UNIVERSIDAD CATÓLICA SANTO TORIBIO DE MOGROVEJO

SCHOOL OF MEDICINE

TEORICAL SESSION N° 1
THE CLINICAL LABORATORY: PREANALYSIS,
ANALYSIS AND POSTANALYSIS
MEASUREMENT OF RENAL
SYSTEM FUNCTION AND
DISORDERS
Blgst. JOSÉ LLONTOP NUÑEZ, MSc.
CLINICAL LABORATORY-2022-II
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

Competencias:

 Conoce las bases de organización de un laboratorio

clínico acreditado nacional e internacionalmente.

 Explica los fundamentos fisiopatológicos y la

propuesta de un plan diagnóstico laboratorial para el
estudio bioquímico de la función y trastornos del
sistema renal.

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.

CLINICAL LABORATORY-2022 II
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

THE CLINICAL LABORATORY

Point-of-care testing Central laboratory
(POCT) analysis
Test request Test request Pre analytical phase
(Preanalytic factors include patient-related
variables: diet, age, sex, etc., specimen
collection and labeling techniques, specimen
Patient identification preservatives and anticoagulants, specimen
transport, and processing and storage)

Obtaining the Obtaining the Specimen Transport to the

specimen specimen identification laboratory

Reception and
Preparation classification

Analytical phase
(Analytic instruments in the clinical Lab that
Quantification Quantification Result validation
provide the clinician with the best possible
data to be of value to the patient)

Post analytical phase

(Provide general tools for the
Delivery of the objective interpretation of
result laboratory results taking into
account applying critical values,
reference ranges, pretest and
posttest probability, etc.)

Clinical decision Clinical decision

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.

CLINICAL LABORATORY-2022 II González, A.2010. Principios de Bioquímica Clínica y Patología Molecular
Measurement
of Renal
System
Function
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

THE RENAL SYSTEM

The functional unit of the kidney is the

nephron. The functions of the kidneys
include:
• Regulation of water, electrolyte and
150g
5x12 cm acid–base balance.
• Excretion of the products of protein
and nucleic acid metabolism: e.g.
urea, creatinine and uric acid; and
metabolites of xenobiotics.
• Endocrine, EPO (Erythropoietin),
prostaglandins and thromboxanes,
renina-aldosterona and vitamin D3.

The vascular and anatomical relationships of the kidneys in humans. (From

Leaf A, Catran RS. Renal pathaphysialogy, 3rd ed. Oxford: Oxford University
Press, 1985. By pennission of Oxford University Press, Inc.)

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.

CLINICAL LABORATORY-2022 II Burtis and Et. Al., 2008. Fundamentals of Clinical Chemistry
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

RENAL PHYSIOLOGY IN BRIEF: THE NEPHRON

NaHCO3(85%), glucose (100%), amino
acids (100%), NaCl (85%) water and uric K+ (Hyposmotic)
acid both obligatory (Isosmotic) H+ OLYGURIA: < 0.2
(GLOMERULAR FILTRATE= Plasma L/24 h in adults.
without proteíns, Ultrafiltrate isoosmótic,
NaCl, water: requires Causes: Physiological,
ADH (Isosmotic)
density= 1.008-1,012; pH= 7.4) NaCl decreased fluid intake,
NaCl, water (Isosmotic) K+, H+
excessive sweat,
Cortex vomiting or
Medulla diarrea,mechanical
NaCl obstruction of urinary
POLYURIA: > 2.5 L/24 flow, etc.
h in adults. Causes: H2O
Physiological, increased NaCl
Urea
fluid intake, diuretics, Urea H2O (Requires ADH: Hyperosmotic)
body cooling,
nervousness, anxiety,
etc. (Hyperosmotic)
Afferent arteriole
Ac.úrico NH4 700-1200 ml of blood (625-650 ml/min)=
Creatinine Solut.disuelt. Renal Blood Flow=RBF

Urea
120-130 ml/min=Glomerular Filtration Rate(GFR)
(20-25% BLOOD VOLUME)
Efferent arteriole
Glomerular filtrate (GF) is about
170 to 180 L/day, out of which
Urine volume H2O only 1.5 liters are excreted as
1.5-2.0 L/day Glucose Ions
urine. This means that most of the
AAs water content of GF is
(400-2000 mL/day) Bowman's capsule 180 ml/min (1 %) reabsorbed.
Blgst. JOSÉ LLONTOP NUÑEZ, MSc.
CLINICAL LABORATORY-2022 II Burtis and Et. Al., 2008. Fundamentals of Clinical Chemistry
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

CLASSIFICATION OF RENAL FUNCTION TESTS

To screen for kidney disease To assess for renal function

• Complete urine analysis (Urinalysis).
• Plasma urea and creatinine. To assess tubular function
• Plasma electrolytes.
• Reabsorption studies
• Secretion tests
• Concentration and
dilution tests
To assess glomerular function • Renal acidification (Urine
pH and the acid load test)

