Measuring renal function - Investigations and procedures

Measuring renal function

Renal function testing involves measuring urea and creatinine and glomerular filtration rate (GFR). Urea and creatinine may remain normal until more than half of renal function is lost.

Normal kidneys receive 25% of the cardiac output. The volume that is ultrafiltrated per minute is the GFR, and it is the sum of the filtration that occurs in all the functioning nephrons. When nephrons are lost or are not functioning properly, there is compensation by the remaining nephrons by hyperfiltration, and improved solute clearance. If there is poor blood supply to the kidneys, due for example to hypotension or cardiac failure, the GFR will fall – even though the nephrons are intact.

Serum urea: Urea is freely filtered at the glomeruli, but variably reabsorbed by the tubules, and its production fluctuates considerably, even within an individual. It is higher following protein intake, in a catabolic state, after steroids or gastrointestinal (GI) haemorrhage, and lower when patients are not eating, and in liver disease. In dehydration, urea rises proportionally more than creatinine because it is avidly reabsorbed at the proximal tubules in a fluid-depleted state.

A urea above normal therefore suggests renal failure, GI bleeding or dehydration. If the creatinine is also proportionally raised (creatinine is normally ∼20× urea) above normal, this indicates intrinsic renal failure.

Serum creatinine: Creatinine is produced as a waste product when creatine phosphate is broken down in muscle. The amount produced is lower in those with low muscle bulk, in women, children and the elderly. It is freely filtered, a small amount is also secreted at the tubules. Plasma creatinine is increased by strenuous exercise, ingestion of meat, certain drugs (trimethoprim and cimetidine) impair tubular secretion. It is decreased in malnutrition, wasting diseases, immediately after surgery and by corticosteroids. For these reasons there is wide variation in normal creatinine levels between individuals. In most patients, serial or previous measurements of creatinine are useful to monitor the progress of renal function.

Glomerular filtration rate (GFR): To assess the GFR the rate at which a substance is cleared from the plasma is measured. The normal GFR = 80–130 mL/min/1.73 m² body surface area. Clearance is defined as the ‘virtual’ volume of blood cleared (by the kidney) of solute per unit time. If a substance is completely filtered by the glomeruli and not secreted, absorbed or metabolised by the renal tubules then its urinary clearance equals GFR. Creatinine almost fulfils these criteria, and is used in clinical practice to measure GFR using a 24-hour urine collection:

where U = urinary concentration, V = urine flow rate and P = plasma creatinine.

Blood creatinine levels are inversely related to clearance. This means that with normal renal function a small rise in creatinine means a large fall in GFR. Conversely in patients with moderate to severe renal failure, i.e. a low GFR, even a small further fall in GFR will result in a large increase in creatinine (see Fig. 6.2).

24-hour urinary collections are inconvenient and inaccurate. The creatinine clearance can be calculated from a patient’s serum creatinine using formulae correcting for factors like the patient’s age, sex and weight (which adjust for muscle mass). The best known of these is the Cockcroft and Gault formula:

For women multiply by 1.04 rather than 1.23. When accurate GFR measurement is needed the rate of clearance of a radioisotope is used. This is indicated in severe renal failure (creatinine clearance becomes inaccurate), for kidney donors and patients receiving chemotherapy.