Ina Kidney

Indonesian Journal of Kidney and Hypertension
Steering Comittee Peer Reviewer (Vol 2 Issue 2 May - Aug 2019) :

Head of Indonesian Society of Nephrology ex officio Arwedi Arwanto
Chief Editor Chandra Irwanadi Mohani
Suhardjono Emma Syarifih Moeis
Vice Chief Editors Endang Susalit
Lucky Aziza Bawazier Haerani Abdu Rasyid
Rudi Supriyadi Imam Effendi
Ketut Suwitra
Excutive Editors
Maruhum Bonar H. Marbun
Aida Lydia Zulkhair Ali
Pranawa
Rully Roesli Ginova Nainggolan
Yenny Kandarini
Syakib Bakri Harnavi Harun
Lestariningsih
Journal Manager:
Research Methodology and Statistics Editors Dwitya Wilasarti
I Gde Raka Widiana
Pringgodigdo Nugroho IT:
Ahmad Syafii
International Honorary Editors
Anil Agarwal Layout and design:
Mona Alrukhaimi Dwitya Wilasarti
Norbert Lameire
Wim van Biesen Mark Thomas
Jonathan Barratt Jayakhrisnan K. Pisharam
Indonesian Journal of Kidney Disease and Hypertension is an open accessed online scientific journal managed and
published by Perhimpunan Nefrologi Indonesia/Indonesian Society of Nephrology (Pernefri/Inasn). This journal aims to
publish internationally peer-reviewed and edited scientific articles to provide novel scientific information in nephrology
and hypertension. Authors are encouraged to submit research articles, case reports, evidence-based case report, and review
articles that focus in the field of nephrology and hypertension. The subjects eligible for publication include, but not limited
to chronic kidney disease, electrolyte and pH imbalance, hyperparathyroidism, CKD-MBD, renal anemia, acute kidney
injury renal replacement therapy (dialysis, transplantation), hypertension, onconephrology, nephrotic and nephrtitic
syndromes, glomerulonephritis and other glomerulopathies.
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Journal manager: Dwitya Wilasarti
2 InaKidney | Vol. II | Is. 2| May - Aug 2019

Table of Contents
pages
04 Editor’s letter
Suhardjono
05 Survival Rate of Living Related Kidney Transplant

Patients in Surabaya
Decsa Medika, Aditiawardana, Chandra Irwanadi, Djoko Santoso, Pranawa, Widodo
10 Correlation between Urinary Cyclophillin A with Urinary

Albumin Levels on Diabetic Kidney Disease
Rangga Lunesia, Harnavi Harun, Syaiful Azmi
17 Incidence and Risk Factors of Cardio-Cerebrovascular

Event, Hospitalization, and Mortality in Patients Undergoing
Regular Hemodialysis
Ida Bagus Nyoman Mahendra, Yenny Kandarini, I Gde Raka Widiana
27 Effect of a Sigle Dialysis Session on Cognitive Function in

Chronic Kidney Disease Stage 5 Hemodialysis Patients
Andi Rahmat Hidayat, Haerani Rasyid, Syakib Bakri, Hasyim Kasim, Saidah
Syamsuddin, Arifin Seweng
34 Angioplasty in CKD patients with immature AV fistula:

A Case Report
Atma Gunawan , Sulih Yekti Ngutamani, Achmad Rifai, Nursamsu
InaKidney | Vol. II | Is. 2| May-Aug 2019 3

Editor’s Letter
We are proud to hereby publish our third edition, the May-August 2019 issue of Indonesian Jour-
nal of Kidney and Hypertension. We strive to improve our publication in the future and we are ecstatic to
inform you that our journal is now indexed in Indonesia’s indexing library, Garba Digital Indonesia (Garu-
da). Hopefully this will encourage authors to submit their scientific articles and help improve healthcare in
Indonesia especially in the field of nephrology and hypertension.
Kidney transplant as a form of renal replacement therapy is not relatively new in Indonesia; how-
ever, very scarce data are available regarding its success rate, especially in the long term. In this issue, we
publish an article analyzing the kidney transplant patients’ survival rate in 1, 3, and 5 years after transplant
in Surabaya.
The more popular renal replacement therapy in Indonesia, which is dialysis, remains an interesting
topic to study. Dialysis consists of multiple mechanisms which interact and have multiple consequences to
the human bodily functions. Two of our articles discussed interesting issues about dialysis patients, which
are cerebro-cardiovascular risks and cognitive function. Given the social stigma on dialysis in Indonesia,
many patients have to undergo arteriovenous fistula surgery after having a double lumen catheter placed
for acute renal replacement therapy. Challenges arise as this condition leads fistulas to be more prone to
restenosis. Our case report described a successful attempt of repairing an immature AVF using limited
resources.
Lastly, prevention remains the mainstay target for CKD. Patients with higher risk factors for CKD,
such as diabetic patients, need to actively screen for early signs of CKD. One of our articles addresses the
potential of Cyclophilin A as a biomarker to predict diabetic kidney diseases. We hope this issue sheds
more light to new strategies in managing cases in nephrology and hypertension. Constructive commentar-
ies and criticism are more than welcomed to further improve our publication.
Best Regards,
Chief Editor
Suhardjono
4 InaKidney | Vol. II | Is. 2| May - Aug 2019

Available online at http://inakidneyhypertension.co.id Indonesian Journal of Kidney and Hypertension
ORIGINAL ARTICLE
Title
Survival Rate of Living Related Kidney Transplant Patients in Surabaya
Authors:
Decsa Medika, Aditiawardana, Chandra Irwanadi, Djoko Santoso, Pranawa, Widodo
Nephrology Division – Internal Medicine Department
RSUD Dr. Soetomo – Universitas Airlangga Surabaya, Indonesia
Editor:
Ginova Nainggolan
Received 7 April 2019, revised 1 July 2019, accepted 17 July 2019, published 1 August 2019
Abstract factors for kidney transplant patients’ survival.

Background The survival outcome of transplant Keyword: kidney transplantation, survival rate
patients have improved in the past three decades. The
Corresponding author:
short and long term survival of grafts and patients e-mail: aditiawardana@gmail.com (Aditiawardana A)
are still being widely studied. Many factors affect the
survival rate such as age, gender, diabetes mellitus, and BACKGROUND
immunosuppressive therapy.
Chronic kidney disease (CKD) continues to be the
Objective The study aimed to provide patients’ main health problem in many countries. The global
survival rates 1, 3, and 5 years after transplant. prevalence of CKD, especially stage 3-5, reaches 10-
Methods The study used a descriptive approach to 67 14% of the general population and over one-third of
kidney transplant patients undergoing outpatient treat- the geriatric population.1,2
The prevalence of end-stage
ment from 1996 to 2016. The data collected were ana- kidney disease (ESKD) in the United States was 369
lyzed using SPSS with the Kaplan-Meier curve to ob- per million population in 2010 alone and continues to
serve the survival rate. increase. The modalities of renal replacement therapy
(RRT) widely available for ESKD patients are hemo-
Result: The survival rate of patients in 1, 3, and 5 years dialysis, continuous ambulatory peritoneal dialysis
were 100%, 97%, and 94% respectively. The survival (CAPD), and kidney transplant. Kidney transplant is
rate in geriatric and non-geriatric patients in the first deemed as the ideal RRT for ESRD patients, for it tends
year post-transplantation was both 100%, the third to result in better outcomes for survival and quality of
year post-transplantation survival rate was 100% and life.3,4
94.7%, and the five year post-transplantation survival
rate were 100% and 89.5%. The survival rate of patients The survival rate is a crucial indicator to evaluate the5
receiving tacrolimus vs cyclosporine were both 100% benefit of therapy, especially in kidney transplant.
in the first year, 97.1% vs 97% in the third year, and Survival rate of living-related kidney donor recipients
97.1% vs 90.9% in the fifth year after transplant. have increased significantly for the past 3 decades,
in particular, the first-year survival rate. However,
Conclusion The survival rate of kidney transplant multiple studies have found the short term survival rate
patients in 1, 3, and 5 years after transplant were 100%, improvement is not followed by the long term surviv-
97%, and 94%. Geriatric patients and patients who al rate.3 Factors affecting the survival rate of kidney
received tacrolimus have the tendency for a higher transplant patients are mainly of three categories: host
survival rate. Further study with a bigger sample and factor, kidney factor, and immunosuppressant factor.7
appropriate design is needed to determine the risk The most frequent causes of death in kidney transplant
5
InaKidney | Vol. II | Is. 2| May - Aug 2019
InaKidney Original Article
patients are cardiovascular disease (CVD), infection, Table 1. Subjects’ Characteristics
and malignancy.4
Characteristics Total
This study aimed to describe the survival rate of living Sample size 67
related kidney transplant patients after having a mini-
mum of 3 months of outpatient treatment in 1, 3, and 5 Age
years after transplantation in Surabaya. The study also < 60 y.o. 38 (56.7%)
aims to describe factors affecting the survival rates in ≥ 60 y.o. 29 (43.3%)
said patients. Gender
Male 54 (80.6%)
METHODS Female 13 (19.4%)
Etiology of CKD
Subjects Diabetic 10 (14.9%)
Secondary data were obtained from the medical Non-diabetic 57 (85.1%)
records of all kidney transplant patients in the Calcineurin In-
outpatient setting in Surabaya from 1996 to 2016 and hibitor
have undergone treatment for a minimum of three Tacrolimus 34 (50.7%)
months after transplant surgery.
Cyclosporine 33 (49.3%)
Data Collection
The data collected consisted of patients’ age,
gender, the etiology of CKD and the use of calcineurin
inhibitors.
Statistical Analysis
The data collected were analyzed using SPSS 16th
version. The data of patients’ age was further divided
into geriatric (≥60 years old) and non-geriatric cat-
egory (< 60 years old). The collected data regarding
the etiology of CKD were categorized into diabetic
and non-diabetic, and the use of calcineurin inhibitors
was categorized based on the use of tacrolimus and
cyclosporine.
Figure 1. Kaplan Meier curve for 1, 3, and 5-year sur-

RESULTS vival
Sixty-seven patients were found to be eligible for the
study, consisting of 54 male patients (80.6%) and 13
female patients (19.4%). Subjects’ characteristics were
further described in Table 1.
The general survival outcome in the first year was
100%, in the third year 96.9%, and in the fifth year
94%. Figure 1 shows the Kaplan Maier curve from this
study. In the geriatric group, survival in 3 years and
5 years are both 100%, whereas in the non-geriatric
group the 3 and 5-year survival was 94.7% and 89.5%
(Figure 2).
Figure 2. Kaplan Meier curve for 5-year survival of

