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Renal Function Tests

Prof. Dr. Raid M. H. Al-Salih

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Clinical Chemistry


Renal Functions

Production of urine

◦ Elimination of metabolic end products (Urea/Creatinine)

◦ Elimination of foreign materials (Drugs)

◦ Control of volume & composition of ECF

Water and electrolyte balance

Acid/Base status

Endocrine Functions

Vit D, Erpo, Renin

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Clinical Chemistry


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Clinical Chemistry


GLOMERULAR FUNCTION

The glomerulus has three layers separating the blood in the

glomerular capillaries from the glomerular lumen : capillary

endothelial, basement membrane, and visceral epithelium.

The basement membrane is the primary barrier. An overall

negative charge due to abundant sialic acid groups in the

glomerular layers helps prevent large anions, such as most

proteins, from crossing. The hydrostatic pressure across the

membrane which carries the ultrafiltrate is only about 1 kPa,

and if blood pressure falls only moderately, the oncotic

pressure due to the plasma proteins is sufficient to cause

filtration to slow or even stop. This explains the oliguria in

shocked patients.

(polyuria = more than normal urine; oliguria = less than

normal; anuria = no urine).

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Clinical Chemistry


TUBULAR FUNCTION

1. PROXIMAL TUBULE

Designed to reabsorb only what you need - 80% of sodium

and water

- K+ : 95% absorbed usually, but diet dependant

- phosphate : active reabsorption which is inhibited by PTH

- HCO3- : mostly absorbed, but see acid-base lectures for

details

- glucose and amino acid absorption is normally nearly

complete

- also secretes: organic acids, urate, drugs

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Clinical Chemistry


2. LOOP OF HENLE

It is responsible about creating either dilute or

concentrated urine. Key features are an active NaCl pump in

the thick ascending limb, and water impermeability of the

whole of the ascending limb.

Fluid emerges hypotonic at the end of the loop of Henle, at

about ½ the osmolality of body fluids (~ 120-150

mosmoles/l, as compared with 250-300 mosmoles/l in

plasma). Further salt may be removed in the collecting ducts

under conditions of water diuresis, causing further dilution.

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Clinical Chemistry


3. DISTAL CONVOLUTED TUBULE (DCT)

Little change in volume or concentration

Secretion of Aldosterone causes sodium to be exchanged

for K+ and/or H+. Conn's syndrome, Addisons disease,

and RTA type I all affect DCT function.

4. COLLECTING DUCTS

Anti Diuretic Hormone (ADH, Vasopressin, Pitressin),

synthesized in the hypothalamus and released from the

posterior pituitary in response to an increase in

extracellular osmolality, increases water permeability of

tubular cells (and urea permeability in the lower medullary

part).

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Clinical Chemistry


ADH linked pathology exerts its effect here and

consists of:-

4.1 Diabetes insipidus

: pituitary form, where no ADH is synthesized due to

damage to the pituitary.

: nephrogenic form, where renal tubular cells do not

respond to normal levels of ADH. Both forms give rise to

polyuria with dilute urine.

4.2 Syndrome of inappropriate secretion of ADH

(SIADH): low output of inappropriately concentrated

urine in the presence of hypervolaemia and dilutional

hyponatraemia.

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Clinical Chemistry


Renal function tests

Glomerular function tests: all the clearance tests (innulin, creatinine, urea)

Tubular function test: urine concentration or dilution test or urine acidification test

Analysis of blood/serum: blood urea, serum creatinine, protein and electrolytes

Urine examination: simple routine examination of urine for volume, pH, proteins, blood, ketone bodies, glucose

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Clinical Chemistry


Renal Function Tests

Why Test Renal Function? 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. chemotherapy).

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Clinical Chemistry


GLOMERULAR FUNCTION TESTS:

These depend on examination of substances which

depend on glomerular function for their elimination:

• SERUM CREATININE:

1- Filtered at the glomerulus and eliminated without

significant reabsorption or secretion in the tubules.

2- Derived from creatine phosphate in muscle.

3- Serum levels are related to muscle mass, and

influenced by dietary meat intake.

4- Increases as renal mass is lost in chronic renal

disease and acute renal failure.

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Clinical Chemistry


Clinical Chemistry

Prof. Dr. Raid M. H. Al-Salih 12

• CREATININE CLEARANCE (Cr Cl): Owing

to creatinine not being significantly reabsorbed or

secreted by the renal tubules, Cr Cl provides a

measure of the glomerular filtration rate (GFR). It

is calculated as follows:

Cr Cl. = (Urine Creatinine conc. x volume) /

(Plasma Creatinine conc.)

Note that the units are a flow rate, ml/min. It can

be difficult to measure well since the timed urine

collection (should be over 24 hrs) is in practice

unreliable and requires good patient and staff

cooperation. Normal Cr Cl. is about 120 ml/min.

• BLOOD UREA: Derived in the liver from protein

breakdown: is a useful measure of decreased filtration. About

30-40 % is normally reabsorbed in tubules. Levels are affected

by high protein intake, catabolic states, post-surgery and

trauma, and gastro-intestinal haemorrhage, all of which cause

increased urea production from protein.

