Conversion from calcineurin inhibitors to sirolimus in chronic allograft dysfunction: changes in glomerular haemodynamics and proteinuria

Abstract

Background: The study was conducted in order to describe possible intraglomerular haemodynamic changes inducing proteinuria after 14 patients with chronic allograft dysfunction were converted from calcineurin inhibitors (CIs) to sirolimus without changing concomitant immunosuppression or antihypertensive treatment.

Methods: Creatinine, glomerular filtration rate (GFR), proteinuria, renal functional reserve (RFR) and effective renal plasma flow (ERPF) were determined before and 8 months after conversion. Intraglomerular pressure (P(G)), afferent arteriolar resistance (AAR) and efferent arteriolar resistance (EAR) were calculated using Gomez's formula.

Results: Creatinine (1.97 vs 2.075 mg/dl; P = 0.270) and GFR (40 vs 43 ml/min; P = 0.505) remained unchanged, proteinuria increased (338 vs 1146 mg/24 h; P = 0.006), RFR decreased (34.84 vs 13.47%; P = 0.019), ERPF (248 vs 310.6 ml/min; P = 0.0625) and P(G) (42.72 vs 46.17 mmHg; P = 0.0625) tendentially increased and AAR tendentially decreased (14.12 vs 10.28 dyne/s/cm(5); P = 0.0625).

Conclusion: After conversion, P(G) shows a tendency to increase and RFR decreases significantly-characteristics of hyperfiltration, which could possibly partially explain the increase of proteinuria. Therefore, the application of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers seems promising. To avoid hyperfiltration, conversion should be performed early when renal insufficiency is still moderate.