Nephrotic syndrome with crescent formation and massive IgA deposition following allogeneic bone marrow transplantation for natural killer cell leukemia/lymphoma

We describe herein a case of nephrotic syndrome (NS) following allogeneic bone marrow transplantation (allo-BMT) for natural killer cell leukemia/lymphoma. Histologic studies defined the diagnosis as crescentic glomerulonephritis with massive immunoglobulin A (IgA) deposition, which has never been reported in NS cases following allo-BMT. Most of the massive infiltrated cells in the interstice were CD3(+)CD4(-)CD8(+) T cells derived from the donor. We observed mesangial deposition of Haemophilus parainfluenza outer membrane (OMHP) antigen and decreased glycosylation of the IgA1 hinge in the recipient's samples is consistent with the recently reported pathogenesis of IgA nephropathy. Further, the titer of IgA antibody against the donor serum was as high as other IgA nephropathy cases. These findings suggest that NS and crescentic glomerulonephritis in this case occurred as one of the forms of chronic graft-versus-host disease (GVHD), and that IgA deposition was associated with H parainfluenza and decreased glycosylation of the IgA1 hinge.     

Immunoglobulin A in the skin of patients with ankylosing spondylitis.

Cutaneous immunofluorescence studies were carried out in 21 patients with ankylosing spondylitis (AS) and the results compared with those for 18 healthy subjects. The most prominent finding was the presence of IgA in dermal vessels of patients with AS (71% compared with 17% of the control group). IgG and IgM cutaneous deposits were also observed in patients with AS, but these results did not differ from those of the control group. A renal biopsy was performed in three of the patients presenting with unexplained microscopic haematuria. One of them had an IgA nephropathy, but no correlation was found between kidney and skin deposits of IgA. These findings suggest that IgA cutaneous deposits in AS are not a marker of IgA nephropathy but stress the role of immunoglobulin A in the pathogenesis of this disease.     

中国北方汉族IgA肾病患者UG基因G38A基因多态性与临床和预后的关系

目的　探讨中国北方汉族IgA肾病患者UG基因G3 8A基因多态性的分布及与临床和预后的关系。方法　选 3 0 0例北方汉族IgA肾病患者 (对其中 93例患者进行 2～ 6年的随访。)及北方汉族健康献血者 14 5例 ,盐析法提取外周血基因组DNA ,PCR 限制性片段长度多态性法确定UG基因G3 8A基因型 ,分析不同基因型与IgA肾病临床、病理及预后的关系。结果　 (1)IgA肾病患者UG基因的 3种基因型 (3 8AA、3 8AG和 3 8GG)与健康对照者间差异无显著性 (P >0 0 5)。 (2 ) 3种基因型与IgA肾病患者的性别、肾穿刺时的年龄、血尿、蛋白尿、肾功能、血清IgA水平及病理间无显著关系。 (3 )相对于其他基因型 ,3 8AA型预后差 (OR =2 3 7,95%CI =1 12～ 5 0 1,χ2 =8 2 48,P <0 0 1)。结论　UG基因G3 8A基因多态性与中国北方汉族人群IgA肾病的发病及临床无关 ,3 8AA基因型可能是IgA肾病慢性化进展的危险因子之一。     

Néphropathie à IgA et LGM au cours d’un syndrome de Sézary

IntroductionThe Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) requiring a rapid diagnosis due to its poor prognosis.Case reportWe report the first case of an eighty-nine-year-old woman who presented with concomitant Sezary syndrome and anasarca, revealing a nephrotic syndrome caused by a minimal change nephropathy associated with immunoglobulin A (IgA) deposits. Scarce literature described rare cases associating these two entities (nephrotic syndrome and nephropathy). However, the nephrotic syndrome was delayed from disease onset, secondary to immunosuppressive treatment of SS, or due to the weaning of SS therapy. Thus, the direct link between the glomerular lesion and the cutaneous lymphoma was difficult to establish. However, the synchronous occurrence of both SS and glomerulopathy in our patient, along with Sezary cells in both urines (urinary cytology) and biopsy, and resolution of nephropathy after treatment of SS, support the likely attributability of SS in glomerulopathy.ConclusionPractitioners must acknowledge the possible occurrence of glomerular involvement in SS.     