Glomerular Filtration Rate (GFR) Glomerular Permeability

GFR is considered to be a reliable measure of the functional
capacity of the kidneys and is often thought of as indicative
of the number of functioning nephrons.
• Clearance tests
GFR measuremenrs may be based on either the urinary or plasma clearance of the
marker. The renal clearance of a substance is defined as "the volume of plasma
from which the substance is completely cleared by the kidneys per unit of time."
Blgst. JOSÉ LLONTOP NUÑEZ, MSc.
CLINICAL LABORATORY-2022 II Vasudevan, DM., 2013. Textbook of Biochemistry for Medical Students
• Proteinuria
The normal urinary total protein excretion is less than
150 mg/24 h. The pattern of urinary protein excretion
is used to identify the cause and to classify the
proteinuria, of which there are three main types:
glomerular, overflow, and tubular proteinuria.
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

ESTIMATION OF RENAL FUNCTION

Glomerular filtration rate (GFR)
The GFR (mL/min) determine the number of ml of plasma from which the clearance substance
is completely removed during 1 minute is necessary (140 mL/min) in a healthy adult, but varies
enormously with body size. Conventionally, it is corrected to a body surface area (BSA) of 1.73
m2 (so the units are mL/min/1.73 m2).
Exogenous Markers of GFR: Inulina (Gold standard) and Iohexol (silver standard) Clearance.
Endogenous Markers of GFR: Plasma creatinine, and Creatinine Clearance.

Ideal Marker of GF
 Have stable concentration in plasma.

 Be freely filtered in the glomerulus.

 It is neither reabsorbed nor secreted

by the tubules.

Creatinine clearance
The amount of creatinine excreted in urine over
a given period of time: (ml/min)=UxV/P
Or with surface area, Ccr(mL/min)= U ÷ P × V × 1.73/A

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.

CLINICAL LABORATORY-2022 II Gaw, A. et al., 2013. Clinical Biochemistry, An illustrate color Text
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

ESTIMATION OF RENAL FUNCTION

Formulas to Estimate Creatinine Clearance as an Estimate of GFR
Cockroft and Gault in 1976:.

GFR(mL/min) (MEN) = [140–age (y)] × weight (kg)/72 x serum creatinine (mg/dL)

GFR(mL/min) (WOMEN) = [140–age (y)] × weight (kg)/72 x 0.85 x serum creatinine (mg/dL)

Normal Reference values: Adult male: 95-115 ml/min; serum creatinine= 0.7-1.4 mg/dl.
Adult female: 85-110 ml/min; serum creatinine=0.6-1.3 mg/dl.
Children: serum creatinine=0.5-1.2 mg/dl.

MDRD (Modification of Diet in Renal Disease study):

GFR(mL/min) (MDRD) = 186 x (Creat. Ser/88.4)-1.154 × (Age)-0.203 x 0.742 (if female)

Schwartz Formula (Children):

GFR = 0.55 × height (cm) serum creatinine (mg dL)

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.

CLINICAL LABORATORY-2022 II Provan, D. and A. Krentz, 2002. Oxford Handbook of Clinical and Laboratory Investigation
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

ESTIMATION OF GLOMERULAR FILTRATION RATE

Adults Pedriatics
Schwartz´ Formula
Healthy Other clinical situation CrCl(ml/min/1.73m2)=KxL/Scr

Patients with Morbidly Patients with low serum Patients with Renal Unstable renal
different weight than obese Patients creatinine levels: amputation insufficiency function
their ideal weight
Cockroft-Gault´ formula: - Elderly patients. Chronic Renal Dialysis patients
- Low body weight. insufficiency
CrCl (men)(ml/min)=(140- - Very small muscle Liver disease
mass. patients
age)(weight)/72xScr
CrCl(women)(ml/min)=CrCl(m Cockroft- Salazar-Corcoran´ Cockroft-
en)x0.85 Gault´ formula formula: Gault´ formula
Ideal Body Weight with ideal with ideal MDRD
weight (no CrCl Cockroft- weight minus
(IBW)(men)(Kg)=50+[0.9(Heig equation
ideal patient (men)(ml/min)=[137 Gault´ formula the weight GFR stimation
ht-152)] GFR(men)(ml/
weight) - with rounding corresponding equations
IBW(women)(Kg)=45.5+[0.9( min/1.73m2)=
age][0.285xweight( up of serum to the are not
Height-152)] 186xScr-
Kg)+(12.1xheight(m) creatinine amputated recommended
1.154xage-
/51xScr levels (lower extremity
Jellife´ Ecuation (CrCl 0.203x(if
limit)
adjustment to body Surface): black)x0.742(if
CrCl CrCl women).
(men)(ml/min/1.73m2,BSA)={ (women)(ml/min)=[ Where Scr is
98-[0.8(age-20)]}/Scr 146- serum
CrCl age][0.287xweight( cratinine
(mujeres)(ml/min/1.73m2,BS Kg)+(9.74xheight(m) expressed in
A)=CrCl (men)x0.9 /60xScr mg/dl.

