Injection of recombinant FcalphaRI/CD89 in mice does not induce mesangial IgA deposition.

BACKGROUND: Earlier studies have suggested that complexes of the human IgA receptor FcalphaRI/CD89 with mouse IgA are pathogenic upon deposition in the renal mesangium. Transgenic mice expressing FcalphaRI/CD89 on macrophages/monocytes developed massive mesangial IgA deposition and a clinical picture of IgA nephropathy (IgAN). Based on these findings, the purpose of this study was to design an experimental model of IgAN by injection of human CD89 in mice. The interaction of mouse IgA with CD89 was investigated further. METHODS: Recombinant human soluble CD89 and a chimeric CD89-Fc protein were generated, produced, purified and injected in mice. Renal cryosections were stained for IgA and CD89. The interaction of mouse IgA with CD89 was analysed by fluorescence-activated cell sorting (FACS) analysis, enzyme-linked immunosorbent assay (ELISA) and plasmon resonance technology. RESULTS: Injection of recombinant human CD89 did not result in significant IgA or CD89 deposition in the renal mesangium. However, CD89 staining in the liver was found to be positive. CD89 was rapidly cleared from circulation without signs of complex formation with IgA. FACS analysis, ELISA and plasmon resonance techniques all revealed a dose-dependent binding of human IgA to recombinant CD89, while no detectable binding was seen of mouse IgA, either of serum IgA or of different monoclonal mouse IgA preparations. CONCLUSIONS: An experimental model for IgAN in mice could not be obtained by injection of recombinant CD89. This is compatible with our in vitro biochemical data showing a lack of binding between recombinant human CD89 and mouse IgA.     

Reduced binding of immunoglobulin A (IgA) from patients with primary IgA nephropathy to the myeloid IgA Fc-receptor, CD89

Background. Primary IgA nephropathy (IgAN) is associated with elevated levels of circulating IgA and is characterized by deposition of primarily IgA1 in the renal mesangium. It has not yet been clarified which mechanisms govern the deposition of IgA1 in the mesangium. One of the factors which may play a role in trapping of IgA in the mesangial area is the interaction of IgA with specific IgA receptors (Fc&agr;R, CD89) on the mesangial cells. Methods. In the present study IgA derived from patients with IgAN and controls was investigated for its interaction with human CD89, expressed on the surface of the murine B cell line IIA1.6. Results. IgA binding to Cd89 expressing cells was specific, concentration dependent and binding of dIgA and pIgA occurred in a more efficient fashion than that of mIgA. IgA binding to CD89 directly from serum of patients compared to controls showed no significant difference. However these experiments are affected by differences in IgA concentration and combinations of different sizes of IgA. Using purified fractions of mIgA, dIgA, and pIgA isolated from serum, a significantly reduced binding of mIgA to CD89 from patients compared to controls was observed. Finally, the binding of aIgA2 to CD89 was less inhibited using mIgA from patients with IgAN compared to controls. Conclusions. The reduced binding of mIgA to CD89 seems to contradict a direct role for CD89 in deposition of IgA. However reduced binding of mIgA to CD89 may affect IgA clearance, leading to higher serum IgA. Furthermore, since it has been demonstrated that mIgA can interfere with binding of di- and pIgA deposition in the mesangial area.     

CD19+CD5+ B cells in primary IgA nephropathy

The source of IgA and the mechanism for deposition of IgA in the mesangium remain unknown for primary IgA nephropathy. Because CD19(+)CD5(+) B cells are important producers of IgA and contribute to several autoimmune diseases, they may play an important role in IgA nephropathy. In this study, flow cytometry, quantitative PCR, and confocal microscopy were used to assess the frequency, distribution, Ig production, CD phenotypes, cytokine production, and sensitivity to apoptosis of CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies of 36 patients with primary IgA nephropathy. All patients with IgA nephropathy were significantly more likely to have CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies than were five control subjects and 10 patients with active systemic lupus erythematosus. The 33 patients who had IgA nephropathy and responded to treatment demonstrated a significant decrease in CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney (all P < 0.01). In the three patients who had IgA nephropathy and did not respond to treatment, the frequency of CD19(+)CD5(+) B cells did not change. CD19(+)CD5(+) B cells isolated from patients with untreated IgA nephropathy expressed higher levels of IgA, produced more IFN-gamma, and were more resistant to CD95L-induced apoptosis than cells isolated from control subjects and patients with lupus; these properties reversed with effective treatment of IgA nephropathy. In conclusion, these results strongly suggest that CD19(+)CD5(+) B cells play a prominent role in the pathogenesis of primary IgA nephropathy.     

