Natural history of idiopathic IgA nephropathy: Role of clinical and histological prognostic factors

D’Amico, Giuseppe

doi:10.1053/ajkd.2000.8966

Cited by 437 publications

(335 citation statements)

References 40 publications

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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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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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“…Even though this was a prospective observational study, factors after the initial RCT period were difficult to control between the two groups. Therefore, proper analyses of long-term follow-up data are important to evaluate disease outcome and treatment effectiveness (13,14). Valid statistical evaluation using a multivariate Cox model was thought to work effectively in this study.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Results of a Randomized Controlled Trial in Childhood IgA Nephropathy

Kamei¹,

Nakanishi

Ito³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Children with IgA nephropathy showing diffuse (Ͼ80%) mesangial proliferation are at high risk for end-stage renal failure (ESRF). A previous controlled trial showed that combination therapy consisting of prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease reduces immunologic renal injury and prevents the progression of sclerosed glomeruli. The objective of this study was to evaluate the long-term effectiveness of combination therapy in children with IgA nephropathy showing diffuse mesangial proliferation.Design, setting, participants, & measurements A secondary analysis of a multicenter, randomized, controlled trial involving 78 children with IgA nephropathy who received either 2-year combination therapy or heparin-warfarin and dipyridamole (control) therapy was conducted.Results The median duration of observation was 10 years (range, 0.5 to 18). Two of 40 patients (5%) who received combination therapy and five of 34 patients (14.7%) who received control therapy developed ESRF. A Kaplan-Meier plot of renal survival showed that the outcomes of patients in the combined therapy group were better than those in the control therapy group (log-rank P ϭ 0.03). The 10-year renal survival probability of each group was 97.1% (95% confidence interval, 81.4 to 99.6%) and 84.8% (95% confidence interval, 55.4 to 95.5%), respectively. The Cox proportional hazards model showed that the 2-year combination therapy was significantly associated with renal survival in both univariate and multivariate analyses.Conclusions Two-year combination therapy not only ameliorated the activity of the acute phase of nephritis but also improved the long-term outcome of severe childhood IgA nephropathy.

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“…8 Among these pathological changes, renal arterio-arteriolosclerosis is important, because it is known to be related to renal function and prognosis. [9][10][11][12] However, whether clinical factors other than hypertension have an impact on renal arterioarteriolosclerosis remains to be elucidated. Therefore, we noted glucose metabolism/insulin resistance as a cause of renal arterioarteriolosclerosis in this study.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12] Hypertension is known to have an important function in the pathogenesis of renal arterio-arteriolosclerosis. [12][13][14] In clinical practice, however, the evidence of renal arterio-arteriolosclerosis is sometimes found even in renal biopsy specimens of patients without hypertension.…”

Section: Introductionmentioning

confidence: 99%

Postprandial hyperglycemia and hyperinsulinemia associated with renal arterio-arteriolosclerosis in chronic kidney disease

et al. 2010

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Hypertension has an important function in the formation of renal arterio-arteriolosclerosis. However, renal arterioarteriolosclerosis is sometimes found in biopsy specimens of normotensive patients, which indicates unknown factors may contribute to renal arterio-arteriolosclerosis. In this study, we aimed to evaluate the effects of glucose metabolism/insulin resistance on renal arterio-arteriolosclerosis. Forty-eight patients with biopsy-proven non-diabetic chronic glomerular disease were included. Renal arterio-arteriolosclerosis was evaluated as the percentage of vessels showing hyaline changes or wall thickening. We correlated renal arterio-arteriolosclerosis with clinical parameters including indices obtained by 75 g oral glucose tolerance test. Of the 48 patients, 30 had hypertension. The results of univariate analysis showed significant association of renal arterio-arteriolosclerosis with hypertension, increased serum creatinine (S-Cr), hypertriglyceridemia, increased 2-h plasma glucose (PG) and increased 2-h plasma insulin (PI). In stepwise multiple regression analysis, hypertension (b¼0.344, P¼0.009), S-Cr (b¼0.287, P¼0.03) and 2-h PG (b¼0.274, P¼0.03) were independently associated with renal arterioarteriolosclerosis. Eleven of the 30 hypertensive patients did not have renal arterio-arteriolosclerosis. The hypertensive patients with renal arterio-arteriolosclerosis showed significantly higher 2-h PG (134 ± 25 vs. 106 ± 26 mg per 100 ml, P¼0.008) and higher 2-h PI (67.7 ± 34.9 vs. 48.3 ± 30.0 lU ml À1 , P¼0.04) compared with those without renal arterio-arteriolosclerosis, but the difference in S-Cr was not significant. Postprandial hyperglycemia and hyperinsulinemia may contribute to the formation of renal arterio-arteriolosclerosis independently of hypertension.

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Natural history of idiopathic IgA nephropathy: Role of clinical and histological prognostic factors

Cited by 437 publications

References 40 publications

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Long-Term Results of a Randomized Controlled Trial in Childhood IgA Nephropathy

Postprandial hyperglycemia and hyperinsulinemia associated with renal arterio-arteriolosclerosis in chronic kidney disease

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