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

Abstract

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) ~nd 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 ~arly rejection or whole-blood CyA levels. These results Indicate that nifedipine significantly improves immediate and medium-term graft function.

Influence of nifedipine on interstitial fibrosis in renal transplant allografts treated with cyclosporin A.

“…Group B showed sig-nificantly lower serum creatinine than group A at one, six, and 12 months, while glomerular filtration rate was significantly higher in both groups B and C than group A at six and 12 months. 20 In previous morphometric studies Ruiz et alP showed an increase in interstitial volume fraction in patients treated with cyclosporin A compared with those who were not, however, as in the present study, this increase was only apparent in biopsy specimens taken six months or more after transplantation.…”

Hypertension, antihypertensive agents and outcomes following renal transplantation

“…ACE inhibitors, alpha-blockers were only used in a small number of patients and had no adverse effect on patient survival ( Table 5). The popularity of dihydropyridine calcium antagonists is a reflection of their role in ameliorating cyclosporine nephrotoxicity (22). The popularity of beta-blockers reflects the high level of general use and the high prevalence of concomitant ischaemic heart disease in this population.…”

Chronic Allograft Nephropathy

“…The choice of antihypertensive class depends on the individual patient. Calcium channel blockers can be used as first line therapy, especially in the early period of the transplantation because they are effective in counteracting the vasoconstrictive effect of high-dose calcineurin inhibitors (Harper et al, 1992). In opposition, in proteinuric chronic kidney disease patients, dihydropiridinic-calcium channel blocker has been associated with increased risk of renal disease and death (Wright Jr et al, 2002, Agodoa et al, 2001.…”