Radiation nephropathy is treatable with an angiotensin converting enzyme inhibitor or an angiotensin II type-1 (AT1) receptor antagonist.
OBJECTIVE
Previous studies showed that progression of established radiation nephropathy could be delayed by continuous treatment with high doses of captopril, an angiotensin-converting-enzyme (ACE) inhibitor. The current studies were designed to determine whether a lower dose or a shorter treatment with captopril would be effective and whether an angiotensin II type-1 (AT1) receptor antagonist (AII blocker) would be effective.


METHODS
In the captopril studies, rats were given renal irradiation at doses sufficient to produce radiation nephropathy. Six months after irradiation, animals were stratified by azotemia and assigned to no treatment, continuous high- or low-dose captopril, or 6 weeks of high-dose captopril. Captopril was given in drinking water at 62.5 mg/l (low dose) or 500 mg/l (high dose). The AII blocker study had a similar design, except that the nephropathy was the result of total body irradiation and bone marrow transplantation and the treatments were no treatment or continuous treatment with an AII blocker, L-158,809 (20 mg/l in drinking water). Animals were followed for 1 year with periodic studies of renal function.


RESULTS
Survival and renal function were significantly enhanced by all treatments. Continuous captopril treatment was more effective than the 6-week course of treatment, but there was no difference in effectiveness between the high and low doses of captopril. In continuous therapy, captopril and the AII blocker had roughly equivalent efficacy.


CONCLUSIONS
Both the ACE inhibitor and the AII blocker were effective treatments for established radiation nephropathy. The best results with the ACE inhibitor required continuous therapy, but could be achieved with a low dose of the drug.
Moulder
J E
JE
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA.
Fish
B L
BL
Cohen
E P
EP
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002216:Captopril / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D007677:Kidney Function Tests; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D044140:Receptor, Angiotensin, Type 1; D015996:Survival Rate; D013777:Tetrazoles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C070967:L 158809; D002216:Captopril