Precipitates from urine of patients with cerebral/renal salt‐wasting syndrome (RSW) inhibit transcellular sodium transport in a renal epithelial cell line

Abstract

The persistent elevation in fractional excretion (FE) of urate after correction of hyponatremia identifies patients with RSW, common in those with neurosurgical (NS) diseases. Our study sought to demonstrate whether natriuretic activity previously found in the plasma of NS patients with increased FEurate >10% and normonatremia is also present in urine, as compared to controls (NS and SIADH patients with normal FEurate). Ammonium precipitates (ppts) of urine were dialyzed (10 kDa), lyophilized, and quantitated by protein content. Ppts were applied to monolayers of a proximal tubule cell line (LLC-PK1) cultured on commercial transwells and movements of Na followed with 22Na. Ppts from 4 of 5 RSW patients inhibited absorptive Na flux, by −17±4% and −13 ± 4% at 5 and 10 ug protein/ml respectively. Both values differed significantly from zero (P<.001 and P=.004; 4 pts, 3–5 repetitions ea) and from values for identically-prepared ppts from the non-RSW control patients (P=.002 and P=.003; 3 pts, 2–4 repetitions). Means for controls showed some stimulation of Na absorption, which did not reach significance (P=.18 and P=.14). In paired experiments in which different concentrations of ppt were measured in the same run, a dose-response was evident, inhibition being greater at 10 than 5 ug protein/ml (−23±4% vs. −9.3±4%, P=.035). The results suggest that a substance recoverable in urine may contribute to the Na loss seen in RSW.