Are Calcineurin inhibitors (CNIs) needed in HLA-identical living related donor kidney transplantation
A very interesting observational study of 453 HLA identical living related transplants is from Minneapolis has recently been reported . The authors have examined the outcome of HLA identical living related donor transplants in 3 eras. Era 1, up to 1984, induction with ALG was used and maintenance immunosuppression comprised azathioprine and prednisone; era 2a – from 1984 to 1999, calcineurin inhibitors were added and induction was changed from ALG to thymoglobulin and azathioprine for maintenance was changed to mycophenolate; era 2b – there was a rapid discontinuation of prednisone after thymoglobulin induction, and maintenance immunosuppression was a CNI and mycophenolate. There was no difference in patient or graft survival in the three eras, but graft loss from chronic allograft nephropathy and hypertension were greater in the two CNI eras. Surprisingly renal function is no different although one would have expected it to be rather better in the azathioprine-prednisone era. The authors also review the available literature, but there are no RCTs only observational studies and the outcome of most of these reports is compatible with the findings of the Minneapolis group. The authors conclude that the addition of a CNI, either with or without steroids, to immunosuppressive regimens does not offer any additional benefit in recipients of HLA identical LRD kidneys in comparison with the older immunosuppression with azathioprine and prednisolone, and in fact there may be more problems with the use of a calcineurin inhibitor. Thus the authors suggest that perhaps mono-therapy or early discontinuation of CNI should be given serious consideration in these patients. But I fail to see why their conclusion isn’t for us to go back to azathioprine and prednisone immunosuppression in recipients of HLA identical LRD kidneys. There is certainly a need to look at this issue again and perhaps a large multicentre RCT might be justified.