Elevation of serum IgA in spondyloarthropathies and IgA nephropathy and its pathogenic role.

Ankylosing spondylitis and IgA nephropathy share some immunologic features, eg, elevated serum IgA and IgA-immune complex levels. These entities are frequently found as being associated. IgA and IgA immune complex catabolism involves asialoglycoprotein receptors and specific IgA Fc receptors (FcalphaR or CD89) on tissue and blood cells. Recent studies revealed impaired CD89 expression in both diseases. These abnormalities, which are associated with receptor saturation, might generate the increase in serum IgA and IgA immune complex levels by either altered recycling or failure of degradation. This article reviews the literature on IgA abnormalities and discusses the potential role of FcalphaR in IgA nephropathy and AS and the consequences of its similar defect in the two diseases.     

CD44在IgA肾病中的表达及临床意义

目的研究CD44在IgA肾病各病变阶段肾组织中的表达及其与临床指标之间的关系,探讨CD44在IgA肾病发病机理中的生物学意义.方法应用免疫组织化学S-P法检测34例IgA肾病肾组织、6例正常肾组织中的CD44的表达情况,同时测定IgA肾病患者的24小时尿蛋白定量、血压、血肌酐(Cr)、肌酐清除率(Ccr)等.分析不同临床分组、病理分级、有无高血压、蛋白尿程度、血Cr水平等对CD44表达的影响.结果 CD44主要于系膜增生、新月体、小管间质炎性细胞浸润的部位表达,于细胞性新月体表达最强.整个球性硬化时,CD44表达近消失.CD44表达与蛋白尿程度正相关(P＜0.05);与血cr水平无明显相关性(P＞0.05);有高血压者CD44表达阳性率92%(23/25),无高血压者为33.3%(3/9),两者比较有显著性差异(P＜0.01).CD44在肾组织中的表达与IgA肾病患者的年龄、性别无相关性.结论 CD44与IgA肾病的活动性进展有关,CD44可作为判定IgA肾病早期进展的可靠指标.     

Abdominal pain associated with IgA nephropathy. Possible mechanism

A 36-year-old man presented with IgA nephropathy (Berger's disease) and acute abdominal pain. Surgical biopsy of the ileum revealed deposits of IgA, C3, and fibrin in segments of the wall of submucosal arteries. The immune deposits appeared associated with areas of fibrinoid necrosis. These findings support the hypothesis that Berger's disease is a systemic disease, and provide a possible explanation for the abdominal pain associated with IgA nephropathy.     

Antineutrophil cytoplasmic autoantibody (ANCA) positive immunoglobulin A (IgA) nephropathy: Case reports and review of literature

BackgroundThere are reports of circulating antineutrophil cytoplasmic autoantibodies (ANCA) in patients with immunoglobulin A (IgA) nephropathy with an uncertain pathogenic role.Aim of the workTo present the findings of myeloperoxidase (MPO) ANCA-positive patients amid a different course of IgA nephropathy with crescents and to discuss the efficacy of immunosuppressive therapy.Case presentationTwo cases of IgA nephropathy associated with positive ANCA are reported and a review of the literature data is presented. The first patient presented with a progressive nephropathy and significantly impaired renal function at baseline, whereas in the second patient renal function remained stable over 10 years, despite the recurrent exacerbations of the disease. Both patients had extrarenal manifestations (joint pain and/or anemia) and elevated markers of inflammation (erythrocyte sedimentation rate, C-reactive protein) that are not typical features for IgA nephropathy. In the first case, immunosuppressive therapy with corticosteroids and cyclophosphamide resulted in improvement of kidney function. The second case showed the potential efficacy of rituximab as an induction remission and maintenance therapy for ANCA-positive IgA nephropathy.ConclusionWhether the association of IgA nephropathy with ANCA positivity is coincidental or constitutes a novel entity remains debated. Circulating ANCA can be found in patients with IgA nephropathy. They can be truly pathogenic and contribute to kidney damage and may induce overt systemic vasculitis or at least extrarenal signs and symptoms. ANCA-positive IgA nephropathy can respond to immunosuppressive regimens, including rituximab, similar to patients with ANCA-associated vasculitis (AAV).     

