The Role of Renal Transplantation in Systemic AL Amyloidosis.

Abstract

Kidneys are the commonest site of amyloid deposition in AL amyloidosis (AL) and many patients present in advanced renal failure. Successful treatment of the underlying plasma cell dyscrasia may not prevent development of end stage renal failure and dialysis dependence. Even in the presence of good clonal response the prognosis of these patients on dialysis is poor with mortality being 3 times that for patients with diabetes (UK renal registry data 2003). Renal transplantation is controversial due to the systemic and progressive nature of AL amyloidosis. We report the experience with renal transplantation in 16 patients with AL seen at the National Amyloidosis Centre UK between 1986 and 2000. All patients had histologically proven amyloidosis with an underlying plasma cell dycrasia. None of the patients had extra-renal organ dysfunction. Median age at diagnosis of AL was 64 years (range 49–74) with 3 males and 13 females. 15 (93%) had monoclonal gammopathy as the underlying clonal disorder while 1 (7%) patient had Waldenstroms macroglobulinaemia. The median time from diagnosis of renal failure to renal transplantation was 5.5 yrs (range 0.3–17) including a median of 1.7 yrs on dialysis. Median age at renal transplantation was 56yrs (42–67). There were 2 (12%) live related renal transplants and 14 (88%) from cadaveric donors; there were no procedure-related deaths and none had primary graft non-function. Graft function remains well-preserved with the median creatinine clearance at last follow-up was 41.6 ml/min (range 25.1–68); the only cause of graft failure was death. 13 patients received cytotoxic treatment as follows: autologous stem cell transplantation (ASCT) 3 (18%), VAD chemotherapy 5 (31%), melphalan and prednisone 4 (25%), chlorambucil 1 (6%). 2 (15%) had a partial response to treatment while 11 (84%) had no response (this included the three patients with ASCT). The median age at death was 71.4 yrs. Six patients have died, all of progressive multi-organ amyloidosis, at a median 7.5yrs from renal transplantation (which is 12.2 yrs and 12.9 yrs respectively from the diagnosis of amyloidosis and ESRF). Four of these patients had evidence of amyloid accumulation in their renal graft. There was no significant difference in the median survival of patients with recurrent amyloid in the graft versus those without (p=0.78) and the only cause of graft loss was death with a functioning graft. The patients without amyloid in the graft had a trend for better OS (median not reached vs 12.9 yrs) and survival from renal transplantation (7.59 yrs vs. 5.5 yrs). In summary, this study shows that the overall survival of patients with predominant renal AL who underwent renal transplantation was remarkably good. Renal allograft survival was 7.4 yrs (median) despite a very poor haematological response to treatment in many patients. This study suggests that renal transplantation may have been underutilized in AL amyloidosis and should be considered in selected patients.