P. K. Donnelly

The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients- a randomised prospective study

The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P=0.0223) and 4-year (P=0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P<0.01). Group B also experienced fewer rejection episodes than groups A and C (P<0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.

Donor-recipient age difference—an independent risk factor in cyclosporin-treated renal transplant recipients

Whilst HLA matching is routine in renal transplantation the possible benefits of matching donor to recipient age have not been previously explored. The simultaneous effect on graft survival of donor and recipient age was therefore investigated for 274 consecutive first cadaver transplant recipients treated by cyclosporin immunosuppression in two centres. The overall graft survival was 77%, and was not significantly different between the two centres. Individually there was no significant effect of donor or recipient age but taken together, the difference in age significantly affected graft survival (P<0.01) regard-less of the mode of failure. The 1-year graft survival for all failures was 66.2% when the donor was 5 or more years older, 84.5% when the donor was 5 or more years younger and 71.7% when the donor was within 5 years of the recipients age. Multivariate analysis, taking into account other variables (HLA matching, dialysis time and type, donor/recipient sex, local/imported kidneys, sensitivity, operation time, total ischaemic time, pre-operative transfusions) indicated that age difference was the single most important variable (P<0.01). The only other important covariate risk factor in improving graft survival was HLA-DR matching (P<0.05). Donor-recipient age difference is a potentially important recipient selection criterion in cyclosporin-treated renal transplant patients.

Cyclosporin, Nifedipine and gingival hyperplasia: a randomized controlled study

Abstract Nifedipine increases the frequency and severity of gingival hyperplasia associated with CyA therapy in renal transplant recipients and this effect appears to be independent of whole‐blood CyA levels. De novo malignancies have been reported arising in areas of gingival hyperplasia, in a group already at high risk of malignancy. Patients receiving CyA and nifedipine should receive advice regarding the need for strict oral hygiene to control the initial development of gingival hyperplasia, with severe cases being promptly referred for gingivectomy and histological examination.

Nifedipine improves immediate, and 6- and 12-month graft function in cyclosporin A (CyA) treated renal allograft recipients.

To investigate the effect of oral nifedipine, a calcium channel blocker known not to modify cyclosporin A (CyA) pharmacokinetics, on immediate transplant function and CyA nephrotoxicity, 68 adult renal transplant recipients were pre-operatively randomized to one of three regimes: A (high-dose CyA, initial dose 17 mg/kg per day, maintenance dose 7 mg/kg per day); B (regime A plus oral nifedipine); C low-dose CyA, initial dose 10 mg/kg per day, maintenance 4 mg/kg per day plus azathioprine 1 mg/kg per day). All three groups received identical steroid regimes. Calcium channel blockers of all types were avoided in groups A and C. Delayed graft function (dialysis dependence by day 4) was seen least frequently in group B (P < 0.02). Group B had improved graft function at 6 months compared with group A, identified by differences in serum creatinine (P < 0.05), GFR (P < 0.01) and ERPF (P < 0.05). Similar differences in serum creatinine (P < 0.05) and GFR (P < 0.05) were also identified at 12 months. Group C also had better 6- and 12-month GFR values than group A (P < 0.05 each). The three groups did not differ in donor or recipient age, HLA matching, ischaemic or anastomosis times, frequency of early rejection or whole-blood CyA levels. These results indicate that nifedipine significantly improves immediate and medium-term graft function.

Specific and nonspecific immunoregulatory factors and renal transplantation

From a study population of 208 consecutive first cadaver renal transplant recipients a proportional hazard model was used to simultaneously quantify the role in graft failure of matching for specific HLA antigens and constitutional factors (age, sex, duration of dialysis (Dt), and pre- (PTr) and peri-(PerTr) operative transfusions) that influence nonspecific immune response. A comparison was also made of graft survival in patients treated by the two principal methods of dialysis, hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). The advisability of including nonimmunological failures in studies of graft survival was also considered. The analysis indicated that factors influencing a patients innate nonspecific immune response (e.g., Dt and PTr) are important determinants of graft survival and should be taken into account when considering matching for specific HLA-B or DR antigens prior to transplantation. While there was no overall effect of dialysis type on graft survival, the influence of other risk factors depended on the method of dialysis. Failure to identify and exclude graft loss for nonimmunological reasons can give rise to misleading conclusions in analysis of immunoregulatory factors in organ transplantation.

Polyarthropathy--a delayed reaction to low osmolality angiographic contrast medium in patients with end stage renal disease.

Since the introduction of low osmolality non-ionic media, acute reactions to radiographic contrast are uncommon and delayed reactions are especially rare, consisting mostly of mild flu-like symptoms. We report two patients suffering from end-stage renal failure and treated by continuous ambulatory peritoneal dialysis (CAPD) who developed a severe constitutional illness including acute polyarthropathy 6 and 16 h after injection of the low osmolality non-ionic contrast medium, iopamidol. Although the clinical presentation of the reactions was similar to a systemic lupus syndrome there was no immunological evidence to support this as an aetiological mechanism. Since CAPD is a relatively inefficient method of clearing contrast media prolonged high circulating levels of iopamidol may have been a contributory factor to these unusually severe delayed contrast reactions.

Age Matching is Fairer Than HLA Matching in Renal Transplantation

To cope with the ever increasing demand for transplantable kidneys, several centres have advocated the increased use of older donors (>50 years) [1, 2]. Unfortunately, older donors are associated with inferior graft survival and renal function compared to younger donors despite human leukocyte antigen (HLA) matching [3, 4]. Optimum matching for HLA antigens is advocated and is the main basis for organ sharing [5]. Inevitably this increases cold ischaemic time, which is a risk factor for graft survival of kidneys taken from older donors [6]. Little attention has been given to the possible benefits of matching for the relative ages of donor and recipient. In this study we investigated the effect of cadaveric donor age on graft survival of Leicester patients whilst allowing for recipient age.