Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation.
OBJECTIVE
Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy.


METHODS
Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests.


RESULTS
Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy.


CONCLUSIONS
Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy.
Lawton
C A
CA
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226.
Fish
B L
BL
Moulder
J E
JE
D000666:Amphotericin B / Q000009:adverse effects; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002066:Busulfan / Q000009:adverse effects; D016572:Cyclosporine / Q000009:adverse effects; D005839:Gentamicins / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000209:etiology*; D008297:Male; D051381:Rats; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D005839:Gentamicins; D000666:Amphotericin B; D016572:Cyclosporine; D002066:Busulfan