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Calcium channel blockers for kidney protection
U Frei1, A Harms, R Bakovic-Alt
1Department of Nephrology, Medizinische Hochschule Hannover, F.R.G.
Abstract:
Acute postischemic renal failure (ARF) is a major complication in surgery and in particular in renal transplantation. Calcium channel blockers (CCBs) are able to prevent or ameliorate ARF in different experimental models when given before ischemic injury. Because ARF, which is observed in 20-60% of graft recipients, carries the risk of undetected rejections and nephrotoxic injury and is also expensive, we tested the hypothesis, suggested by animal experiments, that there is also a beneficial effect of CCBs when given after ischemic injury. A total of 134 recipients of first or second cadaver grafts were randomly assigned to a diltiazem pretreatment (DZ) or control (C) group. Kidney grafts were pretreated immediately prior to transplantation by reperfusion with 500 ml Euro-Collins (preservation fluid), with or without DZ. The DZ patients also received a 74-h infusion of DZ (0.12 mg/kg/h), starting 2 h prior to surgery. DZ was continued (90 mg b.i.d. p.o.) until day 30. Immunosuppression consisted of low-dose steroids and cyclosporine A (CSA) (10 mg/kg p.o.). CSA was instituted 6 h after surgery and later adjusted to achieve whole-blood trough levels of 300-600 ng/ml [by polyclonal radioimmunoassay (RIA)]. A total of 129 patients were available for efficacy analysis. There were no significant differences concerning donor demographics, human lymphocyte antigen (HLA) match, or ischemic times. ARF was defined as a need for dialysis in the first week. Our data show a significant reduction in ARF in grafts pretreated with DZ.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Calcium channel blockers (CCBs) significantly reduced acute postischemic renal failure (ARF) in kidney transplant recipients. This study investigated the beneficial effects of CCBs, specifically diltiazem, in preventing ARF after ischemic injury.
Area of Science:
- Nephrology
- Transplantation immunology
- Pharmacology
Background:
- Acute postischemic renal failure (ARF) is a significant complication in surgery and renal transplantation.
- Calcium channel blockers (CCBs) have shown promise in preventing ARF in experimental models when administered before ischemic injury.
- The potential benefit of CCBs administered after ischemic injury in ARF remains to be fully elucidated.
Purpose of the Study:
- To test the hypothesis that CCBs offer a beneficial effect when given after ischemic injury in renal transplantation.
- To evaluate the efficacy of diltiazem in preventing or ameliorating ARF in cadaveric kidney graft recipients.
Main Methods:
- A randomized trial involving 134 recipients of first or second cadaver grafts assigned to diltiazem pretreatment (DZ) or control (C) groups.
- Kidney grafts were reperfused with preservation fluid, with or without DZ. DZ patients received a 74-h infusion and subsequent oral administration until day 30.
- Immunosuppression included low-dose steroids and cyclosporine A (CSA), with CSA levels monitored by RIA.
Main Results:
- A significant reduction in ARF was observed in kidney grafts pretreated with diltiazem (DZ).
- ARF was defined as the need for dialysis within the first week post-transplantation.
- No significant differences were noted in donor demographics, HLA match, or ischemic times between groups.
Conclusions:
- Diltiazem pretreatment demonstrates a significant beneficial effect in reducing acute postischemic renal failure in kidney transplant recipients.
- These findings support the use of CCBs, like diltiazem, in the management of kidney transplantation to mitigate ischemic injury.
- Further research may explore optimal timing and dosage for CCB administration in preventing ARF.