THE CLINICAL BIOCHEMISTRY

OF KIDNEY FUNCTIONS

Dr Boldizsár CZÉH
The kidneys are vital organs

Functional unit: Nephron

 RENAL FUNCTIONS
Electrolyte & Fluid Balances
Acid-Base Balances
Elimination of Metabolic Wastes
Blood Pressure Regulation
Endocrine functions: Vitamin D Synthesis, EPO,
RAA system
Red Blood Cell Production
Prostaglandins Synthesis
Why do we test renal functions?

To identify renal dysfunction.

To diagnose renal disease.

To monitor disease progress.

To monitor response to treatment.

To assess changes in function that may impact

on therapy (e.g. Digoxin, chemotherapy).
Urinalysis

Liquid „biopsy‟ of the

urinary tract.

Painless, non-invasive,
inexpensive.

Yields much information

quickly.
 The 3 stages of urine analysis

FRESH SAMPLE!!
Urine in different colors
 Gross appearance
Amount
– 800 – 1800 mL / die
– Polyuria > 2.5 L / die
– Oliguria < 400 mL / die, Anuria 100 ml / die
– Pollakisuria: frequent, but small amount, becasue of tumor or
infection
Color
– Normally yellowish
– Food, drugs
– Blood, myoglobin
Transparency
– Infection, blood, bacteria, fungi
Odor
typical urine smell
sweet: sugar
ammoniac
 Urine sediment: microscopic examination
from freshly passed urine
Looking for cells, casts
(Tamm-Horsfall protein), fat
droplets
Red Cell casts : haematuria
= glomerular disease
White cell cast :
polymorphs + bacteruria =
pylonephritis
Lower UTI: polymorphs, but
no casts
Acute glomerulonephritis = Erythrocyte Leucocyte
haematuria, cells, casts cylinder cylinder
Chronic glomerulonephritis
= less sediment
Biochemical Tests of Renal Function
– Specific gravity and osmolality
– pH: normal pH 4.8 – 7.5
– Glucose
– Protein
– Bilirubin
– Keton bodies
Biochemical Tests of Renal Function
Glucose
– Increased blood glucose
– Low renal threshold or other tubular disorders
Proteinuria
– Normal < 200 mg / 24h. Urine sticks = > 300mg/L
– Causes: -
overflow (raised plasma Low MW Proteins,
Bence Jones, myoglobin)
glomerular leak
decreased tubular reabsorption of protein
protein with renal origin
Functional tests
Glomerular Function = GFR
Measurement of Glomerular Filtration Rate:
determination of clearance

GFR is essential to renal function

Most frequently performed test of renal function.
Measurement is based on concept of clearance:
“clearance is a pharmacokinetic measurement
of the volume of plasma from which a substance
is completely removed per unit time;
the usual units are mL/min”
Measurement of Glomerular Filtration Rate:
determination of clearance
Clearance = (U x V) / P where
U = is the urinary concentration of a given substance
V = is the volume of urine produced (mL/min)
P = is the plasma concentration of the given substance

Unit = volume / time (mL/min)

If clearance = GFR then:

– freely filtered by glomerulus
– glomerulus = sole route of excretion from the body
– (no tubular secretion or reabsorption)
– Non-toxic and easily measurable
Creatinine Clearance

1-2 % / day of
muscle creatine
converted to
creatinine.
Amount produced
relates to muscle
mass.
Freely filtered at the
glomerulus.
Some tubular
excretion.
 Creatinine Clearance
Timed urine collection for
creatinine measurement
(usually 24h)
Blood sample taken within the
period of collection.
Problems:
Practical problems of accurate
urine collection and volume
measurement.
Within subject variability =
11%
Interference in creatinine
measurement
In vitro interference:
acetoacetate, ascorbic
acid, fructose, pyruvate,
cephalosporins, creatine,
proline, chronic lidocaine
administration, bilirubin.
In vivo inhibition of
creatinine secretion
occurs with cimetidine or
trimethoprim.
 Estimated GFR (eGFR)
Plasma Creatinine Concentration
 Estimated GFR (eGFR)
Plasma Creatinine Concentration
Difficulties:
Concentration depends on
balance between input and
output.
Production determined by
muscle mass which is related to
age, sex and weight.
High between subject variability
but low within subject.
Concentration inversely related
to GFR.
– Small changes in creatinine
within and around the reference
limits = large changes in GFR.
Reference limits can be
misleading
Plasma creatinine can increase
following protein loads.
– Goulash effect. 80% rise in
creatinine after 300g of cooked
beef.
– Less variability in early morning
creatinine
Strenuous exercise may increase
creatinine by 14%
Muscle mass more difficult to
predict in oedematous patients and
late pregnancy
Patients with muscle wasting
Patients with liver disease
Drugs inhibiting tubular secretion
can raise creatinine conc.
Effect of Muscle Mass on Serum Creatinine
Increased
Normal Normal Muscle
Reduced
Muscle Muscle Mass
Muscle
Mass Mass Mass
Creatinine
Input
Plasma
Pool
Content
Output
Kidney