Cutaneous vasculitis and IgA glomerulonephritis in ankylosing spondylitis.

Two patients with ankylosing spondylitis were found to have IgA nephropathy and leucocytoclastic cutaneous vasculitis. Immunofluorescence showed perivascular deposition of IgA in the skin of one patient and in the mesangium of both patients. Such an association has been reported only once before. This supports the concept of abnormal IgA immune stimulation in the pathogenesis of ankylosing spondylitis.     

Crohn's disease associated with IgA nephropathy]

Crohn's disease is a condition of chronic inflammation potentially involving any location of the alimentary tract from mouth to anus. Numerous extraintestinal manifestations can also be present. Urologic complications of inflammatory bowel disease are seen in up to 25% of patients, but renal parenchymal disease has been rarely reported. IgA nephropathy is recognized worldwide as a most common form of primary glomerulonephritis. Clinical manifestations vary, ranging from microscopic hematuria to nephrotic syndrome. Recently, IgA nephropathy associated with systemic diseases has been reported. We describe a case of a 22 year-old man with Crohn's disease associated with IgA nephropathy. At the age of 8 years, microscopic hematuria appeared. After fourteen years, he presented with melena, mild fever, recurrent oral ulcer, microscopic hematuria and proteinuria. Colonoscopic examination revealed characteristic features of Crohn's disease such as multiple ulcers. Microscopic findings showed superficial ulceration with small noncaseating granulomas. Renal biopsy revealed IgA nephropathy. The patient was treated with oral prednisolone, olsalazine, and metronidazole followed by maintenance therapy with sulfasalazine and azathioprine resulting in clinical improvement of Crohn's disease and IgA nephropathy.     

Association of liver cirrhosis related IgA nephropathy with portal hypertension

A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.     

A case of rapidly progressive IgA nephropathy in a patient with exacerbation of Crohn's disease

ABSTRACT: BACKGROUND: IgA nephropathy has been reported as a renal involvement in Crohn's disease. Crescentic IgA nephropathy, which accounts for fewer than 5% of cases of IgA nephropathy, has a poorer prognosis than other forms of crescentic glomerulonephritis. We recently experienced a case of rapidly progressive IgA nephropathy concurrent with exacerbation of Crohn's disease. Case Presentation. An 18-year-old male diagnosed with Crohn's disease underwent a hemicolectomy 2 years previously. He had maintained a state of Crohn's disease remission with 5-aminosalicylic acid treatment. Four months prior to referral to the nephrology clinic, he experienced non-bloody diarrhea. He simultaneously developed proteinuria and microscopic hematuria with deterioration of renal function. Based on renal biopsy findings, the patient was diagnosed with crescentic IgA nephropathy. Immunostaining for interkeukin-17 in renal tissue and previous exacerbated colonic ulcers was positive. Steroid pulse therapy was administered, followed by high-dose glucocorticoid and oral cyclophosphamide therapy. The patient's renal function recovered and his gastrointestinal symptoms were alleviated. CONCLUSIONS: We report a case of crescentic IgA nephropathy presenting with exacerbation of Crohn's disease, and present a review of the literature focusing on the pathophysiologic relationship between these two conditions.     

Infliximab treatment for Crohn’s disease in a patient with IgA nephropathy

We describe herein a case of IgA nephropathy in a 34-year-old woman with Crohn’s disease (CD) treated with infliximab. CD first appeared at the age of 15 years. An elemental diet was started for remission maintenance. Ten years later, the patient suffered from a recto-vaginal fistula and subtotal colectomy with stoma formation was performed. At the age of 33 years, the patient was investigated for painless macroscopic hematuria and proteinuria. Renal biopsy revealed IgA nephropathy. Mizoribine was started but proteinuria persisted. Due to diarrhea she was admitted to our hospital, and scheduled maintenance therapy with infliximab was initiated. After the first infliximab infusion, the patient presented significant clinical improvement in both diarrhea and proteinuria with concomitant decrease of C-reactive protein to normal levels and proteinuria ~1 g/day. This represents the first report of infliximab treatment in a patient with IgA nephropathy associated with CD and clarifies the importance of tumor necrosis factor-alpha (TNFα) in immunity to renal disease. Further studies are needed to draw firm conclusions for the safety of infliximab in patients with IgA nephropathy.     

