Factors associated with proteinuria in renal transplant recipients treated with sirolimus

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.