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      Early post-transplant serum IgA level is associated with IgA nephropathy recurrence after kidney transplantation

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          Abstract

          IgA nephropathy (IgAN), the most frequent primary glomerulonephritis, affects young patients and is associated with a high risk of progression to end-stage renal disease. Consequently, patients with IgAN constitute an important proportion of candidates for kidney transplantation. Several studies showed a significant risk of IgAN recurrence on kidney graft, but the risks factors for recurrence remain to be accurately evaluated. Indeed, early identification of at risk patients may allow the optimization of treatment and the reduction of recurrence rate on the graft. In the present work, we studied the relationship between post-transplant serum IgA (sIgA) levels and the risk of IgAN recurrence after kidney transplantation. Recipients with IgAN had higher levels of sIgA as compared to patients with other nephropathies (p<0.05). The prevalence of IgAN recurrence was 20.8% during the period of analysis (mean follow-up of 6 ± 3.2 years). Serum IgA levels at M6, M12 and M24 post-transplant were significantly higher in patients with IgAN recurrence as compared to those without (p = 0.009, p = 0.035 and p = 0.029, respectively). Using receiver operating curve (ROC), sIgA at M6 and M12 post-transplant were significantly associated with IgAN recurrence (AUC = 0.771, p = 0.004 and AUC = 0.767, p = 0.016, respectively), while serum creatinine and proteinuria were not. Serum IgA level at month 6 was significantly associated with the occurrence of post-transplant IgA recurrence, whether it was analyzed as a continuous or a categorical variable. After successive adjustment on age, gender and proteinuria, sIgA remained a significant risk factor of post-transplant IgAN recurrence. Finally, survival free of IgAN recurrence was significantly better in patients with sIgA<222 mg/dL at month 6 as compare to IgAN patients with sIgA≥222 mg/dL (p = 0.03). Thus, the present work supports a link between post-transplant sIgA levels and IgAN recurrence and suggests that sIgA may be a valuable predictive biomarker of IgAN recurrence in kidney transplant recipients.

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          Most cited references 17

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          Predicting the risk for dialysis or death in IgA nephropathy.

          For the individual patient with primary IgA nephropathy (IgAN), it remains a challenge to predict long-term outcomes for patients receiving standard treatment. We studied a prospective cohort of 332 patients with biopsy-proven IgAN patients followed over an average of 13 years. We calculated an absolute renal risk (ARR) of dialysis or death by counting the number of risk factors present at diagnosis: hypertension, proteinuria ≥1 g/d, and severe pathologic lesions (global optical score, ≥8). Overall, the ARR score allowed significant risk stratification (P < 0.0001). The cumulative incidence of death or dialysis at 10 and 20 years was 2 and 4%, respectively, for ARR=0; 2 and 9% for ARR=1; 7 and 18% for ARR=2; and 29 and 64% for ARR=3, in adequately treated patients. When achieved, control of hypertension and reduction of proteinuria reduced the risk for death or dialysis. In conclusion, the absolute renal risk score, determined at diagnosis, associates with risk for dialysis or death. Copyright © 2011 by the American Society of Nephrology
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            Posttransplant recurrence of primary glomerulonephritis.

            All forms of primary GN may recur after kidney transplantation and potentially jeopardize the survival of the graft. IgA nephritis (IgAN) may recur in approximately one third of patients, more frequently in younger patients and in those with a rapid progression of the original disease. However, with the exception of few patients with rapid progression, there is no evidence that recurrence of IgAN has a deleterious effect on graft survival at least up to 10 years. Recurrence of focal segmental glomerulosclerosis (FSGS) is often associated with nephrotic proteinuria and is more frequent in children, in patients with rapid progression of the original disease, and in those who lost a previous transplant from recurrence. The natural course of recurrent FSGS is usually unfavorable. Early and intensive plasmapheresis may obtain complete or partial response in several patients. Good results have also been reported with rituximab. Idiopathic membranous nephropathy (IMN) may recur in 30% to 40% of patients. The graft survival in patients with IMN is not different than that of patients with other renal diseases. Good results with rituximab have been reported. Membranoproliferative GN (MPGN) may recur in 27% to 65% of patients. The recurrence is more frequent and the prognosis is more severe in type II MPGN. Although recurrent GN is relatively frequent and may worsen the outcome of renal allografts in some patients, its effect is diluted by several other risk-factors that may have a greater effect than recurrent GN on the long-term graft survival.
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              Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes.

              IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, frequently leads to end-stage renal disease and kidney transplantation. However, disease recurrence often occurs after transplantation. Here we evaluated the predictive value of three markers for IgAN recurrence: the presence of galactose-deficient IgA1, IgG anti-IgA autoantibodies, and IgA-soluble (s) CD89 complexes. This was analyzed in 38 kidney transplant recipients with IgAN recurrence and compared with 22 patients transplanted for IgAN but without recurrence and with 17 healthy controls. Pre-transplantation galactose-deficient IgA1 serum levels were significantly higher in the recurrence compared with the no recurrence or control groups. IgA-IgG complexes were significantly elevated in the recurrence group. Both the recurrence and no recurrence groups had increased values of IgA-sCD89 complexes compared with healthy controls, but values were significantly lower in patients with recurrence compared with no recurrence. Areas under the receiver operating curve of the markers in pre-transplantation sera were 0.86 for galactose-deficient-IgA, 0.82 for IgA-IgG, and 0.78 for sCD89-IgA; all significant. Disease recurrence was associated with decreased serum galactose-deficient IgA1 and appearance of mesangial-galactose-deficient IgA1 deposits, whereas increased serum IgA-sCD89 complexes were associated with mesangial sCD89 deposits. Thus, galactose-deficient-IgA1, IgG autoantibodies, and IgA-sCD89 complexes are valuable biomarkers to predict disease recurrence, highlighting major pathogenic mechanisms in IgAN.
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                Author and article information

                Contributors
                Role: Data curationRole: Writing – original draftRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 April 2018
                2018
                : 13
                : 4
                Affiliations
                [1 ] LUNAM Université, Angers, France
                [2 ] Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France
                [3 ] Département de pathologie cellulaire et tissulaire, CHU Angers, Angers, France
                INSERM1163, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Article
                PONE-D-17-38781
                10.1371/journal.pone.0196101
                5919069
                29694420
                © 2018 Garnier et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 4, Tables: 3, Pages: 11
                Product
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Proteinuria
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Proteinuria
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Renal Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Urinary System Procedures
                Renal Transplantation
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Creatinine
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Immunosuppressives
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biopsy
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Transplantation Immunology
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Transplantation Immunology
                Medicine and Health Sciences
                Immunology
                Clinical Immunology
                Transplantation Immunology
                Custom metadata
                All relevant data are within the paper.

                Uncategorized

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