Major research findings

Cyclosporine (CsA) has been shown to improve early graft survival after kidney transplantation. 1 However, long-term use of CsA is associated with impaired renal function and increased cardiovascular risk factors. 1 To avoid long-term adverse effects of CsA, patients were switched to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation. 1 Another study found that long-term use of CsA reduces long-term graft survival. 5 The group that used CsA for a short period of time and then switched to AZA and prednisolone had higher graft survival rates and better kidney function. 5 CsA improved 1-year graft survival and reduced the incidence of acute rejection episodes after renal transplantation compared to azathioprine (Aza). 8 However, CsA has many side effects, and reducing exposure to 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 SRL patients received lower cyclosporine doses and showed lower cyclosporine concentrations compared with AZA patients. 4 SRL patients showed reduced 3-month primary end point and reduced incidence of biopsy-confirmed acute rejection at 3 months but not at 12 months. 4 CsA and tacrolimus, which are calcineurin inhibitors, are effective in treating lupus nephritis. 10 The tacrolimus group was better at reducing daily urinary protein compared with the CTX group, and the difference was statistically significant. 10 Tacrolimus resulted in better total remission than CTX and had fewer side effects. 10 Tacrolimus causes fewer pancreas graft losses and fewer drug discontinuations due to side effects compared to CsA. 7 Basiliximab significantly reduces the need to modify the initial treatment regimen in patients scheduled to receive steroid-free CsA therapy. 6 The proportion of patients experiencing biopsy-proven rejection was not significantly different between the basiliximab and placebo groups. 6 Tacrolimus and cyclosporine have different effects on renal hemodynamics and blood pressure in healthy subjects. 2 CsA can be safely withdrawn from immunosuppressive regimens containing mycophenolate mofetil (MMF; CellCept). 3 Cyclosporine can increase blood pressure. 9

Benefits and Risks

Benefit summary

Cyclosporine has the potential to improve early graft survival after kidney transplantation and reduce the incidence of acute rejection episodes. 1 8 It may also be effective in treating lupus nephritis. 10 Short-term use of cyclosporine, followed by a switch to other immunosuppressants, could lead to better maintenance of kidney function and improved long-term graft survival. 5 Combining cyclosporine with sirolimus may also prevent acute rejection and associated side effects. 4 Combining cyclosporine with basiliximab may reduce the need for steroid therapy. 6

Risk summary

Cyclosporine has many side effects, including impaired renal function and increased cardiovascular risk factors due to long-term use. 1 8 It can also increase blood pressure. 9 Cyclosporine may increase the risk of pancreas graft thrombosis. 7

Comparison of studies

Similarities of studies

Many studies have shown that cyclosporine improves early graft survival after kidney transplantation and reduces the incidence of acute rejection episodes. 1 5 8 In addition, studies have reported side effects of cyclosporine, such as impaired renal function and increased cardiovascular risk factors due to long-term use. 1 8

Differences of studies

There are different results depending on the study regarding the effects of long-term cyclosporine use. 5 Some studies have shown that long-term use of cyclosporine reduces long-term graft survival. 5 However, other studies have shown that long-term graft survival can be maintained by using cyclosporine for a short period of time and then switching to other immunosuppressants. 5 The effects of combining cyclosporine with other immunosuppressants vary depending on the study. 4 7 6

Consistency and contradictions of results

Further research is needed on the effects of long-term cyclosporine use because there are different results depending on the study. 5 More detailed research is also needed on the effects of combining cyclosporine with other immunosuppressants as results vary by study. 4 7 6

Things to keep in mind when applying results to real life

Cyclosporine has the potential to improve graft survival, but it also comes with the risk of side effects due to long-term use. 1 8 Therefore, the use of cyclosporine should be carefully evaluated on a case-by-case basis, weighing the risks and benefits. 1 8 If long-term use of cyclosporine is unavoidable, kidney function and cardiovascular risk factors should be monitored regularly. 1 8

Limitations of current research

Many studies have been conducted on a relatively small number of patients, and it is unclear whether the results are applicable to all patients. 5 4 7 6 In addition, many studies have been conducted on specific patient populations, and it is unclear whether the results are applicable to other patient populations. 5 4 7 6

Future research directions

More large-scale, long-term studies are needed on the effects of long-term cyclosporine use. 5 More detailed research is needed on the effects of combining cyclosporine with other immunosuppressants. 4 7 6

Conclusion

Cyclosporine has the potential to improve early graft survival after kidney transplantation, but it also comes with the risk of side effects due to long-term use. 1 8 The use of cyclosporine should be carefully evaluated on a case-by-case basis, weighing the risks and benefits. 1 8 If long-term use of cyclosporine is unavoidable, kidney function and cardiovascular risk factors should be monitored regularly. 1 8