geriatric and non-geriatric patients
6
InaKidney | Vol. II | Is. 2| May-Aug 2019
Medika et al InaKidney
.
Survival of transplant patients between male and f
emale after 3 and 5 years were 100% vs 96.3% and
100% vs 92.6% respectively (Figure 3). Survival of
kidney transplant patients divided into diabetics and
non-diabetics group in the first year was 100%, in the
third year was 100% vs 96.5%, and in the fifth year
100% vs 93% (Figure 4). The survival rate in patients
receiving calcineurin inhibitors was categorized into
those with tacrolimus and cyclosporine. Subjects in the
tacrolimus group showed 100% 1-year survival and
97.1% of 3 and 5-year survival. Subjects in cyclospo-
rine showed 100% 1-year survival, 97.1% 3-year sur-
vival, and 90.9% 5-year survival (Figure 5).
Figure 5. Kaplan Meier curve for 5 year-survival of pa-
tients with cyclosporin and tacrolimus
DISCUSSION
Most kidney transplant patients have a high survival
rate, usually well above 95%, supported by various
researches with similar results. In 2010, the survival
rate of kidney transplant patients in Iran for 1, 3, and
5 years after surgery were 98.5%, 96.4%, and 92.5%.8
The high survival rate for kidney transplant patients
is influenced by a multitude of factors such as the ad-
vancement of surgical procedures, minimum cold isch-
Figure 3. Kaplan Meier curve for 5 year-survival of
emia time, and the development of immunosuppressive
male and female patients
therapies.9 The observation of kidney transplant sur-
vival rate is conducted after three months post-surgery,
due to the high risk of complications in the said period
of time.
In theory, geriatric patients have a higher tendency to
develop complications such as cardiovascular disease
and infection. Fabrizi et al studied the relationship
between patients’ age and the survival rate of kidney
transplants and found second-year survival rate of
non-geriatric patients were better than the geriatric pa-
tients (96% vs 90%).10 Another study also found the
5-year survival rate of kidney transplant subjects in
the non-geriatric category was 90% compared to the
geriatric category survival of 82%.11 In this study, the
Figure 4. Kaplan Meier curve for 5 year-survival of di- geriatric subjects were found to have higher 5-year
abetic and non-diabetic patients survival outcomes (94.7% vs 89.5%). The explana-
tion for this result could be that geriatric patients have
a lower chance of rejection due to a weaker immune
system, leading to less immunosuppressive therapy.10
This is yet to be elucidated, but the latest study has
found that acute graft rejection was found higher in
non-geriatric patients, further supporting the role of the
7
lower immune system in geriatric patients survival.11 STUDY LIMITATIONS
Distribution of age between the subjects is also a con-
This study is a single-center study with relatively
founding factor that needs to be considered. small sample size. Being a descriptive study, this study
The role of patients’ gender in survival outcome in also did not analyze the significant difference and
kidney transplant have been identified in past studies; association between variables. The subjects were
also observed starting from three months after
male patients were at higher risk for cardiovascular surgery, some have succeeded in surviving immediate
diseases and female patients were found to be more complications of the procedure. The range of time of
compliant to immunosuppressive regimens and routine available data collected might also subject patients to
lab tests, leading to less graft rejection.3 In this study, the varying immunosuppressive regimen.
the association between gender and survival rate can-
not be assessed because of the uneven distribution of
the subjects’ gender. CONCLUSION
The prevalence of cardiovascular diseases, post- The survival rate of living-related kidney transplant
transplant rejection, and infection in diabetic post- patients in 1, 3, and 5 years after transplant were 100%,
transplant patients have been reported to increase in 97%, and 94%. Factors associated to the higher survival
2004. However, the survival rate for diabetic post- rate were geriatric patients, female gender, diabetes,
and the use of cyclosporine in the immunosuppressant
transplant patients continues to improve over the therapy regimen. Further study with an appropriate
years.12 In this study, diabetic patients have 100% design and bigger sample size is needed to determine
1-year survival rate, 96.5% 3-year survival rate, and the risk factors related to patient survival.
93% 5-year survival rate. A study by Mamoun et
al found diabetic post-transplant subjects have the
survival rate of 80.4%, lower in comparison to the REFERENCES
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6 months post-surgery, but the overall 1-year survival Chronic Kidney Disease- Renal Epidemiology
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used for immunosuppressive therapy in transplant ogy, natural history, and pathophysiology of
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rine group were 100%, 97.1%, and 97.1%. In a study RH, Lee PH, et al. Gender differences in renal
observing the 6-month survival, transplant patients transplant graft survival. J Formos Med As-
receiving tacrolimus and cyclosporine have a survival soc. 2013 Dec;112(12):783-8. DOI: 10.1016/j.
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M, Mohammad K, Fazeli F, et al. Patient sur- Rep. 2018 Nov; 3(6): 1249–52. doi: 10.1016/j.
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Dilip R. Comparison of patient and graft sur-
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Chronic allograft injury. In Johnson R, Feehally immunosuppressive regimes in renal transplant
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9
Indonesian Journal of Kidney and Hypertension Available online at http://inakidneyhypertension.co.id
ORIGINAL ARTICLE
Title
Correlation between Urinary Cyclophilin A and Urinary Albumin Levels on

Diabetic Kidney Disease
Authors:
Rangga Lunesia , Harnavi Harun2, Syaiful Azmi2
1
1
Department of Internal Medicine, Faculty of Medicine Universitas Andalas - M. Djamil
General Hospital
2
Division of Nephrology and Hypertension, Department of Internal Medicine, Faculty of Med-
icine Universitas Andalas - M. Djamil General Hospital
Editor:
Syakib Bakri
Received 19 March 2019, revised 11 July 2019, accepted 17 July 2019, published 1 August 2019
Abstract met the inclusion and exclusion criteria. The samples

were examined for urinary Cyp A and albumin levels.
Background: Diabetic kidney disease (DKD) is a
complication of diabetes mellitus characterized by Results: The mean level of urinary Cyp A in patients
albuminuria persisting within 3 to 6 months, the with DKD is 4.96 (2.03) ng/ml. Median urinary albumin
earliest clinical evidence is microalbuminuria (30-299 levels in DKD patients is 287.89 (30.79-394.57) mg/24
mg/24hours or 20-199 ug/i). Cyclophilin A (Cyp A) is hours. Correlation analysis between urinary Cyp A and
an 18 kDa 165-amino acid long cytosolic protein also albumin levels showed a significant (p < 0.05) with
known as peptidylprolyl isomerase A. In DKD, hyper- a positive and strong correlation (r = 0.776) in DKD
glycemia will cause Cyp A secretion by human kid- patients.
ney-2 (HK-2) cells from PTEC and mesangial-13 cells
Conclusion: There was an increase of urinary Cyp A
(MES-13) and causes kidney damage.
and urinary albumin levels, with a positive and strong
Objectives: To elucidate the correlation between correlation between them in DKD patients.
urinary cyclophilin A and urinary albumin levels in
Keywords: Urinary Cyclophilin A, urinary albumin,
patients with DKD.
diabetic kidney disease
Material and Methods: This study was an analytic
observational, cross-sectional study conducted at the Corresponding author:
clinic and inpatient internal medicine installation at e-mail: harnavi.harun@yahoo.com (Harun H)
dr. M. Djamil General Hospital, Padang for 6 months.
Samples were selected by consecutive sampling, as Introduction
many as 60 people with postprandial blood glucose > Diabetic kidney disease (DKD) is a health problem
180 mg/dl and urinary albumin > 30 mg/24 hours and throughout the world including Indonesia. DKD is
10
InaKidney
. Lunesia et al
a complication of diabetes mellitus (DM) which is tubular epithelial cell (PTEC) after hyperglycemia. 5
characterized by albuminuria persisting through at
Hyperglycemia will induce the secretion of Cyp A,
least two examinations within 3 to 6 months, where the
the highest secreted by human kidney-2 (HK-2) cells
earliest clinical evidence of DKD is microalbuminuria
from PTEC because Cyp A expression is at a relative-
(30 - 299 mg/24hours or 20 - 199 ug/i).1
ly high level in PTEC compared to other kidney cells.
According to the World Health Organization (WHO), Apart from tubular changes, the histological changes of
the prevalence of DM will increase throughout the mesangial cells in DKD will cause Cyp A secretion
world in this third millennium. Data from WHO in from mesangial-13 (MES-13) cells in mesangial.6
54 countries showed the prevalence of DKD has an
Tsai et al (2015) in his research on human studies found
average of 55%.2 Indonesian Renal Registry (2015)
urinary Cyp A level correlated with the development of
obtained the data that DM was the second largest
kidney function based on albuminuria levels. The study
etiology (25%) after hypertension, where the incidence
showed that when the concentration of urinary Cyp A
of DKD in West Sumatra had a percentage of 28.6% of
was more than 0.7250-2 ng/ml, DKD stage 2 could be
all CKD events registered in the dialysis unit.3
diagnosed with a sensitivity of 90.0% and specificity
The pathogenesis of DKD is the activation of metabolic of 72.7%.5 In cellular studies with given MES-13
pathways, increased production of proinflammatory and HK-2 cells with high glucose and H2O2 treatment
cytokines, and hemodynamic pathways. The metabolic increased expression of Cyp A. The Tsai study
pathway due to chronic hyperglycemia will cause concluded that urinary Cyp A is a good biomarker for
nonenzymatic glycosylation which causes an increase early DKD detection in humans, can be released from
and accumulation of advanced glycation end products mesangial or tubular kidney cells, and has a role in the
(AGEs). In addition, it also activates the signaling path- pathophysiology of DKD.5
ways such as diacylglycerol-protein kinase C (DAG-
The earliest clinical evidence of DKD is microalbu-
PKC) pathway, polyol pathway, and hexosamine. The
minuria (30-299 mg/24hours or 20-199 ug/i) which
effect of metabolic pathway action and the production
is called incipient nephropathy. Without specific
of inflammatory mediators will cause glomerular and
interventions, albumin excretion will increase by
tubular disturbances which will end in decreasing the
10-20% per year and will eventually become overt
glomerular filtration rate (GFR) and proteinuria.4
nephropathy (> 300 mg/24hours or > 200 ug/i)
In addition to activation of the metabolic pathway and within 10-15 years. If overt nephropathy has occurred,
the activation of profibrotic cytokines and hemody- without specific intervention, GFR will gradually
namic pathways, there is another pathway that caus- decrease over several years with different variations
es DKD, cyclophilin A (Cyp A). Cyclophilin A has a between individuals (2-20 ml/year) which will end in
role in the occurrence of tubulointerstitial fibrosis. terminal kidney failure.7
Cyclophilin A is an 18 kDa protein 165-amino acid long
Based on the background described above, a study was
cytosolic protein, also known as peptidylprolyl isom-
conducted on the correlation between urinary cyclophilin
erase A, is a distributed protein in almost every part of
A and urinary albumin levels in patients with DKD to
the body. Cyclophilin A can regulate various biological
determine the role of cyclophilin A in the process of
processes such as intracellular signaling, transcription,
kidney damage in DKD.
inflammation, and apoptosis. 5 Cyclophilin A is secreted
rapidly and directly by mesangial cells and proximal
11
Materials and Methods in this study was 63.3%. On examination of the lipid
profile, most patients were classified as dyslipidemia,
This was an analytic observational study with cross-
which amounted to 56.7%. The mean postprandial
sectional approach conducted in outpatients and
blood glucose is 234.86 (50.10).
inpatient internal medicine installation of Dr. M.
Djamil Hospital Padang for 6 months. The population Table.1 Characteristic of sample
of the study was patients with DKD. The inclusion Characteristic N (%) Mean (SD)
criteria were patients with DM with postprandial blood
Age (year) 55.83 (8.25)
glucose > 180 mg/dl dan urinary albumin >30 mg/24 <60 40 (66.7)
hours. The exclusion criteria were fever, doing heavy ≥60 20 (33.3)
exercises one day prior to urinary sample collection, BMI (kg/m ) 23.30 (2.88)
2
Normal 24 (40)
rheumatoid arthritis, systemic lupus erythematosus,
Overweight and obese 36 (60)
urinary tract infections, hepatic cirrhosis, cardiovascular Hypertension
disease, and currently on immunosuppressant therapy. Yes 38 (63.3)
The sample size was calculated using the coefficient No 22 (36.7)
Triglyserides (mg/dl) 159.53 (55,35)
correlation formula and the sample size needed was 60
<150 26 (43.3)
patients. ≥150 34 (56.7)
Postprandial blood glucose 234.86 (50,10)
Diabetic kidney disease was defined as patients with
(mg/dl)
diabetes and post-prandial blood glucose exceeding 180 <230 34 (56.7)
mg/dl and albuminuria > 30 mg/24 hours. Albuminuria ≥230 26 (43.3)
was measured using enzyme-linked immunoabsorbent
The mean level of urinary cyclophilin A in patients
assay (ELISA) and categorized into normal (<30 mg/24
with DKD is 4.96 (2.03) ng/ml with the lowest levels
hr), microalbuminuria (30-300 mg/24hr), and macro
was 1.07 ng/ml and the highest was 8.36 ng/ml. The
albuminuria (>300mg/24 hr). Urinary cyclophilin
results of the Shapiro Wilk normality test showed that
-A was also measured using ELISA, categorized into
urinary cyclophilin A level in this study were normally
normal (<0.725 ng/dl) and elevated (>0.725 ng/dl).
distributed (p> 0.05).
Two milliliters of 24-hour urine collected was used for
laboratory examination. Median urinary albumin level in patients with DKD
was 287.89 (30.79-394.57) mg/24 hour with the lowest
urinary albumin level was 3.79 mg/24 hours and the
Results and Discussion highest is 394.57 mg/24 hour. The results of the Shapiro
Wilk normality test showed that urinary albumin level
Results
in this study was not normally distributed (p <0.05) as
Table.1 presents the characteristic of 60 DKD patients. shown in Figure.1.
Characteristics include age, blood pressure, body mass
Correlation analysis between urinary cyclophilin A and
index, dyslipidemia, and fasting blood sugar levels. In
albumin levels used Spearman correlation test. The
this study, the average age was 55.83 (8.25) years. Av-
results showed a significant correlation between uri-
erage body mass index is 23.30 (2.88) kg.m2. In this
nary cyclophilin A and albumin in patients with DKD
study, 60% of subjects were classified as overweight
(p <0.05) with a positive and strong correlation (r =
and obese. The number of patients with hypertension
0.776).
12
Lunesia et al InaKidney
.
cause a decrease in kidney function in DKD patients
differ from each other. A decrease in GFR and an in-
crease in urinary albumin is important as a marker of
DKD severity, so this will lead us to include groups
with high BMI as a consideration in the management
of DKD.13
Patients with hypertension were more than patients

