Long-term impact of discontinued or reduced calcineurin inhibitor in patients with chronic allograft nephropathy

Background Chronic allograft nephropathy is the major cause of progressive renal failure in renal transplant recipients. It has no definitive treatmen t. Methods. One hundred eighteen renal transplant recipients with declining ki dney function and biopsy-proven chronic allograft nephropathy had their cyc losporine or tacrolimus dose reduced or discontinued with either the additi on or continuation of mycophenolate mofetil and low-dose steroids at a mean of 853.3 days post-transplantation. Their renal function was modeled befor e and after this intervention by two methods: A least-square regression was used to assess the decay of renal function after the intervention and to c ompare that with the slope pre-intervention, whereas a hinge regression lin e method was used to assess the correlation of the intervention with the in flection point and the impact of the intervention on the decay of renal fun ction. Mean follow-up was 651.0 days after the intervention. Serum creatini ne at the time of intervention was 2.5 +/- 0.9 mg/dL in the reduced dose cy closporine (N = 67) and reduced dose tacrolimus (N = 33) groups, and was 2. 7 +/- 0.7 mg/dL in the group with discontinued calcineurin inhibitor (N = 1 8). Results. Using the least-square method, 91.7% of the no calcineurin inhibit or group, 51.6% of the reduced dose cyclosporine group, and 59.3% of the re duced dose tacrolimus group had improved or lack of deterioration in slope after the intervention. Using the hinge regression line method, there was a statistically significant correlation of the inflection point with the int ervention (P = 0.001). Moreover, there was a similar relationship with stab ilized or improved graft function observed with the hinge regression line m ethod and the least-square method, as 72.2% of the calcineurin inhibitor wi thdrawal group, 54.4% of reduced-dose cyclosporine group, and 40% of the re duced-dose tacrolimus group had improved the slope of decay of renal functi on or lack of deterioration after the inflection point. The difference betw een the calcineurin inhibitor withdrawal group and the reduced-dose cyclosp orine/tacrolimus groups on the decay in renal function was significant (P = 0.038) with the least-square method and nearly significant (P = 0.056) usi ng the hinge regression line method. Conclusion. This intervention was safe, well tolerated, and associated with a minimal risk of acute rejection. We conclude that the reduction and poss ible withdrawal of calcineurin inhibitors may be necessary to slow the rate of loss of renal function in patients with chronic allograft nephropathy a nd deteriorating renal function.