Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions.

BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNIs) is partially responsible for the development of chronic allograft nephropathy (CAN). Sirolimus has demonstrated its potential to substitute for CNIs because it lacks significant nephrotoxicity and shows a short-term immunosuppressive capacity comparable with that of cyclosporine. This results in the maintenance of better renal function when cyclosporine is eliminated, but it has not been demonstrated whether this benefit is associated with an improvement in the pathologic substrate and a reduction in CAN. METHODS: We analyzed pretransplant and 1-year renal-allograft biopsies from 64 patients enrolled in a multicenter trial. Patients received cyclosporine and sirolimus during the first 3 months after transplant and were then randomly assigned to continue with cyclosporine or have it withdrawn. Histologic chronic allograft lesions were compared between groups. RESULTS: The percentage of patients in whom chronic pathologic lesions progressed was lower in the group of cyclosporine elimination. Significant differences were observed in chronic interstitial and tubular lesions (70% vs. 40.9% [P<0.05] and 70% vs. 47.8% [P<0.05], respectively), whereas no differences were observed in acute lesions (subclinical rejection). Prevalence of CAN at 1 year was lower in this group, as was the severity and incidence of new cases (P<0.05). CONCLUSIONS: Early cyclosporine withdrawal associated with sirolimus administration is followed by an improvement in renal function, a reduction in the progression of chronic pathologic allograft lesions, and a lower incidence of new cases and severity of CAN during the first year after transplantation. This benefit may result in better long-term graft outcome.

Management of proteinuria in clinical practice after kidney transplantation.

Proteinuria is a marker of poor prognosis in kidney transplant recipients as well as in nontransplant patients with chronic kidney disease. It negatively influences the rate of deterioration of graft renal function, graft survival, and more importantly, patient survival. This review analyzes the current knowledge on the management of this crucial aspect in kidney transplantation. The reduction of proteinuria has demonstrated a beneficial effect on kidney function and also on patient survival in nontransplant patients with chronic kidney disease, but unfortunately, to date, it has not been possible to demonstrate the same benefit in the kidney transplant population (although it probably exists). Nevertheless, the appearance of proteinuria in a renal transplant patient must always be followed by an investigation on its etiology, and many times, it should include a graft biopsy to adequately categorize the underlying process responsible for the proteinuria and to establish a correct therapy. Furthermore, in spite of the cause of proteinuria, it should be treated to reduce to normal or near-normal levels with the objective to eliminate or reduce its negative effects on the graft and the cardiovascular system of the patient. The drugs that interfere with the renin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, are the cornerstone of the management of this complication, and recently, direct renin inhibitors have added to the armamentarium. Mono-, dual-, and triple-therapy modalities are discussed, as well as other therapies and nonpharmacologic measures.