without hypertension (63.3%). Chul-Woo et al study
(2011) found that the incidence of hypertension was
76.05% in DKD patients.14 Hsu et al study (2012) also
found a greater number of DKD patients with hyper-
Figure.1 Correlation between urinary cyclophilin A and
tension, about 56.1% .15 Tsai et al study (2015) found
urinary albumin levels in patients with DKD
patients with hypertension in DKD 6 was 5.65% .6
While studies from Amer et al (2018) obtained 68.37%
Discussion of DKD patients with hypertension. 9
The mean age obtained from this study was 55.83 Based on this study and other studies, it can be concluded
(8.25) years. The mean age of DKD patients from that most DKD patients have hypertension. The
Behradmanesh et al (2013) was 57 (8.3) years.8 Tsai et mechanismof the occurrence of hypertension in DKD
al study (2015) found that the average age of patients is complex and not yet fully understood. Its main
with DKD was 57.3 (11.6) years.6 While the study from causes include volume expansion due to increased renal
Amer et al (2018) in 60 DKD patients, the mean age sodium reabsorption and peripheral vasoconstriction
was 53.03 (8.09).9 due to dysregulation of the factors that
regulate peripher al vascular resistance, RAAS
Chowta et al (2009) conducted a study of 100 people with activation, an increase of ET-1 regulation, ROS regula-
type 2 diabetes found a significant correlation between tion and d ecrease of NO regulation. Many pathogenic
age and incidence of albuminuria. From existing factors that affect local non-hemodynamic effects can
epidemiological studies, it has been proven that the acceleratethe occurrence of DKD. 16
incidence of albuminuria increases with age.10
The proportion of patients with dyslipidemia was
The average body mass index (BMI) in this study was also higher (56.7%). The mean triglyceride levels in
23.30 (2.88) kg/m2. Most subjects are classified as this study were 159.53 (55.35) mg/dl. Syrjanen et al
overweight and obese (60%). Noha et al (2012) also (2000), Masahiko T et al (2008) and Nakhjavani et al
showed a high average BMI of 29.9 kg/m2.11 Study of (2008) found a significant relationship between dys-
Amer et al (2018) found a mean BMI in DKD patients lipidemia and albuminuria. 12,17,18 Based on consensus
was 26.34 (3.96) kg/m2.9 This is in accordance with the from PERKENI (2015), dyslipidemia is often seen in
study of Masahiko T (2008) who found that body mass DM patients are elevated triglycerides (> 150 mg/dl),
index significantly correlated with the incidence of al- decreased HDL (<40 mg/dl) and normal or slightly
buminuria.12 elevated LDL cholesterol level.19 Triglycerides have
Yassamine et al study (2013) found that BMI does not a lipotoxicity effect which will cause long-chain fatty
directly cause a decrease in GFR and risk factors that acids to be delivered to the kidneys via serum albumin
13
and stored in the kidney cells and tubules. This will or in conditions of microalbuminuria. Tsai et al study
cause tubulointerstitial inflammation and fibrosis in (2015) obtained a mean level of urinary cyclophilin
mild cases and kidney failure and death in severe cases. A was 3.16 (5.36) ng/ml where DKD stage 2 can be
Triglycerides will be transported from VLDL to HDL detected in levels of urinary cyclophilin A 0.7250 ng/
which is rich in TG particles, which will then be hydro- ml. 6 Amer et al (2018) found that the mean level of
lyzed by the liver lipase enzyme and will be eliminated urinary cyclophilin A in microalbuminuria patients was
from the plasma.20 4.79 (1.25) ng/ml and in patients with macroalbumin-
uria was 7.23 (0.76) ng/ml. The level of urinary cyclo-
Mean of postprandial blood glucose level was 234.86
philin A was 1.69 (0.87) in DKD stage 2 patients. The
(50.10) mg/dl. Based on PERKENI (2015) and ADA
conclusion is that urinary cyclophilin A level began to
(2015) fasting and postprandial blood glucose levels is
increase significantly in DKD stage 2 and higher levels
one of the criteria for controlling diabetes mellitus.19
in higher DKD stages.9
Whoerle et al (2007) found, when the fasting blood
glucose level was on target, only 64% of patients Hyperglycemia is an initial process that causes struc-
reached HbA1C levels ≤ 7%, and when fasting and tural and functional changes of the kidneys, such as
postprandial blood glucose was in target levels, 94% glomerular hyperfiltration and microalbuminuria,
of patients achieved HbA1C level ≤ 7%. This was which lead to overt proteinuria and eventually end-
also obtained from the study of Monnier et al (2003). stage kidney disease. In this study, it was found that the
The postprandial blood glucose was more pronounced median of subjects’ urinary albumin level was 287.89
in the long-term micro and macrovascular complica- (30.79-394.57) mg/24 hours. Kundu D et al found the
tions abnormalities while fasting blood glucose shows average ACR level in DKD patients was 449 (160) ug/
the initial progression of DM.21 Tsai et al study (2015) mg creatinine. 22 Dizin et al (2013) obtained an average
showed the mean fasting blood sugar in DKD patients ACR level was 528.9 (165.4) ug/mg creatinine. 23 Aziz
was 142.9 (50.5) mg/dl.6 While studies from Amer et al KM (2015 ) obtained an average ACR level in patients
(2018) showed the mean of fasting blood sugar levels with DKD was 78.1 (109.3) ug/mg creatinine.23 The
in DKD patients were 176.33 (88.90) mg/dl. Based on difference in urinary albumin level in this study might
the results of these studies it was concluded that the be to abnormally distributed data because the subjects
condition of hyperglycemia can cause kidney damage in this study were taken from all stages of chronic kid-
in patients with diabetes mellitus.9 ney disease.
The condition of hyperglycemia will cause cyclophilin Correlation analysis of urinary cyclophilin A with
A to be secreted from mesangial cells and excessive albumin level was used by Spearman correlation

tubular cells. This Cyclophilin A will later bind to test with confidence level p <0.05. The results of the
CD147 as its receptor and cause activating p38, which analysis showed a significant correlation between
will later cause Epithelial Mesenchymal Transition levels of u rinary cyclophilin A and albuminuria with a
(EMT) reactions via p38 MAPK signaling pathway positive and strong correlation (p = 0.001, r = 0.776).
which will cause glomerulosclerosis and tubulointer- This shows that there is an increase in urinary cyclo-
stitial fibrosis. philin A level along with increased albuminuria.
The mean level of urinary cyclophilin A was 4.96 Tsai et al study (2015) found significant differences
(2.03) ng/ml. Urinary cyclophilin A level of 1.07 ng/ml (p <0.001) of urinary cyclophilin A level in all DKD
can be detected at albumin levels 30.79 mg/24 hours groups except in DKD stage I. This study also found
14
Lunesia et al InaKidney
.
an increase in urinary cyclophilin A 0.030 ng/ml each 4. Macisaac RJ, Ekinci EI, Jerums G. Markers of
increase of albumin-creatinine-ratio (ACR) of 1 ug/ and risk factors for the development and pro-
mg creatinine with linear R2 0.054.36. Amer et al who gression of diabetic kidney disease. Am J Kid-
also examined the correlation of urinary cyclophilin A ney Dis. 2014;63:S39–S62.
with urinary albumin found a statistically significant (p
5. Tsai SF, Su CW, Wu MJ, Chen CH, Fu CP,
<0.05 ) and very strong correlation (r = 0.93) in DKD
Liu CS, et al. Urinary cyclophilin A as a new
patients.9
marker for diabetic nephropathy. Medicine.
Based on this study and other studies examining the 2015:94(42):1–10.
correlation between urinary cyclophilin A and a lbumin
6. Hsieh M, Tsai MF. The role of secreted cyclo-
levels in DKD patients, it was found that urinary
philin A in diabetic nephropathy. Tunghai Uni-
Cyclophilin A had a positive correlation with albu-
versity Taiwan. 2016;1–92.
minuria. This condition is caused by hyperglycemia-
induced secretion of Cyclophilin A which can cause 7. Ali Z. Albuminuria sebagai penanda progre-
damage to the glomerular and tubular cell, and it is one sivitas penyakit ginjal diabetik. Dalam : Nas-
of the proteins that cause an increase of albuminuria. kah Lengkap The 11th Jakarta Nephrology and
hypertension Course and Symposium on Hy-
pertension. Pernefri. 2011;53–63.
Conclusion
8. Behraadmanesh S, Horestani MK, Nasri H. As-
There was an increase of urinary Cyp A and urinary sociation of serum uric acid with proteinuria in
albumin levels, with a positive and strong correlation type 2 diabetic patients. J Res Med Sci. 2013
between them, in DKD patients. Jan;18(1):44-6.
9. Amer HMA, Sabry IM, Bekhet MM, Moham-

med RNS. The role of urinary cyclophilin A as
Conflicts of Interest
a new marker for diabetic nephropathy. Egypt J
There are no conflicts of interest regarding the publi- Hosp Med. 2018;70(9):1431–9.
cation of this paper.
10. Chowta NK, Pant P, Chowta MN. Microalbu-
minuria in diabetes mellitus: association with
age, sex, weight and creatinine clearance. Indi-
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16
ORIGINAL ARTICLE
Title
Incidence and Risk Factors of Cardio-Cerebrovascular Event,
Hospitalization, and Mortality
in Patients Undergoing Regular Hemodialysis
Authors:
Ida Bagus Nyoman Mahendra, Yenny Kandarini, I Gde Raka Widiana
Division of Nephrology and Hypertension, Departement of Internal Medicine
Medical Faculty of Udayana University, Sanglah General Hospital-Denpasar
Editor
Lucky Aziza Bawazier
Received 15 October 2018, revised 7 April 2019, accepted 17 July 2019, published 1 August 2019
Abstract composite outcome based on CKD etiology (p=0.03) were as fol-