Minimal-change disease with mesangial IgA deposits associated with Sjogren syndrome

Sj?gren's syndrome may be accompanied by a dysregulation of IgA system implying the presence of increased serum polymeric IgA or circulating immune complexes and their consequent deposition within the kidney. In this context IgA nephropathy may only represent one of the complications brought by IgA deposition. Glomerular involvement and primary Sj?gren's syndrome has been described previously only in isolated case reports, membranous nephropathy and membranoproliferative glomerulonephritis have been reported. We have not found any case of minimal change disease and glomerular IgA deposition associated with Sj?gren's syndrome. In this patient nephrotic syndrome was related to serum increase of CA 19-9; this association has been reported in only three previous cases.     

Serum IgA levels in patients with diabetic nephropathy and IgA nephropathy superimposed on diabetes mellitus

The aim of this study was to examine the relationship between serum immunoglobulin A (IgA) levels and diabetic nephropathy in patients with type 2 diabetes mellitus, and to describe the role of IgA nephropathy superimposed on diabetes mellitus. A total of 127 type 2 diabetic patients were studied. Of these diabetics, 74 had no proteinuria, 35 had diabetic glomerulosclerosis confirmed by renal biopsy, 13 had superimposed IgA nephropathy, and five had superimposed non-IgA nephropathy. We also studied 93 non-diabetic patients with IgA nephropathy, 24 non-diabetic patients with non-IgA nephropathy, and 38 non-diabetic controls. Serum IgA levels were significantly higher in IgA nephropathy patients (350+/-130 mg/dl) than in non-diabetic controls (228+/-56 mg/dl) and diabetics without proteinuria (268+/-104 mg/dl). Serum IgA levels were also significantly higher in diabetics with superimposed IgA nephropathy (470+/-208 mg/dl) than in non-diabetic controls, non-IgA nephropathy patients (270+/-133 mg/dl), diabetics without proteinuria, diabetic glomerulosclerosis alone (302+/-126 mg/dl), and diabetics with superimposed non-IgA nephropathy (248+/-137 mg/dl). The prevalence of high serum IgA levels was significantly higher in diabetics with superimposed IgA nephropathy (76.9%) than in diabetic glomerulosclerosis alone (31.4%) and diabetics with superimposed non-IgA nephropathy (25.0%). In conclusion, our findings indicate that high serum IgA level is a sign of the existence of IgA nephropathy superimposed on diabetes mellitus.     

Coexistence of IgA nephropathy and undifferentiated spondyloarthropathy in a female patient

We report a female patient with IgA nephropathy associated with undifferentiated spondyloarthropathy. The patient manifested proteinuria and microhematuria and was diagnosed as having IgA nephropathy based on the histopathologic findings of the renal biopsy. Two years later, the bone X-ray demonstrated syndesmophytes and multiple calcifications in the ligament and tendon insertions, suggestive of long-term enthesitis, but the patient had occasionally noticed mild lumbago up to the time she visited our hospital, with spontaneous pain in the bilateral shoulders and lower back. IgA nephropathy can be concomitant with a mild form of seronegative spondyloarthropathy in women. Possible association of this disorder should be carefully checked in patients with IgA nephropathy irrespective of clinical symptoms suggesting the arthropathy, particularly in women.     

IgA Nephropathy with Minimal Change Disease

Background and objectives

Patients with IgA nephropathy typically present with hematuria and subnephrotic proteinuria. Nephrotic syndrome is uncommon in IgA nephropathy, and when present, it is usually associated with severe histologic features, such as endocapillary proliferation, segmental sclerosis, and crescent formation. Rarely, patients with IgA nephropathy present with nephrotic syndrome and only mild mesangial disease. This study sought to better characterize these patients.

