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Primary membrane nephropathy (PMN) and IgA nephropathy (IgAN) are the most common glomerular diseases in China. Because of different pathogenesis, prognosis is significantly different. When the two diseases coexist (PMN/IgAN), the clinicopathological manifestations and prognosis remain unclear. In the present study, we analyzed the clinicopathological characteristics of PMN/IgAN patients, with only IgA deposition (PMN/IgA deposition) patients as controls. Galactose-deficient IgA1(KM55) and M-type Phospholipase A2 Receptor(PLA2R), both in circulation and renal tissues, were detected. Furthermore, prognosis of PMN/IgAN was explored. We found that PMN/IgAN also had some clinical features of IgAN in addition to PMN, such as higher serum albumin, along with a similar heavy proteinuria and lower titers of serum anti-PLA2R antibody. The positive rate of glomerular KM55 in PMN/IgAN was 23.5% (20/85), and 0% (0/29) in PMN/IgA deposition. Among those glomerular KM55 positive patients, KM55 and IgA colocalized mainly along the glomerular mesangial and capillary areas. Unfortunately, there was no significant difference in serum level of Gd-IgA1 between KM55+ and KM55− subgroups in PMN/IgAN patients, similar to the PMN/IgA deposition group. Notably, glomerular KM55 positive may predict a poorer prognosis in PMN/IgAN patients. In conclusion, our study suggested that, when glomerular KM55 staining was positive, this special coexisting PMN/IgAN disorder was prone to have more characteristics of IgAN besides PMN, and may predict poorer prognosis, while the mechanism requires further investigation. [ABSTRACT FROM AUTHOR]

Primary membrane nephropathy (PMN) and IgA nephropathy (IgAN) are the most common glomerular diseases in China. Because of different pathogenesis, prognosis is significantly different. When the two diseases coexist (PMN/IgAN), the clinicopathological manifestations and prognosis remain unclear. In the present study, we analyzed the clinicopathological characteristics of PMN/IgAN patients, with only IgA deposition (PMN/IgA deposition) patients as controls. Galactose-deficient IgA1(KM55) and M-type Phospholipase A2 Receptor(PLA2R), both in circulation and renal tissues, were detected. Furthermore, prognosis of PMN/IgAN was explored. We found that PMN/IgAN also had some clinical features of IgAN in addition to PMN, such as higher serum albumin, along with a similar heavy proteinuria and lower titers of serum anti-PLA2R antibody. The positive rate of glomerular KM55 in PMN/IgAN was 23.5% (20/85), and 0% (0/29) in PMN/IgA deposition. Among those glomerular KM55 positive patients, KM55 and IgA colocalized mainly along the glomerular mesangial and capillary areas. Unfortunately, there was no significant difference in serum level of Gd-IgA1 between KM55+ and KM55− subgroups in PMN/IgAN patients, similar to the PMN/IgA deposition group. Notably, glomerular KM55 positive may predict a poorer prognosis in PMN/IgAN patients. In conclusion, our study suggested that, when glomerular KM55 staining was positive, this special coexisting PMN/IgAN disorder was prone to have more characteristics of IgAN besides PMN, and may predict poorer prognosis, while the mechanism requires further investigation.

Background: The clinicopathological significance of immunofluorescent findings in IgA nephropathy remains controversial.Methods: The relations of the deposition of IgA, IgG, IgM, C3, C1q and fibrinogen (Fib) with pathological findings, baseline clinical findings, and renal outcome were evaluated in 688 patients with IgA nephropathy. Pathological features included cellular or fibrocellular crescents, endocapillary or mesangial hypercellularity, segmental or global glomerulosclerosis and the Oxford classification.Results: The median age at biopsy was 30 years. There were 289 men. With 74 months median follow-up, 32% of patients received steroids. Twelve percent of patients developed end-stage renal disease (ESRD). The degree of IgA was closely related to the degree of C3, IgG and IgM deposition. The degree of IgA, C3, IgG and Fib deposition was significantly related to the percentage of glomeruli with crescent, endocapillary and mesangial hypercellularity. IgM deposition showed significant association with crescent, mesangial hypercellularity, segmental sclerosis, global glomerulosclerosis and tubular atrophy/interstitial fibrosis. In the patients treated with steroids, the risk for ESRD in patients with 2-3+ IgA deposition was significantly lower with reference of 1+ IgA deposition.Conclusion: We found the different roles of glomerular immune reactants' deposition in the inflammatory process from acute to chronic stage. IgA deposition together with IgG, Fib and C3 may produce acute inflammatory injury. IgM deposition might occur in the early stage of inflammation and remains until late sclerotic stage. The prominent deposition of IgA related to low risk for ESRD in patients who received steroids might suggest effectiveness of steroids in such patients. [ABSTRACT FROM AUTHOR]