lows: 1) Diabetic nephropathy (OR=1.33; CI 95% 0.16-11.06); 2)
Background: CKD patients undergoing regular HD experience a
Hypertensive nephrosclerosis (OR=0.98; CI 95% 0.11 - 8.47); 3)
high rate of hospitalization and mortality compared to the gener-
Chronic pyelonephritis (OR=0.36; CI 95% 0.05 – 2.74); 4) Chron-
al population. The main contributing factors were cardiovascular
ic Glomerulonephritis (OR=0.23; CI 95% 0.02 – 2.66) and. Protec-
event and infection. In Indonesia, there has been no comprehen-
tive factor for mortality outcome were AV fistula (p = 0.028; OR
sive and representative data available. This study aims to discover
= 0.46; 95% CI 0.23 - 0.92) and age <52 years old (OR=0.51; CI
the incidence and risk factors of cardio-cerebrovascular events,
95% 0.26 to 0.99; p=0.047); AV fistula was also found to be a pro-
hospitalization, and mortality, as well as the survival rate among
tective factor for composite outcome (CCV, hospitalization, and
patients undergoing regular HD at Sanglah general hospital Den-
death) (OR=0.37; CI 95% 0.17 – 0.77; p=0.01). The cumulative
pasar.
survival rate for composite outcome was 165.83±3.57 days with
Methods: This study was an analytic retrospective cohort study the cumulative survival rate for mortality was 177.34±2.00 days.
conducted in Sanglah general hospital Denpasar from July 1st to
Conclusion: This study concluded that the incidence of mortality
December 31st 2017. Inclusion criteria were patients with CKD
outcome was 8.11% within 6 months (184 days), with the cardio-
stage 5, ≥ 18 years old, and have undergone regular HD for at least
vascular event as the major cause (56%), the significant protective
3 months. Patients with malignancy and requiring elective hospi-
factors for mortality outcomes were AV fistula and age, whereas
talization were excluded. The Kaplan-Meier method was used to
the cumulative survival rate for mortality was 177.34±2.00 days.
calculate the cumulative survival rate, and the log-rank test was
used for extracting the risk factors that influenced the survival rate. Keywords: CKD, regular HD, cardio-cerebrovascular, hospitaliza-
Multivariate Cox regression analysis was used to test contributing tion, mortality.
risk factors towards composite outcomes (cardio-cerebrovascular
Corresponding author:
events, hospitalization, and mortality) and mortality outcome. The
risk factors contributors were declared with a value of relative risk IBN Mahendra; e-mail dr.ibmahendra@yahoo.com
and odds ratio adjusted with the confidence interval (CI) 95%, the
level of significance (α) was specified in the value of p<0.05. Background
Results: The composite outcome of incidence in 222 subjects Patients with end-stage renal disease (ESRD) under-
within 6 months (184 days) was 18.09% and mortality outcome going chronic hemodialysis (HD) have a significantly
was 8.11%, with cardiovascular event as a major cause (56%) of
increased risk for hospitalization and mortality com-
mortality outcome. The risk factors significantly contributed on
pared to the g eneral population.1 One of the most prom-
17
inent cause for hospitalization and mortality among cause impaired phagocytosis function that leads to in-
HD patients is cardiovascular event; this population creased risk of infection. Adaptive immunity was also
has 10-20 times higher risk for cardiovascular events impaired, causing decreased T and B cells. Undergo-
compared to the general population after adjustments ing HD in itself also pose patients to risks such as di-
of age, gender, and the presence of type 2 diabetes.1,2 alyzer membrane incompatibility,dialysate impurity,
Cerebrovascular events were also frequent among HD endotoxin exposure, back-filtration, and vascular ac-
patients, approximately 6 times higher than the gen- cess infection.2
eral population after age adjustments. Anotherpreva-
There has been no comprehensive and representative
lent cause for increased mortality in HD patients was
data available in Indonesia regarding cerebro-cardio-
pneumonia; HD patients were at 10-times higher risk
vascular events and infection among HD patients. This
of pneumonia, where 1 in 5 patients develop pneumo-
study aims to discover the incidence and risk factors
nia during the first year of dialysis. HD patients suffer
of cardio-cerebrovascular events, hospitalization, and
more severe clinical manifestations of pneumonia and
mortality, as well as the survival rate among patients
at 14-16 times higher risk of death.3,4,5
undergoing regular HD at S
anglah General Hospital,
The National Kidney Foundation (NKF) classified Denpasar.
chronic kidney disease (CKD) patients as a high-risk
group for cardiovascular disease. This is due to the
majority of these patients having both traditional and Methods
non-traditional risk factors for cardiovascular diseas- This study is a retrospective cohort study, done in
es. The traditional risk factors are the ones mentioned Sanglah General Hospital, Denpasar from July 1st –
in the Framingham Heart Study such as age, male December 31st2017. Subjects were ESRD patients un-
gender, tobacco use, hypertension, diabetes, phys- dergoing regularHD for at least 3 months before the
ical inactivity, dyslipidemia, family history of car- study, aged ≥ 18 years old. Subjects underwent twice
diovascular disease, left ventricular hypertrophy, and a week hemodialysis session, with 4-5 hours duration
menopause. The non-traditional risk factors or CKD- for each session. Exclusion criteria were the presence
associated risk factors are related to the impairment of malignancy and hospitalization for elective pro-
of glomerular filtration rate such as anemia, oxidative cedures. All subjects have agreed to participate after
stress and chronic inflammation, malnutrition, nitric signing a written informed consent. The number of
oxide depression, hyperparathyroidism, vascular and samples needed was calculated for descriptive study
myocardial calcification, electrolyte imbalance, fluid with single population and dichotomous dependent
overload, and sympathetic over-reactivity.6,7,8 Oth- variable, with the 6-month survival rate of HD pa-
er than increasing the risk of cardiovascular disease, tients was 72.3% according to the Indonesian Renal
the impaired glomerular filtration caused retention of Registry (mortality rate 27.7%). The minimum num-
toxic molecules known as the uremic toxins. These ber of sample needed for the study was 171, however,
molecules induce both activation and deficiency of to anticipate a loss of data this study included 200 sub-
the immune system.2 The retention of uremic toxins jects. Baseline characteristics obtained from the sub-
caused increased activation of polymorphonuclear jects include etiology of CKD, age, gender, nutritional
cells (PMNs) and monocytes/macrophages, causing status (body mass index, albumin), blood pressure and
increased production of reactive oxygen species
hypertension grade, electrolyte imbalance (calcium
(ROS) that leads to persistent inflammation but also
18
Mahendra et al InaKidney
.
and phosphate), anemia, and dialysis factors (the type tal Denpasar. The basic characteristics of the research
of dialyzer and vascular access, and HD adequacy). subjects are presented in Table 1.
The outcome measured were cerebro-cardiovascular
Of the 40 subjects who experienced composite out-
events, hospitalization and its cause, and mortality by
come, 22 (55%) subjects experienced hospitalization
cause of death. Additional data obtained were the his-
and 18 (45%) subjects died. Based on the causes of
tory of severe infection and the presence of hepatitis
hospitalization from 22 subjects, 13 (59%) of the
B and C. The study protocol was approved by the Eth-
subjects were treated because of healthcare-associat-
ical CommitteeSanglah General Hospital, approval
ed pneumonia (HCAP), while 5 (23%) subjects were
number: 2439/UN.14.2/KEP/2017. Study data were
treated because of the incidence of CV, 4 (18%) sub-
analyzed using SPSS version 23.0 for Windows. The
jects due to other causes. Whereas from 18 subjects
analysis for cumulative survival for the effect of risk
that died, 10 (56%) of the subjects died of cardiovas-
factors on the composite outcome (cardio-cerebrovas-
cular (CV) events and 8 (44%) subjects due to septic
cular event, hospitalization, and death) was done us-
shock. There were no deaths due to cerebrovascular
ing Kaplan-Meier bivariate analysis. The log-rank test
events.
was used to compare the cumulative survival curve
between subjects with risk factors and subjects with- In 6 months there were 40 composite outcomes (CV
out risk factors. Statistical power was measured with incidence, hospitalization, and death) of 222 CKD pa-
p<0.05. The correlation between certain risk factors tients who underwent regular HD at Sanglah General
with composite outcome and mortality were present- Hospital in Denpasar, so composite outcome incidents
ed as adjusted odds ratio (OR) and relative risks (RR) were 18.09%, with cumulative average survival time
with a confidence interval of 95%. Cox’s regression (composite output) of 164,83 ± 3.57 days (Figure 1a).
multivariate analysis was done to adjust other risk There were 18 deaths from 222 HD patients who un-
factors for the composite outcome of cumulative sur- derwent regular HD at Sanglah Hospital Denpasar, the
vival and mortality outcome. Total life sustainability incidence of death outcomes was 8.11%, and with cu-
and cerebro-cardiovascular outcome hazard were an- mulative average survival time (the outcome of death)
alyzed using survival curve. Data of proportion and for 177.34 ± 2.00 days (Figure 1b).
frequency was presented as percentages with 95% The cumulative survival for mortality in patients with
confidence interval. Continuous data with normal dis-
CKD who underwent regular HD at Sanglah Gener-
tribution will be presented as mean value with stan- al Hospital Denpasar based on etiology: 1) Diabetic
dard deviations, whereas abnormally distributed data nephropathy was 73% with an average survival of
will be presented as median value with interquartile 165.87 ± 11.34 days, p log rank = 0.05; 2) Hyperten-
range. sion was 86.7% with a mean survival of 180.36 ± 2.74
days, p log rank = 0.05; 3) Chronic pyelonephritis is
93.5% with an average survival of 176.71 ± 2.42 days,
Results
p log rank = 0.05; 4) Chronic glomeruonephritis is
During the study period, 222 subjects met the inclu- 94.4% with a mean survival of 175.17 ± 12.14 days, p
sion and exclusion criteria. There were 40 (18.09%) log rank = 0.05; 5) Obstructive nephropathy of 100%
subjects with composite outcome (CV incidence, with a mean survival of 184.00 ± 0.00 days, p log rank
hospitalization, and death). Two subjects underwent = 0.05 (Figure 2b).
kidney transplantation procedures at Sanglah Hospi-
19
Table 1. Subjects’ baseline characteristics
Mean±SD or
Baseline Characteristics Percentage
Age (years) 51.11±12.42
Male/Female 144 (65%)/78 (35%)
Body mass index (Kg/m2) 22.42±3.60
Weight (kg) 59.45±11.21
Height (m) 1.62±0.07
Systolic blood pressure (mmHg) 132.93±22.19
Diastolic blood pressure (mmHg) 81.71±11.25
Total cholesterol (mg/dL) 157.83±38.67
LDL (mg/dL) 95.96±34.02
HDL (mg/dL) 36.73±11.94
TG (mg/dL) 151.24±98.71
Uric acid (mg/dL) 7.80±1.73
Albumin (mg/dL) 3.91±0.39
Natrium (mmol/L) 137.40±3.98
Kalium (mmol/L) 5.01±0.94
Calcium (mg/dL) 8.92±0.84
Phosphate(mg/dL) 5.76±1.96
Hemoglobin (g/dL) 10.97±4.19
Serum iron (μg/dL) 66.53±37.78
TIBC (μg/dL) 203.04±44.43
TS (%) 33.84±20.32
Ferritin (ng/mL) 750.05±451.43
Dialysis vintage (months) 52.48±33.80
Urea pre-HD (mg/dL) 67.98±18.53 Figure 1. a. The cumulative survival for the composite out-
Urea post-HD (mg/dL) 22.11±12.94
come and b.mortality outcome in regular HD patients at
Body weight pre-HD (kg) 61.06±12.08
Sanglah Hospital Denpasar
Body weight post-HD (kg) 58.47±11.87
UFG (L) 2.71±1.06
URR (%) 73.43±11.23
Kt/V 1.66±0.24 The cumulative survival for composite outcomes in
CKD patients undergoing regular HD at Sanglah Hos-
LDL: low-density lipoprotein; HDL: high-density lipopro-
tein; TG: triglyceride; TIBC: total pr iron-binding capacity; pital Denpasar based on etiology were as followed:
TS: transferrin saturation; HD: hemodialysis; UFG: ultra-fil- 1) Diabetic nephropathy by 60% with an average sur-
tration goal; URR: urea reduction ratio; K: dialyzer clearance vival of 157.20 ± 12.41 days, p log rank = 0.07; 2)
of urea; t: dialysis duration time; v: volume of distribution for Hypertension is 66.7% with a mean survival of 150.09
urea in the body.
± 16.08 days, p log rank = 0.07; 3) Chronic pyelone-
phritis is 84.7% with a mean survival of 165.52 ± 4.19
days, p log rank = 0.07; 4) Chronic glomerulonephri-
tis is 88.9% with a mean survival of 173.98 ± 8.72
days, p log rank = 0.07; 5) Obstructive nephropathy of
75.0% with a mean survival of 182.75 ± 1.08 days, p
log rank = 0.07 (Figure 2a).
20
.
Cox’s regression with step-wise backward analysis
(10 steps), it was seen that the effect on survival of
composite outcome was significantly lower based on
etiological risk factor (p = 0.03), respectively: 1) Dia-
betic nephropathy (OR = 1.33; 95% CI 0.16 - 11.06);
2) hypertensive nephrosclerosis (OR = 0.98; 95% CI
0.11 - 8.47); 3) chronic pyelonephritis (OR = 0.36;
95% CI 0.05 - 2.74); 4) chronic glomerulonephritis
(OR = 0.23; 95% CI 0.02 - 2.66). Risk factors for vas-
cular access (AV Fistula +) also significantly affected
survival of composite outcome (p = 0.01; OR = 0.37;
95% CI 0.17 - 0.77). Meanwhile, from a multivariate
analysis between 11 risk factors and cumulative sur-
vival of mortality using Cox’s regression with back-
ward analysis step-wise (9 steps), it appears AV Fistu-
la (+) has higher cumulative survival of mortality (p =
0.028; OR = 0.46; 95% CI 0.23 - 0.92). Subjects aged
younger than the median 52 years also had higher cu-
mulative survival for mortality (p = 0.047; OR = 0.51;
95%CI 0.26 - 0.99).
Figure 2. a. The cumulative survival for composite outcome and
b. mortality outcome based on etiology of CKD in regular HD
patients at Sanglah Hospital Denpasar
Discussion
Cumulative survival for composite outcome and mor-
tality was done to analyze survival between subjects The survival rate of this study’s subjects did not deviate
with risk factors and without risk factors. (Table 1 and from the currently available data. Based on The Dial-
Table 2). The risk factors analyzed were hypertension ysis Outcomes and Practice Patterns Study (DOPPS),
(systolic blood pressure ≥ 140 mmHg and/or diastolic which is a prospective study, observational of 16,720
blood pressure ≥ 90 mmHg), malnutrition defined as representative samples of HD patients were followed
BMI < 23 kg/m2, hypoalbuminemia (<3.5 g/dl), high for 5 years in v arious countries (Japan, France, Ger-
Ca2+xPO42+ (≥55 mg/dl), anemia defined as hemoglo- many, Italy, Spain, the United Kingdom and the Unit-
bin level < 10 g/dl, vascular access of arteriovenous ed States), the lowest incidence of death in 1 year was
fistula, and dialysis membrane surface area of 1.5 m2 found in Japan (6.6%), followed in Europe (15.6%)
vs 1.8 m2, Kt/V value < 1.8, male gender, and age > 52 and highest in the United States (21.7%).9,10,11
years old (median age of subjects). From all these risk Both the causes of death and hospitalization in this
factors, only age older than 52 years old were found study’s subjects were also in accordance with current-
to have significantly lower cumulative survival for the ly available data. The 2014 Indonesian Renal Registry
composite outcome (Table 2). (IRR) reported the cause of death in HD patients due
From multivariate analysis between 11 risk factors to the incidence of CV is 47% and as a result of cere-
and cumulative survival for composite outcome using brovascular events is 12%.12 The results of this study
21
Table 2. Composite Outcome
Risk Factors Cumulative Mean survival rate (days) Relative P log rank
survival rate Risk
Hypertensive vs Non-hyper- 86.3% vs 79.9% 168.51 ± 5.48 vs. 163.05 ± 4.66 0.7 0.27
tensive
Malnourished (BMI < 23 kg/ 82.9% vs 80.5 % 165.38 ± 4.87 vs 163.18 ± 5.72 0.9 0.62
m2) vs Non-malnourished
Hypoalbuminemia (<3.5 g/dl) 75.0% vs 83.1% 150.79 ± 15.34 vs 166.41 ± 3.57 1.5 0.22
vs non-hypoalbuminemia
High (≥55 mg2/dl2) vs Low 80.5% vs 83.0 % 166.02 ± 5.37 vs 163.90 ± 4.86 1.1 0.71
Ca2+xPO42+
Anemia (Hb< 10 g/dl) vs 77.9% vs 85.4 % 162.80 ± 5.67 vs 166.02 ± 4.83 1.5 0.15
non-anemia (Hb ≥ 10 g/dl)
AVF vs non-AVF 84.1% vs 72.5 % 168,12 ± 3,56 vs 149,89 ± 11,6; 0.6 0.058
Dialyser membrane 1.5 m2 vs 80,3% vs 84,3 % 165,19 ± 4,81 vs 164,11 ± 5,31 1.3 0.51
1.8 m2
Kt/V <1.8 vs ≥1.8 79,9% vs 85,9 %, 153,6 ± 4,99 vs 169,48 ± 4,86 1.4 0.24
Male vs Female 81,9% vs 82,1% 165,37 ± 4,28 vs 163,88 ± 6,35 1 0.99
Age > 52 vs ≤52 years old 76,1% vs 87,6%, 160,94 ± 5,47 vs 168,62 ± 4,56 2 0.035
Table 3. Mortality Outcome
Risk Factors Cumulative survival Mean survival rate (days) Relative P log
rate Risk rank
Hypertensive vs Non-hypertensive 95.9% vs 89.9 %. 180.75 ± 2.79 vs 175.68 ± 2.76 0.4 0.13
Malnourished (BMI < 23 kg/m2) vs 92.2% vs 92.0 %. 178.14 ± 2.47 vs 176.07 ± 3.81 1 0.94
Non-malnourished
Hypoalbuminemia (<3.5 g/dl) vs 87.5% vs 92.8% 176.07 ± 5.97 vs 177.54 ± 2.16 1.9 0.27
non-hypoalbuminemia
High (≥55 mg2/dl2) vs Low Ca2+x- 90.9% vs 92.9 %. 177.52 ± 3.33 vs 177.31 ± 2.69 1.3 0.64
PO42+
Anemia (Hb< 10 g/dl) vs non-anemia 89.5% vs 94.3 % 176.03 ± 3.27 vs 178.37 ± 2.76 1.8 0.17
(Hb ≥ 10 g/dl)
AVF vs non-AVF 92.2% vs 87.5% 178,88 ± 1,90 vs 170,36 ± 7,61 0.5 0.21
Dialyser membrane 1.5 m2 vs 1.8 m2 91,7% vs 92,1 % 179,40 ± 1,97 vs 174,20 ± 3,96 1 0.93
Kt/V <1.8 vs ≥1.8 92,5% vs 90,6 % 178,99 ± 2,25 vs 174,49 ± 4,05 0.8 0.63
Male vs female 91,0% vs 93,6%, 176,57 ± 2,61 vs 178,77 ± 3,03 1.5 0.5
Age > 52 vs ≤52 years old 88,1 % vs 95,6% 175,59 ± 3,17 vs 179,04 ± 2,44 3 0.047
22
.
also correspond to reports from the United States Re- tients have other traditional risk factors for cardio-
nal Data System (USRDS) which stated that CV dis- vascular diseases. DKD can also cause hypercoagula-
ease is also the main cause of death (53.5%), while bility state, platelet dysfunction, and altered levels of
septicemia and other infections are the cause of 11.4% plasma coagulation factors and fibrinolysis mediators.
of deaths in the late stages of CKD in the United Therefore, the coexistence of DKD and CKD will in-
States between 2012-2014.13 The results obtained are crease the risk of thrombosis.16The higher mortality
based on reports from HD units at Gezira Hospital for outcome of subjects aged > 52 years old is similar to
Renal Diseases and Surgery in Sudan-Africa in 2011, study by Urrutia et al that showed in addition to the fe-
which stated that infection was the main cause of male gender, the age of > 52 years old was associated
death (45%), while the incidence of CV was only 22% with higher mortality.17
of causes of death.11 In general, the results obtained in
The use of AVF in this study posed as a significant
the study this is in accordance with a survey conducted
protective factor for both morbidity and mortality
in 2014 on 3 populations (Asian, European and Amer-
of HD patients. This finding is consistent with prior
ican populations) as published in Nature. The survey
studies such as the study by Hicks et al from Society
stated that although there were variations among 3
for Vascular Surgery that found the mortality risk is
populations, approximately 50% of the known causes
lowest in patients with AVF access compared to AV
of death were caused by the incidence of CV.14
graft and dialysis catheter, in all age groups.18 Fur-
It was also found that subjects had a cumulative aver- ther assessment of the association of AVF access and
age survival time for a composite outcome of 164.83 mortality was studied by Brown et al, where 1 year
± 3.57 days, while the cumulative survival rate for mortality was found to be lowest in patients who used
mortality was 177.34 ± 2 days. In 2014 InaSN tried AVF since their first HD session (17%, HR 0.5, CI
to see the s urvival of new patients for 1 year, as stated 95% 0.48-0.52, p<0.001), followed by those who used
in the 7th Report of I ndonesian Renal Registry. After dialysis catheter after AVF failure (25%, HR 0.66, CI
going through the process of selecting data, there were 95% 0.64-0.68, p<0.001), when compared to those
3,907 data that could be a nalyzed with the results that who used dialysis catheter since their first HD session
the chances of 1-year survival of hemodialysis pa- (46%).19 A retrospective cohort study by Malas et al
tients were 46.7% with 95% CI 42.8 - 50,6.15 Whereas on 510.000 hemodialysis patients for 4 years (2006 –
up to the last IRR (in 2017), there is no publication 2010) showed patients who use AVF access had 35%
of survival (survival) of CKD patients who undergo lower mortality outcome compared to those with di-
regular HD in Indonesia based on the average survival alysis catheter(adjusted HR 0.65; 95% CI 0.64-0.66.
time as in this study. p<0.001).20The use AFV from the first dialysis session
had a 23% lower risk of death even compared to those
This study showed ESRD etiology of diabetic
who use catheter while waiting for fistula maturation
nephropathy was a significant risk factors associat-
(adjusted HR 0,77; 95% CI 0.76-0.79, p<0.001).20This
ed with composite outcome of cardiovascular events,
is in alignment with recommendation by N/KDOQI
hospitalization, and death, whereas the use of AVF
(National Kidney Foundation/ Kidney Disease Out-
and age < 52 was particularly associated with higher
comes Quality Initiative)-2006 which suggest ESRD
survival of mortality. Diabetic kidney disease (DKD)
patients have permanent vascular access 6 months pri-
have been associated with higher mortality based on
or to estimate time of dialysis initiation.21
current evidence. This might be due to diabetic pa-
23
An interesting relationship was found between hy- Kalantar-Zadeh, et al. Data in the general population
pertension, BMI, and the mortality outcome. In this were taken from Calle et al. (1991) whereas data in
study, the cumulative survival was found to be higher the regular HD population were taken from Leavy et
in the hypertensive group compared to the non-hy- al. (2001). Based on the research conclusions, the rel-
pertensive group. This phenomenon is what some ative risk of death will increase in accordance with the
experts have described as “reverse epidemiology” in increase in BMI in the general population, whereas in
HD patients as reported by Nurmohamed SA. et al the regular HD patient population, the relative risk of
and Borsboom H. Et al., published in the Netherlands death will decrease in accordance with the increase of
Journal of Medicine.22,23 Several large-scale longitudi- BMI. With the BMI limit of 23 kg / m2 as the value of
nal cohort studies have shown a paradoxical inverse the relative risk of death 1.0 (reference) it was found
relationship between blood pressure and mortality in that the overweight category (BMI 25-29.9 kg / m2) in
HD patients, where higher blood pressure was asso- the general population in the study had a relative risk
ciated with lower mortality rate and vice versa.24,25On of death 1.1-1.3 ; whereas in regular HD patients the
the contrary, higher blood pressure had been associ- relative risk of death is 0.7-0.9.25 However, it should
ated with left ventricular concentric and dilative hy- be noted that the regular HD patient population in the
pertrophy, both of which have been strongly related Leavy et al study is a combination of data from Amer-
to mortality in HD patients.26 However, the target of ica and Europe. The research conducted by Wong JS.
optimal blood pressure in the regular HD patient pop- Et al in the Asian American population got different
ulation is unknown. The recommendations issued by results, where the effect of BMI on the relative risk
K-DOQI -2005 regarding blood pressure targets in of death if depicted in a U-shape graph, which indi-
HD patients were pre-dialysis blood pressure <140/90 cates that with a 23 kg/m2 BMI limit as a reference;
mm Hg and post-dialysis blood pressure <130/80 mm it is found that the relative risk of death will increase
Hg. Different recommendations are submitted based according to the BMI increase.29
on the DOPPS-2012 study, where the target blood
In this study, there was no significant mortality out-
pressure of patients with pre-dialysis HD <130-159
come difference between subjects with different di-
/ 60-99 mm Hg and the target of post-dialysis blood
alyzer surface area (RR=1). This can be explained
pressure <120-139 / 70-89 mm Hg. 27,28 A prospective
by the different characteristics of the dialyzer used
randomized study is needed to compare the effects of
in Sanglah General Hospital. The Nipro® machine
different blood pressure targets on mortality outcomes
(ELISIO-15H) used dialyzers with polyethersulfone
in regular HD patients.
material (PES) and surface area of 1.5
m2, KUF 67
Meanwhile, subjects with malnutrition (BMI <23 kg / ml/hr/mmHg. This dialyzer’s clearance of various
m2) were found to have a higher cumulative mortality uremic toxins (at Qb / Qd 300/500 ml/min) was 278
survival compared to non-malnourished (BMI ≥ 23 kg ml/min for urea, 259 ml/min for creatinine, and 241
/ m2) subjects. At first glance, the results of this study ml/min for phosphate. Meanwhile, the dialyzer used
are not in accordance with the Reverse Epidemiology by Fresenius® machines (FXclass-10) was of poly-
concept of BMI risk factors for the outcome of regular sulfone material (PSf) with a surface area of 1.8
m2,
HD patient deaths that were obtained in the American KUF 14 mL / hr / mmHg, had the clearance of uremic
and European populations. A comparative study be- toxins (at Qb / Qd 300/500 ml/min): 261 ml/min for
tween the effect of BMI on mortality outcomes in the urea, 231 ml/min for creatinine and 210 ml/min for
general population and regular HD was published by phosphate. From this, it can be concluded that despite
24
InaKidney
.Mahendra et al
the smaller surface area, the 1.5 m2 dialyzer has bet- 3. Naqvi SB, Collins AJ. Infectious Complications in
ter performance in uremic toxin clearance. For the in- Chronic Kidney Disease. Adv Chronic Kidney Dis.
2006 Jul;13(3):199-204.
fluence of dialysis adequacy on mortality, it is found
that inadequate HD (<1.8) has RR=0.8 compared to 4. Judd E, Ahmed MI, Harms JC, Terry NL, Sonavane
SK, Allon M. Pneumonia in hemodialysis patients:
adequate HD. The phenomenon may be explained in
a challenging diagnosis in the emergency room. J
light of the currently acceptable assessment of HD Nephrol. 2013;26(6):1128-35
adequacy using blood urea as a surrogate marker for
5. Guo H, Liu J, Collins AJ, Foley RN. Pneumonia in
small uremic BM toxins. There has been no develop- incident dialysis patients – the United States Renal
ment of the use of phosphate as a surrogate marker for Data System. Nephrol Dial Transplant. 2008;23:
the assessment of HD adequacy, whereas phosphate is 680-6
known as an independent risk factor for the incidence 6. Weiner DE, Sarnak MJ. Cardiac Function and Car-
of KV in dialysis patients. It was found that phosphate diovascular Disease in Chronic Kidney Disease. In:
National Kidney Foundation’s PRIMER ON KID-
clearance did not follow the same diffusion kinetic
NEY DISEASES. 6th Ed. Gilbert SJ, Weiner DE,
pattern with urea because of the complex mobilization Gipson DS, Perazella, Tonelli M, editors. Philadel-
of phosphate from the body’s phosphate stores during phia: Elsevier; 2014. p 488-96
dialysis, the mechanism of which are not yet widely 7. D’Marco L, Bellasi A, Raggi P. 2015. Cardiovas-
known.30 cular Biomarkers in Chronic Kidney Disease: state
of Current research and Clinical Applicability. Dis
Markers. 2015;2015:1-16
Conclusion 8. Usta S, Basbug HS, Cakiroglu Y. High-sensitivity

