Reversible Acute Nephrotoxicity in Sandimmun Neoral(R) Treated Kidney Transplants

So, Byung Jun; Chae, Kwon Mook; Lee, Kyung Keun; Lee, Jae Seung; Park, Dong Eun

Abstract

Cyclosporine(CsA) has been used a prime immunosuppressive drug since Calne et al reported the excellent results of cyclosporin in renal transplantation, 1978. But many adverse effects has been reported, one of them, nephrotoxicity is a well-known adverse effect which is developed in high CsA blood level. When previously used Sandimmun was used in the field of various kinds of organ transplantation, there were many difficulties to keep optimal, consistent and stable CsA blood level because of the nature of lipophilic characteristics of drug, wide interpersonal and even intrapersonal variability of its dose and blood concentration. So, there has been the possibility of adverse effects caused by overdosage and rejection phenomenon caused by low dosage. The objective of this study is to assess the significance of drug dosage and CsA blood level in patients developed nephrotoxicity when Sandimmun Neoral was used as a major immunosupressive drug. From January 1995 to September 1996, a total of 21 renal transplant patients from Wonkwang University Hospital entered in this study. We retrospectively analysed CsA dosage, CsA blood level and serum creatinine concentration at postoperative 1, 3, 6, 12 months. These patient were divided into 3 groups according to occurrence of acute rejection and nephrotoxicity. The group A has no nephrotoxicity and no rejection(n=7), the group B has nephrotoxcity only(n=6) and the group C has acute rejection and nephrotoxicity(n=8). There is statistical significance at postoperative 1 month of drug dosage between groups, 10.0+/-2.18, 12.9+/-1.40, 10.5+/-2.01 mg/kg, respectively (p=0.035). Mean CsA blood trough level(ng/ml) in Group A are 427.2+/-73.73, 301.0+/-43.94, 224.8+/-48.39, 175.8+/-46.09 ng/ml at postoperative 1, 3, 6, 12 months, respectively; in Group B, 684.5+/-162.08, 409.5+/-60.67, 278.5+/-27.34, 169.1+/-37.87 ng/ml; in Group C, 484.3+/-131.99, 372.7+/-46.95, 270.8+/-61.17, 188.3+/-48.35 ng/ml. Statistical significance was shown in CsA at postoperative 1, 3 months (P=0.005, P=0.043). Mean serum creatinine concentration(mg/dl) in Group A are 1.3+/-0.20, 1.4+/-0.25, 1.3+/-0.22, 1.4+/-0.20 mg/dl at postoperative 1, 3, 6, 12 months, respectively; in Group 2, 1.7+/-0.24, 2.2+/-0.31, 1.7+/-0.37, 1.5+/-0.31 mg/dl; in Group C, 1.6+/-0.40, 2.8+/-0.38, 2.2+/-0.56, 1.9+/-0.19 mg/dl. Statistical significance in serum creatinine concentration was shown between groups at all index time(P=0.05, P=0.001, P=0.002, P=0.001). Nephrotoxic groups(B,C) regained the serum creatinine concentrations close to basal level according to lowering dosage, but it usually took 5~6 months. This article shows that nephrotoxicity caused by CsA peaked around 3 months and it lasted several months even after adequate dosage adjustment and blood trough level. For the best renal function and avoiding nephrotoxicity, adequate dose adjustment based on the whole blood trough level is needed.