Renal dysfunction

Renal dysfunction occurs to a varying degree in virtually all liver allograft recipients receiving cyclosporine. Cyclosporine is a moderately potent nephrotoxin, which produces dose related and rarely irreversible renal dysfunction. Cyclosporine produces these deleterious effects on the kidneys by producing a vasoconstriction of the afferent renal arterioles therefore decreasing glomerular filtration rate. Attempts to ameliorate this effect with verapamil and certain experimental prostaglandin compounds has been successful in experimental animals, but clinical application of these drugs await appropriate clinical trials.

The irreversible type of dysfunction may be categorized into two types: rapidly progressive, and chronic. The rapidly progressive type has only been described in kidney transplant patients. This type of dysfunction produces severe renal dysfunction over a few days and is associated with increased LDH and severe thrombocytopenia. The mechanism of this type of dysfunction is a cyclosporine related intravascular thrombosis. The treatment is discontinuance of cyclosporine and full heparinization of the patient. We have not seen this type of nephrotoxicity in our patients. The chronic irreversible type of renal dysfunction produces slow, progressive dysfunction over years and may be associated with a obliterative vasculopathy on renal biopsy. There is no known treatment for this cause of renal dysfunction.

Following an extensive study of the renal function both before and following liver transplantation, we have found that the majority of the recipients lose approximately half their GFR immediately following transplantation, but remain stable afterwards. Only two patients in our series of 270 patients have required chronic dialysis following transplantation, although approximately 5% of our patients have significantly elevated Creatinine level (i.e., > 2.5 mg/dl).

Patients that continue to have serum creatinine levels greater than 2.5 mg/dl despite the lowering of cyclosporine dosages to 3 mg/kg per day and/or exhibit whole blood cyclosporine levels to 120 to 80 ng/ml are begun on azathioprine (Imuran) at approximately 1.0 mg/kg per day. This is done so that the cyclosporine dosage can be further reduced to approximately 2 mg/kg per day or to cyclosporine levels of 70 to 90 ng/ml (12 hour through whole blood level by HPLC). In selected cases, cyclosporine may be stopped completely while maintaining immunosuppression with azathioprine and corticosteroids. Furthermore, all other nephrotoxin such as Motrin, Bactrim etc. should be eliminated. (see "Immunosuppression").