MECHANISMS OF ACIDOSIS-INDUCED PROTEINURIA

Abstract

For more than 50 years it has been noted that systemic acidosis induces proteinuria. Proteinuria was found to increase with increasing acidosis (Gardner, JCI, 1961, 40:525) and was attributed to an increase in filtered load. The present study was designed to delineate the mechanisms for this increase. Acute (<6 hr) and chronic (10-20 d) acidosis was produced in rats by oral feeding of NH₄Cl. Acute and chronic acidosis was associated with an increase in protein excretion (41.2±15.8 vs 22.0±5.1 (SD) μgm/min p<.02). This was predominantly due to an increase in albuminuria (12.90±8.50 vs 3.26±1.63 μgm/min p<.02), so that in acidosis albumin represented a greater proportion of total urine protein. Non-albumin proteinuria increased to a lesser extent. Acidosis was not associated with any significant change in GFR (2.29±0.52 vs 2.66±0.63 ml/min). filtration fraction (32.8±10.2 vs 36.0±9.14%), or total serum protein (6.73±0.74 vs 6.73±0.18 gm/dl). Glomerular polyanion as determined by staining with both colloidal iron and alcian blue was not altered in acute acidosis but appeared to decrease with chronic acidosis. Glomerular permeability to inert polydisperse polyvinyl pyrrolidone (mol.size 20-45 8)was increased significantly in acidotic rats.

We postulate that the proteinuria of acidosis results from the documented alteration in glomerular permeability. The conformational changes in protein molecules associated with pH changes may also contribute. Both of these mechanisms would increase the filtered protein load resulting in proteinuria.

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