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Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides.

ABSTRACT: Background:Despite being the leading cause of graft failure, there is a lack of published data about the rates of rejection in kidney transplant patients with glomerulonephritis as the cause of end-stage renal disease. Methods:We examined all consecutive adult (>18 years) renal transplant recipients with biopsy-proven native renal glomerular disease who underwent kidney transplant between 1994 and 2013. Glomerulonephritis groups included were IgA nephropathy (IgAN) (N = 306), focal segmental glomerulosclerosis (FSGS) (N = 298), membranous nephropathy (MN) (N = 81), and lupus nephritis (LN) (N = 177). Results:In the total cohort of 862 patients, 363 patients had an episode of acute rejection during the follow-up period of 19 years (incidence rate of 7.2% per year). Forty-five of 81 patients with MN had an episode of acute rejection during the follow-up period. Patients with MN had significantly higher incidence of acute rejection (12.1 per 100 person years, P < 0.05) in comparison to IgAN (7.2 per 100 person years), FSGS (7.4 per 100 person years), and LN (7.9 per 100 person years). Patients with MN had 1.9 times higher risk of developing acute rejection after transplant in comparison to IgAN (P < 0.005). In patients with MN, 33 of 45 (73.3%) rejection events were acute cellular rejection, 8 (17.8%) of 45 were acute antibody-mediated rejection and 6 of 45 (13.3%) were combined cellular and antibody-mediated acute rejection. Despite higher rates of acute rejection, 10-year allograft survival was similar in all subgroups. Conclusions:Patients with MN have higher incidence of acute rejection after kidney transplant but have similar 10-year allograft survival in comparison to the other glomerular diseases like IgAN, FSGS, and LN.

SUBMITTER: Singh T

PROVIDER: S-EPMC5682767 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides.

Singh Tripti T Astor Brad B Zhong Weixiong W Mandelbrot Didier D Djamali Arjang A Panzer Sarah S

Transplantation direct 20171018 11

<h4>Background</h4>Despite being the leading cause of graft failure, there is a lack of published data about the rates of rejection in kidney transplant patients with glomerulonephritis as the cause of end-stage renal disease.<h4>Methods</h4>We examined all consecutive adult (>18 years) renal transplant recipients with biopsy-proven native renal glomerular disease who underwent kidney transplant between 1994 and 2013. Glomerulonephritis groups included were IgA nephropathy (IgAN) (N = 306), foca ...[more]

PMID: 29184911

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Project description:Rationale & objectiveDonor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation.Study designProspective cohort.Setting & participants862 deceased donors for 1,137 kidney recipients at 13 centers.ExposuresWe measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI.OutcomesThe primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year.Analytical approachMultivariable Fine-Gray models with death as a competing risk.ResultsMean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA.LimitationsBPAR was ascertained through for-cause biopsies, not surveillance biopsies.ConclusionsIn a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.

Project description:Background and objectivesThe current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes.Design, setting, participants, & measurementsUsing data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models.ResultsOf the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94).ConclusionsHLA-DQ mismatches are associated with acute rejection, independent of HLA-ABDR mismatches and initial immunosuppression. Clinicians should be aware of the potential importance of HLA-DQ matching in the assessment of immunologic risk in kidney transplant recipients.

Dataset Information

Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides.

Publications

Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides.

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