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Diltiazem in renal allograft recipients receiving cyclosporine
A Chrysostomou1, R G Walker, G R Russ
1Royal Melbourne Hospital, Parkville, Victoria, Austalia.
Insights
Adding diltiazem to standard therapy reduced cyclosporine (CsA) requirements by 35% in renal transplant patients. This combination therapy also decreased primary nonfunction and the severity of rejection episodes, including vascular rejection, without impacting graft function or outcomes.
Area of Science:
- Nephrology
- Immunosuppression
- Transplantation
Background:
- Cyclosporine (CsA) is a cornerstone immunosuppressant in renal transplantation.
- Optimizing CsA dosage while maintaining efficacy and minimizing toxicity is crucial for graft survival.
Purpose of the Study:
- To evaluate the effect of adding diltiazem to standard therapy on CsA requirements and clinical outcomes in primary renal allograft recipients.
Main Methods:
- A randomized controlled trial involving 113 primary renal allograft recipients.
- Patients were assigned to standard therapy without diltiazem (ND group) or standard therapy plus diltiazem (D group).
- Outcomes including CsA blood levels, blood pressure, renal function, graft loss, rejection episodes, and primary nonfunction were monitored up to 24 months.
Main Results:
- The diltiazem group (D) required 35% less CsA than the non-diltiazem group (ND) at 12 months, with no difference in CsA blood levels.
- No significant differences were observed in blood pressure, serum creatinine, or graft loss between the groups.
- The D group experienced fewer and less severe rejection episodes, particularly vascular rejection (3 vs. 14 episodes, P=0.005), and a lower incidence of primary nonfunction (5 vs. 16 patients, P=0.05).
Conclusions:
- Diltiazem co-administration with CsA in renal transplant recipients leads to a significant reduction in CsA dosage requirements.
- This combination therapy is associated with improved outcomes, including reduced primary nonfunction and less severe rejection episodes, without compromising graft function or survival.
- Diltiazem represents a valuable adjunct to CsA therapy in renal transplantation.
Abstract:
Of 113 cyclosporine-treated primary renal allograft recipients, 60 were randomized to receive standard therapy without diltiazem (ND) and 53 received standard therapy plus diltiazem (D). There was no difference in CsA blood levels between ND and D at all intervals between 3 and 24 months follow-up, yet the D group required 35% less CsA than the ND group (measured at 12 months). At all intervals to 24 months there was no difference in blood pressure, renal function (as measured by serum creatinine), or in the number of grafts lost between the 2 groups (ND, 4 lost; D, 3 lost). There was no significant difference in the total number of rejection episodes in the 2 groups (ND, 89 episodes; D, 71 episodes). However, the severity of rejection episodes was greater in the ND group as evidenced by a significant difference in the usage of OKT3 (ND, 17 courses; D, 8 courses of OKT3, P < 0.05). Of the biopsy-proven episodes of rejection, there were more episodes of vascular rejection in the ND group (ND, 14 episodes; D, 3 episodes, P = 0.005). The incidence of primary nonfunction was less in the D group (ND, 16 patients; D, 5 patients, P = 0.05). It was concluded that the use of diltiazem was associated with a markedly reduced requirement for CsA without any adverse effect on graft function or graft outcome. Diltiazem with CsA was associated with fewer episodes of primary nonfunction and less-severe rejection episodes and in particular fewer episodes of vascular rejection.