Glomerular and Tubular Function in Renal Transplant Patients Treated with and without Ciclosporin A

Abstract

The present study evaluated whether chronically administered low-dose (<5 mg/kg) ciclosporin A (CsA) affects renal haemodynamics and tubular function in renal transplant recipients (RTx) when studied at nadir CsA blood levels. The renal clearance of lithium was used as an index of proximal tubular outflow of sodium and water. Effective renal plasma flow, glomerular filtration rate, and renal clearance of lithium were studied in 67 stable non-diabetic RTx and 44 healthy controls. Forty-eight of the RTx were treated with CsA, prednisone, and azathioprine. Nineteen were treated exclusively with prednisone and azathioprine. In RTx with a good graft function (serum-creatinine <125 µmol/l), no specific CsA-induced renal haemodynamic and tubular dysfunctions were evident. In CsA-treated RTx with a slightly reduced renal function (serum creatinine 125–180 µmol/l) a decrease in fractional proximal tubular reabsorption was found. The renal clearances of urate and magnesium were comparable between RTx treated with or without CsA, and a significant correlation between glomerular filtration rate and renal clearance of urate was found. CsA-treated RTx had a significantly higher blood pressure, independent of glomerular filtration rate and segmental tubular function. In conclusion, at nadir CsA blood levels, no specific CsA-induced tubular dysfunction evaluated by the renal lithium clearance method could be demonstrated in RTx receiving chronically low-dose CsA. The hyperuricaemia commonly seen in RTx seems to be mainly caused by the reduced glomerular filtration rate.

Hyperuricemia after orthotopic liver transplantation: divergent associations with progression of renal disease, incident end-stage renal disease, and mortality

“…Cyclosporine can cause hyperuricemia by increasing net tubular urate reabsorption [30] or decreasing the glomerular filtration of uric acid [31]. However, our study did not find associations between CNI sub-type and either uric acid level after OLT or ESRD incidence, perhaps because the frequency of cyclosporine use was less than 10% in this cohort and we were not able to take the effects of CNI use on UA fully into account.…”

Physiologic Impact of Low-Dose Dopamine on Renal Function in the Early Post Renal Transplant Period

“…CsA has been extensively studied in human renal transplant patients and been shown to increase blood pressure and renal vascular resistance as assessed by Doppler spectrum analysis (22). Others have confirmed the hypertension and, using lithium clearance, also found a decrease in fractional proximal tubular reabsorption, but only in those patients with reduced renal function (creatinine, 125-180 M) (23). An acute reduction of GFR in renal allograft recipients after CsA has been shown (24).…”

Replacement of Calcineurin-Inhibitors With Sirolimus as Primary Immunosuppression in Stable Cardiac Transplant Recipients

“…Use of CsA appears to be an independent risk factor for the development of new onset gout after transplantation (42). This can occur through a number of mechanisms including increased tubular urate reabsorption (43,44) as well as decreased glomerular filtration (45) with a decrease in the filtered load of uric acid (46). In addition, hyperuricemia is recognized as an independent risk factor for cardiovascular disease and has been shown to activate smooth muscle cell proliferation in animal models (47).…”