Prognostic Factors in Mesangial IgA Glomerulonephritis: An Extensive Study With Univariate and Multivariate Analyses

Alamartine, Éric; Sabatier, Jean-Charles; Guérin, Claude; Berliet, Jean-Marc; Berthoux, F

doi:10.1016/s0272-6386(12)80284-8

Cited by 251 publications

(166 citation statements)

References 31 publications

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“…By contrast, we demonstrate that chronicity factors, such as the percentage of interstitial fibrosis and of global sclerotic glomeruli, are unfavorable risk factors. These variables are usually described in other glomerulonephritis, particularly IgA nephropathy (32,35,40,41).…”

Section: Discussionmentioning

confidence: 99%

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Henoch-Scho[Combining Diaeresis]nlein Purpura in Adults

Pillebout¹,

Thervet²,

Hill³

et al. 2002

Journal of the American Society of Nephrology

490

439

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Abstract. Henoch-Schönlein Purpura nephritis (HSPN) has been extensively studied in children but, its natural history in adults is much less known. A cohort of 250 adults suffering HSP was retrospectively analyzed for a median follow-up period of 14.8 yr. All patients had biopsies consistent with HSP (predominant IgA mesangial deposits) associated with purpura, bowel angina, and/or abdominal pain. At presentation, palpable purpura was present in 96% of patients, and arthritis was reported in 61%, and gastrointestinal involvement in 48%. Thirty-two percent of the patients showed renal insufficiency (Creatinine clearance [CrCl] Ͻ50 ml/min), usually associated with proteinuria (99%) and/or hematuria (93%). Endocapillary glomerulonephritis was the most frequent lesion on renal biopsy (61%). At the end of follow-up, patient survival was only 74%. The first cause of death was carcinoma (most of them of respiratory or digestive tract). Regarding renal function, 11% of patients reached end-stage renal failure, 13% exhibited severe renal failure (CrCl Ͻ30 ml/min), and 14% moderate renal insufficiency (CrCl Ͻ50 ml/min). Clinical remission defined as the absence of proteinuria, hematuria, and a normal renal function was achieved in only 20%. This is a retrospective study; therefore, it is not possible to demonstrate any steroid and/or cyclophosphamide efficacy in diminishing the incidence of renal insufficiency. Multivariate analysis demonstrated that renal function impairment and proteinuria level at presentation and, on renal biopsy, the degree of interstitial fibrosis, percentage of sclerotic glomeruli, and presence of glomeruli with fibrinoid necrosis were associated with a poor renal prognosis. The data indicate that clinical presentation of HSPN in adults is severe and its outcome relatively poor, worse than in children. Identification of clinical and histologic prognostic factors may permit the design of appropriate therapeutic prospective studies.Henoch-Schönlein purpura (HSP) is a leukocytoclastic vasculitis involving small vessels with the deposition of immune complexes containing IgA. It is characterized by the association of skin, joint, and gastrointestinal manifestations that may occur in successive episodes (1). In addition to these manifestations, renal involvement is common, and the long-term prognosis depends on its severity.HSP primarily affects children, and its incidence is approximately 15 cases/100,000 children per yr (2); it is less common in adults. Although HSP has been extensively studied in children, much less is known about its natural history in adults. Apart from a recent multicenter Italian study (3,4), data on this disease in adults are confined to small series with relatively short follow-up (5-15). In adults, however, the incidence of HSP and the severity of its clinical manifestations appear not to be the same as in children.The incidence of renal involvement in adults varies from 45 to 85% of cases, depending on the data for patients and the definition of renal involvement (16). Among c...

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Section: Discussionmentioning

confidence: 99%

“…In this respect, HSP nephropathy may resemble IgA nephropathy. Many authors indeed had initially reported a favorable outcome for IgA nephropathy until the point in time when follow-up was long enough to enable them to conclude that end-stage renal disease was a frequent complication (31)(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Henoch-Scho[Combining Diaeresis]nlein Purpura in Adults

Pillebout¹,

Thervet²,

Hill³

et al. 2002

Journal of the American Society of Nephrology

490

439

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“…As demonstrated by several studies, serum creatinine, proteinuria, and arterial hypertension at presentation are the strongest predictors of an unfavorable outcome (18)(19)(20)(21)(22)(23)(24). Among pathologic data, mesangial hypercellularity, glomerular sclerosis, interstitial fibrosis, and tubular atrophy have been recognized as independent predictors of renal failure (6).…”