Normal Diseased Normal Diseased

Kidneys Kidneys Kidneys Kidneys
 Cystatin-C
Cysteine proteinase
inhibitor C (MW13 000)
Small size = freely filtered
at glomerulus
Constant production rate
by all nucleated cells
No known extra-renal
excretion routes
Not influenced by muscle
mass, diet or sex
Estimation of GFR for/in:
– Early detection of kidney
disease
– Acute and chronic renal
disease
– Renal transplantation and
haemodialysis
– Diseases associated with
kidneys, e.g. diabetes
mellitus, hypertension
– Patients receiving
nephrotoxic drugs
– Liver failure
– Paediatrics and elderly
Tubular Functions
 Tests of Tubular Functions
Proximal Tubular
Function
– Phosphate reabsorption
– Aminoaciduria
– Glycosuria
– Fractional HCO3-
excretion.
Distal Tubular Function
– Acidification
– Concentration

Concentrating capacity of the kidneys

Renal failure: laboratory studies
Serum Studies
– BUN = blood urea nitrogen (2.5-6.4 mmol/L)
– Creatinine (70-124 umol/L)
– Hematocrit
– Albumin
– Electrolytes (K+, Na+, Ca2+, Mg++ & Phosphate)
Urine Studies
– Urine Analysis (UA)
Color, appearance, pH, specific gravity, glucose, protein,
WBC, RBC and casts.
– Culture & Sensitivity (C&S): Bacteria
– Urinary Collection:
24 Hour Urine: i.e. creatinine or electrolytes
Spot / Random Urine: first a.m. void preferred
Combination Studies
– Creatinine Clearance (110-120 ml/min)
24 hour urine and a serum sample
Acute Renal Failure (ARF)
Sudden loss of kidney function over a
period of hours or days
– Characterized by:
A rapid ↓ GFR
Retention of metabolic waste
– A progressive ↑ BUN and ↑ Creatinine (Azotemia)
– Associated with:
Classic finding of Oliguria (UO < 400ml/day)
Fluid, electrolyte and acid-base imbalances
– Usually reversible with prompt treatment
 Classification of ARF: according to the
location of the insult
– Prerenal
↓ Blood flow to kidneys
Occurs in about 50-70% of all
ARF cases
– Intrarenal
actual damage to kidneys
Occurs in about 20-30% of all
ARF cases
– Postrenal
obstruction of urinary excretion
Occurs in about 1-10% of all ARF
cases
 Pre-Renal ARF
Renal blood flow is decreased before reaching
the kidney.
– ↓ Renal Perfusion = ↓ GFR leading to Oliguria
– Most common type of ARF
– Common Causes:
Hypotension (severe and abrupt)
Hypovolemia
Low Cardiac Output States
– Treatment to correct cause, if not corrected it may
cause intrarenal failure i.e. acute tubular necrosis
(ATN)
 Intrarenal ARF: a condition that leads to actual
damage of the renal tissue (parenchyma) resulting
in malfunction of nephrons.

