Membranous nephropathy with renal salt wasting: role of neurohumoral factors in sodium retention.

The role of neurohumoral factors in the sodium retention of nephrotic syndrome is controversial. We report a case with abrupt onset of severe nephrotic-range proteinuria and hypoalbuminemia due to membranous glomerulonephritis that was associated with renal salt wasting and hypovolemia without edema. Further evaluation showed hypoaldosteronism, hyporeninemia, and primary autonomic failure principally affecting the sympathetic nervous system, determined by the Valsalva maneuver. Administration of exogenous mineralocorticoid and oral salt caused edema and accelerated hypertension. The severe hypoaldosteronism likely was due to use of the angiotensin-converting enzyme inhibitor lisinopril, and it improved after this drug treatment was discontinued. The nephrotic proteinuria resolved after treatment with cyclosporine and prednisone, but the primary autonomic failure with hyporeninemic hypoaldosteronism persisted. The case shows that intratubular factors activated by nephrotic proteinuria are not sufficient to produce sodium retention in the absence of aldosterone and an intact sympathetic nervous system.