Knut P. Nordal

A prospective study of the natural course of cytomegalovirus infection and disease in renal allograft recipients.

Background. Cytomegalovirus (CMV) infection is the single most frequent infectious complication inrenal transplant recipients. Because no CMV-prophylaxis is given and ganciclovir is used only as deferred therapy for CMV disease at our center, we have been able to study the natural course of CMV infections. The aim was to assess risk factors for CMV infection and disease and thus identify subgroups of patients likely to benefit from CMV prophylaxis or preemptive therapy. Methods. Between October 1994 and July 1997, 477 consecutive renal transplant recipients (397 first transplants and 80 retransplants) were included in the study. The patients were followed prospectively for 3 months with serial measurements of CMV pp65 antigen for monitoring activity of CMV infections. Results. The incidence of CMV infections in first transplants was 68% in D+R− and D±R+ serostatus groups, whereas the incidence of CMV disease was higher in D+R− (56%) than in D±R+ (20%, P <0.001). No difference in severity of CMV disease in D+R− and D±R+ was seen except for an increased incidence of hepatitis in primary infections. One of 14 deaths could be associated with CMV disease in a seropositive recipient. Cox regression analysis showed that rejection (RR 2.5, P <0.01) and serostatus group D+R− (RR 3.9, P <0.001) were significant risk factors for development of CMV disease. The maximum CMV pp65 antigen count had significant correlation to disease only in CMV seropositive recipients, P <0.001. Conclusion. Renal transplant recipients can safely be given deferred ganciclovir therapy for CMV disease if they are intensively monitored for CMV infection. Patients with primary CMV infection (D+R−), CMV infected patients undergoing anti-rejection therapy and R+ patients with high CMV pp65 counts seem to have a particular potential for benefit from preemptive anti-CMV-therapy.

Sustained improvement of renal graft function for two years in hypertensive renal transplant recipients treated with nifedipine as compared to lisinopril

BACKGROUND Treatment of posttransplant hypertension is still a matter of debate. Calcium antagonists may ameliorate renal side effects of cyclosporin. Angiotensin converting enzyme- (ACE) inhibitors may be more effective in sustaining renal function in native chronic renal disease. We prospectively compared the effect of controlled release nifedipine and lisinopril on long-term renal function in hypertensive kidney transplant patients treated with cyclosporin. METHODS A total of 154 renal transplant patients presenting with hypertension (diastolic blood pressure >or=95 mmHg) during the first 3 weeks after transplantation were randomised to receive double-blind nifedipine 30 mg or lisinopril 10 mg once daily. A total of 123 patients completed 1 year of treatment (69 nifedipine, 54 lisinopril) and 64 patients completed 2 years of double-blind treatment (39 nifedipine, 25 lisinopril). Baseline glomerular filtration rate was measured as 99 mTc-diethylene-triaminepentaacetate clearance in a stable phase 2 to 5 weeks after inclusion and repeated at 1 and 2 years. RESULTS Baseline glomerular filtration rates were similar (46+/-16 ml/min with nifedipine, 43+/-14 ml/min with lisinopril). The changes in glomerular filtration rates from baseline were statistically significant between the groups after 1 year (9.6 ml/min mean treatment difference (95% confidence interval [CI]s 5.5-13.7 ml/min, P=0.0001) and remained statistically significant also after 2 years (10.3 ml/min mean difference (95% CIs 4.0-16.6], P=0.0017). After 1 year glomerular filtration rates averaged 56+/-19 ml/min in the nifedipine group and 44+/-14 ml/min in the lisinopril group. CONCLUSIONS Both nifedipine and lisinopril were safe and effective in treatment of hypertension in renal transplant patients treated with cyclosporin. Patients receiving nifedipine but not lisinopril improved kidney transplant function over a period of 2 years.

Fifteen years' experience with renal transplantation in systemic amyloidosis

Abstract. At our center 62 renal transplantations (31 living donor and 31 cadaveric donor grafts) have been performed in 58 patients with amyloid renal disease since 1974. The amyloidosis was secondary to rheumatic disease in 74 % of the patients. Predialytic transplantation was performed in 28% of the patients. Mean follow‐up time was 5.1 years (0.3–14.5 years). One‐year actuarial patient survival was 79%, decreasing to 65% after 5 years. First graft survival was 74 % at 1 year and 62 % at 5 years. Patient death with a functioning graft caused 16 out of 25 graft losses. Infections caused 11 out of 18 deaths (61 %), more than half of them within 3 months. Renal transplant amyloid was diagnosed in about 10% of the cases (6/ 62); however, only about 3% of the grafts (2/62) were lost. These long‐term results encourage transplantation in amyloid renal end‐stage disease.