Acute Tubular Necrosis (ATN)

Damage to the renal tubules
caused by ischemia or toxins
Characterized by varying degrees
of cellular damage or death.
– Ischemic: trauma to kidneys,
massive hemorrhage or post-
surgery
– Nephrotoxic: I.V. contrast dyes,
heavy metals or antibiotics
(aminoglyclosides)
 Pre-renal versus renal ARF

TEST RESULT

Pre-renal Renal

Urea & Creatinine Urea Both

in serum Creatinine

Protein in the urine - +

 Pre-renal versus renal ARF

TEST RESULT
Pre-renal Renal

Urine Na+ (mmol / L) < 20 > 40

Urine / Plasma
Osmolality > 1.5 : 1 < 1.1 : 1

Urine urea cc /
Plasma urea cc > 10 < 5
Postrenal ARF: conditions that block
urine flow distal to kidneys
– Caused by an obstruction below
the kidneys in the urinary tract
Calculi (stones)
Tumors or masses
Blood clots
Benign prostate hypertrophy (BPH)

– ↓ Urine Output common; Oliguria

or anuria (UO < 50 ml/day)
Causes urine to back up into the
kidneys; eventually increases
pressures leading to a ↓ GFR
 Chronic Renal Failure
A progressive and irreversible loss of renal function over a
period of months to years

– The kidneys can loose up to 80% of all nephrons with

relatively few overt changes in functioning of the body

– Nephrons are destroyed and replaced with scar tissue;

remaining nephrons become hypertrophied and do not
function as well.

– Resulting in systemic disease involving all of the body‟s

organs (Uremic syndrome of CRF)
Chronic Renal Failure

Diabetes Mellitus
Hypertension
Vascular disorders
Infections
Nephrotoxic medications
Toxic agent exposure
Sickle cell anemia
Systemic lupus erythematosus
Chronic glomerulonephritis
Pyelonephritis
Obstructions of the urinary tract
Polycystic kidney disease
 Three Stages of CRF
Stage 1
– Reduced renal reserve Stage 3
Characterized by a 40-75% loss of – End-stage renal
nephron function disease (ESRD)
Usually asymptomatic; normal BUN Final Stage
& Creatinine
Characterized by
Stage 2 a >90% loss of
– Renal Insufficiency nephron function
Characterized by a 75-90% loss of Characterized by
nephron function ↑BUN ↑Creatinine
↑BUN and ↑Creatinine and electrolyte
– Kidneys loose ability to concentrate imbalances
urine; client may report polyuria
or/and nocturia; Anemia develops
Uremic
symptoms
Requires Life-
long Dialysis
Nephrotic syndrome
 Most common syndromes
associated with glomerular disease

Acute
Glomerulonephritis
Rapidly Progressive
Glomerulonephritis
Chronic
Glomerulonephritis
Nephrotic Syndrome
 Pathophysiology of nephrotic syndrome
Increased glomerular
capillary permeability

Heavy proteinuria

Hypogammaglobulinemia Hypoalbuminemia Loss of antithrombin-3

Susceptibility Compensatory
Edema
to infection Increase in lipoprotein
synthesis

Hyperlipemia Hypercoagulability
Systemic biochemical manifestations,
complications
Anemia
– Inadequate erythropoietin production
– Decreased life span of RBC
– Nutritional deficits
S/SX: fatigue, shortness of breath
and even angina
Renal Osteodystrophy
– A syndrome of skeletal changes
found in CRF from alterations in
calcium & phosphate metabolism and
elevated PTH levels:
↑ PTH reabsorbs calcium &
phosphorous from bone stores in an
attempt to increase serum calcium
levels.
Long term effects: bone deformity
and weakness
– Increased triglyceride
levels
Occurs in 30-70% in CFR
– Increased blood sugars
Usually moderate; alterations
cellular use of glucose
– Increased tendency to
bleed
Altered platelet function and
coagulation factors
– Increased risk of Infection
Impaired leukocyte function
and immune responses
– Reproductive Dysfunction
Infertility and decreased libido
 Biochemical manifestations: electrolyte
imbalances
– Hyperkalemia
Kidney‟s can‟t excrete 80-90% of body‟s potassium like normal
Irritability, restlessness, weakness, diarrhea and abdominal
pain/cramping
– Hyperphosphatemia
Primarily excreted by kidneys; ↓UO = decreased excretion
– Hypocalcemia
The active form of Vitamin D is required for Ca2+ to be absorbed;
only functioning kidneys can activate Vitamin D
– Hypermagnesemia
Usually normal or slightly elevated
– Hyponatremia
Sodium levels maybe decreased due to hemodilution from fluid
overload.
Thank you!