IgA Nephropathy

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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“…It is characterized by a highly variable course ranging from a totally benign condition (2) to ESRD (3,4).…”

Section: Introductionmentioning

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

181

162

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“…Immunoglobulin A nephropathy (IgAN), an immune complex-mediated glomerulonephritis, is the most common form of primary glomerulonephritis worldwide and is characterized by deposits of IgA as either the dominant or codominant immunoglobulin (1,2). Proteinuria is regarded as a risk factor for an unfavorable renal prognosis and the reduction of proteinuria is considered an important therapeutic goal in clinical practice (3–5).…”

Section: Introductionmentioning

confidence: 99%

Continuation of immunosuppressive treatment may be necessary in IgA nephropathy patients with remission of proteinuria: Evaluation by repeat renal biopsy

Luo

Yao

et al. 2013

Experimental and Therapeutic Medicine

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The present study aimed to evaluate the effects of an individualized, low-dose multi-drug immunosuppressive regimen for the treatment of immunoglobulin A nephropathy (IgAN). A preliminary investigation of the course of IgAN following immunosuppressive treatment was conducted based on repeat renal biopsies. Clinical and pathological data of 17 patients with IgAN who received repeat renal biopsies were analyzed retrospectively. In addition to basic treatment, 16 patients regularly received an individualized low-dose immunosuppressive regimen according to their clinical manifestations and pathological patterns following the first biopsy. Clinical parameters, including 24-h urinary protein excretion and levels of serum albumin, uric acid and total cholesterol were collected. Glomerular deposits of IgA and C3, as well as the activity and chronicity indexes of renal lesions were evaluated by semi-quantitative methods. The 24-h urinary protein excretion of the patients decreased significantly from the first biopsy (2.53±2.17 g/day) to the repeated biopsy (0.26±0.55 g/day) (P<0.001). Deposits of IgA and C3 in the glomerulus were persistent, but were reduced in quantity at the second biopsy. Although active renal lesions were observed in the majority of patients, the activity index decreased significantly from 3.18±1.33 prior to therapy to 2.47±0.80 following therapy (P<0.05), while the chronicity index did not change significantly (2.59±2.00 versus 2.76±1.89, respectively). The individualized, low-dose multi-drug immunosuppressive regimen used in the present study significantly minimized proteinuria, stabilized renal function and alleviated histological lesions in patients with IgAN without causing overt adverse effects during the short-term follow-up. In addition to proteinuria, renal pathological changes should be appraised when considering the withdrawal of immunosuppressants from IgAN treatment.

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“…IgA nephropathy (IgAN) is an immune complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits accompanied by a variety of lesions identified histopathologically in the absence of systemic disease (1). It has been demonstrated that IgAN is a worldwide disease causing end-stage renal disease (ESRD) in up to 15-20% of affected patients within 10 years from the apparent onset of disease and in up to 30-40% of individuals within 20 years from diagnosis (2,3), and it is especially frequent in the East among the Chinese and Japanese.…”

Section: Introductionmentioning

confidence: 99%

Antithrombotic Drug Therapy for IgA Nephropathy: A Meta Analysis of Randomized Controlled Trials

Liu

Geng

Xin³

et al. 2011

Intern. Med.

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Background Antithrombotic agents, including antiplatelet agents, anticoagulants and thrombolysis agents, have been widely used in the management of immunoglobulin A (IgA) nephropathy in Chinese and Japanese populations. To systematically evaluate the effects of antithrombotic agents for IgA nephropathy. Methods Data sources consisted of MEDLINE, EMBASE, the Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodicals Databases (CNKI) and Japana Centra Revuo Medicina (http://www.jamas.gr.jp) up to April 5, 2011. The quality of the studies was evaluated from the intention to treat analysis and allocation concealment, as well as by the Jadad method. Meta-analyses were performed on the outcomes of proteinuria and renal function. Results Six articles met the predetermined inclusion criteria. Antithrombotic agents showed statistically significant effects on proteinuria (p<0.0001) but not on the protection of renal function (p=0.07). The pooled risk ratio for proteinuria was 0.53, [95% confidence intervals (CI): 0.41-0.68; I 2 =0%] and for renal function it was 0.42 (95% CI 0.17-1.06; I 2 =72%). Subgroup analysis showed that dipyridamole was beneficial for proteinuria (p=0.0003) but had no significant effects on protecting renal function. Urokinase had statistically significant effects both on the reduction of proteinuria (p=0.0005) and protecting renal function (p<0.00001) when compared with the control group. Conclusion Antithrombotic agents had statistically significant effects on the reduction of proteinuria but not on the protection of renal function in patients with IgAN. Urokinase had statistically significant effects both on the reduction of proteinuria and on protecting renal function. Urokinase was shown to be a promising medication and should be investigated further.

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IgA Nephropathy

Cited by 672 publications

References 85 publications

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Association of C4d Deposition with Clinical Outcomes in IgA Nephropathy

Continuation of immunosuppressive treatment may be necessary in IgA nephropathy patients with remission of proteinuria: Evaluation by repeat renal biopsy

Antithrombotic Drug Therapy for IgA Nephropathy: A Meta Analysis of Randomized Controlled Trials

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