Natural history of primary IgA nephropathy

Primary IgA nephropathy (IgAN) is the most frequent type of primary glomerulonephritis worldwide. The characteristic presentation is gross hematuria at the time of an infectious episode. A renal biopsy still is mandatory for the diagnosis. The natural history of the disease is characterized by clinical and pathologic progression over time, which can vary from a few years to more than 50 years. It is possible to make a broad prediction at the time of diagnosis of the long-term (20 years) risk of progressive chronic kidney disease, and then to end-stage renal disease requiring renal replacement therapy (20-year cumulative end-stage renal disease risk range, 14%-39%). The 3 major independent risk factors are arterial hypertension, proteinuria more than 1 g/d, and severe renal histopathologic lesions including hyalinosis, crescents, or defined by histopathologic scoring systems. When any clinical risk factors are present, patients should be targeted closely by appropriate treatments in the following order: (1) precise control of hypertension, (2) control of proteinuria when persisting for greater than 1 g/d, and (3) evidence-based treatment where available for severe lesions. This is a symptomatic treatment strategy because pathogenesis and etiology still remain unclear.     

PDGF-B gene single-nucleotide polymorphisms are not predictive for disease onset or progression of IgA nephropathy

BACKGROUND: Few genetic factors have been identified that determine susceptibility to and progression of IgA-nephropathy (IgAN). Given that IgAN is usually characterized by mesangioproliferative glomerulonephritis and that PDGF-B is of central pathophysiological relevance in this process, we analyzed four single-nucleotide polymorphisms (SNPs) of the PDGF-B gene to evaluate a possible association of these SNPs with disease onset and progression, histological grading and responses to ACE inhibitor (ACEi) therapy. METHODS: The total study population consisted of 195 IgAN patients (127 from southern Italy and 68 from northern Germany) and 200 healthy controls (100 from each region). All four SNPs were in Hardy-Weinberg equilibrium and genotype distributions did not differ between patients and controls in either region. RESULTS: SNP distribution in Italian patients reaching end-stage renal disease (n=45) also was not significantly different from patients maintaining a serum creatinine below 1.2 mg/dl (n=60) during 5.6 +/- 5.5 years of follow-up. Furthermore, we failed to detect significant effects of any SNP on the slope of 1/serum creatinine, proteinuria level or the antiproteinuric response to ACEi. Additionally, particular PDGF-B genotypes did not correlate with histological grading using the Lee classification. CONCLUSION: We conclude that none of the four PDGF-B SNPs is related to the onset of IgAN in two different populations and that none of them has a major influence on the course of IgAN.     

Clinical significance of costimulatory molecules CD80/CD86 expression in IgA nephropathy

BACKGROUND: IgA nephropathy (IgAN) is the most common form of human glomerulonephritis. Tubulointerstitial inflammation with infiltration of mononuclear cells plays an important role in the progression of IgAN. Activation of T cells requires costimulatory signals through binding of CD28 receptor with cognate ligands (CD80/CD86) located on antigen-presenting cells (APC). To assess the clinical significance of this regulatory pathway participation in the pathogenesis of IgAN, a comprehensive immunohistologic evaluation was conducted on renal tissue of IgAN in different phases of progressive injury. METHODS: Thirty-three cases of IgAN and ten cases of non-IgA mesangial proliferative glomerulonephritis (PGN) with minor tissue damage as controls were investigated. Monoclonal antibodies were used to assess the expression of CD80, CD86, CD68, CD14, CD45RO, human leukocyte antigen-DR (HLA-DR), and intercellular adhesion molecule-1 (ICAM-1) in renal tissues. Clinical and expression data were compared at the time of renal biopsy. RESULTS: CD80+ and CD86+ cells were observed more in IgAN patients with progressive renal injury than in mild cases and controls. CD80 was limited to tubular epithelial cells and was complemented by HLA-DR expression. CD86 was expressed in the glomerulus, periglomerular area, and peritubular interstitium. Activated T cells (CD45RO+), monocytes (CD14+), macrophages (CD68+), and CD86 showed similar distributions. Positive correlations were found between CD86+ cells and CD45RO, CD14, and CD68 positive cells and between CD80+ tubuli and peritubular interstitial CD45RO+ cells. The number of interstitial CD86 positive cells and the percentage of CD80+ tubuli were correlated with renal function. Most CD86+ cells were monocyte/macrophages. CONCLUSION: This study suggested that CD80 and CD86 activate T cells in IgAN, CD80/CD86 expressions correlated with renal function at the time of renal biopsy, and monocyte/macrophages and tubular epithelial cells act as APC.     

