Renal function and structure
The kidneys’ principal role is the elimination of waste material and the regulation of the volume and composition of body fluid . The kidneys have a unique system involving the free ultrafiltration of water and non-protein-bound low-molecular-weight compounds from the plasma and the selective reabsorption and/or excretion of these as the ultra filtrate passes along the tubule.
The functioning unit is the nephron, of which there are approximately one million in each kidney. A conventional diagrammatic representation is shown and a physiological version. An essential feature of renal function is that a large volume of blood-25% of cardiac output or approximately 1300 ml min-I-passes through the two million glomeruli.
A hydrostatic pressure gradient of approximately 10 mmHg (a capillary pressure of 45 mmHg minus 10 mmHg of pressure within Bowman’s space and 25 mmHg of plasma oncotic pressure) provides the driving force for ultrafiltration of virtually protein-free and fat-free fluid across the glomerular capillary wall into Bowman’s space and so into the renal tubule.
The ultrafiltration rate (glomerular filtration rate; GFR) varies with age and sex but is approximately 120- 130 ml min ” per 1.73 m2 surface area in adults. This means that each day ultrafiltration of between 170 and 180 litres of water and unbound small-molecular-weight constituents of blood occurs. The ‘need’ for this high filtration rate relates to the elimination of compounds present in relatively low concentration in plasma (e.g. urea). If these large volumes of ultra filtrate were excreted unchanged as urine, it would be necessary to ingest huge amounts of water and electrolytes to stay in balance. This is avoided by the selective reabsorption of water, essential electrolytes and other blood constituents, such as glucose and amino acids, from the filtrate in transit along the nephron. Thus, 60-80% of filtered water and sodium are reabsorbed in the proximal tubule along with virtually all the potassium, bicarbonate, glucose and amino acids . Further water and sodium chloride are reabsorbed more distally, and fine tuning of salt and water balance is achieved in the distal and collecting tubules under the influence of aldosterone and antidiuretic hormone (ADH). The final urine volume is thus 1-2 litres daily. Calcium, phosphate, and magnesium are also selectively reabsorbed in proportion to need to maintain a normal electrolyte composition of body fluids.
The urinary excretion of some compounds is more complicated. For example, potassium is freely filtered at the glomerulus, almost completely absorbed in the proximal tubule, and excreted in the distal tubule and collecting ducts. An important clinical consequence of this is that the ability to eliminate unwanted potassium is less dependent on GFR than is the elimination of urea Dr creatinine. Other compounds filtered and reabsorbed or excreted to a variable extent include urate and many organic acids, including many drugs or their metabolic breakdown products. The more tubular secretion of a compound occurs, the less dependent is elimination on the GFR; penicillin and cephradine are examples of compounds secreted by the tubules.
Tubular function is also critical to the control of acidbase balance. Thus, filtered bicarbonate is largely reabsorbed and hydrogen ion is excreted mainly buffered by phosphate.
Glomerular filtration rate
In health the GFR remains remarkably constant owing to intrarenal regulatory mechanisms. In disease, with a reduction in intrarenal blood flow, damage to or loss of glomeruli, or obstruction to the free flow of ultrafiltrate along the tubule, the GFR will fall and the ability to eliminate waste material and to regulate the volume and composition of body fluid will decline. This will be manifest as a rise in the blood level of urea or the plasma level of creatinine and in a reduction in measured GFR.
The concentration of urea or creatmme in blood or plasma, respectively, represents the dynamic equilibrium between production and elimination. In healthy subjects there is an enormous reserve of renal excretory function and serum urea and creatinine do not rise above the normal range until there is a reduction of 50-60% in the GFR. Thereafter, the level of urea depends both on the GFR and the production rate. The latter is heavily influenced by protein intake and tissue catabolism.
The level of creatinine is much less dependent on diet but is more related to age, sex and muscle mass. Once it is elevated, serum creatinine is a better guide to GFR than urea and, in general, measurement of serum creatinine is a good way to monitor further deterioration in the GFR.
It must be re-emphasized that a normal serum urea or creatinine is not synonymous with a normal GFR. Measurement of the glomerular filtration rate Measurement of the GFR is necessary to define the exact level of renal function. It is essential when the blood urea or serum creatinine are within the normal range.
Inulin clearance-the gold standard of physiologists is not practical or necessary in clinical practice. The most widely used measurement is the creatinine clearance.
The use of creatinine clearance is dependent on the fact that daily production of creatinine (principally from muscle cells) is remarkably constant and little affected by protein intake. Serum creatinine and urinary output thus vary very little throughout the day. This permits the use of 24-hour urine collections, which reduce collection errors, and the measurement of a single serum creatinine value during the 24 hour.
Creatinine excretion is, however, by both glomerular filtration and tubular secretion, although at normal serum levels the latter is relatively small. As most laboratory methods for measurement of serum creatinine give slight overestimates, the calculation of clearance fortuitously gives a value close to that of inulin.
With progressive renal failure, creatinine clearance may overestimate GFR but, in clinical practice, this is seldom important. Certain drugs-for example cimetidine, trimethoprim, spironolactone and amiloride-reduce tubular secretion of creatinine, leading to a rise in serum creatinine and a fall in measured clearance. Given these observations, creatinine clearance, nevertheless, is a reasonably accurate measure of GFR in those situations in which it is most required-normal or near normal renal function.
Where urine collections are difficult (e.g. with ileal conduits) or deemed inaccurate, the GFR may be measured by the single injection of compounds such as [SICrlEDTA (ethylenediamine tetra-acetic acid), [99ffiTclDTPA (diethylenetriaminepenta-acetic acid) or [‘2SIliothalamate, their excretion being primarily by glomerular filtration. Following intravenous injection of the compound, three blood samples are obtained at 2, 3 and 4 hours (or rather longer intervals if the patient is oedematous or if renal failure is suspected). The GFR may then be calculated from the slope of the exponential fall in blood level of the compound. Urea clearance is not an accurate measure of GFR, particularly when urine flow rate is low, and should not be used as a measure of GFR.