C-reactive protein: Could it be used as a cardio-
From this study, it can be concluded that cardiovas- vascular risk predictor in hemodialysis patients?
cular events and infection remain the highest cause of Appl Med Res. 2015; 1(1): 12-15. doi:10.5455/
amr.20150127120710
morbidity and mortality in dialysis patients. Diabetic
nephropathy was highly associated with a lower sur- 9. Goodkin DA. Bragg-Gresham JL, Koenig KG,
vival rate for the composite outcome (cardiovascular Wolfe RA, Akiba T, Andreucci KG, et al. Associ-
ation of Comorbid and Mortality in Hemodialysis
event, hospitalization, and death) whereas and the use Patients in Europe, Japan, and the United States:
of AVF was associated with a higher survival rate for The Dialysis Outcomes and Practice Patterns Study
the composite outcome. The mean age of < 52 years (DOPPS). J Am Soc Nephrol. 2003;14:3270-7
old and AVF was associated with higher survival for 10. Nguyen B, Fukuuchi F. Survival rates and cause of
mortality. death in Vietnamese chronic hemodialysis patients.
Ren Replace. 2017:3(22);1-10
11. Elsharif ME. Mortality Rate of Patients with End-
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Paoletti S, Sara B. 2012. Biomarkers of Chronic
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2. Cohen G, Horl WH. Immune Dysfunction in Ure-
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962–90. al Data Report.. Cardiovascular Disease in patients
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14. De Jager DJ, Vervloet MG, Dekker FW. Noncar- ney Int. 2003; 63:793-808
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perspective. Nat Rev Nephrol. 2014:10;208-14 26. Parfrey PS, Foley RN, Harnet JD. Outcome and
risk factors for left ventricular disorders in chronic
15. Indonesian Society of Nephrology. 7th Annual Re- uremia. Nephrol Dial Transplant. 1996;11:1277-
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InaSH; 2014
27. Robinson BM, Tong L, Zhang J, Wolfe RA, Good-
16. Palsson R, Patel UD. Cardiovascular Complica- kin DA, Greenwood RN, et al. Blood Pressure
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Practice Pattern Study. Kidney Int. 2012; 82(5):
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Survival Analysis of Patients with End-Stage Renal
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10 hemodialysis patients. Kidney Int. 2017; 92: 816-
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DS, Qazi U, Reifsnyder T, et al. Mortality benefits 29. Wong JS, Port FK, Hulbert-Shearon TE, Carroll
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AS. The Survival Benefit of “Fistula First, Catheter 30. Spalding EM, Chamney PW, Farrington K. Phos-
Last” in Hemodialysis Is Primarily Due to Patient phate kinetics during hemodialysis: Evidence for
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risk factors in maintenance dialysis patients. Kid-
26
ORIGINAL ARTICLE
Title
Effect of a Sigle Dialysis Session on Cognitive Function in Chronic Kidney
Disease Stage 5 Hemodialysis Patients
Authors:
Andi Rahmat Hidayat1, Haerani Rasyid2, Syakib Bakri2, Hasyim Kasim2, Saidah Syamsuddin3, Arifin Seweng4
1. Departement of Internal Medicine, Faculty of Medicine, Hasanuddin University
2. Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University
3. Departement of Psychiatric, Faculty of Medicine, Hasanuddin University
4. Departement of Biostatistics, Faculty of Public Health, Hasanuddin University
Editor:
Rully M.A. Roesli
Received 7 April 2019, revised 1 July 2019, accepted 17 July 2019, published 1 August 2019
Abstract sis. Cognitive function reached its best 24 hour after

