CLINICAL APPLICATION OF UREA MEASUREMENTS METABOLIC ASPECTS OF KIDNEY METABOLISM

Clinical application Measurement of urea is used to:  Evaluate renal function  Assess hydration status  Determine nitrogen balance  Aid in the diagnosis of renal disease  Verify adequacy of dialysis

Pathophysiology  An elevated concentration of urea in the blood is called azotemia  Very high plasma urea concentration accompanied by renal failure is called uremia  This condition is eventually fatal if not treated by dialysis or transplantation  Conditions causing increased plasma urea are classified according into 1.Prerenal 2.Renal 3.postrenal

Pre-renal azotemia  A result of: 1.Reduced blood flow (Less blood is delivered to the kidney and thus less urea is filtered) 2.Amount of protein metabolism (High protein diet, increased protein catabolism)  Stress  Fever  Corticosteroid treatment

Renal azotemia  Decreased renal function which cause compromised urea excretion  Acute renal failure  Chronic renal failure  Glomerulonephritis  Tubular necrosis

Postrenal azotemia  Obstruction of urine flow  Bladder cancer  Prostate cancer  Renal calculi  Severe infection

Decreased concentration  Low protein intake  Severe liver disease  Late pregnancy and early infancy as a result of negative nitrogen balance

CLINICAL APPLICATION OF CREATININE MEASUREMENTS METABOLIC ASPECTS OF KIDNEY METABOLISM

Clinical application  Creatinine is released into the circulation at a constant rate  Creatinine release rate is proportional to an individual muscle mass  Creatinine is removed from the circulation by flitration and excreted in urine  Daily creatinine excretion is relatively stable

 Measurement of creatinine concentration is used to:  Determine sufficiency of kidney function  Determine severity of kidney damage  Monitor progression of kidney disease

Creatinine and GFR  GFR can be by measured from the urinary excretion of a substance that is:  Completely filtered  Not secreted  Not absorbed  Not metabolized by the nephrons Inulin (a plant polysaccharide) meets these requirements Use of inulin requires infusion into the blood and is not used in routine clinical practice

 The most widely used clearance test is based on measuring creatinine in plasma and urine  Creatinine clearance is calculated using the formula:

Relationship between creatinine concentration and GFR

Disadvantages of using Creatinine clearance to measure GFR  Patients may forget the time or forget to include some urine in the collection  Incontinent patients  Creatinine is actively secreted by the tubules (creatinine clearance is higher than GFR) N.B: above point is especially important when GFR is low ( < 10 ml/min)  Drugs (spironolactone, cimetidine, fenofibrate, trimethoprim, amiloride) reduce creatinine secretion

An alternative approach to determine the GFR in clinical practice is to derive an estimated GFR from the plasma creatinine concentration

Plasma creatinine  Plasma creatinine concentration is a simple biochemical test of glomerular function  Blood samples should be collected after an overnight fast  Strenuous exercise causes a transient, slight increase in plasma creatinine concentrations Plasma creatinine concentration is related to muscle bulk

 The reference range for plasma creatinine in the adult population is 60–120 μmol/L  GFR can decrease by 50% before plasma creatinine concentration rises beyond the normal range  A normal plasma creatinine does not necessarily imply normal renal function  A raised creatinine does usually indicate impaired renal function

 A change in creatinine concentration does suggest a change in GFR, even if both values are within the population reference range

Changes in carnitine concentration independent of renal function  Changes in plasma creatinine concentration can occur owing to changes in muscle mass A decrease occur as a result of:  Starvation  Wasting diseases  Immediately after surgery  In patients treated with corticosteroids

Cystatin C  Produced by all nucleated cells  It is cleared from the plasma by glomerular filtration  its plasma concentration reflects the GFR more accurately than creatinine  It is not influenced by gender or muscle mass  May be increased in malignancy, hyperthyroidism and by treatment with corticosteroids