IgA nephropathy in a young man with primary hyperparathyroidism

We report the first documented case of IgA nephropathy occurring after treatment of primary hyperparathyroidism. A 29-year-old man with a history of kidney stones and primary hyperparathyroidism underwent kidney biopsy for persistent proteinuria and microhematuria 18 months after resection of an ectopic parathyroid adenoma with subsequent normalization of serum calcium and parathyroid hormone levels. On ultrasound, renal intraparenchymal calcifications were noted. Renal biopsy revealed IgA nephropathy in addition to tubulointerstitial microcalcifications. The development of IgA nephropathy may have been influenced by hyperparathyroidism and/or its treatment. The case highlights the role of renal biopsy in patients with a history of kidney stones and abnormal urinary findings.     

Aberrantly glycosylated serum IgA1 are closely associated with pathologic phenotypes of IgA nephropathy

BACKGROUND: IgA nephropathy (IgAN) is the most common glomerulonephritis with various histologic and clinical phenotypes. The mechanisms underlying the pathogenesis of IgAN remained unclear. But now altered O-glycosylation of serum IgA1 observed in these patients was considered to be a key contributory factor. The aim of the current study is to investigate whether aberrantly glycosylated IgA1 was associated with pathologic phenotypes of IgAN. METHODS: Sera from 107 patients with IgAN recently diagnosed were collected. Fifty patients were with mild mesangial proliferative IgAN, the others were with focal proliferative and sclerosing IgAN. Sera from 22 normal blood donors were used as normal controls. Biotinylated lectins were used in enzyme-linked immunosorbent assay (ELISA) to examine different glycans on IgA1 molecules. The alpha2,6 sialic acid was detected by elderberry bark lectin (SNA), the exposure of terminal galactose (Gal) and N-acetylgalactosamine (GalNAc) were detected by arachis hypogaea [peanut agglutinin (PNA)] and vilsa villosa lectin (VVL), respectively. The serum IgA1 glycans levels corrected by serum IgA1 concentrations were compared between patients and controls. RESULTS: Reduced terminal alpha2,6 sialic acid (1.16 +/- 0.21 vs. 0.98 +/- 0.31) (P= 0.008) and galactosylation (0.30 +/- 0.29 vs. 0.16 +/- 0.19) (P= 0.029) increased exposure of (GalNAc) (0.00 vs. 0.03) (P= 0.024) were demonstrated in serum IgA1 from patients with IgAN as compared with those in controls. More important, the exposures of 2,6 sialic acid and Gal were significantly decreased, especially in patients with focal proliferative and sclerosing IgAN compared with that in patients with mild mesangial proliferative IgAN (0.91 +/- 0.34 vs. 1.05 +/- 0.25) (P= 0.014) (0.108 +/- 0.137 vs. 0.221 +/- 0.219) (P= 0.018). However, no significant difference was found between patients with mild mesangial proliferative IgAN and normal controls (P > 0.05). The exposure of GalNAc of serum IgA1 from patients with focal proliferative and sclerosing IgAN was significantly higher than that of controls (P= 0.017), but had no statistical difference with that of patients with mild mesangial proliferative IgAN. CONCLUSION: The desialylation and degalactosylation of IgA1 in sera of patients with IgAN were closely associated with pathologic phenotypes.     

Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy

Transferrin receptor (TfR) has been identified as a candidate IgA1 receptor expressed on human mesangial cells (HMC). TfR binds IgA1 but not IgA2, co-localizes with mesangial IgA1 deposits, and is overexpressed in patients with IgA nephropathy (IgAN). Here, structural requirements of IgA1 for its interaction with mesangial TfR were analyzed. Polymeric but not monomeric IgA1 interacted with TfR on cultured HMC and mediates internalization. IgA1 binding was significantly inhibited (>50%) by soluble forms of both TfR1 and TfR2, confirming that TfR serves as mesangial IgA1 receptor. Hypogalactosylated serum IgA1 from patients with IgAN bound TfR more efficiently than IgA1 from healthy individuals. Serum IgA immune complexes from patients with IgAN containing aberrantly glycosylated IgA1 bound more avidly to TfR than those from normal individuals. This binding was significantly inhibited by soluble TfR, highlighting the role of TfR in mesangial IgA1 deposition. For addressing the potential role of glycosylation sites in IgA1-TfR interaction, a variety of recombinant dimeric IgA1 molecules were used in binding studies on TfR with Daudi cells that express only TfR as IgA receptor. Deletion of either N- or O-linked glycosylation sites abrogated IgA1 binding to TfR, suggesting that sugars are essential for IgA1 binding. However, sialidase and beta-galactosidase treatment of IgA1 significantly enhanced IgA1/TfR interaction. These results indicate that aberrant glycosylation of IgA1 as well as immune complex formation constitute essential factors favoring mesangial TfR-IgA1 interaction as initial steps in IgAN pathogenesis.     

Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89-IgA and IgG-IgA complexes: common mechanisms for distinct diseases

Abnormalities of IgA arise in alcoholic cirrhosis, including mesangial IgA deposits with possible development of secondary IgA nephropathy (IgAN). Since little is known about circulating immune complexes in cases of secondary IgAN, we analyzed IgA-associated parameters in the serum of 32 patients with compensated or advanced alcoholic cirrhosis. Galactose deficiency and decreased sialylation of IgA1, as well as increased amounts of abnormally glycosylated polymeric IgA1, were detected in the serum of patients with advanced alcoholic cirrhosis. Moreover, aberrant IgA1 formed complexes with IgG and soluble CD89 in serum of patients with advanced alcoholic cirrhosis, similar to those found in primary IgAN. The IgA1 of alcoholic cirrhosis, however, had a modified N-glycosylation, not found in primary IgAN. In patients with alcoholic cirrhosis and IgAN, IgA deposits were associated with CD71 overexpression in mesangial areas, suggesting that CD71 might be involved in deposit formation. Although the IgA1 found in alcoholic cirrhosis bound more extensively to human mesangial cells than control IgA1, they differ from primary IgAN by not inducing mesangial cell proliferation. Thus, abnormally glycosylated IgA1 and soluble CD89-IgA and IgA-IgG complexes, features of primary IgAN, are also present in alcoholic cirrhosis. Hence, common mechanisms appear to be shared by diseases of distinct origins, indicating that common environmental factors may influence the development of IgAN.     

Decreased IgA1 response after primary oral immunization with live typhoid vaccine in primary IgA nephropathy.

INTRODUCTION: Patients with primary IgA nephropathy (IgAN) have an increased level of immunological memory to certain parenteral recall antigens. We recently found a deficient IgA1 immune response after intranasal challenge with a neo-antigen: cholera toxin subunit B. In the present study, we assessed the specific IgA1 and IgA2 antibody response in plasma, peripheral blood cells and mucosal secretions after primary enteral immunization. METHODS: Twenty eight IgAN patients, 26 patients with non-immunological renal disease and 32 healthy subjects were immunized orally with three sequential doses of live, attenuated, Salmonella typhi Ty21a. The humoral immune response in body fluids and antibody synthesis by circulating B cells was assessed in specific ELISAs and ELIPSAs respectively. RESULTS: Oral immunization resulted in significantly (P<0.0001) increased IgM, IgG, IgA, IgA1 and IgA2 responses in all groups, both in plasma and in circulating B cells in vitro. The IgA1 response in plasma was significantly (P<0.05) lower in IgAN patients, while no significant differences in IgM (P=0.36), IgG (P= 0.79) or IgA2 (P=0.45) responses were found as compared with matched control groups. The amount of IgA1 synthesized by circulating B cells tended to be lower in IgAN patients. No significant IgA response after oral immunization with S. typhi Ty21a was found in saliva (P=0.11) or tears (P=0.10). CONCLUSIONS: These data suggest an IgA1 hyporesponsiveness in patients with IgAN that is not only apparent after primary challenge of the nasal-associated lymphoid tissue but also after presentation to the gut. Previous results after parenteral recall immunization may be explained by assuming that IgAN patients require more frequent and/or longer exposure to IgA1-inducing antigens on their mucosal surfaces before they reach protective mucosal immunity. As a consequence, overproduction of IgA1 antibodies occurs in the systemic compartment, accompanied by an increased number of IgA1 memory cells.     