dialysis (MoCA INA score 23,65, p < 0.001) and all
Background: The incidence of cognitive impairment
the domain of cognitive function was improved except
(CI) has been widely reported in various studies among
naming that didn’t change over the dialysis session.
chronic kidney disease (CKD) patients. Many factors
influence cognitive function including the hemodialy- Conclusion: There is an effect of single HD session
sis (HD) process itself. There is much evidence that a on global cognitive function where executive func-
single HD session brings about changes in the cognition, attention, language, and recall deteriorated during
tive status of patients, but just a few studies assessing HD while abstraction and orientation didn’t change.
whether cognitive performance varies with dialysis. All cognitive domains were recovered 24 hours after
HD except naming that didn’t change from baseline
Aim: To know the effect of single dialysis session on
throughout the whole process.
cognitive function in HD patients.
Method: Sixty medically stable CKD stage 5 pa-
tients on HD maintenance for at least three months Keywords: cognitive function, chronic kidney disease,
were enrolled. Cognitive testing performed thrice, 1-2 hemodialysis
hour prior to dialysis (T1), 3-4 hour into the session
(T2) and 24 hour after the session (T3) using a well-
validated neuropsychological test battery, Montre- Corresponding author :
al Cognitive Assessment (MoCA) Indonesian ver-
sion which assess the domain of cognitive function Email : dr.1andi2rahmat1990@gmail.com (Hidayat,
including visuospatial, executive function, naming,
AR), phone : +6281356308094
memory, attention, language, abstraction, recall, and
orientation.
Introduction
Result: Subjects’ mean age was 45,45 ± 11,28 years,
dialysis vintage 10,12 ± 11,88 months, 44 patients Chronic kidney disease (CKD) is a major public health
(73,3%) had CI at baseline. Cognitive function decline problem varying in severity from asymptomatic to end
during dialysis (T2) (MoCA INA score 21,65 to 19,67, stage renal disease (ESRD) requiring hemodialysis
p < 0.001) and visuospatial, executive function, atten- (HD).1 Patients with CKD are frequently associated
tion, language and recall was impaired during dialy- with neurological complication. Common neurological
27
Participants and Setting complications in CKD include stroke, cognitive im-
pairment (CI), encephalopathy and peripheral neuro
The design of this study was cross-sectional. Patients
pathy.2,3 Cognitive impairment in patients with CKD are
were selected among those attending the HD unit of
frequent and show increasing prevalence rates. Several
Dr. Wahidin Sudirohusodo General Hospital, Makas-
risk factors such as uremia, anemia, fluid and electro-
sar from June – October 2018. Inclusion criteria were
lyte disorder, related comorbidities include hyperten-
patients over the age of 18 years old, medically stable,
sion (HT), diabetes mellitus (DM) and cerebrovascular
and willing to participate in the research, being on
diseases have been linked to cognitive decline.4-8
HD maintenance for at least 3 months, twice to thrice
a week. Exclusion criteria were patients over the age HD process itself has also been suggested as the
of 60 years old because dementia is reported common potential cause of CI. Potential HD-specific mecha-
over this age, unconscious, vision and hearing im- nisms include acute fluid shift, dialysis disequilibrium
pairment, unable to read and to write, severe mental syndrome and brain micro-bleeding due to anticoagu-
disorder, and consuming narcotics, psychotropic, and lant during dialysis. However, there are also bioche
addictive drugs. mical change induced by HD that potentially lead to
cognitive improvement including uremic toxin elimi-
nation, correction of fluid and electrolyte disorder and
Neuropsychological Assessment and Clinical Variables partial correction of anemia. This mechanism possibly
cause a fluctuation of cognitive function over a single
Cognition was assessed in a quiet and spacious room HD session.9-11
with adequate lighting and using a screen to isolate
patients for privacy. Cognitive test was done using a Cognitive function is needed to access health ser-
well validated neuropsychological test, the MoCA vices, process, understand, and recall written and
INA tool.18,19 It assess 8 cognitive domains, generating spoken information and assimilate and express deci-
a score of between 0 to 30 – Visuospatial/executive sions about health care.12 Impaired cognition has been
function (5), naming (3), memory (0), attention (6), linked to r educed health literacy, decreased medication
language (3), abstraction (2), delayed recall (5) and adherence, impaired physical and mental health, and
orientation (6). Cognitive impairment was defined as greater risk for death.12-14 Therefore, even when cogni-
MoCA INA score < 26. tive improvement is temporary, such as after dialysis
or between dialysis, it is important to sustain a good
Cognitive test was done thrice, T1 was done 1-2 hour quality of life.11
before the start of HD, T2 was done 3-4 hour into the
session in the same day of T1, and T3 was done 24 There have been few studies examining cognitive func-
hours after the HD session. For each assessment, the pa- tion following a single dialysis session. The majority
tients were allowed up to 30 minutes. All patients were of studies had established that cognitive performance
dialyzed in the morning and afternoon, no medications of HD patients was best approximately 24 hours after
were administered during dialysis except paracetamol, the last HD session compared to shortly before the ses-
erythropoietin, and blood transfusion if required. sion.15,16 To our knowledge, there was just one study
with a small sample size that conducted cognitive tests
Patients who were the subject of the study underwent an during dialysis and at other times to measure acute vari-
examination starting with anamnesis to get the socio- ations in cognitive function during the dialysis cycle.17
demographic details (age, sex, and years of education), In addition, there was no study assessing the cognitive
medical history, current medication, and comorbidities. function of HD patients in Indonesia in recent years.
Clinical data also included dialysis vintage, duration of
each dialysis session, blood flow rate (QB), ultrafiltra- Hence the aim of this study was to assess the ef-
tion volume (UF). We also did physical examinations fect of a single HD session on cognitive function using
including pre- and post-dialysis body weight, pre- and the Indonesian version of well-validated neuropsycho-
intra-dialysis blood pressure (BP). We also obtained logical test battery, Montreal Cognitive Assessment
some laboratory testing including hemoglobin (Hb), (MoCA INA).
plasma glucose, albumin, urea and creatinine, and elec-
trolyte (all taken pre dialysis except for urea that was Materials and Methods
taken also at the end of the dialysis session to calculate
28
Hidayat et al InaKidney
.
urea reduction rate [URR] and Kt/V). The protocol of
the study was informed to all subjects regarding the
Table 2. Subject Characteristics-Part 2
risks and benefits of the study. Informed consent was
acquired from all subjects. Variable Min Max Mean SD
Age (years) 18 60 45,45 11,28
Result Dialysis Vintage 3 60 10,12 11,88
(months)
Subject characteristic 35 85 54,62 9,96
Pre HD Weight (kg)
Sixty CKD stage 5 patients on maintenance HD com- Post HD Weight (kg) 34 83 53,07 9,86
pleting all three cognitive testing were recruited. The Change in Weight -3 0 1,55 0,70
(kg)
mean age was 45,45 ± 11,28 years, 31 patients (51,7%)
Pre HD Blood Pres- 150,83/83,67 18,80/13,65
were male, 41 patients (68,3%) with education level sure (mmHg)
≤ 12 years, dialysis vintage 10,12 ± 11,88 months, 50 Intra HD Blood
patients (83,3%) with non adequate HD. Socio-demo- Pressure (mmHg) 149,5/80 21,10/14,61
graphic and medical characteristics of the study partic- Change in Systolic -30 30 -1,33 12,5
ipants are shown in table 1 and 2. BP (mmHg)
Change in Diastolic
In this study, mean change of systolic BP -1,33 ± 12,55 BP (mmHg) -40 20 -3,67 10,89
mmHg, mean change of diastolic BP -3,67 ± 10,8 120 300 177,17 26,69
Blood Flow Rate
mmHg, 10 patients (16,7%) had hypotension (systol- (QB) (ml/men)
ic BP drop ≥ 20 mmHg or MAP drop > 10 mmHg) Ultrafiltration
during dialysis. Mean change in bodyweight over di- Volume (ml)
500 3500 1798,33 708,18
alysis -1,55 ± 0,70 kg. Blood flow rate during dialysis Kt/V
0,24 2,06 0,94 0,41
120-300 ml/min (mean 177,17 ± 26,69 ml/min), ultra- 15,46 97,17 52,67 17,24
URR (%)
filtration volume 500-3.500 ml (mean 1.798 ± 708,18 5,1 11,0 8,04 1,30
ml), range of Kt/V 0,24-2,06 (mean 0,94 ± 0,41) while Hb (gr/dl)
2,0 4,3 3,18 0,54
URR range from 15,46-97,17 (mean 52,67 ± 17,24%). Albumin (gr/dl)
65 288 121,45 45,59
Plasma Glucose
(mg/dl)
Table 1. Subject Characteristic (n=60)-Part 1 Sodium (mmol/l) 126 146 138,23 4,43
Potassium (mmol/l) 3,3 6,7 4,56 0,75
Variable n %
Sex Men 31 51,7
Women 29 48,3
Age (years) 18-40 17 28,3
41-60 43 71,7
Education <=12 41 68,3
(years)
Cognitive test
>12 19 31,7
Dialysis Vin- <6 33 55,0 Forty four patients (73,3%) had CI before the start of
tage HD session (T1) (MoCA INA score < 26) while during
(months) 6-12 27 45,0 HD (T2) the participant who had CI increased to 55 pa-
HD Frequency 3 45 75,0 tients (91,7%) and 24 hr after HD (T3) the participant
(time/week) 2 15 25,0 who had CI decreased to 37 patients (61,7%) (Table 3).
Duration in HD 4 56 93,3
The total MoCA INA score T2 was significantly lower
(hours) 5 4 6,7
than T1 (19.67 to 21.65 (p <0.001). Whereas T3 was
significantly higher than T1 (23.65 to 21.65 (p <0.001).
(Table 4) A significant change was found in cognitive
function in T2 compared to T1 (p <0.001) where 11 out
of 16 subjects (68.8%) whose cognition changed from
29
Table 6. Comparison of Cognitive Function Domains
normal to abnormal in T2. While a significant change
in cognitive function also found in T3 compared to T1
(p <0.05) where 7 out of 44 subjects (15.9%) whose Cognitive Domains Mean SD p
cognition changed from abnormal to normal after HD. Executive (T1) 2,95 1,84
(Table 5) Executive function, attention, language and Executive (T2) 2,52 1,74 0,000
recall was lower in T2 compared to T1 (p <0.05), Ab- Executive (T3) 3,20 1,85 0,001
straction and orientation weren’t different between T1 Naming (T1) 2,63 0,71
and T2 (p > 0.05). All cognitive domains improved in Naming (T2) 2,63 0,71 1,000
T3 (p < 0.05) compared to T1 and T2 except naming Naming (T3) 2,63 0,71 1,000
that didn’t change over the session. (Table 6) Attention (T1) 4,27 1,33
Attention (T2) 3,57 1,18 0,000
Attention (T3) 4,68 1,31 0,000
Language (T1) 1,92 0,89
Language (T2) 1,73 0,84 0,040
Language (T3) 2,20 0,73 0,000
Table 3. Distribution of Cognitive Impairment
Abstraction (T1) 1,15 0,73
Test time Cognitive Function n % Abstraction (T2) 1,18 0,72 0,419

