Urodilatin, a new therapy to prevent kidney failure after heart transplantation

Kidney failure after heart transplantation still remains a crucial problem, especially when cyclosporine is used for early postoperative immunosuppressive therapy. To preserve good renal function during immunosuppression with cyclosporine, urodilatin (CDD/ANP-95-126), the kidney-born analogue to the circulating cardiac peptide hANP (CDD/ANP-99-126), was given for the first time as a long-term, low-dose infusion in addition to the usual drug therapy immediately after heart transplantation. From November 1990 to January 1992, 47 patients (44 men and three women; mean age, 51 years) were treated by a 20 ng/kg body weight/min infusion for 96 hours after heart transplantation. Renal function and hemodynamic parameters of these patients were compared with a group of 40 patients (34 male and six female; mean age, 50 years) as controls, who underwent heart transplantation from May 1990 to November 1991. Both groups did not differ significantly with respect to age, sex, indication for heart transplantation, and preoperative renal function. With urodilatin treatment, renal function was significantly improved with lower peak plasma creatinine (1.83 +/- 0.1 versus 2.47 +/- 0.19 mg/dl; p = 0.003), lower peak serum urea (118 +/- 7 versus 178.3 +/- 10.3 mg/dl; p = 0.0036) and absence of hemodialysis (0% versus 10%; p = 0.026). Additionally, adequate diuresis was maintained although furosemide was reduced by more than 50% (p = 0.005) on each day of urodilatin treatment. Mean central venous pressure was significantly lower (-2 mm Hg; p = 0.02) during application of urodilatin, despite reduction of vasodilator therapy with nitroglycerin by about 50% (p = 0.02). Because of the significantly improved renal function and beneficial hemodynamic effects, the recommendation is therefore to introduce urodilatin in the postoperative treatment protocol after heart transplantation.