Glomerulonephritis: post-infectious and IgA dominant

Srinivasaraghavan R, et al. IgA dominant post-infectious glomerulonephritis in a 12-year-old child. Indian J Pediatr. 2015 Aug 25. [Epub ahead of print]

Predisposing conditions for IgA-dominant PIGN include old age, diabetes, Staphylococcus aureus infections, malignancy, intravenous drug abuse, alcoholism, HIV infection and atopic dermatitis [1]. The histopathological features of IgA-dominant PIGN are similar to classical post-streptococcal glomerulonephritis, except that there is co-dominant IgA and IgG deposition with stronger staining for C3 compared to IgA [3]. IgA-dominant PIGN has been reported only twice below 18 y of age; the youngest being a 16-y-old child [4]. There is no consensus on management of this entity. Many authors have suggested antibiotics for associated urinary tract infections or systemic infections [5]. IgA-dominant PIGN has been reported in the absence of systemic infections too, as in our case [2]. Steroids are indicated in the presence of RPGN [4, 5]. Despite immunosuppressive therapy and/or antibiotics, only 16 % of adults had complete renal recovery [1].

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Couser WG, Johnson RJ. The etiology of glomerulonephritis: roles of infection and autoimmunity. Kidney Int. 2014 Nov;86(5):905-14.

Despite major advances in understanding genetic predispositions (‘first hits’), pathogenic immune responses, and the mediators of tissue injury in glomerulonephritis (GN), there remains a dearth of knowledge about the etiologic events, or ‘second hits’, which trigger these diseases. This paper reviews evidence that infections initiate most forms of GN through numerous simultaneous and/or sequential pathways that begin with activation of the innate immune response and lead to autoimmunity. These pathways include immune dysregulation, adjuvant or bystander effects, epitope spreading, molecular mimicry, epitope conformational changes, and antigen complementarity that, in genetically susceptible individuals, result in the nephritogenic autoimmune responses that underlie GN. Infections may also have direct effects on glomerular cells. Rapid expansion in knowledge of the microbiome and its role in health and disease, as well as systems biology approaches to glomerular disease offer the potential to develop preventive approaches to GNs that can now be treated only with immunosuppression.

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Stratta P,  et al. New trends of an old disease: the acute post infectious glomerulonephritis at the beginning of the new millenium. J Nephrol. 2014 Jun; 27(3): 229-39.

The association between acute renal disease and infection has been known since the mid ‘800s: acute post-infectious glomerulonephritis (PIGN) is a reactive immunological process against the kidney secondary to an infection, classically caused by a Streptococcus. The typical clinical presentation of PIGN is an acute nephritic syndrome with macro- or microscopic hematuria, proteinuria, hypertension, edema and renal function impairment of variable degree. The histology is characterized by an intracapillary glomerular proliferation, but may rarely be associated with an extracapillary proliferation. The classical childhood form is still present nowadays, even with severe cases, in developing countries, while in the last decades it almost disappeared in industrialized countries, where post-infectious GN are often found in elderly patients with multiple comorbidities. These clinical variants are usually related to other infective agents, like Staphylococcus aureus, both methicillin resistant (MRSA) and susceptible, and may be characterized by an IgA-dominant deposition. Kidney biopsy is rarely needed, especially in the child, while in the adult or old patient a biopsy is warranted if there is an atypical presentation or evolution, like rapidly progressive renal failure, absent or delayed function recovery, persisting low C3, nephrotic range proteinuria and persisting high proteinuria. Current therapy strategies rely on culture-guided systemic antibiotics, especially in the old patient, in which MRSA are relatively frequent, support therapy and only in very selected cases on steroids. These latter cases include the rare PIGN with crescents and those with a severe interstitial inflammation.

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Nasr SH, D’Agati VD. IgA-dominant postinfectious glomerulonephritis: a new twist on an old disease. Nephron Clin Pract. 2011;119(1):c18-25; discussion c26.

IgA-dominant acute postinfectious glomerulonephritis (APIGN) is an increasingly recognized morphologic variant of APIGN, particularly in the elderly. In contrast to classic APIGN, in which there is typically glomerular deposition of IgG and C3 or C3 only, IgA is the sole or dominant immunoglobulin in IgA-dominant APIGN. Because the vast majority of reported cases occur in association with staphylococcal infections, the alternative designation ‘IgA-dominant acute poststaphylococcal glomerulonephritis’ has been applied. Diabetes is a major risk factor, likely reflecting the high prevalence of staphylococcal infection in diabetics, particularly involving skin. Patients typically present with severe renal failure, proteinuria and hematuria. Prognosis is guarded with less than a fifth of patients fully recovering renal function. This variant of APIGN must be distinguished from IgA nephropathy. Features that favor IgA-dominant APIGN over IgA nephropathy include initial presentation in older age or in a diabetic patient, acute renal failure, intercurrent culture-documented staphylococcal infection, hypocomplementemia, diffuse glomerular endocapillary hypercellularity with prominent neutrophil infiltration on light microscopy, stronger immunofluorescence staining for C3 than IgA, and the presence of subepithelial humps on electron microscopy. The pathogenetic mechanism of selective IgA deposition in patients with poststaphylococcal glomerulonephritis likely involves specific host responses to the inciting pathogen.

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Barratt J, Feehally J. Primary IgA nephropathy: new insights into pathogenesis. Semin Nephrol. 2011 Jul;31(4):349-60.

Since its first description more than 40 years ago, IgA nephropathy has become the most common pattern of primary glomerulonephritis identified in all areas of the world where renal biopsy is routinely performed. This review discusses advances in our understanding of the pathogenesis of IgA nephropathy, principally focusing on work published in the past 5 years. It has been recognized for some time that one of the most consistent features of IgA nephropathy is an alteration in the complement of serum IgA1 O-glycoforms, with an overrepresentation of poorly galactosylated IgA1 O-glycoforms both in the serum and mesangial deposits of patients with IgA nephropathy. New data suggest that poorly galactosylated IgA1 O-glycoforms might act either as autoantigens driving the formation of glycan-specific antibodies, or antigens for cross-reactive antimicrobial antibodies. Formation of these circulating and mesangial IgA-containing immune complexes appears pivotal to the pathogenesis of IgA nephropathy and there is strong in vitro data to support their role in activation of mesangial cells, induction of podocyte injury, and activation of proximal tubular epithelial cells. Genetic factors are likely to influence many facets of pathogenesis both in primary and familial IgA nephropathy, however, to date work in this area has failed to identify consistent candidate genes.

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More PubMed results on IgA nephropathy and post-infectious glomerulonephritis.

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