• Estimated GFR (eGFR): This is only used in adults (>18

years) estimated GFR (eGFR) should be calculated using the 4-

variables (i.e. serum creatinine concentration, age, gender and

ethnic origin):

GFR (mL/min/1.73 m2) = 175 x [serum creatinine

(µmol/L) x 0.011312]-1.154 x [age]-0.203 x [1.212 if

black] x [0.742 if female]

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Clinical Chemistry


CAUSES OF ABNORMAL SERUM UREA TO CREATININE RATIO

Decreased Increased

Low protein intake High protein intake

Dialysis (urea crosses

dialysis membrane easier)

G.I. haemorrhage

Severe liver disease

(decreased urea synthesis)

Hypercatabolic state

Dehydration

Urinary Stasis

Muscle wasting or amputation

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Clinical Chemistry


Clinical Chemistry


1. TUBULAR FUNCTION TESTS

1.1 Urinary Na+ concentration. Normally low

relative to serum concentration unless on a dietary

high salt intake.

1.2 Concentration tests and Dilution tests, after a

water load. Ratio of osmolality (or urea) in urine

relative to that in plasma is a simple practical

measure.

2.3 Acidification tests, after administration of NH4Cl

( → NH3 + H+ + Cl- ). Seldom done except in

differentiation of type I and II renal tubular

acidoses (RTA).

Clinical Chemistry


MISCELLANEOUS TESTS:

3.1 Microscopy : look for casts, cells, or crystals.

3.2 Protein :> 2.5 g/day indicates nephrotic syndrome

:Bence-Jones Protein indicates myeloma

:ß2-microglobulin, small protein, filtered then absorbed by

tubules, which is a sensitive test of tubular function (but also ↑

in some malignancies and inflammatory conditions).

:Modest proteinuria is associated with many types of

pathology but a mild increase can sometimes be normal

(pregnancy).

3.3 Urinary cAMP :Administer ADH: No increase in urinary

cAMP indicates nephrogenic diabetes insipidus

:Administer PTH: No increase in urinary cAMP indicates

pseudohypoparathyroidism.

Clinical Chemistry


RENAL DISORDERS

NEPHROTIC SYNDROME

Characterised by increased permeability of the

glomerulus to proteins, with proteinuria of greater

than 2.5 g/day, & oedema (why?), hypoproteinaemia, and

increased serum lipids. It is sometimes useful to

measure the selectivity index, which is the ratio of the

clearance of a high M.W. protein such as IgG and a low

MW protein such as albumin:

UIgG/PIgG

Selectivity Index = ------------- x 100

Ualb/Palb

This index will increase as the disease

progresses.

Clinical Chemistry


There are many causes of the nephrotic syndrome; some of

them responsive to steroid therapy.

Note the ↑ in α2 globulins (α2 macroglobulin - too large to

be filtered easily, and increased as part of an attempt by the

liver to compensate for the protein loss by increasing overall

synthesis of serum proteins)

There is also hypercholesterolaemia and ↑ in other serum

lipids (cause of elevated β globulins above)

Clinical Chemistry


ACUTE RENAL FAILURE (ARF)

Definition: Urine output less than 450 ml/day

(in adult) with a rising blood urea (N = 1.7 -

6.7 mmoles/l)

The blood urea typically rises by 5

mmoles/l/day, but in surgical, trauma, or gastro-

intestinal bleeding it can rise by up to 15

mmoles/l/day.

Clinical Chemistry


ARF is a common medical emergency with some

critical urgent decisions facing the clinician (i.e. -

you): the diagnostic problem is : has the patient got :

1. Pre-renal failure (defect before the kidney)

2. Intra-renal failure (defect in the kidney e.g. acute

tubular necrosis, glomerulonephritis)

3. Post-renal failure (defect after the kidney, e.g.

prostatic enlargement, urolithiasis).

Clinical Chemistry


To decide between these three categories of acute renal failure

is urgent because

1. Pre-renal failure if not rapidly treated can progress to the

much more serious intra-renal failure (acute tubular

necrosis).

2. Some aspects of the treatment of intra-renal failure are the

opposite of those for pre-renal failure.

Tubular function will be defective in Intra-renal failure but

normal (for a while) in pre-renal failure. Some

appropriate tests to distinguish between these two are

therefore:

Clinical Chemistry


PRE-RENAL INTRA-RENAL

Urinary sodium

concentration < 20 > 40 mmol/l

Urine/plasma

osmolality ratio > 1.4 < 1.1

Urine/plasma

urea ratio > 14 < 10

* The urinary Na+ is low in pre-renal failure because the low

blood volume causes a marked stimulation of aldosterone-

mediated Na+ uptake. In Intra-renal failure the damaged

tubules can't respond fully.

Clinical Chemistry


MANAGEMENT OF ACUTE RENAL FAILURE

1. Post-renal - relieve the obstruction, but then watch

out for subsequent polyuria

2. Pre-renal - restore blood volume, then blood pressure and

GFR will return to normal levels.