Abstraction (T3) 1,27 0,71 0,007
T1 Normal 16 26,7
Recall (T1) 2,90 1,49
Abnormal 44 73,3 Recall (T2) 2,17 1,51 0,000
T2 Normal 5 8,3 Recall (T3) 3,55 1,62 0,000
Abnormal 55 91,7 Orientation (T1) 5,17 0,72
T3 Normal 23 38,3 Orientation (T2) 5,18 0,70 0,709

Orientation (T3) 5,45 0,70 0,000
Abnormal 37 61,7
Discussion
Table 4. Comparison of Total MoCA INA Score We evaluated the cognitive function in CKD stage 5
Test Time Mean SD P patients before, during and after a single HD session.
The results revealed that on general assessment of cog-
T1 21,65 5,32
nition, the patients had low score of cognitive functions
T2 19,67 4,82 0,000 (MoCA INA < 26) in pre, intra and post HD. Our data
T3 23,65 5,38 0,000 suggest that HD patients with CI is common as seen
Table 5. Change in Cognitive Function during and after HD
T1 T2 T3
Normal Total p Total p
Abnormal Normal Abnormal

Normal N 5 11 16 16 0 16
% 31,3% 68,8% 100,0% 100% 0.0% 100%
Abnormal n 0 44 44 7 37 44 0,016
0,001
% 0,0% 100,0% 100,0% 15,9% 84,1% 100%
38,3
Total n 5 55 60 23 37 60
% 8,3% 91,7% 100,0% 61,7% 100%
30
Hidayat et al InaKidney
.
there were at least 44 patients (73,3%) who had CI at This study have a significant clinical implications.
the start of HD (baseline). Consistent with Dasgupta Cognitive impairment during HD is associated with
et.al who reported 76% patients had at least mild CI at impaired capacity to actively process and retain in-
the start of HD session and 15% had severe CI.20 formation.20 Providing information regarding health
status, treatment plans, medication use, diet and other
In this study, we found a significant decline of cogni- lifestyle changes is very important when patients have
tive function during HD in majority of patients as seen good attention, can remember the information commu-
from MoCA INA score (21,65 ± 5,32 to 19,67 ± 4,82, p nicated, plan and execute the steps needed to meet the
< 0.001) and also 11 out of 16 patients (68.8%) whose goals of the treatment plan.11,27 Thus providing infor-
cognition changed from normal to abnormal during mation to patients during HD may not be recommend-
HD (p < 0.001). A single HD session lead to cognitive ed especially after second half of the session because at
improvement as seen from MoCA INA score (21,65 ± that time it showed a significant deterioration in cogni-
5,32 to 19,67 ± 4,82 to 23,65 ± 5,38, p < 0.001) and also tive function.
7 out of 44 patients (15.9%) whose cognition changed
Limitation
from abnormal to normal after HD (p < 0.001). This
shows an acute fluctuating change in cognition over Our study has a number of limitations; firstly,
a single HD session and cognitive impairment can be MOCA-INA we used has good sensitivity in diagnos-
exacerbated by the HD process itself.21 One prior study ing cognitive disorders but cannot determine the degree
had addressed similar questions regarding the acute of cognitive impairment. Secondly, the HD process it-
variation in cognitive function over a single HD ses- self may not be the only factor affecting the cognitive
sion. Murray et al17 performed cognitive testing in 28 function in CKD patients. Further studies are needed
HD patients at four different time periods: 1 hr before, to evaluate factors that affect the cognitive function in
during (45–90 min from start), 1 hr after, and 24–30 hr CKD.
after. Consistent to our finding that the cognitive func-
tion being worst during HD and best the day after. Conclusion
There is an effect of single HD session on global cogni-
The relationship between CI and HD is still not fully tive function where executive function, attention, lan-
understood and the etiology is thought to be multifac- guage, and recall were deteriorated during HD while
torial.22,23 Hemodynamic stress during HD lead to tem- abstraction and orientation didn’t change. All Cogni-
porary deterioration of cognitive function which sub- tive domains were recovered 24 hours after HD except
sequently improves several hours after HD as an effect naming that didn’t change since the beginning
of uremic toxin elimination.20,22,24 Hemodynamic stress
during HD will be transmitted to and causes dysregu-
lation of cerebral circulation.20,25 Fluid and electrolyte References
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cause brain edema, decreased intracerebral pressure 1. Weiner DE. Public Health Consequences of Chron-
ic Kidney Disease. Clin Pharmacol Ther. 2009;
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86(5): 566–9.
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long-term CI in HD patients.20 2. Bello AK, Alrukhaimi M, Ashuntantang GE, et.al.
Complication of Chronic Kidney Disease: Current
State, Knowledge Gaps, and Strategy for Action.
In this study, we found there were deterioration of mul- Kid Int Supp. 2017; 7: 122-9.
tiple cognitive domains during HD including visuo
spatial, executive function, attention, language, and 3. Arnold R, Issar T, Krishnan AV, et.al. Neurological
Complications in Chronic Kidney Disease. JRSM
recall. After HD, we found an improvement of all Cardiovasc Dis. 2016; 5: 1-13.
cognitive domain except naming that didn’t change
over HD session. Consistent to our study, Murray et.al 4. Etgen T. Kidney Disease as a Determinant of Cog-
nitive Decline and Dementia. Alzheimers Res Ther.
found deterioration in attention, memory and execu- 2015; 7(1): 29-30.
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found deterioration in attention, language, abstraction, 5. Yaffe K, Ackerson L, Kurella M, et al. Chronic
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and delayed recall.17,20 Adults: Findings from the Renal Insufficiency Co-
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lieu and the Potential Therapeutic Role of Exercise. sesment Versi Indonesia (MoCa-INA). Jurn Fisio.
BioMed Research Int. 2017; 1-10. 2013: 1: 55-67.
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Cognitive Disorders and Dementia in CKD: The Function Declines Significantly during Haemodial-
Neglected Kidney-Brain Axis. J Am Soc Nephrol. ysis in a Majority of Patients: A Call for Further Re-
2013; 24: 353–63. search. Blood Purif. 2018; 45: 347–55.
8. Pereirea A, Weiner DE, Scott T, et.al. Cognitive 21. Iyasere O, Brown EA. Cognitive Function before
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9. Murray AM. Cognitive Impairment in the Aging
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An Occult Burden. Adv Chronic Kidney Dis. 2008; Executive Function before and after Dialysis Initi-
15(2): 123–32. ation in Adults with Chronic Kidney Disease. Kid-
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InaKidney
. Hidayat et al
APPENDIX
33
Indonesian Journal of Kidney and Hypertension Available online at http://inakidneyhypertension.co.id
CASE REPORT
Title
Angioplasty in CKD patients with immature AV fistula: A Case Report
Authors:
Atma Gunawan , Sulih Yekti Ngutamani, Achmad Rifai,Nursamsu
Division of Nephrology and Hypertension, Department of Internal Medicine
Faculty of Medicine Universitas Brawijaya, Malang, Indonesia
Editor:
Anil Agarwal
Received 28 February 2019, revised 1 July 2019, accepted 31 July 2019, published 1 August 2019
Background
Abstract Patients with end-stage chronic kidney disease (CKD)
must undergo renal replacement therapy, such as hemo-
Arteriovenous fistula has been preferred to other vascu- dialysis. With chronic hemodialysis, patients must have
lar access for dialysis due to better patient outcome for proper vascular access; arteriovenous fistula (AVF) is
morbidity and mortality. However, AVF failure is quite the preferred type of access due high prevalence of
prevalent. One of the cause for AVF failure is due to infection and other complications and mortality for
venous stenosis, diagnosed through Doppler ultrasound central venous catheter (CVC).1 Compared to arterio-
and venography. Angioplasty is one of the methods that venous graft (AVG), AFV provided longer lasting pa-
can be used to repair and salvage an immature AVF. tency and lower morbidity and mortality.2 There are
In this report, a 59 year old female patient was diag- three aspects in in the establishment of an AVF, which
nosed with CKD with a long history diabetes mellitus are AVF surgery, AVF maturation, and AVF function.3
type 2 and admitted for routine hemodialysis. An AVF The surgical procedure for AVF involves the anasto-
was created on her left radiocephalic vein, and upon mosis of the selected vein to adjacent artery.3 The mat-
evaluation was found to not mature properly. Doppler uration of AVF is evaluated using the rule of 6; after
ultrasound examination showed fistula diameter of 3 4-6 weeks, diameter of 6 mm, less than 6 mm distance
mm and volume flow of 160 ml/min, whereas venog- from body surface, and flow of over 600 ml/min.3 The
raphy showed stenosis in radiocephalic fistula. Balloon success of AVF function is then evaluated through its
angioplasty was then performed with balloon diameter ability to be used as dialysis vascular access and re-
of 4 mm and balloon pressure of 10, 15, and 20 atm peated cannulation.3 Primary AVF failure is defined as
for three minutes each. After the procedure, the fistula AVF that cannot be used or failed to be used as hemo-
exhibit dilatation with minimum residual stenosis and dialysis vascular access under 3 months post-surgery.
adequate as vascular access for hemodialysis. Risk factors for primary AVF failure is advanced age,
obesity, female gender, diabetes with or without periph-
eral arterial disease or coronary disease, and of African
Keyword: vascular access, hemodialysis, venous ste- descent.4,5,6 The management of venous stenosis in AVF
nosis, AV fistula, angioplasty failure can be done through surgical procedure or per-
cutaneous intervention. Percutaneous intervention has
the advantage of lower risk of complication compared
Corresponding author: to surgical procedures; however, there’s still 15% risk
A. Gunawan, e-mail: atmagunawan2010@yahoo.com of restenosis.7,8
34 InaKidney | Vol. II | Is. 1| Jan - Apr 2019

