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Protective effects of calcium antagonists in human renal transplantation
H H Neumayer1, U Kunzendorf, M Schreiber
1Department of Internal Medicine, University of Erlangen-Nürnberg, Germany.
Abstract:
To test the hypothesis that calcium antagonists decrease the incidence and severity of delayed graft function, we conducted three separate, prospective, randomized trials. In these trials, we investigated the effects of diltiazem and those of the prostacyclin analogue iloprost. In the first study, 22 control patients and 20 diltiazem patients received grafts perfused with either vehicle or diltiazem 20 mg/liter in the Euro-Collins solution. Subsequently, the diltiazem subjects were given the drug as a bolus of 0.28 mg/kg, followed by a continuous infusion of 0.002 mg/min/kg for the following two days. Thereafter, diltiazem 60 mg was given to the treated subjects orally for up to four years. In the second study, 11 control subjects and 10 diltiazem subjects received the same postoperative regimen, but all grafts were harvested without addition of diltiazem to the perfusion solution. In the third protocol, four groups were studied as follows: 19 control subjects who received no specific treatment, 16 subjects who received diltiazem, 16 subjects who were given iloprost, and 14 subjects who received both iloprost and diltiazem. The donor kidney of treated patients was perfused with either diltiazem, iloprost, or both drugs. Primary graft function occurred more commonly in the groups receiving diltiazem. Further, in the first study the number of hemodialyses per patient was reduced in those patients with delayed graft function. Fewer rejection episodes occurred in patients receiving diltiazem. Plasma levels of soluble interleukin-2 receptors decreased significantly during diltiazem treatment. Moreover, renal biopsies showed less severe signs of Cyclosporin A (CsA) nephrotoxicity in diltiazem-treated patients compared to controls, even though these patients also exhibited higher CsA trough levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Calcium antagonists like diltiazem may reduce delayed graft function and rejection episodes after kidney transplants. Studies show diltiazem improves primary graft function and reduces hemodialysis needs in transplant patients.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Delayed graft function (DGF) is a significant complication following kidney transplantation.
- Calcium antagonists are being investigated for their potential to mitigate DGF and improve graft outcomes.
Purpose of the Study:
- To evaluate the efficacy of calcium antagonists, specifically diltiazem and iloprost, in reducing the incidence and severity of delayed graft function after kidney transplantation.
- To assess the impact of these agents on graft rejection, nephrotoxicity, and overall graft survival.
Main Methods:
- Three prospective, randomized trials were conducted involving kidney transplant recipients.
- Interventions included perfusion of donor kidneys with diltiazem or iloprost, postoperative diltiazem administration, and a combination of both drugs.
- Outcomes measured included primary graft function, need for hemodialysis, rejection episodes, and Cyclosporin A (CsA) nephrotoxicity.
Main Results:
- Diltiazem administration was associated with a higher incidence of primary graft function.
- Patients receiving diltiazem experienced fewer rejection episodes and reduced requirements for hemodialysis.
- Renal biopsies indicated less severe Cyclosporin A (CsA) nephrotoxicity in diltiazem-treated patients, despite higher CsA trough levels.
Conclusions:
- Diltiazem demonstrates a beneficial effect in improving early kidney graft function and reducing complications such as delayed graft function and rejection.
- Calcium antagonists may play a role in mitigating CsA-induced nephrotoxicity, warranting further investigation in kidney transplant management.