Formula of CKD-EPI:
GFR(ml/min/1.73m2)...

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.

CLINICAL LABORATORY-2022 II
Tests of Renal
System
Disorders
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

DISEASES OF THE KIDNEY

Glomerular diseases Tubular and intersticial Other renal-related disease

 Morphologic changes:  Acute tubular necrosis  Systemic diseases:
 Cellular proliferation  Poststreptoccocal glomerulonephritis  SLE(Systemic lupus erithematosus)
 Leucocyte infiltration  Amyloidosis
 Tubular dysfunction
 Glomerular basement-membrane  Diabetes mellitus
 Fanconi´syndrome
thickening
 Cystinosis  Nephrotic syndrome
 Hyalinization
 Immunologic Disorders :  Tubulointerstitial disease  Renal calculi
 Glomerulonephritis :  Calculi of calcium
 Urethritis, cystitis, pyelitis, pyelonephritis
 Acute glomerulonephritis
 Calculi of calcium oxalate
 Crescentic (rapidly progressive)  UTIs
glomerulonephritis  Calculi of calcium-phosphate
 Acute pyelonephritis
 Membranous glomerulonephritis  Calculi of magnesium ammonium
 Chronic pyelonephritis phosphate hexahydrate
 Mesangiocapillary glomerulonephritis
 Acute intertitial nephritis  Calculi of uric acid and urate
 In focal glomerulonephritis
 Calculi of cystine
 Chronic glomerulonephritis  Acute Renal Failure

 Minimal change disease  Chronic Renal Failure

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.
CLINICAL LABORATORY-2022 II Hubbard, J., 2010. A Concise Review of Clinical Laboratory Science
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

DEFINITIONS OF AKI, CKD and AKD

The definition for each is based on alterations in kidney function or structure.

GFR assessed from measured or estimated GFR. Estimated GFR does not reflect measured GFR in AKI as accurately as in CKD. Kidney damage
assessed by pathology, urine or blood markers, imaging, and—for CKD—presence of a kidney transplant. NKD indicates no functional or
structural criteria according to the definitions for AKI, AKD, or CKD. Clinical judgment is required for individual patient decision-making regarding
the extent of evaluation that is necessary to assess kidney function and structure. AKD, acute kidney diseases and disorders; AKI, acute kidney
injury; CKD, chronic kidney disease; GFR, glomerular filtration rate; NKD, no known kidney disease; SCr, serum creatinine.

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.

CLINICAL LABORATORY-2022 II Kidney International Supplements, 2012. KDIGO Clinical Practice Guideline for AKI
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

MARKERS OF KIDNEY DAMAGE IN AKD and CKD

Kidney damage is not required for diagnosis of AKI. In the presence of AKI, findings of kidney damage do not indicate a separate diagnosis of
AKD. AKD, acute kidney diseases and disorders; CKD, chronic kidney disease; RBC, red blood cells; RTE, renal tubular epithelial cells; WBC, white
blood cells.
Blgst. JOSÉ LLONTOP NUÑEZ, MSc.
CLINICAL LABORATORY-2022 II Kidney International Supplements, 2012. KDIGO Clinical Practice Guideline for AKI
CLINICAL LABORATORY: The Clinical Laboratory-Estimation of Renal Function VI-MEDICINE USAT

THE RIFLE CRITERIA FOR ACUTE KIDNEY INJURY(AKI)

GFR Criteria Urine Output Criteria

Increated Screat x 1.5 or

Risk UO < 5 ml/kg/h x 6.0 h
GFR decrease > 25%

High
Sensitivity
Increated Screat x 2.0 or
Injury UO < 0.5 ml/kg/h x 12.0 h
GFR decrease > 50%

Increate Screat x 3.0 or

UO < 0.3 ml/kg/h x
Failure GFR decrease > 75%
Or Screat ≥ 4 mg/dl 24.0 h or
Acute rise ≥ 0.5 mg/dl Anuria x 12 h
High
Persistent ARF = Complete loss of kidney Specificity
Loss function > 4 weeks

End Stage Kidney Disease

ESKD (3 months)

Blgst. JOSÉ LLONTOP NUÑEZ, MSc.

CLINICAL LABORATORY-2022 II Kidney International Supplements, 2012. KDIGO Clinical Practice Guideline for AKI
GRACIAS