Characteristics of long-term renal transplant survivors.

Despite the high rates of rejection, allograft failure, and patient death in the early years of renal transplantation, some patients have done remarkably well. Forty-three (17 living related donor and 26 cadaver donor recipients) such patients with an allograft that functioned for 19 years or more (range, 19 to 29 years) were followed up at this center. The patients included 24 men and 19 women, with a mean age at transplantation of 29 years, of whom 39 were white and four were black. At most recent follow-up, the mean daily dose of azathioprine was 104 mg (range, 50 to 175 mg) and that of prednisone was 10 mg (range, 5 to 20 mg). Mean serum creatinine level was 1.6 mg/dL (range, 0.7 to 5.4 mg/dL). Acute rejection occurred in 14 (33%) patients. Nine patients had one episode and five patients had two episodes of acute rejection. Long-term risks to the recipients appeared in the form of coronary artery disease in 10 (23%) patients; malignancy in 13 (30%) patients, which included nine patients with skin malignancy; and chronic hepatitis C virus (HCV) infection in four patients, two of whom died of complications of liver failure. Other complications included avascular bone necrosis in five patients, which required total hip replacement in two patients; hyperlipidemia requiring treatment in 16 (37%) patients; posttransplantation diabetes mellitus in 10 (23%) patients after a median of 17.5 years (range, 1 to 23 years); and hypertension in 23 (53%) patients. There were seven deaths (three of coronary artery disease, two of liver failure, one each of sepsis and malignancy) and eight graft losses (five to death with function, two to chronic rejection, and one to focal and segmental glomerulosclerosis). Although long-term allograft success results in patients receiving minimal amounts of immunosuppression and having good renal function, long-term renal transplant survivors are at risk for significant morbidity even in the third decade posttransplantation.

Lack of effect of pregnancy on renal allograft survival or function.

To determine whether pregnancy had a long-term influence on the survival or function of renal allografts, a case-control study was conducted. Patients were selected from a pool of 915 patients transplanted at the University of Cincinnati from 1967 to 1990. The pregnancy group consisted of 18 women who became pregnant 3 months to 17 years after transplantation and who elected to continue pregnancy. There were 26 nonpregnant female controls, and 23 male control renal transplant recipients. Matching criteria were cause of end-stage renal disease (ESRD), donor source, age at transplantation, calendar year of transplantation, time from transplantation to pregnancy, and serum creatinine concentration at the time corresponding to conception. Matching was performed by one investigator, who had no knowledge of long-term outcome in any of the patients. The three groups were well-matched with regard to these criteria. Male controls had higher baseline creatinine clearances than pregnancy cases or female controls. During pregnancy, serum creatinine levels fell by 20%, and creatinine clearance rose by 53%. Immediately after pregnancy, these values returned to baseline. Graft survival, with a mean posttransplant follow-up of 11-12 years, was 77.8% in the pregnancy cases, 69.2% in the female controls, and 69.6% in the male controls. By life-table analysis, none of these differences was significant. Among surviving grafts, serum creatinine levels and creatinine clearances remained stable throughout the follow-up period. In this study, using well-matched male and nonpregnant female cohorts for comparison, pregnancy did not have an adverse long-term effect on renal allograft function or survival.

Prednisone withdrawal in HLA identical and one haplotype-matched live-related donor and cadaver renal transplant recipients.

Prednisone withdrawal was attempted in 121 of 915 renal transplants recipients between 1967 to 1992. There were 57 males, 64 females. Age range was 21 to 62 (mean 39.2 years). Etiology of renal failure was chronic glomerulonephritis (54), diabetic nephropathy (36), interstitial disease (17), hypertensive nephrosclerosis (6), and other (8). Kidney source was from HLA-identical living-related donors (LRD) in 54 (Group I), one haplotype-matched LRD in 23 (Group II), and cadaver in 44 (Group III). Prior to the introduction of cyclosporin A (CsA) in 1984, prednisone withdrawal was attempted only in Group I. After 1984, prednisone withdrawal was also attempted in patients in Groups II and III, selected on the basis of having had no rejection episodes during the six months after transplantation. Forty-five patients in Group I were treated with azathioprine (Aza) and prednisone, and the remaining patients in Groups I to III were treated with Aza, prednisone and CsA. Mean follow-up was 93 months (6 to 207). Prednisone was gradually tapered and withdrawn in 94 of 121 patients after a mean period of 22.5 months (9 to 60). In 27 other patients, the prednisone dosage has been tapered to 5 mg/day or less with the aim of discontinuing the drug. There were seven episodes of acute rejection (3 during taper, and 1 each at 6, 7, 24 and 114 months after prednisone withdrawal); all seven were successfully reversed. Four other patients developed chronic vascular rejection (2 during taper and 2 after withdrawal).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine-ketoconazole interaction. Long-term follow-up and preliminary results of a randomized trial.

Forty-three renal transplant recipients receiving cyclosporine were started on 200 mg/day of oral ketoconazole 10 days to 75 months posttransplant. The cyclosporine dose was reduced by 70% when ketoconazole was started. The mean cyclosporine dose was 5.6 mg/kg/day preketoconazole, and 0.9, 0.8, and 0.7 mg/kg/day at one, two, and three years after addition of ketoconazole (cyclosporine dose reduction 84%, 86%, and 88% at one, two, and three years, respectively). Two patients died after two years of combination therapy, six patients returned to dialysis, and ketoconazole was discontinued in four. Renal function in patients on ketoconazole remained stable (serum creatinine 1.8, 1.7, 1.7, and 1.8 mg/dl preketoconazole and at one, two, and three years, respectively). In a second study, 52 patients were randomized to standard doses of cyclosporine (n = 28), or reduced doses of cyclosporine with ketoconazole (n = 24); seven of the patients were not started on ketoconazole. In 28 patients on standard-dose cyclosporine, there were two deaths and one graft loss. In 17 patients receiving ketoconazole there were two deaths and no graft losses. Renal function and the frequency of rejection episodes was similar in the two groups. In the ketoconazole group, the cyclosporine dose was < 20% of that in the patients on standard doses. In both studies addition of ketoconazole to cyclosporine-treated patients resulted in significant inhibition of cyclosporine metabolism and decrease in dosage in patients followed for up to four years. This drug interaction provides a significant reduction in cost of immunosuppressive therapy in organ transplant recipient.