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IgA nephropathy (IgAN) is the most common primary glomerulonephritis, frequently leading to end-stage renal disease, as there is no disease-specific therapy. IgAN is diagnosed from pathological assessment of a renal biopsy specimen based on predominant or codominant IgA-containing immunodeposits, usually with complement C3 co-deposits and with variable presence of IgG and/or IgM. The IgA in these renal deposits is galactose-deficient IgA1, with less than a full complement of galactose residues on the O -glycans in the hinge region of the heavy chains. Research from the past decade led to the definition of IgAN as an autoimmune disease with a multi-hit pathogenetic process with contributing genetic and environmental components. In this process, circulating galactose-deficient IgA1 (autoantigen) is bound by antiglycan IgG or IgA (autoantibodies) to form immune complexes. Some of these circulating complexes deposit in glomeruli, and thereby activate mesangial cells and induce renal injury through cellular proliferation and overproduction of extracellular matrix components and cytokines/chemokines. Glycosylation pathways associated with production of the autoantigen and the unique characteristics of the corresponding autoantibodies in patients with IgAN have been uncovered. Complement likely plays a significant role in the formation and the nephritogenic activities of these complexes. Complement activation is mediated through the alternative and lectin pathways and probably occurs systemically on IgA1-containing circulating immune complexes as well as locally in glomeruli. Incidence of IgAN varies greatly by geographical location; the disease is rare in central Africa but accounts for up to 40% of native-kidney biopsies in eastern Asia. Some of this variation may be explained by genetically determined influences on the pathogenesis of the disease. Genome-wide association studies to date have identified several loci associated with IgAN. Some of these loci are associated with the increased prevalence of IgAN, whereas others, such as deletion of complement factor H-related genes 1 and 3, are protective against the disease. Understanding the molecular mechanisms and genetic and biochemical factors involved in formation and activities of pathogenic IgA1-containing immune complexes will enable the development of future disease-specific therapies as well as identification of non-invasive disease-specific biomarkers.

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and a common cause of end-stage renal disease. Evaluation of a kidney biopsy is necessary for diagnosis, with routine immunofluorescence microscopy revealing dominant or co-dominant IgA immunodeposits usually with complement C3 and sometimes IgG and/or IgM. IgA nephropathy reduces life expectancy by more than 10 years and leads to kidney failure in 20–40% of patients within 20 years of diagnosis. There is accumulating clinical, genetic, and biochemical evidence that complement plays an important role in the pathogenesis of IgA nephropathy. The presence of C3 differentiates the diagnosis of IgA nephropathy from the subclinical deposition of glomerular IgA. Markers for the activation of the alternative and mannan-binding lectin (MBL) pathways in renal-biopsy specimens are associated with disease activity and portend a worse renal outcome. Complement proteins in the circulation have also been evaluated in IgA nephropathy and found to be of prognostic value. Recently, genetic studies have identified IgA nephropathy-associated loci. Within these loci are genes encoding products involved in complement regulation and interaction with immune complexes. Put together, these data identify the complement cascade as a rational treatment target for this chronic kidney disease. Recent case reports on the successful use of humanized anti-C5 monoclonal antibody eculizumab are consistent with this hypothesis, but a better understanding of the role of complement in IgA nephropathy is needed to guide future therapeutic interventions.

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Background Nutrition is strongly linked with health outcomes in chronic kidney disease (CKD). However, few studies have examined relationships between dietary patterns and health outcomes in persons with CKD. Study Design Observational cohort study. Setting & Participants 3,972 participants with CKD (defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2 or an albumin-creatinine ratio ≥30 mg/g at baseline) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort study of 30,239 black and white adults at least 45 years of age. Predictors Five empirically derived dietary patterns identified via factor analysis: “Convenience” (Chinese and Mexican foods, pizza, other mixed dishes), “Plant-Based” (fruits, vegetables), “Sweets/Fats” (sugary foods), “Southern” (fried foods, organ meats, sweetened beverages), and “Alcohol/Salads” (alcohol, green-leafy vegetables, salad dressing). Outcomes All-cause mortality and end-stage renal disease (ESRD). Results A total of 816 deaths and 141 ESRD events were observed over approximately 6 years of follow-up. There were no statistically significant associations of Convenience, Sweets/Fats or Alcohol/Salads pattern scores with all-cause mortality after multivariable adjustment. In Cox regression models adjusted for sociodemographic factors, energy intake, co-morbidities, and baseline kidney function, higher Plant-Based pattern scores (indicating greater consistency with the pattern) were associated with lower risk of mortality (HR comparing fourth to first quartile, 0.77; 95%CI, 0.61–0.97) whereas higher Southern pattern scores were associated with greater risk of mortality (HR comparing fourth to first quartile, 1.51; 95%CI, 1.19–1.92). There were no associations of dietary patterns with incident ESRD in multivariable-adjusted models. Limitations Missing dietary pattern data, potential residual confounding from lifestyle factors. Conclusions A Southern dietary pattern rich in processed and fried foods was independently associated with mortality in persons with CKD. In contrast, a diet rich in fruits and vegetables appeared to be protective.