Section: Discussionmentioning

confidence: 99%

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Espinosa¹,

Ortega²,

Sánchez³

et al. 2014

Clinical Journal of the American Society of Nephrology

177

162

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Background and objectives Several studies have suggested that activation of the complement system is a contributing pathogenic mechanism in IgA nephropathy (IgAN). C4d staining is an inexpensive and easy-toperform method for the analysis of renal biopsies. This study aimed to assess the clinical and prognostic implications of C4d staining in IgAN.Design, setting, participants, & measurements This retrospective cohort study included 283 patients with IgAN in 11 hospitals in Spain who underwent a renal biopsy between 1979 and 2010. The primary predictor was mesangial C4d staining. Secondary predictors included demographic, clinical, and laboratory characteristics, and Oxford pathologic classification criteria. The primary end point was the cumulative percentage of patients who developed ESRD, defined as onset of chronic dialysis or renal transplantation. C4d was analyzed by immunohistochemical staining using a polyclonal antibody. Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate the effect of C4d staining on renal survival.Results There were 109 patients (38.5%) and 174 patients (61.5%) who were classified as C4d positive and C4d negative, respectively. Renal survival at 20 years was 28% in C4d-positive patients versus 85% in C4d-negative patients (P,0.001). Independent risk factors associated with ESRD were as follows: proteinuria (hazard ratio [HR] per every 1 g/d increase. 1.16; 95% confidence interval [95% CI], 1.03 to 1.31; P=0.01), eGFR (HR per every 1 ml/min per 1.73 m 2 increase, 0.96; 95% CI, 0.94 to 0.97; P,0.001), T2 Oxford classification (tubular atrophy/ interstitial fibrosis, .50%; HR, 4.42; 95% CI, 1.40 to 13.88; P=0.01), and C4d-positive staining (HR, 2.45; 95% CI, 1.30 to 4.64; P=0.01).Conclusions C4d-positive staining is an independent risk factor for the development of ESRD in IgAN. This finding is consistent with the possibility that complement activation is involved in the pathogenesis of this disease.

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“…The study of Goto et al, in which 2283 Japanese patients were followed up for a median of 7.3 years, had the limitations inherent in a mail-based survey: namely, the authors could not collect complete data for about a quarter of the participants or check the quality of the datasets (2,28). Berthoux et al made a risk score from the data of 332 French patients for a median 11.3-year follow-up (8), but their score evaluated histologic lesions using their own original pathologic classification system (29,30), which is not generally accepted. Xie et al developed a risk score for predicting ESRD in 619 Chinese patients followed for an average of 3.4 years and showed that their score had a better predictive performance on their dataset than previously published risk scores (17).…”

Section: Variables Scoresmentioning

confidence: 99%

Development and Validation of a Prediction Rule Using the Oxford Classification in IgA Nephropathy

Tanaka

Ninomiya

Katafuchi

et al. 2013

Clinical Journal of the American Society of Nephrology

105

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SummaryBackground and objectives The risk assessment for developing ESRD remains limited in patients with IgA nephropathy (IgAN). The aim of this study was to develop and validate a prediction rule for estimating the individual risk of ESRD in patients with IgAN.Design, setting, participants, & measurements A total of 698 patients with IgAN diagnosed by renal biopsy at Kyushu University Hospital (derivation cohort) between 1982 and 2010 were retrospectively followed. The Oxford classification was used to evaluate the pathologic lesions. The risk factors for developing ESRD were evaluated using a Cox proportional hazard model with a stepwise backward elimination method. The prediction rule was verified using data from 702 patients diagnosed at Japanese Red Cross Fukuoka Hospital (validation cohort) between 1979 and 2002.Results In the derivation cohort, 73 patients developed ESRD during the median 4.7-year follow-up. The final prediction model included proteinuria (hazard ratio [HR], 1.30; 95% confidence interval [95% CI], 1.16 to 1.45, every 1 g/24 hours), estimated GFR (HR, 0.84; 95% CI, 0.74 to 0.96, every 10 ml/min per 1.73 m 2 ), mesangial proliferation (HR, 1.85; 95% CI, 1.10 to 3.11), segmental sclerosis (HR, 3.21; 95% CI, 1.37 to 7.51), and interstitial fibrosis/tubular atrophy (T1: HR, 5.30; 95% CI, 2.63 to 10.7; T2: HR, 20.5; 95% CI, 9.05 to 46.5) as independent risk factors for developing ESRD. To create a prediction rule, the score for each variable was weighted by the regression coefficients calculated using the relevant Cox model. The incidence of ESRD increased linearly with increases in the total risk scores (P for trend ,0.001). Furthermore, the prediction rule demonstrated good discrimination (c-statistic=0.89) and calibration (Hosmer-Lemeshow test, P=0.78) in the validation cohort.Conclusions This study developed and validated a new prediction rule using clinical measures and the Oxford classification for developing ESRD in patients with IgAN.

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Prognostic Factors in Mesangial IgA Glomerulonephritis: An Extensive Study With Univariate and Multivariate Analyses

Cited by 251 publications

References 31 publications

Henoch-Scho[Combining Diaeresis]nlein Purpura in Adults

Henoch-Scho[Combining Diaeresis]nlein Purpura in Adults

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Development and Validation of a Prediction Rule Using the Oxford Classification in IgA Nephropathy

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