Design, setting, participants, & measurements

A retrospective review of cases of IgA nephropathy diagnosed from 2004 to 2011 identified patients with nephrotic range proteinuria and histologically mild IgA nephropathy. Specifically, using the Oxford Classification of IgA Nephropathy, we identified cases that lacked endocapillary proliferation or segmental sclerosis.

Results

The cohort consisted of 17 patients, including 10 men and 15 adults. The median serum creatinine was 0.9 mg/dl (range=0.7–3.1), median 24-hour urine protein was 8.0 g/d (3.0–18.0 g), and 14 patients were fully nephrotic, whereas the remaining 3 patients fulfilled two of three criteria for nephrotic syndrome. Biopsies revealed IgA-dominant or codominant deposits accompanied by mesangial proliferation in 14 patients (82.4%). Electron microscopy showed mesangial deposits and extensive foot process effacement (median=90%). Initial treatment consisted of corticosteroids, although many patients required additional agents to maintain remission status. Over a median follow-up of 20 months (2.2–82 months), 14 patients experienced a complete response, and 3 patients showed a partial response, with a median response time of 2 months (0.5–27 months). At least one relapse of nephrotic syndrome occurred in nine patients (53%). All patients exhibited stable or improved renal function over the follow-up period.

Conclusions

The findings in this cohort and previous studies suggest that rare cases of mild IgA nephropathy with nephrotic range proteinuria exhibit a clinical presentation, biopsy findings, treatment response, and outcome more typical of IgA nephropathy with superimposed minimal change disease. This study favors the view that such cases represent a dual glomerulopathy.     

Glomerulonephropathy in ankylosing spondylitis

Aim: Renal abnormalities have been reported in ankylosing spondylitis (AS). The purpose of this study was to elucidate the nature of glomerulonephropathy in AS. Methods: Two hundred and sixty‐six patients with definite AS diagnosed at Taipei Veterans General Hospital, Taiwan, were enrolled. Urinary analysis and renal biopsy were performed in this study. The nature of glomerulonephropathy in AS was analyzed. Results: Twelve out of 266 (4.5%) patients had AS‐associated nephropathy manifesting as haematuria alone (11 patients) or haematuria and proteinuria (1 patient). Renal biopsy in seven patients showed IgA nephropathy in two cases, mesangial nephropathy with isolated C3 deposits in three cases, and IgM nephropathy in two cases, one of which had accompanied infectious endocarditis. Conclusion: AS‐associated nephropathy is not uncommon and mesangial nephropathy is the most common form. Microscopic haematuria and proteinuria are the most common manifestations of renal involvement.     

IgA nephropathy associated with ankylosing spondylitis: occurrence in women as well as in men.

Two patients (one male, one female) with ankylosing spondylitis (AS) and IgA nephropathy are described. The female patient is the first reported case to have AS and IgA nephropathy concurrently. Contrary to previously reported cases, her renal manifestation preceded her rheumatic symptoms. It is suggested that women with IgA nephropathy and AS may be overlooked as the severity of spondylitis and joint involvement is less than in men.     

Increased expression of proliferating cell nuclear antigen mRNA in peripheral blood mononuclear cells from patients with IgA nephropathy.

Proliferating cell nuclear antigen (PCNA)/cyclin is an intranuclear polypeptide antigen whose appearance correlates with the proliferative state of cells. The authors investigated the expression of PCNA from peripheral blood mononuclear cells (PBMC) in 23 patients with IgA nephropathy and 10 healthy age-matched controls, using ribonucleic acid hybridization techniques. The majority of patients with IgA nephropathy (22 of 23 patients) showed elevated PCNA expression in PBMC, while no PCNA expression was detected in PBMC of normal controls. A positive correlation was noted between PCNA expression of PBMC and glomerular injuries and PCNA expression and urinary protein excretion. Sixty-three percent of patients with grade III and IV histological findings showed strong PCNA (more than ) expression in their PBMC. The urinary protein excretion in patients who showed more than ( ) PCNA expression was more than 2.5 g/d, while that in patients with less than (+) PCNA expression was less than 1.0 g/day. These findings indicate that abnormally regulated PCNA expression in PBMC may play an important role in the progression of IgA nephropathy, and that PCNA expression in PBMC may be a useful indicator of disease activity.