Alexander Beardsley, Anthony Morris, Francis
Rawles, John Delavall and Samuel Richardson to use their
endeavors to get what is unpaid of the said subscriptions, and
they are desired to pay what money they receive unto Robert
Turner and give account thereof to the next Monthly Meeting.
[223]
The rates paid by parents in the earlier years of [Sidenote: Rates

their colony are seen in the establishment of charged]
Flower’s school in 1683.[224] The next references
made to the amounts paid for instruction, under the rate system, are
in the report of the school committee of the Overseers in 1784.[225]
Flower received four shillings per quarter for teaching reading, six
shillings for reading and writing, and eight for reading, writing and
casting accounts; if by the year, then everything was furnished for
ten pounds. In 1784 Isaac Weaver received thirty shillings per
quarter for teaching the same subjects which Flower had taught for
eight.[226] William Brown also received the same amount for the
same subjects which he taught the whole day.[227] Joseph Clarke
was teaching for thirty shillings. For instruction in the three R’s it
appears that the general tendency for the cost in 1784 was about
twenty-two shillings higher than it was in 1683.[228] Small children
were taught generally at about fifteen shillings per quarter, or half the
customary price for older pupils whatever that might be. The general
custom was that in cases where the school corporation sent poor
children to a teacher they were admitted for a lesser rate than the
others; if fifteen shillings were paid by others, then ten shillings might
be paid for the poor children, schooled at the trustees’ expense.
These prices for teaching among the Quaker masters are quite
comparable with those demanded by other private masters in the city
at about the same dates.[229]
As was cited previously in this work,[230] the [Sidenote: Special
practice of making special donations, bequests and bequests and
legacies
legacies was urged by the yearly meeting as a recommended
proper means of support for the schools or other and their probable
institutions. These recommendations of the yearly effect]
meeting which were written in the form of letters,
were transmitted to the quarterly meetings and through them
reached all members of the monthly and preparative meetings in the
compass of the general assembly. It cannot be doubted that they
were a very important means to instill a desire to give to a worthy
cause, and the very similar procedure in all monthly meetings seems
to indicate that they constituted the most effectual means for getting
anything definite done towards establishing any permanent
foundation.
Nothing in the way of a complete survey of [Sidenote: Will of
various legacies and donations given to the John Lineham]
schools in Philadelphia will be attempted here,
[Sidenote:
even granting that it might be interesting enough, Legacies of Wade
but a few of them will be treated briefly. The first and Richards]
example of this individual philanthropy came before
the monthly meeting in 1699, when the will of John Lineham was
read, by which he proposed to leave “twenty pounds for the use of
the public school.”[231] This sum was not to be expended at once for
present needs but was to be kept as a “stock forever for that use.”
Two members, John Kinsey and Ralph Jackson, were ordered to pay
in the said amount that it might be turned over to Edward Shippen
the treasurer. Other legacies were left by Robert Wade[232] and Mary
Richards.[233] In regard to the former there was trouble about getting
it settled, which lasted for many years.[234] The above names are

Textbook Hemodiafiltration Theory Technology and Clinical Practice 1St Edition Menso J Nube Ebook All Chapter PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Textbook Hemodiafiltration Theory Technology and Clinical Practice 1St Edition Menso J Nube Ebook All Chapter PDF

Uploaded by

Copyright:

Available Formats

Hemodiafiltration: Theory, Technology

and Clinical Practice 1st Edition Menso

Biota Grow 2C gather 2C cook Loucas

Web Technology Theory and Practice 1st Edition Akshi

Randomization in clinical trials : theory and practice

Microforming Technology Theory Simulation and Practice

Juvenile Delinquency: Theory, Practice, and Law Larry

Advanced MR Neuroimaging: From Theory to Clinical

Psychoanalytic Theory and Clinical Relevance What Makes

Dementia in Clinical Practice A Neurological

Muriel P.C. Grooteman

ISBN 978-3-319-23331-4 ISBN 978-3-319-23332-1 (eBook)

Library of Congress Control Number: 2015956130

Springer Cham Heidelberg New York Dordrecht London

Printed on acid-free paper

Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.

Amsterdam, The Netherlands Menso J. Nubé

1 History and Current Status of Online Haemodiafiltration . . . . . . . . 1

Part I Technical Aspects

Part II Hemodiafiltration Equipment

5 Baxter Online Hemodiafiltration Systems . . . . . . . . . . . . . . . . . . . . . . 71

Part III Effects of Hemodiafiltration on Various Biomarkers

11 Effects of Convective Dialysis Techniques

Part IV Clinical Aspects of Hemodiafiltration

16 Clinical Trials on Hemodiafiltration . . . . . . . . . . . . . . . . . . . . . . . . . . 199

Part V Practical Issues

23 Practical Guide to Performing High Volume

Part VI Summary and Conclusions

25 Summary and Current Status of Hemodiafiltration. . . . . . . . . . . . . . 333

Claudia Barth Department of Medical Scientific Affairs, B. Braun Avitum AG,

Denis Fouque, MD, PhD Department of Nephrology Nutrition Dialysis,

Luciano A. Pedrini, MD Department of Nephrology and Dialysis,

Richard A. Ward, PhD Kidney Disease Program, University of Louisville,

Bernard Canaud and Ingrid Ledebo

Abstract The genesis of hemodiafiltration (HDF) has followed the general

Introduction: Why Hemodiafiltration Was Needed?

The development of a new renal replacement therapy corresponds to a need

B. Canaud, PhD (*)

© Springer International Publishing Switzerland 2016 1

conventional hemodialysis was performed with low-flux cuprophane membranes,

Conceptual Phase: How Did We Get There?

In 1975 Henderson et al. using a synthetic ultrafiltration membrane (XM50, Amicon,

HDF is technically complex to perform because it requires components needed for

Clinical Implementation: What Are the Results?

Online preparation of substitution solution by cold sterilization process from fresh

HDF Versus HD in Short and Mid-term Studies

HDF in Long-Term Studies: Patient Outcome

Convective Dose Concept

Dutch nephrologists designed the CONTRAST study aiming for 24 L of ultrafil-

Remaining or Unsolved Questions Related to Online HDF:

Online hemodiafiltration is no longer an experimental treatment, it is a mature renal

Future Development of Online HDF

Online hemodiafiltration can today be considered a mature renal replacement ther-

1. Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged

6. Vanholder R, Baurmeister U, Brunet P, Cohen G, Glorieux G, Jankowski J, European Uremic

The number of children who attended this school [Sidenote: A

A paper for the encouragement of a free school was this

William Penn True and absolute Proprietary and Governor

The charter of 1701 was confirmed and enlarged [Sidenote:

growth was very rapid. Pastorius and Makin had

time he had returned again to the school in 1715.[194] Thomas Makin

The recommendations of the Yearly Meeting of Philadelphia in

2. John Todd taught reading, English, writing, arithmetic