3. Acute tubular necrosis –

3.1 Water : if blood volume is low, replace with care, since fluid

overload can lead to cardiac failure

3.2 Na+ : if oliguric – restrict, in diuretic phase - may need to

administer Na+ ++.

Clinical Chemistry


3.3 K+ :if oliguric - restrict - administer if hypokalaemia.

3.4 H+ :high anion gap metabolic acidosis, may need

bicarbonate to neutralise a severe acidosis, but danger of

Na+ overload if too much NaHCO3 is given in oliguric

phase.

3.5 Dialysis is indicated if

: blood urea is greater than 50 mmol/l and rising

: bicarbonate is less than 10 mmol/l

: K+ is greater than 7.0 mmol/l (or ECG changes)

Clinical Chemistry


Clinical Chemistry


CHRONIC RENAL FAILURE (CRF)

This has many causes, of which the most common are

glomerulonephritis,

diabetes mellitus,

hypertension,

but the net effect is a progressive loss in the number

of functioning nephrons.

The key characteristic of well developed CRF is

polyuria - the opposite to the oliguria or anuria of

ARF.

Clinical Chemistry


Initial features are those of decreasing

glomerular function

-increase in urea, giving chronic uraemia, (sometimes

called azotaemia)

-increase in creatinine and progressive decrease in Cr

clearance

-increase in urate, phosphate, sulphate.

Clinical Chemistry


Later are added features of decreasing

tubular function caused by:

-actual tubular damage

-increased tubular flow due to (urea) osmotic

diuresis

Features are then:

- polyuria with fixed output

- loss of concentrating and diluting abilities

- metabolic acidosis with increased anion gap

- sodium instability - overload or deficiency can easily

occur

Clinical Chemistry


MANAGEMENT OF CRF:

1. Water intake is controlled by thirst since output is

fixed.

2. Careful control of Na+, K+ and protein intake.

3. Treatment of anaemia with erythropoietin.

4. Oral bicarbonate if acidosis is severe.

5. In end-stage CRF : dialysis - haemodialysis or

peritoneal dialysis

: renal transplantation.

Clinical Chemistry


POLYURIA

1. Water diuresis (urinary osmolality <200)

1.1 Compulsive water drinking

1.2 Diabetes insipidus - neurogenic or nephrogenic

2. Osmotic diuresis (urinary osmolality + 300)

Caused by the presence of incompletely reabsorbed

solutes in the tubular lumen:

2.1 Na+ - dietary, iatrogenic, diuretics, salt-losing

nephritis.

2.2 Urea – CRF, recovery phase of acute tubular

necrosis or post-renal failure

2.3 Glucose (diabetes mellitus)

2.4 Mannitol, and some other therapeutic agents.

Clinical Chemistry


RENAL STONES (Nephrolithiasis)

Causes

1. A high concentration of a substance in the

urine due to:

- low urine volume

- high excretion rate

2. pH changes

- alkaline urine predisposes to Ca deposition (e.g.

infection)

- acid urine predosposes to uric acid deposition.

3. Stagnation, usually due to obstruction.

Clinical Chemistry


Types of stones (or calculi)

1. Calcium - oxalate (+ phosphate)

- phosphate

2. Uric acid - in about 10% of gouty cases. May

be associated with low urinary pH due to

inadequate buffer production.

3. Rare forms

- cystine: cystinuria,

- xanthine: xanthine oxidase deficiency

- 2,8 dihydroxyadenine:

Calculi are only partly mineral; up to 60% may

consist of protein, the rest being varying

proportions of calcium, magnesium, ammonium,

phosphate.

Clinical Chemistry


Treatment

-fluids ++ to keep urine dilute (in all cases)

-Potassium citrate and thiazide diuretics may help

prevent Ca stone formation - urinary citrate helps

solubilise calcium.

- alkalinisation may help prevent uric acid (but not 2,8

dihydroxyadenine) stone formation

Clinical Chemistry


RENAL ACIDOSIS

There are 2 components to H+ excretion by the

kidney:

(i) reabsorption of filtered bicarbonate in the

proximal tubule

(ii) H+ secretion in the distal tubule.

1. URAEMIC ACIDOSIS.

Seen in acute or chronic renal failure. Decreased H+

excretion due to both glomerular and tubular

failure.

Clinical Chemistry


2. RENAL TUBULAR ACIDOSIS (RTA).

Type 1 (distal) RTA:

Due to inability of distal nephron to excrete H+. The

urine pH is inappropriately high (pH > 5.5), with

hypokalemia.

Type 2 (proximal) RTA:

Due to defective proximal bicarbonate reabsorption.

urine pH can be appropriately acidic (< 5.5) since

distal tubular H+ excretion is normal. Associated with

hypokalemia, glycosuria, phosphaturia and amino

aciduria – (Fanconi syndrome).

renal function tests - جامعة ذي قارsci.utq.edu.iq/images/pdf/dr33.pdf · renal function...

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