Acute haemodynamic and proteinuric effects of prednisolone in patients with a nephrotic syndrome.
BACKGROUND
Administration of prednisolone causes an abrupt rise in proteinuria in patients with a nephrotic syndrome.


METHODS
To clarify the mechanisms responsible for this increase in proteinuria we have performed a placebo controlled study in 26 patients with a nephrotic syndrome. Systemic and renal haemodynamics and urinary protein excretion were measured after prednisolone and after placebo.


RESULTS
After i.v. administration of 125-150 mg prednisolone total proteinuria increased 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, IgG4 and beta2-microglobulin) it became apparent that the increase of proteinuria was 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 flow and endogenous creatinine clearance remained unchanged. As a result filtration fraction was 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 prednisolone on proteinuria after pretreatment with 3 months of the angiotensin-converting enzyme inhibitor lisinopril or after 2 weeks of the prostaglandin synthesis inhibitor indomethacin. Neither drug had any effect on prednisolone-induced increases of proteinuria.


CONCLUSIONS
Prednisolone increases proteinuria by changing the size selective barrier of the glomerular capillary. Neither the renin-angiotensin axis nor prostaglandins seem to be involved in these effects of prednisolone on proteinuria.
Reichert
L J
LJ
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Koene
R A
RA
Wetzels
J F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000652:urine; D007213:Indomethacin / Q000627:therapeutic use; D007275:Injections, Intravenous; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000503:physiopathology* / Q000652:urine; D010919:Placebos; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D011507:Proteinuria; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D014168:Transferrin / Q000652:urine; D001613:beta 2-Microglobulin / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D007074:Immunoglobulin G; D010919:Placebos; D014168:Transferrin; D001613:beta 2-Microglobulin; D011239:Prednisolone; D017706:Lisinopril; D007213:Indomethacin