Abstract IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, and disease recurrence often occurs after transplantation. On the other hands, Asymptomatic IgA deposition (IgAD) is occasionally observed in donated kidney. It is recognized that IgAD does not progress to IgAN, but the mechanism has not demonstrated yet. In IgAN, aberrant IgA1 O- glycan structure in the hinge region (HR) of serum IgA is suggested as one of the most convincing key mediators. However, little is known about IgA1 O- glycan structure in IgAD patients. Herein, we investigated the prevalence of IgAD in living renal transplant donors in our cohort. IgAD was observed in 21(13.0%) among 161 renal transplant donors and have statistically significant blood relationship with IgAN recipients (28.6% in relatives vs. 9.8% in non-relatives, respectively; p = 0.0073). Next, we evaluated the IgA1 O- glycan structure of serum IgA from IgAN recipients (n = 26), IgAD donors (n = 17), and non-IgAD helthy donors (n = 27) using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI–TOF MS). The numbers of GalNAc and Gal and the Gal/GalNAc ratio in the HR of the IgAN recipients had significantly lower comparing to the IgAD and non-IgAD healthy donors. The decreased Gal/GalNAc ratio in IgAN recipients means the increased ratio of galactose-deficient IgA1. To the best of our knowledge, this is the first report to compare the O -glycan structures in IgAN recipients and IgAD donors using MALDI–TOF MS. We concluded that IgAD was more common in IgAN related donors. Overall, decreased GalNAc and Gal contents in HR could play a material pathogenic role in IgAN. Highlights • IgA deposition (IgAD) was observed in 13.0% of renal transplant donors. • IgAD was often observed in blood relatives with IgA nephropathy (IgAN) recipients. • We analyzed IgA1 O-glycosylation in IgAN and IgAD with mass spectrometry. • The numbers of O-glycans in IgAN recipients were significantly lower than IgAD. • O-glycosylation pattern in IgAD donors were similar with healthy donors. [ABSTRACT FROM AUTHOR]

We examined the pathogenesis of glomerular damage in Th2 type-dependent GATA-3 transgenic (GATA-3 Tg) mice with IgA nephropathy (IgAN). GATA-3 Tg mice were immunized orally using OVA plus cholera toxin B (CTB), and measurement of the serum IgA antibody level and histopathological examination were performed. Marked increases in the serum levels of OVA-specific IgA antibody, IgA and IgG, C3 deposits analogous to those seen in IgAN, and expansion of the matrix in association with mesangial cell proliferation were observed. Furthermore, glomerular IgA deposits were co-localized with mannan-binding lectin (MBL) deposits, which might actually have been abnormal IgA deposits. In GATA-3/TCR-Tg mice that had been orally sensitized with CTB plus OVA and were re-stimulated with OVA in vitro, cultured Peyer’s patch cells showed the enhanced production of IL-5 and supernatants from cultures of spleen cells showed a reduction of TGF-β production with a simultaneous increase in IL-2 production and the recovery of IFN-γ formation. The amount of TGF-β produced by the spleen cells was found to be correlated with the amount of IFN-γ and IL-IL-2 produced by the cells. Also, the percentage of regulatory T cells (Treg) in the spleens of mice sensitized with OVA plus CTB was lower than that in mice orally sensitized with OVA alone. These results suggest that the increased production of IL-5 from Peyer’s patch cells (PPc) and the restored Th1-type immune response might cause the production of abnormal IgA and might induce the deposition of IgA in glomeruli. [ABSTRACT FROM AUTHOR]

Introduction Latent mesangial immunoglobulin A ( Ig A) deposition in the donated kidney has been investigated in the context of kidney transplantation. However, few studies have examined the impact of mesangial expansion accompanied with Ig A deposition. Therefore, we investigated the effects of latent Ig A deposition and mesangial expansion on transplant prognosis following living-donor kidney transplantation. Methods We retrospectively analyzed 68 consecutive adult living-donor kidney transplantations performed at Kagawa University Hospital. Biopsies were performed at pre-implantation and at one yr after transplantation. Results Twenty kidneys exhibited latent Ig A deposition in pre-implantation biopsies, including 14 with mesangial expansion. Latent Ig A deposition was not associated with renal function or donor urinalysis after donation, irrespective of mesangial expansion. Latent Ig A deposition was not significantly associated with graft survival rate, allograft function, abnormal urinalysis, or the recurrence of Ig A nephropathy, irrespective of mesangial expansion. At one yr after transplantation, Ig A deposition had disappeared in 14/20 allografts. Estimated glomerular function rate >40 mL/min/1.73 m2 was significantly associated with the disappearance of Ig A deposition. Conclusions The present study showed that latent Ig A deposition from the donor kidney, irrespective of mesangial expansion, does not affect transplant prognosis following living-donor kidney transplantation. [ABSTRACT FROM AUTHOR]