Practice variations in the evaluation of adult candidates for cadaveric kidney transplantation: a survey of the European Transplant Centers

Background. This survey was conducted to investigate similarities and differences in the diagnostic evaluation of adult candidates for cadaveric renal transplantation and the criteria for acceptance to the cadaveric renal transplant waiting-list in the European transplant centers. Methods. A questionnaire listing 45 diagnostic procedures (consultations of 9 specialties, 18 imaging techniques and 18 laboratory investigations), 45 medical conditions constituting possible reasons for exclusion from renal transplantation, and 10 properties characterizing the responding transplant center was sent to 214 European transplant centers. Results. A completed questionnaire was returned by 154 of 214 centers (72%). Significant disagreement (P <0.001) exists about the necessity of 28 of the 45 surveyed diagnostic procedures and about the acceptability of transplant candidates for 15 of the 45 surveyed medical conditions. The influence of center characteristics on the observed practice variations was examined by multinomial logistic regression (factors: Center size, waiting-list pressure, responsibility for organizing the diagnostic work-up, status of transplant center, responsibility for decision about acceptance of candidates and geographic location of center): In 13 of 28 controversial diagnostic procedures, geographic location of the centers turned out to be the only significant determining factor (P <0.001), whereas the dissent about medical conditions is not influenced significantly by the analyzed factors. Conclusion. The detected significant practice variations in the evaluation of renal transplant candidates may either indicate where scientific evidence is missing and more clinical research is needed or where the existing evidence has not been adequately disseminated and convincing guidelines should be established.

Half dose of OKT3 is efficient in treatment of steroid-resistant renal allograft rejection.

Rejection episodes in renal allograft recipients are usually efficiently treated with high doses of intravenous methylprednisolone. Rejection therapy with OKT3 is often reserved for steroid-resistant episodes. However, the optimal dose of OKT3 in the treatment of steroid-resistant rejection is not known. Therefore, we randomized renal transplant recipients with steroid-resistant rejection to treatment with a standard daily intravenous dose of either 5 mg of OKT3 (n=15) or 2.5 mg of OKT3 (n=15) for 10 days. Circulating T cells (measured as CD2+ cells) were adequately and equally depleted in the two groups. Three grafts were lost due to rejection within the first 3 months following OKT3 administration, one in the 2.5 mg OKT3 group and two in the 5 mg OKT3 group. Two nonimmunologic graft losses occurred in the 2.5 mg OKT3 group. Median serum creatinine values were not different between the two groups, neither at the start (median values: 200 micormol/L in the 5 mg OKT3 group vs. 188 micromol/L in the 2.5 mg group) nor immediately after OKT3 rescue therapy (202 micromol/L vs. 185 micromol/L, respectively). Eight cytomegalovirus infections occurred in each group. Two re-rejection episodes occurred in the 5 mg OKT3 group and one occurred in the 2.5 mg OKT3 group. All responded to treatment. Function of the remaining grafts estimated by serum creatinine after a mean long-term follow-up of 18 months (range, 6-36 months) revealed no differences (185 micromol/L in the 5 mg OKT3 group vs. 170 micromol/L in the 2.5 mg OKT3 group). We conclude that OKT3 treatment of steroid-resistant rejections in renal transplant recipients is equally effective in daily doses of 2.5 mg and 5 mg with respect to reversal rate and long-term outcome.

Renal Transplantation in Renal Amyloid End-Stage Disease

Renal amyloid end-stage disease has been treated with renal transplantation (tx.) in 62 cases at our center from 1974 until april 89. 43 cases (74%) of these complicated rheumatoid disease. The average follow-up time is 5.1 years. 42 patients (72%) were transplanted after start of dialysis. 29 of the patients received necro donor grafts, the other half living donor grafts. The actuarial patient survival was 82% at 1 year falling to 65% at 5 years. Graft survival was 76% at 1 year and 60% at 5 years. Most gfaft-losses were due to deaths with functioning grafts. Septicaemia was the major cause of death usually occuring within 3 months after tx. Recurrent graft amyloid was diagnosed in 6 cases (9.6%), but only 2 graft losses could be ascribed to amyloidosis. Despite a high early mortality these long-term results encourage an active transplant program in renal end-stage amyloidosis.