title: Factors associated with proteinuria in renal transplant recipients treated with sirolimus.
abstract: Although sirolimus (SRL) use in renal allograft recipients (RTX) is associated with improved renal function, proteinuria develops in a significant proportion. 48 SRL-treated RTX were evaluated for development of proteinuria and stratified by level of proteinuria after SRL therapy. The Proteinuria Group (n = 25, 52.1%) had new-onset proteinuria or >25% increase in proteinuria following SRL conversion; the Nonproteinuria Group had stable proteinuria <0.5 g/day throughout. There was a higher proportion of male RTX and female donors to male recipients in the Proteinuria Group, (24% vs. 10%, P = 0.008). Calcineurin inhibitor- and statin usage were significantly higher in the Nonproteinuria Group (8% vs. 17%, P = 0.046; 28% vs. 83%, P < 0.001 respectively) whereas biopsy-proven acute rejection was higher in the Proteinuria Group (68% vs. 33%, P = 0.037). SDS-PAGE analysis of urine from 23 RTX in the Proteinuria Group demonstrated glomerular proteinuria in 100% and tubular proteinuria in 87%. While male gender and gender mismatch may impact on glomerular proteinuria through inadequate nephron dose and subsequent hyperfiltration, concurrent cyclosporine use may mitigate the development of proteinuria in SRL-treated patients, through afferent arteriolar vasoconstriction. Glomerular injury occurring following acute rejection may further contribute to glomerular proteinuria. Statins, through their anti-inflammatory and anti-fibrotic effects, may protect against development of proteinuria.
authors.affiliation: Department of Renal Medicine, Singapore General Hospital, Singapore, Singapore.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liew
authors.forename: Gilbert S C
authors.initials: GS
authors.lastname: Chiang
authors.forename: Anantharaman
authors.initials: A
authors.lastname: Vathsala
mesh_terms: D000208:Acute Disease; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D001794:Blood Pressure; D015992:Body Mass Index; D016572:Cyclosporine / Q000008:administration & dosage; D003920:Diabetes Mellitus / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009399:Nephrons / Q000187:drug effects; D015995:Prevalence; D011507:Proteinuria / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology*; D012737:Sex Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D008055:Lipids; D016572:Cyclosporine; D020123:Sirolimus