Interstitial inflammation, sodium retention, and the pathogenesis of nephrotic edema: A unifying hypothesis

Abstract

The pathophysiology of edema in the nephrotic syndrome is controversial. Some investigators believe that sodium retention may result from a primary renal defect that causes an "overfilled" blood volume. In contrast, other authors believe that fluid escapes the vascular compartment due a low oncotic pressure, and sodium retention is a compensatory physiological response to an "underfilled" blood volume. The patients that best fit the "underfilled" hypothesis are children with minimal-change nephrotic syndrome (MCNS). We analyzed critically the available evidence for and against each proposed pathogenic mechanism in the light of recent evidence indicating that the inflammatory infiltrate may play a role in primary renal sodium retention. Inflammatory infiltrate in the kidney is a constant characteristic in nephrotic syndrome associated with primary sodium retention and it is absent in most cases of MCNS in children We propose that primary sodium retention in the nephrotic syndrome depends on the existence and the intensity of renal inflammatory infiltrate, conspicuously absent in most cases of MCNS in children and present in other conditions associated with massive proteinuria. The tubulointerstitial inflammatory infiltrate is associated with increased vasoconstrictive mediators that result in increased tubular sodium reabsorption and with glomerular hemodynamic changes that reduce filtered sodium load.