HLA DQ region gene polymorphism associated with primary IgA nephropathy

IgA nephropathy (IgAN) has been associated with HLA-DR4. We have recently described two non-allelic Taq I DQ beta gene-associated fragments sized 2.0 kb (T2) and 6.0 kb (T6), which strongly associate with DR4. T2 represents a polymorphism of the DQ beta gene and has been redesignated DQw8 (10th International HLA Workshop). The origin of the T6 fragment has not been determined, but probably represents a polymorphism of either the DQ beta or DX beta gene. When present together T2 and T6 define a subgroup of DR4 subjects at high risk of developing autoimmune disease. We have, therefore, studied DQ beta gene polymorphisms in IgAN. The DR antigen distribution was similar in IgAN and normal controls. The T2+/T6+ phenotype was present in 49% patients with IgAN compared to 15% of controls [P less than 0.0001, chi 2 = 32.8, Cramer's V = 0.41; relative risk = 5.5 (range, 2.8-11.0)]. Seventy-two percent of DR4+ IgAN patients and 29% of DR4+ controls were T2+/T6+ (P = 0.007, chi 2 = 17.0). These findings confirm the hypothesis that disease susceptibility genes are important in IgAN, and suggest that the putative gene(s) are located within or near to the DQ subregion. Moreover, similar DQ beta gene associations have been found in IDDM and pemphigus vulgaris, pointing to a common immunogenetic mechanism predisposing to several autoimmune diseases.     

转铁蛋白受体在IgA肾病肾组织中的表达

目的阐明转铁蛋白受体（cD71、TfR）在IgA肾病（IgAN）肾组织中表达的分布特点及其与IgA表达的关系,探讨其在IgAN免疫发病机制中的作用。方法120例肾活检患者根据临床表现和肾活检病理诊断分为原发性IgAN组（原发组）44例、非IgAN性IgA沉积组（继发组）38例、无IgA沉积肾病组（肾病组）38例。用免疫荧光双套色法标记的抗体,在激光共聚焦荧光显微镜下观察四甲基罗丹明（TRITC）标记的CD71和异硫氰荧光素（FITC）标记的IgA在肾组织上的表达。结果CD71的表达强度与IgA的沉积程度相一致。CD71与IgA在原发组肾小球上高表达;在继发组低表达;在对照组微弱表达或不表达。激光共聚焦荧光显微镜下观察到CD71表达与IgA表达呈现共位现象。结论CD71在IgAN患者肾小球呈现高表达,其表达与IgA分子呈现共位状态,提示CD71可能参与了IgAN免疫发病过程。     

B and T cell abnormalities in patients with primary IgA nephropathy

The in vitro function of B and T cells was studied in 16 patients with primary IgA nephropathy (PIgA-N). The distribution of OKT3+ cells (total peripheral T cells) and of regulatory T cell subsets (helper OKT4+ and cytotoxic/suppressor OKT8+ cells) was evaluated and a testing for 47 HLA-A, B, C, DR, and DQ antigens was carried out in the 16. B lymphocyte IgA production, after stimulation by pokeweed mitogen in the presence of T cells from normal donors treated with mitomycin C, was significantly greater in patients than in controls. T lymphocytes from patients with PIgA-N were more efficient than T cells from controls in providing IgA specific helper activity for normal B cells. The analysis of the individual data showed that the overactivity of B cells and the T cell operational dysfunction was present in about 50% of the patients and did not correlate. No numerical imbalance between T lymphocyte subsets nor any association between lymphocyte behavior, HLA antigen distribution, and a number of clinical, laboratory, and immunohistological findings was observed. Our data, therefore, suggest that PIgA-N is an immunologically heterogeneous disease and that an IgA-specific B cell overactivity and/or overall IgA-specific T cell helper activity may be present in some patients.     

An increased polymeric IgA level is not a prognostic marker for progressive IgA nephropathy.