InaKidney
. Gunawan et al
Case Illustration balloon segment was placed in the middle of the le-
sion. Balloon dilatation was done with the pressure of
A 59 year-old female patient was admitted with end-
stage renal disease for 6 months and type 2 diabetes 10 atm, 15 atm, and 20 atm, 3 minutes each.
mellitus (T2DM). Patient had had T2DM for 20 years
and blood glucose was controlled with oral anti-dia-
betics and switched to basal insulin three years ago.
Immediately after diagnosed with ESRD, the patient
had central vein access for dialysis. The patient had un-
derwent surgery for left radiochephalic AVF 5 months
prior, however upon examination using Doppler ul-
trasound the diameter of the fistula was 3 mm and the
blood flow was 160 ml/minute, not adequate as a vas-
cular access. The patient was then planned to have ve-
nography and angioplasty.
Figure 1. Doppler ultrasound imaging of AVF prior to

angioplasty
Before the procedure, patient fasted for 4 hours and an-
tihypertensive medications was administered as sched-
uled. The venography and angioplasty procedure was
performed using local anesthesia. The procedure start-
ed with the insertion the venous segment of the AVF
using intravenous cannula Abbocath 18 G. Afterwards,
RADIOFOCUSTM Guidewire M 0.035 “ (0.89 mm) 50
cm was introduced through the cannula and aimed at the
stenosis. After the cannula was released, PRELUDE®
sheath intoducer 6 French 11 cm was inserted through
the guidewire. After the introducer was properly insert-
ed, the guidewire was removed and the introducer was
fixated. Contrast was then administered to visualize the
lesion, which was a stenosis in the proximal venous
limb adjacent to the fistula.
RADIOFOCUSTM Guidewire M 0.035 “ (0.89 mm)
150 cm was then inserted through the introducer sheath
until it passed the location of stenosis. Balloon angio-
plasty using Boston scientific MUSTANGTM 4.0 mm Figure 2. Venography images prior to angioplasty
x 40 mm 135 cm was inserted over guide wire and the
35
Figure 3. Baloon dilatation using a) 10 atm, b)15 atm, and c) 20 atm pressure
36
Gunawan et al InaKidney
.
diameter balloon catheter. But because this was a pri-
mary failure, where the AV shunt failed to mature, the
dilation of the stenotic lesion was expected to make the
outflow segment further dilated. A month afterwards
the AV shunt matured and produced Qb of 200 ml /
minute on the HD machine, despite being below 600
ml/min this blood flow was adequate for patient’s KT
/ V target of 1.3. The pressure administered for angio-
plasty ranges from 5 atm to 40 atm with mean pressure
below 20 atm.12 Although according to previous studies
there’s no significant difference between the duration
of 1 minute and 3 minutes of pressure time, 3 minutes
was used to ensure adequate dilatation. 13
The National Kidney Foundation (NKF/KDOQI) rec-

ommends the threshold of over 30% for post-procedur-
al restenosis to be deemed as failure of angioplasty. In
this case, the restenosis was minimal and thus the AVF
managed to provide adequate diameter and blood flow
for vascular access 4 weeks after the procedure.
This case might be a usual procedure in the case of
AV shunt stenosis. However, this procedure is quite un-
common in Indonesia, especially in areas with limited
access to necessary equipment for the procedure. Hope-
fully this case will encourage clinicians and stakehold-
ers to embrace a new era of developing endovascular
interventions for AV shunts in Indonesia.
Figure 3. Venography post angioplasty.
Summary
Post angioplasty Doppler evaluation showed volume
blood flow of 200 ml/min and venous diameter was A 59-year-old woman was diagnosed with end-stage
4 mm. Four weeks after the procedure, the AVF was CKD with failing AVF due to stenosis in the proximal
evaluated clinically and showed dilated vein diameter venous limb of the left radiocephalic fistula. Angio-
with adequate thrill. When used as a vascular access plasty was then performed to repair the stenosis using
for hemodialysis , the AVF produced Qb of 250 ml/min 4 mm balloon dilatation with 10, 15, and 20 atm pres-
and the patient managed to achieve KT/V of 1.3. sure, 3 minutes each. After the procedure, the fistula
exhibit minimal restenosis. Upon evaluation 4 weeks
after the procedure, the fistula showed clinically dilat-
ed vein and adequate thrill. The fistula produced Qb of
Discussion 250 ml/min and the patient managed to achieve KT/V
The patient had increased risk for AVF failure due to of 1.3.
age, gender, and 20 years of T2DM.9,10 The use of Dop-
pler ultrasound and venography was enough to provide
the information needed for percutaneous angioplasty References
procedure, for these imaging modalities were proven
to be economically efficient and clinically sensitive and 1. Santoro, D., Benedetto, F., Mondello, P., Pipitò, N.,
effective.11 The balloon should be 20-30% larger than Barillà, D., Spinelli, F., & Buemi, M. Vascular Ac-
the normal vessel diameter judged by comparison with cess for Hemodialysis: Current Perspectives. Int J
the vessel lumen adjacent to the lesion. The use of bal- Nephrol Renovasc Dis. 2014 Jul 8;7;281-94.
loon with 4-8 mm diameter was deemed appropriate for
the AVF stenosis. The balloon for radiocephalic fistula 2. Allon, M., & Robbin, M. L. Increasing Arteriove-
is usually 4-6 mm.8 When procedure was performed nous Fistulas in Hemodialysis Patients: Problems
, in the radiology cathlab only available is a 4 mm
37
and Solutions. Kidney Int. 2002 Oct: 62(4); 1109- loon Inflation Pressures during Treatment of He-
24. modialysis Graft–Related Stenoses. J Vasc Interv
Radiol. 2006:17(4); 623-628.
3. Donnelly, S. M., & Marticorena, R. M. When is
A New Fistula Mature? The Emerging Science of 13. Forauer, A. R., Hoffer, E. K., & Homa, K. Di-
Fistula Cannulation. Semin Nephrol. 2012 Nov: alysis Access Venous Stenoses: Treatment with
32(6); 564-71 Balloon angioplasty—1-versus 3-Minute Inflation
Times. Radiol. 2008:249(1); 375-81.
4. Miller, P. E., Tolwani, A., Luscy, C. P., Deierhoi,
M. H., Bailey, R., Redden, D. T., & Allon, M. Pre-
dictors of Adequacy of Arteriovenous Fistulas in
Hemodialysis Patients. Kidney Int. 1999: 56(1);
275-80.
5. Monroy-Cuadros, M., Yilmaz, S., Salazar-Bañue-
los, A., & Doig, C. Risk Factors Associated with
Patency Loss of Hemodialysis Vascular Access
within 6 months 2010 Oct; 5(10): 1787–1792.
6. Al-Jaishi, A. A., Oliver, M. J., Thomas, S. M.,
Lok, C. E., Zhang, J. C., Garg, A. X., & Moist,
L. M. Patency Rates of The Arteriovenous Fistula
for Hemodialysis: A Systematic Review and Me-
ta-analysis. Am J Kidney Dis. 2014 Mar: 63(3);
464-78
7. Beathard, G. A. Percutaneous Transvenous An-
gioplasty in The Treatment of Vascular Access
Stenosis. Kidney Int. 1992:42(6); 1390-7.
8. Trerotola, S. O., Kwak, A., Clark, T. W., Mond-
schein, J. I., Patel, A. A., Soulen, M. C., & Chit-
tams, J. L. Prospective Study of Balloon Inflation
Pressures and Other Technical Aspects of Hemo-
dialysis Access Angioplasty. J Vasc Interv Radiol.
2005 Dec;16(12):1613-8.
9. 15. Marcus, R. J., Marcus, D. A., Suresh-
kumar, K. K., Hussain, S. M., & McGill, R. L.
Gender Differences in Vascular Access in Hemo-
dialysis Patients in The United States: Developing
Strategies for Improving Access Outcome. Gend
Med. 2007 Sept:4(3);193-204.
10. Davidson, I., & Gallieni, M. (2015). Optimizing
Vascular Access in The Elderly: Words We Use
Affect Patient Care. J Vasc Acc. 2015: 16(6); 437-
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11. Beathard, G. A. Physical Examination of The
Dialysis Vascular Access. Semin Dial. 1998
Jul:11(4); 231-6)
12. Vesely, T. M., & Pilgram, T. K. Angioplasty Bal-
38

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Indonesian Journal of Kidney and Hypertension

Steering Comittee Peer Reviewer (Vol 2 Issue 2 May - Aug 2019) :

2 InaKidney | Vol. II | Is. 2| May - Aug 2019

05 Survival Rate of Living Related Kidney Transplant

10 Correlation between Urinary Cyclophillin A with Urinary

17 Incidence and Risk Factors of Cardio-Cerebrovascular

27 Effect of a Sigle Dialysis Session on Cognitive Function in

34 Angioplasty in CKD patients with immature AV fistula: ­

InaKidney | Vol. II | Is. 2| May-Aug 2019 3

4 InaKidney | Vol. II | Is. 2| May - Aug 2019

Survival Rate of Living Related Kidney Transplant Patients in Surabaya

Abstract factors for kidney transplant patients’ survival.

Figure 1. Kaplan Meier curve for 1, 3, and 5-year sur-

Figure 2. Kaplan Meier curve for 5-year survival of

Correlation between Urinary Cyclophilin A and Urinary Albumin Levels on

Abstract met the inclusion and exclusion criteria. The samples

Patients with hypertension were more than patients

9. Amer HMA, Sabry IM, Bekhet MM, Moham-

12. Masahiko T. Trigliserida, but not total choles-

16. Van Buren PN, Tato R. Hypertension in dia-

17. Syrjanen J. Hypertriglyceridemia and hy-

18. Nakhjavani M, Esteghamati A, Abbasi M. Al-

19. Soelistijo SA, Novida H, Rudijanto A, Soe-

20. Bitzur R, Cohen H, Kamari Y, Shaish H, Harat

21. Woerle HJ, Neumann C, Zschau S, et al. Im-

Abstract composite outcome based on CKD etiology (p=0.03) were as fol-

Table 3. Mortality Outcome

Conclusion 8. Usta S, Basbug HS, Cakiroglu Y. High-sensitivity

Abstract sis. Cognitive function reached its best 24 hour after

Test time Cognitive Function n % Abstraction (T2) 1,18 0,72 0,419

T3 Normal 23 38,3 Orientation (T2) 5,18 0,70 0,709

Table 5. Change in Cognitive Function during and after HD

Abnormal Normal Abnormal

Angioplasty in CKD patients with immature AV fistula: A Case Report

34 InaKidney | Vol. II | Is. 1| Jan - Apr 2019

Figure 1. Doppler ultrasound imaging of AVF prior to

The National Kidney Foundation (NKF/KDOQI) rec-

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34 Angioplasty in CKD patients with immature AV fistula: