Urinary excretion of renal brush border enzymes may serve as an early marker of renal injury. However, the distinction between physiological and pathological levels remains controversial, since enzymuria is affected by physiological parameters. To clarify the influence of diuresis, we investigated the urinary excretion of alanine-aminopeptidase (AAP; EC 3.4.11.2) as function of diuretic state. 17 healthy volunteers of both sexes were subjected to protocols with sudden or prolonged water load preceded and followed by a thirst period. Urinary excretion of AAP was measured using an enzyme kinetic assay. As expected AAP excretion increased with urine flow, the increments diminished yielding an overall excretion pattern that resembled saturation kinetics. This function is described by a mathematical model. This model assumes, that AAP is released in proximal tubules at a constant rate and reabsorbed or inactivated in the distal tubule and collecting duct. Non-linear fits of the model equation to our data allowed two parameters, chi and mu, to be defined. Chi describes the rate of AAP release independent of urinary flow, and mu the ratio of distal tubular reabsorption or inactivation. If a substrate is not reabsorbed at all, mu approximates zero. Since mu fitted for AAP differed significantly from zero, this indicates reabsorption or inactivation of AAP in the distal nephron. Therefore, our study supports the theory of flow-dependent reabsorption or inactivation of AAP in the distal nephron.

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Hypertension has been recognized to be an important cause for the development of end-stage renal disease (ESRD). We assessed the quality of blood pressure control in 103 patients with essential hypertension and correlated renal function and age. Patients were stratified into three subgroups by their blood pressure level under current medication. Group 1 were hypertensive patients with normalized blood pressure (<140/90 mmHg, n = 25), group 2 patients with mild hypertension (140-159/90-99 mmHg, n = 43) and group 3 patients with moderate to severe hypertension (> 160/100 mmHg, n = 35). A negative correlation between age and creatinine clearance (Ccr) could be confirmed for patients of group 1 (correlation coefficient r1 = -0.56; p, < 0.01) and group 2 (r2 = -0.55; P2 < 0.001). Furthermore the regression coefficient (m) of decline in C(Cr) versus age was higher in group 2 patients (m2 = -1.83) than in group 1 (m1 = -1.30). In group 3 we found no correlation of renal function with age, indicating that age may not be the leading variable. Patients in group 1 were all within normal limits of age adjusted Ccr, but 12% in group 2 and 23% in group 3 had impaired C(Cr). Furthermore proteinuria was found to be 20% (group 1), 26% (group 2) and 31% (group 3). This analysis provides further evidence of the importance of blood pressure control in essential hypertension to preserve renal function.

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