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Background: Recent advances in the treatment of immunoglobulin light chain amyloidosis (AL) have dramatically improved survival. Kidney transplantation (KTx) has become more common but the long-term outcomes remain unknown and it is the objective of this study., Methods: Nineteen patients with AL underwent living (n = 18) or deceased (n = 1) KTx at our institution from 1999 to 2008 (median age 57 years, six women). The primary end points were patient and kidney allograft survival and recurrence of AL in the allograft. The secondary end point was kidney transplant rejection. Outcome data were stratified according to three treatment modalities: renal transplantation followed by autologous stem cell transplantation (ASCT) (Group 1, n = 8), ASCT followed by renal transplantation (Group 2, n = 6) and renal transplantation after complete remission achieved with nonmyeloablative therapy (Group 3, n = 5)., Results: The median follow-up was 41.4 months. At the time of study, 79% were still alive. Median graft survival did not differ from median overall survival. There was no difference in survival rates between the treatment groups. Five patients had a cellular rejection. Two of the three patients with a rejection in Group 1 died but neither patient with rejection in Groups 2 and 3. Recurrent amyloidosis was diagnosed by biopsy in one patient in Group 2 (preceding ASCT) and in another patient in Group 3., Conclusions: KTx can be successfully performed in AL patients in complete hematologic response and meet the usual KTx selection criteria. Outcomes appear similar whether hematologic response was achieved with ASCT or by nonmyeloablative therapy.

Background: Late graft failure (LGF) is believed to be the consequence of immunologic and nonimmunologic insults leading to progressive deterioration in kidney function. We studied recipients with new onset late kidney graft dysfunction (n=173) to determine the importance of C4d staining and circulating donor-specific antibody (DSA) in subsequent LGF., Methods: One hundred seventy-three subjects transplanted before October 1, 2005 (mean time after transplant 7.3+/-6.0 years) had a baseline serum creatinine level of 1.4+/-0.3 mg/dL before January 1, 2006 and underwent biopsy for new onset graft dysfunction after that date (mean creatinine at biopsy 2.7+/-1.6 mg/dL). Statistical analysis was based on central DSA and blinded pathology determinations., Results: Subjects were divided into four groups based on C4d and DSA: no C4d, no DSA (group A; n=74); only DSA (group B; n=31); only C4d (group C; n=28); and both C4d and DSA (group D; n=40). Among DSA+ recipients (groups B and D), group D had broader reactivity and a stronger DSA response. After 2 years, groups C and D (C4d+) were at significantly greater risk for LGF than groups A and B. Adjusting for inflammation (Banff i, t, g, and ptc scores) did not change the outcome. Local diagnosis of calcineurin inhibitor nephrotoxicity was spread across all four subgroups and did not impact risk of LGF., Conclusions: Evidence of antibody-mediated injury (DSA or C4d) is common (57%) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.

Death with function causes half of late kidney transplant failures, and cardiovascular disease (CVD) is the most common cause of death in these patients. We examined the use of potentially cardioprotective medications in a prospective observational study at seven transplant centers in the United States and Canada. Among 935 patients, 87% received antihypertensive medications at both 1 and 6 months after transplantation. Similar antihypertensive regimens were used for patients with and without diabetes and CVD, but with wide variability among centers. In contrast, while 44% of patients were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) at the time of transplantation, the proportion taking these agents dropped to 12% at month 1, then increased to 24% at 6 months. Fewer than 30% with CVD or diabetes received ACEI/ARB therapy 6 months posttransplant. Aspirin use was uncommon (<40% of patients). Even among those with diabetes and/or CVD, fewer than 60% received aspirin and only half received a statin at 1 and 6 months. This study demonstrates marked variability in the use of cardioprotective medications in kidney transplant recipients, a finding that may reflect, among several possible explanations, clinical uncertainty due the lack of randomized trials for these medications in this population.