BACKGROUND: Elution of IgA from renal biopsies of patients with primary IgA nephropathy (IgAN) has suggested that mesangial IgA deposits are mainly multimeric in nature. This macromolecular IgA consists of dimeric and polymeric IgA and may be derived from the circulation. In children with IgAN, circulating macromolecular IgA levels correlate with bouts of macroscopic haematuria, but in adults a correlation with disease activity is less clear. Therefore, we have designed a novel method to assess the levels of polymeric IgA (pIgA) in sera from patients and controls. METHODS: A novel precipitation assay using recombinant CD89 was developed to measure pIgA. Polymeric IgA levels were measured in serum samples obtained from healthy volunteers (n = 21) and patients with IgAN (n = 51). Subsequently, serum pIgA levels were correlated with clinical parameters of disease. RESULTS: Serum pIgA levels were significantly increased in patients with IgAN. However, pIgA concentrations relative to total IgA were significantly lower in sera of patients with IgAN. No correlation was found between serum pIgA levels and clinical parameters of IgAN, such as decline of glomerular filtration rate, haematuria or proteinuria. CONCLUSIONS: Although absolute levels of serum pIgA are increased in patients with IgAN as compared with controls, levels of pIgA relative to total serum IgA are lower. No significant correlation was found between serum concentrations of pIgA and clinical parameters of disease. These data support the notion that it is not the size alone, but the physicochemical composition of the macromolecular IgA that is the key factor leading to mesangial deposition.     

Effects of a gluten-free diet in primary IgA nephropathy

In an uncontrolled study a gluten-free diet was given to 29 patients affected by primary IgA nephropathy (IgAGN). All of them followed the diet for 6 months, 23 patients for 1 year and 9 for 2 to 4 years. Mean levels of IgA containing circulating immune complexes (IgAIC), detected by a specific conglutinin assay and by measuring IgA content in 2.5% polyethylene glycol precipitates, on an unrestricted diet, significantly decreased after 6 months of gluten-free diet (p less than 0.01) and remained reduced during the follow-up. A decrease in IgAIC levels was evident in 85.7% of the cases with basal positive data, with complete normalization in 64.3% of them. IgA to gluten antigens (ethanol- or saline-soluble gliadin, glutenin and the lectin fraction termed glyc-gli) as well as to heterologous bovine and egg albumins were found to be significantly increased on an unrestricted diet in the group of 14 IgAGN patients with basal positive IgAIC. The mean levels of IgA to most dietary antigens significantly decreased after 6 months to 1 year of a gluten-free diet. A decrease in IgA to ethanol-soluble gliadin was evident in 81.8% of the cases with basal positive data, with complete normalization in 63.6%. A subgroup of 27.5% of IgAGN patients showed positive IgAIC values associated with increased IgA values to a variety of dietary antigens. A gluten-free diet induced in 75% of the cases a parallel improvement in these abnormal immunological data. Mean proteinuria values were found to be significantly decreased after 6 months of the diet and a reduction was also observed in microscopic hematuria. However, mean blood creatinine levels showed a significant increase after the gluten-free diet. The data of this study indicate that a gluten-free diet can modify some immunological abnormalities in a group of IgAGN patients, reducing levels of IgAIC and IgA to dietary antigens. The clinical course does not seem to be favorably influenced, since a relentless progression towards renal failure was observed.     

小量蛋白尿原发性IgA肾病患者预后影响因素分析

IgA肾病(IgAN)的预后存在明显的异质性[1].小量蛋白尿是IgAN的常见临床表现,一般认为其肾脏预后相对较好,但临床中不乏小量蛋白尿而肾功能持续进展者,故对于此人群预后的分析十分重要.本研究回顾性分析了163例小量蛋白尿原发性IgAN患者的预后,探讨该人群肾功能丧失的危险因素.     

A case of IgA nephropathy and renal hemosiderosis associated with primary hemochromatosis

IgA nephropathy associated with liver cirrhosis is a common disease, unlike hemochromatosis-associated renal involvement, which is uncommon. A 55-year-old man was admitted to our hospital for the acute deterioration of renal function. Laboratory tests showed extremely high transferrin saturation and serum ferritin level. Furthermore, magnetic resonance imaging revealed low-intensity signals in both T1- and T2-weighted images within the liver, diagnosed as primary hemochromatosis. Renal biopsy showed mesangial IgA deposition with cellular crescent and hemosiderin in both glomerular and tubular epithelial cells. Renal function worsened progressively after admission, and thus steroid pulse therapy was started. Renal dysfunction improved, but the patient died of cerebral hemorrhage. The present case was considered IgA nephropathy and renal hemosiderosis secondary to primary hemochromatosis. To our knowledge, this is the first report that describes the above complications in association with primary hemochromatosis.