EFFECT OF NEPHROTOXIC DRUGS ON THE DEVELOPMENT OF RADIATION NEPHROPATHY AFTER BONE-MARROW TRANSPLANTATION

Purpose: Chronic renal failure is a significant cause of late morbidit y in bone marrow transplant patients whose conditioning regimen includ es total body irradiation (TBI). Radiation is a major cause of this sy ndrome (bone marrow transplant nephropathy), but it may not be the onl y cause. These studies use a rat syngeneic bone marrow transplant mode l to determine whether nephrotoxic agents used in conjunction with bon e marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Methods and Materials: Rats rece ived 11-17 Gy TBI in six fractions over 3 days followed by syngeneic b one marrow transplant. In conjunction with the bone marrow transplants , animals received either no drugs, cyclosporine, amphotericin, gentam icin, or busulfan. Drugs were given in schedules analogous to their us e in clinical bone marrow transplantation. Drug doses were chosen so t hat the drug regimen alone caused detectable acute nephrotoxicity. Ani mals were followed for 6 months with periodic renal function tests. Re sults: Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance ra diation nephropathy. Cyclosporin with TBI caused late morbidity that a ppeared to be due to neurological problems, but did not enhance radiat ion nephropathy. Busulfan resulted in a significant enhancement of rad iation nephropathy. Conclusion: Of the nephrotoxins used in conjunctio n with bone marrow transplantation only radiation and busulfan were fo und to be risk factors for bone marrow transplant nephropathy.