Osmolality measurements in plasma and urine

The renal tubules perform a bewildering array of functions. However, in practice, the urine osmolality serves as a proxy or general marker of tubular function. This is because of all the tubular functions, the one most frequently affected by disease is the ability to concentrate the urine. If the tubules and collecting ducts are working efficiently, and if AVP is present, they will be able to reabsorb water. Just how well can be assessed by measuring urine concentration. This is conveniently done by determining the osmolality, and then comparing this to the plasma. If the urine osmolality is 600 mmol/kg or more, tubular function is usually regarded as intact. When the urine osmolality does not differ greatly from plasma (urine : plasma osmolality ratio ~1), the renal tubules are not reabsorbing water.

The water deprivation test

The causes of polyuria are summarized in Table 15.1. Renal tubular dysfunction is one of several causes of disordered water homeostasis. Where measurement of baseline urine osmolality is inconclusive, formal water deprivation may be indicated. The normal physiological response to water deprivation is water retention, which minimizes the rise in plasma osmolality that would otherwise be observed. The body achieves this water retention by means of AVP, the action of which on the renal tubules may be inferred from a rising urine osmolality. In practice, if the urine osmolality rises to 600 mmol/kg or more in response to water deprivation, diabetes insipidus is effectively excluded. A flat urine osmolality response is characteristically seen in diabetes insipidus where the hormone AVP is lacking. In compulsive water drinkers, a normal (rising) response is usually seen.

It should be noted that the water deprivation test is unpleasant for the patient. It is also potentially dangerous if there is severe inability to retain water. The test must be terminated if more than 3 L of urine is passed or there is a fall of >3% in body weight. An alternative approach, which is sometimes used first (or instead of), is to fluid restrict overnight (8 pm–10 am) and measure the osmolality of urine voided in the morning. If the urine osmolality fails to rise in response to water deprivation, desmopressin (DDAVP), a synthetic analogue of AVP, is administered. The subsequent urine osmolality response allows central diabetes insipidus to be distinguished from nephrogenic diabetes insipidus. In the former, the renal tubules respond normally to the DDAVP and the urine osmolality rises. Nephrogenic diabetes insipidus is characterized by failure of the tubules to respond; the urine osmolality response remains flat.

Urine pH and the acid load test

Urine pH measurements may be useful as a first step in the diagnosis of Renal tubular acidosis (RTA), which typically gives rise to hyperchloraemic metabolic acidosis. RTA may be characterized as follows: