Major Findings

Cyclosporine (CsA) has been shown to improve 1-year graft survival and reduce the incidence of acute rejection episodes after renal transplantation compared to azathioprine (Aza). 8 However, CsA has many side effects and reducing exposure of this drug after the first year may benefit long-term patient and graft survival. 8 Sirolimus (SRL), in combination with reduced exposure of cyclosporine, has been investigated to prevent acute rejection and associated side effects. 4 Compared with azathioprine, SRL patients showed reduced 3-month primary endpoint (biopsy-confirmed acute rejection, graft loss, or death) and reduced incidence of biopsy-confirmed acute rejection at 3 months, but not at 12 months. 4 Hyperlipidemia was the only adverse event more frequent among SRL patients. 4 Although cyclosporine improves short-term graft survival, its long-term effects are unclear. 5 In recipients of first cadaver renal transplants, short-term cyclosporine followed by azathioprine and prednisolone significantly improved graft survival compared to long-term cyclosporine use. 5 Long-term cyclosporine use reduces long-term graft survival. 5 Basiliximab significantly reduces the need to modify the initial treatment regimen in patients receiving steroid-free CsA therapy, suggesting that basiliximab induction may be useful as a strategy in other steroid-avoidance regimens. 6 A meta-analysis of calcineurin inhibitors (cyclosporine A and tacrolimus) in the treatment of lupus nephritis showed that tacrolimus was more effective in reducing daily urinary protein and achieving complete remission compared to cyclosporine. 10 Cyclosporine is known to increase blood pressure. 9 In combined kidney-pancreas transplantation, tacrolimus caused fewer pancreas graft losses and fewer drug discontinuations due to side effects compared to cyclosporine. 7

Benefits and Risks

Benefit Summary

Cyclosporine has shown to be effective in improving graft survival and reducing the incidence of acute rejection episodes after renal transplantation. 8 Sirolimus, in combination with reduced cyclosporine exposure, can potentially reduce the risk of acute rejection and associated side effects. 4 Short-term use of cyclosporine followed by azathioprine and prednisolone has been shown to improve long-term graft survival compared to long-term cyclosporine use. 5 Basiliximab can reduce the need for additional immunosuppressive drugs in patients receiving steroid-free CsA therapy. 6 Tacrolimus has shown to be more effective in reducing daily urinary protein and achieving complete remission compared to cyclosporine in patients with lupus nephritis. 10 Tacrolimus has been associated with fewer pancreas graft losses and fewer drug discontinuations due to side effects compared to cyclosporine in combined kidney-pancreas transplantation. 7

Risk Summary

Cyclosporine has numerous side effects, and reducing exposure after the first year may be beneficial for long-term patient and graft survival. 8 Sirolimus has been associated with increased hyperlipidemia. 4 Long-term cyclosporine use has been linked to reduced long-term graft survival. 5 Cyclosporine can induce hypertension. 9

Study Comparisons

Commonalities

Multiple studies suggest that cyclosporine is an effective immunosuppressant after renal transplantation. 8 5 All studies consistently highlight the potential long-term adverse effects of cyclosporine, including nephrotoxicity and hypertension. 5 9

Differences

There are variations between studies in terms of the duration of cyclosporine use, dosage, co-administered medications, and outcome measures, which contribute to differences in findings. 8 4 5 6 10 7 2 3 1 For instance, sirolimus has shown to be effective in preventing acute rejection with reduced cyclosporine exposure. 4 Basiliximab has been shown to reduce the need for additional immunosuppressive drugs in patients receiving steroid-free CsA therapy. 6

Consistency and Contradictions

While cyclosporine is an effective immunosuppressant following renal transplantation, multiple studies highlight the potential long-term risks of nephrotoxicity and hypertension associated with its use. 5 9 However, variations in study design, including cyclosporine duration, dosage, co-administered medications, and outcome measures, can contribute to discrepancies in findings. 4 5 6 10 7 2 3 1 Consequently, individualized care is crucial, tailoring cyclosporine dosage and co-administered medications to each patient's specific needs. 5 9

Implications for Real-Life Applications

Cyclosporine, while an effective immunosuppressant after renal transplantation, carries the risk of hypertension and kidney function deterioration. 5 9 Tailoring dosage and co-administered medications to individual patient characteristics is essential. 5 9 Regular monitoring of blood pressure and kidney function is crucial during cyclosporine therapy. 5 9

Limitations of Current Research

Research evaluating the long-term effects of cyclosporine is limited. 5 Furthermore, discrepancies in study design, including cyclosporine duration, dosage, co-administered medications, and outcome measures, make it challenging to compare findings across studies. 8 4 5 6 10 7 2 3 1

Future Research Directions

Longitudinal studies are needed to thoroughly assess the long-term effects of cyclosporine. 5 Standardizing study design, including cyclosporine duration, dosage, co-administered medications, and outcome measures, across studies would enhance the reliability and comparability of findings. 8 4 5 6 10 7 2 3 1

Conclusion

Cyclosporine is an effective immunosuppressant after renal transplantation, but it is associated with potential side effects. 5 9 Individualized care, including tailored dosage and co-administered medications, as well as regular blood pressure and kidney function monitoring, is essential during cyclosporine therapy. 5 9 Future research should focus on long-term follow-up and standardized study designs to further assess the long-term effects of cyclosporine. 5 8 4 5 6 10 7 2 3 1