The increasing success of cardiac transplantation has been attributed to the availability of potent immunosuppressive agents, including cyclosporine. With improved graft and patient survival, the incidence of chronic renal insufficiency has increased. We reviewed the medical records of patients who had undergone orthotopic cardiac transplantation and had been followed for at least 3 years posttransplantation to determine the risk factors at initial evaluation and in the early posttransplantation period for subsequent renal insufficiency. We followed 80 adult patients over a mean period of 4.7 years: 39 patients had a serum creatinine > or = 2.4 mg/dL at last follow-up (renal insufficiency or RI group); 41 patients had a serum creatinine < or = 1.7 mg/dL at last follow-up (controls). RI patients tended to be older and had a lower mean glomerular filtration rate (GFR) at initial evaluation. There were no differences in race, gender, or previous history of hypertension between the two groups. Although both groups experienced an improvement in GFR at transplantation and a subsequent decline in GFR by 6 months posttransplantation, the RI group achieved a lower peak GFR at transplantation and a far lower mean GFR at the 6-month analysis. Only the RI group showed a continued decline in GFR. The RI group had more severe hypertension and required a significantly greater number of antihypertensive medications. The RI group had a higher mean total cholesterol at 6 months, but this difference was not sustained. They also had higher triglyceride levels and lower high-density lipoprotein (HDL) levels; there was no difference in low-density lipoprotein (LDL) levels.(ABSTRACT TRUNCATED AT 250 WORDS)