Q2 LONG ANSWER 10M ★ High-yield

Classify the renal function tests. Describe the assessment of glomerular filtration rate and the tests of tubular function.

Biochemistry · 1st Professional — Pre-Clinical

Functions of the Kidney

Excretory — urea, creatinine, uric acid, drugs
Regulatory — water, electrolytes, acid–base balance
Endocrine — erythropoietin, renin, 1α-hydroxylase (calcitriol)
Metabolic — gluconeogenesis, ammoniagenesis, peptide degradation

Classification of Tests

Group	Tests
Glomerular function	Blood urea, serum creatinine, creatinine clearance, eGFR, cystatin C, inulin clearance
Tubular function	Urine concentration and dilution, urine specific gravity and osmolality, urinary acidification, PAH clearance
Glomerular integrity	Proteinuria, microalbuminuria, urine microscopy for casts
Others	Electrolytes, acid–base, calcium and phosphate

Glomerular Filtration Rate

GFR = the volume of plasma filtered by the glomeruli per minute. Normal 120–130 mL/min/1.73 m2.

Marker	Merit	Limitation
Inulin clearance	Gold standard — freely filtered, neither secreted nor reabsorbed	Needs infusion; impractical
Creatinine clearance	Endogenous; no infusion needed	Overestimates GFR by 10–20% because some is secreted; needs a complete 24-hour collection
Serum creatinine	Simple, cheap, universal	Insensitive — stays normal until GFR has fallen by about 50%; varies with muscle mass
EGFR (CKD-EPI, MDRD)	Corrects for age, sex and race; no collection needed	Unreliable at extremes of muscle mass, in pregnancy and in acute illness
Cystatin C	Independent of muscle mass; detects early loss	Costlier; affected by steroids and thyroid disease

Creatinine clearance = (U × V) ÷ PU = urine creatinine, V = urine flow (mL/min), P = plasma creatinine

CLINICAL PEARL

The "creatinine blind range" matters clinically. Serum creatinine can remain within the reference interval while half the renal function has already been lost, because of the reciprocal relationship between creatinine and GFR. A rise from 0.8 to 1.6 mg/dL — both "normal-looking" — represents a halving of GFR.

Blood Urea and Creatinine

Feature	Blood urea	Serum creatinine
Normal	20–40 mg/dL	0.6–1.2 mg/dL
Source	Protein catabolism, urea cycle	Creatine phosphate, non-enzymatically
Affected by diet	Yes — high protein raises it	Little
Reabsorbed	40–50%	Negligible
Better index of GFR	No	Yes
Raised in GI bleed	Yes	No

Urea : creatinine ratio above 20:1 suggests a prerenal cause — dehydration, shock, gastrointestinal bleeding, or a high protein load
Blood urea is low in liver failure, pregnancy and a low-protein diet

Tubular Function Tests

Urine concentration test — after overnight fluid deprivation, specific gravity should exceed 1.022 and osmolality 800 mOsm/kg. Loss of concentrating ability is the earliest sign of tubular damage
Urine dilution test — specific gravity should fall below 1.003 after a water load
Urinary acidification (ammonium chloride loading) — urine pH should fall below 5.3; failure indicates renal tubular acidosis
PAH clearance measures effective renal plasma flow (about 600 mL/min), since PAH is completely cleared in one pass
Fractional excretion of sodium — below 1% in prerenal failure, above 2% in acute tubular necrosis

Proteinuria and Albuminuria

Category	Albumin excretion	Significance
Normal	< 30 mg/day	—
Microalbuminuria	30–300 mg/day	Earliest sign of diabetic nephropathy — and reversible
Overt proteinuria	> 300 mg/day	Established nephropathy
Nephrotic range	> 3.5 g/day	With hypoalbuminaemia, oedema and hyperlipidaemia

Ordinary dipsticks detect albumin but miss Bence Jones protein — a critical limitation in suspected myeloma
Albumin : creatinine ratio on a spot sample has largely replaced timed collections

Biochemical Findings in Renal Failure

Parameter	Change	Reason
Urea and creatinine	↑↑	Failure of excretion
Potassium	↑	Failure of excretion; acidosis shifts it out of cells
Bicarbonate, pH	↓	Failure of acid excretion and bicarbonate regeneration
Calcium	↓	Failed 1α-hydroxylation of vitamin D
Phosphate	↑	Failure of excretion
PTH	↑↑	Secondary hyperparathyroidism → renal osteodystrophy
Haemoglobin	↓	Erythropoietin deficiency

Applied Aspects

Annual microalbuminuria screening in diabetes is worthwhile precisely because that stage is reversible with ACE inhibitors and good glycaemic control
Serum creatinine must be interpreted against muscle mass — a frail elderly woman may have marked impairment with a "normal" value, which is why eGFR is reported
Drug dosing must be adjusted to eGFR for renally excreted drugs; metformin, digoxin and aminoglycosides are common pitfalls
Cooked meat transiently raises creatinine, so a fasting sample is preferred
Uraemia is a clinical syndrome, not a number — nausea, pruritus, pericarditis, encephalopathy and bleeding from platelet dysfunction

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