IgA nephropathy is the most common form of progressive glomerulonephritis although the pathophysiology of this nephropathy is unclear. The ddY mouse is a spontaneous animal model with variable incidence and extent of glomerular injury mimicking human IgA nephropathy. Here, we transplanted bone marrow cells from 20-week-old ddY mice with beginning or quiescent IgA nephropathy into irradiated similar ddY mice, C57Bl/6 (Th1 prone) mice, or BALB/c (Th2 prone) mice. Serum IgA/IgG complex and Th1/Th2 polarization of spleen cells was determined by enzyme-linked immunosorbent assay and confirmed by fluorescent cytometric analysis. The ddY mice with commencing IgA nephropathy demonstrated strong polarization toward Th1, while those with quiescent disease were Th2 polarized. Serum levels of IgA/IgG2a immune complex significantly correlated with the severity of the glomerular lesions. Bone marrow taken from mice with commencing IgA nephropathy conferred IgA nephropathy with Th1 polarization in recipient-quiescent mice, while transplantation from the quiescent mice ablated glomerular injury and mesangial IgA/IgG deposition in those commencing IgA disease. However, adoptive transfer of CD4+ T cells from those whose disease began failed to induce any IgA deposition or renal injury. Our study suggests that bone marrow cells, presuming IgA producing cells, may initiate this disease. Th1 cells may be involved in the pathophysiology of the disease after glomerular IgA deposition.Kidney International (2007) 72, 319–327; doi:10.1038/sj.ki.5002300; published online 9 May 2007 [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is an important cause of progressive kidney disease with 25–30% of patients developing end-stage renal disease within 20 years of diagnosis. There is still no treatment to modify mesangial IgA deposition and available treatments are those extrapolated from the management of other patterns of chronic glomerulonephritis. There remains no consensus on the use of immunosuppressive agents for treatment of progressive IgAN and this is compounded by the relative lack in IgAN of randomized controlled trials relevant to current clinical practice. Patients with recurrent macroscopic hematuria or isolated microscopic hematuria and proteinuria <1 g/24 h require no specific treatment. Those with nephrotic syndrome and minimal change on renal biopsy should be managed as for minimal change nephropathy. There is no evidence to support the use of corticosteroids for nephrotic IgAN outside this group of patients. Patients presenting with acute renal failure require evaluation to distinguish acute tubular necrosis, which requires supportive therapy only, from crescentic IgAN, for which treatment with cyclophosphamide and corticosteroids in a regimen similar to that for renal small vessel vasculitis is indicated in the absence of significant chronic histologic injury. Patients at greatest risk of progressive renal impairment are those with hypertension, proteinuria >1 g/24 h, and reduced glomerular filtration rate at diagnosis. All such patients should be treated to a blood pressure of 125/75 mm Hg with dual blockade of the renin–angiotensin system with angiotensin-converting enzyme inhibition and angiotensin receptor blockade. At present, there is insufficient evidence for the additional use of immunosuppressive agents, antiplatelet agents, or anticoagulants.Kidney International (2006) 69, 1934–1938. doi:10.1038/sj.ki.5000419; published online 26 April 2006 [ABSTRACT FROM AUTHOR]

Background: Mesangial deposition of IgA (MCA) is a very rare finding in minimal change disease and has previously been considered a pure coincidence. In the US and Europe only anecdotal case reports exist. To date, there has been no consensus on nomenclature and categorization of this entity. We describe 2 cases of MCA with analogue histological findings but relevant differences in clinical presentation, and we discuss the clinical implications of mesangial IgA deposition in minimal change nephrotic syndrome. Patients: A 47 year-old fe male was admitted to hospital with nephrotic syndrome, microscopic hematuria, arterial hypertension and slight impairment of renal function 3 weeks after an unspecific upper air way infection. A 42-year-old male presented with nephrotic syndrome, microscopic hematuria, normotension and normal renal function. Both of the nephrotic syndromes were steroid-responsive and steroid-dependent. Findings: The clinical presentation of the male patient was consistent with the features of minimal change glomerulopathy, whereas the female patient combined signs of minimal change disease and IgA nephropathy. Light microscopy revealed mesangial IgA immune deposits and slight mesangial hypercellularity. Electron microscopic studies of MCA patients disclose diffuse effacement of glomerular foot processes. Conclusion: Our cases and a review of the literature indicate that the histological diagnosis of MCA may comprise different pathogenetic entities. From the clinical point of view, MCA has to be regarded as a minimal change nephrotic syndrome with symptomatic or asymptomatic mesangial IgA deposition. IgA deposition constitutes a risk factor for impairment of renal function and indicates a frequently relapsing course. [ABSTRACT FROM AUTHOR]