Despite having a much higher likelihood of DGF, obese transplant recipients have only a slightly increased risk of graft loss and experience similar survival to recipients with normal BMI.

Consistent with several other European studies, IgA nephropathy was the most common primary glomerular disease in this UK region. The diagnosis of FSGS was uncommon with no evidence of a rise in incidence.

Dense deposit disease is a rare glomerulonephritis caused by uncontrolled stimulation of the alternative complement pathway. Allograft survival after kidney transplantation is significantly reduced by the high rate of disease recurrence. No therapeutic interventions have consistently improved outcomes for patients with primary or recurrent disease. This is the first reported case of recurrent dense deposit disease being managed with eculizumab. Within 4 weeks of renal transplantation, deteriorating graft function and increasing proteinuria were evident. A transplant biopsy confirmed the diagnosis of recurrent dense deposit disease. Eculizumab was considered after the failure of corticosteroid, rituximab and plasmapheresis to attenuate the rate of decline in allograft function. There was a marked clinical and biochemical response following the administration of eculizumab. This case provides the first evidence that eculizumab may have a place in the management of crescentic dense deposit disease. More information is necessary to clarify the effectiveness and role of eculizumab in dense deposit disease but the response in this patient was encouraging. The results of clinical trials of eculizumab in this condition are eagerly awaited. Key words: Dense deposit disease, eculizumab, kidney transplantAbbreviations: aHUS, atypical hemolytic uremic syndrome; ACR, albumin:creatinine ratio; C3NF, complement factor 3 nephritic factor; C3, complement factor 3; C4, complement factor 4; C5, complement factor 5; DDD, dense deposit disease; ESRD, end stage renal disease; fB, complement factor B; fD, complement factor D; GBM, glomerular basement membrane; MAC, membrane attack complex; MPGN II, membranoproliferative glomerulonephritis type II; PNH, paroxysmal nocturnal hemoglobinuria; TMA, thrombotic microangiopathy; UNOS, United Network for Organ Sharing.

BACKGROUND In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection. METHODS We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 common gene-intersecting deletion polymorphisms in a cohort of kidney transplant recipients. In the second stage, we replicated our findings in three independent cohorts of donor–recipient pairs. We defined genomic collision as a specific donor–recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. Identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays, and Western blot analyses. RESULTS In the discovery cohort, which included 705 recipients, we found a significant association with allograft rejection at the LIMS1 locus represented by rs893403 (hazard ratio with the risk genotype vs. nonrisk genotypes, 1.84; 95% confidence interval [CI], 1.35 to 2.50; P= 9.8×10−5). This effect was replicated under the genomic-collision model in three independent cohorts involving a total of 2004 donor–recipient pairs (hazard ratio, 1.55; 95% CI, 1.25 to 1.93; P = 6.5×10−5). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the nonrisk genotype (hazard ratio, 1.63; 95% CI, 1.37 to 1.95; P = 4.7×10−8). We identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses. CONCLUSIONS We found that the LIMS1 locus appeared to encode a minor histocompatibility antigen. Genomic collision at this locus was associated with rejection of the kidney allograft and with production of anti-LIMS1 IgG2 and IgG3. (Funded by the Columbia University Transplant Center and others.)

Among kidney transplant donors, the CAV1 rs4730751 SNP was significantly associated with allograft failure in 2 independent cohorts.