Importance of early adequate exposure to cyclosporine in renal transplant outcome: study of 1-year creatinine.

INTRODUCTION: One-year serum creatinine (SCr) level has been used as a surrogate marker for graft survival in kidney transplantation. We evaluated the importance of different factors on this parameter, emphasizing the importance of adequate exposure to Cyclosporine (CyA). METHODS: Ninety-six consecutive renal transplant recipients who underwent transplantation between 1996 and 2002 were treated with CyA, steroids, and azathioprine. Univariate and multivariate regression analyses were performed for 1-year SCr, acute rejection episodes (ARE), and duration of delayed graft function (DGF). We considered adequate CyA levels within 1 week to be >250 ng/mL trough levels (38%) or 3 hour postdose level (C3) >1100 ng/mL (62%). RESULTS: Mean 1-year SCr was 1.52 +/- 0.5, ARE rate was 27%, and DGF rate was 31%. Overall, 53% of patients achieved adequate exposure to CyA at 1 week (68% on those monitored by C3). Univariate analysis identified female recipient gender, decreasing donor age, absence of ARE, and decreased DGF duration to yield lower 1-year SCr (P < .05). On multivariate analysis for donor age (lower), ARE rate, and duration of DGF (shorter) were the only factors considered to be significant for a lower 1-year SCr level. Multivariate analysis for ARE showed that adequate CyA exposure and lower HLA mismatch decreased ARE, whereas the ability to achieve adequate exposure to CyA and shorter cold ischemia time (CIT) correlated with a reduced incidence of DGF. CONCLUSIONS: One-year SCr level is affected primarily by the incidence of ARE, by donor age, and by duration of DGF. Adequate CyA exposure is related to lower ARE; however, its relation to DGF may be influenced by the reluctance to increase exposure on patients with a nonfunctioning graft.

Benefits of early biopsy on the outcome of kidney transplantation.

INTRODUCTION: Delayed graft function has been associated with worse long-term kidney allograft survival. Adequate diagnosis of the etiology of dysfunction is crucial, often requiring routine early biopsies. The aim of this article was to report the results and safety of early kidney allograft biopsies and how they influenced its management. METHOD: Between September 1994 and July 2004, 134 renal transplant recipients were prescribed cyclosporine (CsA; Neoral, Novartis, Chile), steroids, and a third agent (azathioprine in 92% of the graft recipients). Thirty-four patients (26%) had a kidney biopsy performed within the first week because of allograft dysfunction. RESULTS: The main diagnosis was acute tubular necrosis (ATN) in 22 patients (65%), whereas 6 (18%) were diagnosed with an acute rejection episode (ARE), allowing prompt initiation of therapy with reversal of rejection in 4 of them. Two patients (6%) showed signs of thrombotic microangiopathy (TMA) induced by CsA, which subsided following a switch from CsA to tacrolimus (Prograf Pharmainvesti, Chile). In 2 patients, the biopsy specimen showed signs of CsA nephrotoxicity that reverted following dose reduction. Finally, in 2 patients, the biopsy specimen showed chronic nephropathy of donor origin, which had not been previously recognized, resulting in graft loss. There was only one major complication related to the biopsy, intraperitoneal bleeding that required surgical treatment. CONCLUSIONS: Early allograft biopsy is safe and, in a significant number of cases (30%), it detects important allograft pathology (ARE, TMA, and drug toxicity), which when adequately and promptly treated may rescue the graft.

C2 monitoring of cyclosporine in stable renal transplant patients results in lower costs and improved renal function.

INTRODUCTION: C2 (2-hour post-absorption levels) monitoring of cyclosporine (CsA) seems to reduce the rate of acute rejection episodes (ARE) without increasing nephrotoxicity during the first months after transplant. There are a few reports on the impact of adopting this strategy in patients with stable renal transplants. We herein report a prospective trial in long-term renal transplant patients (>6 months) monitored by C0 or C3 who were switched to C2 monitoring. METHODS: Seventy-six (mean age = 43 +/- 11 years) kidney transplant patients (mean = 37 +/- 21 months after transplant) receiving CsA, steroids, and azathioprine were switched to C2 monitoring, seeking to achieve a target range of 800 +/- 100 ng/mL. The patients were followed for at least 6 months. RESULTS: At conversion the C2 values of 61% of the patients were above and 17% below the therapeutic range. Six months after conversion there was a significant reduction in BUN (29 +/- 11 vs 27 +/- 10, P < .01), Creatinine (Cr), cholesterol, and triglyceride levels were unchanged. Mean CsA dose was decreased 10% from 244 +/- 63 to 220 +/- 52 (P < .01), implying a net savings of 390 US dollars per patient per year. Among the group of patients who showed a high C2 level, there was also a reduction in BUN (30 +/- 12 vs 27 +/- 10, P < .01) and a nonsignificant decrease in Cr (1.53 +/- 0.6 vs 1.50 +/- 0.6). CONCLUSIONS: C2 monitoring in stable kidney transplant recipients is feasible and safe. The strategy results in reduced drug costs and improved renal function.