Acute haemodynamic and proteinuric effects of prednisolone in patients with a nephrotic syndrome.

Background. Administration of prednisolonecauses an abrupt rise in proteinuriain patients with a nephrotic syndrome. Methods. To clarify the mechanisms responsible for this increase in proteinuriawe have performed a placebo controlled studyin 26 patients with a nephrotic syndrome. Systemic and renal haemodynamics and urinary protein excretion were measured after prednisoloneand after placebo. Results. After i.v. administration of 125--150 mg prednisolonetotal proteinuriaincreased from 6.66±4.42 to 9.37±6.07 mg/min (P<0.001). By analysing the excretion of proteins with different charge and weight (albumin, transferrin, IgG, IgG 4 and (β 2 -microglobulin) it became apparent that the increase of proteinuriawas the result of a change in size selectivity rather than a change in glomerular charge selectivity or tubular protein reabsorption. Glomerular filtration rate rose from 83±34 ml to 95±43 ml/min (P < 0.001) after 5 h. whereas effective renal plasma flowand endogenous creatinine clearance remained unchanged. As a result filtration fractionwas increased, compatible with an increased glomerular pressure, which probably contributes to the size selectivity changes. Since corticosteroids affect both the renin angiotensin system and renal prostaglandins, we have evaluated the effects of prednisoloneon proteinuriaafter pretreatment with 3 months of the angiotensin-converting enzyme inhibitor lisinoprilor after 2 weeks of the prostaglandin synthesis inhibitor indomethacin. Neither drug had any effect on prednisolone-induced increases of proteinuria. Conclusions. Prednisoloneincreases proteinuriaby changing the size selective barrier of the glomerular capillary. Neither the renin--angiotensin axis nor prostaglandins seem to be involved in these effects of prednisoloneon proteinuria.