Immunological comparison of patients with rheumatoid arthritis with and without nephropathy.

Serum immunoglobulins IgG, IgA, and IgM, serum complement components C3 and C4, circulating immune complexes, antinuclear antibodies, and rheumatoid factor were measured in 56 patients with rheumatoid arthritis (RA) and nephropathy (23 with mesangial glomerulopathy; 13 with membranous glomerulonephritis; and 20 with amyloidosis) and 35 patients with RA without nephropathy (controls). Renal immunofluorescence findings in patients with mesangial glomerulopathy were compared with the serologic data. There were no differences in the occurrence of rheumatoid factor, antinuclear antibodies, and circulating immune complexes and the concentrations of serum complement C3 and C4 between various RA nephropathy groups and controls. Serum IgA and IgM concentrations were significantly higher in patients with mesangial glomerulopathy and amyloidosis than in controls. In patients with mesangial glomerulopathy glomerular IgM, IgA, and C3 were the most prominent findings in immunofluorescence examination. The serum IgA concentration was significantly higher in those patients with mesangial glomerulopathy with mesangial IgA deposits than in those without (4.97 (SD 1.03) g/l v 2.07 (1.21) g/l). The highest serum IgA concentrations (5.08 (1.39) g/l) were seen in the four patients with IgA glomerulonephritis. The prevalence of IgA glomerulonephritis in the renal biopsy material of the patients with RA was 5%, which possibly differs little from that seen in the general population. The results suggest that circulating immune complexes may not have any major role in the pathogenesis of various nephropathy types in patients with RA, contrary to their role in most extra-articular manifestations of RA.     

Emerging minimal-change nephrotic syndrome in a patient with chronic mesangial proliferative lupus nephritis

A 41-year-old Japanese woman with a 25-year history of systemic lupus erythematosus was admitted because of abrupt onset of nephrotic syndrome and acute renal failure. Renal biopsy specimen showed only mild mesangial proliferative glomerulonephritis associated with mesangial deposition of immunoglobulins/complements. No significant immune deposits were found in the glomerular capillary walls, but mild foot process effacement was observed on electron microscopy. Further, two-month corticosteroid therapy improved her massive proteinuria and renal dysfunction, indicating that this patient showed minimal-change nephropathy superimposed on mesangial proliferative lupus nephritis.     

Case report: nephrotic syndrome associated with a total hydatidiform mole.

The authors describe a 51-year-old Japanese woman who developed nephrotic syndrome in association with a total hydatidiform mole. The nephrotic syndrome remitted completely following hysterectomy. A renal biopsy performed before the operation showed diffuse mesangial cell proliferation of a moderate degree, and thickened capillary walls with focal and segmental subendothelial deposits, as well as circumferential mesangial interposition. Occasional foci of the mesangiolysis were also observed. Immunofluorescence microscopy revealed granular staining of IgM along the glomerular capillary walls in a fringe pattern. A review of the literature revealed that this patient appears to be the first case of nephrotic syndrome associated with a total mole, although there have been two cases of nephrotic syndrome due to preeclamptic nephropathy associated with a partial or transitional mole.     

Fibronectin Glomerulopathy Confused with Glomerular Endothelial Injury in a Patient with Takotsubo Cardiomyopathy

A 46-year-old woman developed takotsubo cardiomyopathy and nephrotic syndrome. The first kidney biopsy suggested non-immune-complex-mediated membranoproliferative glomerulonephritis (MPGN), and she was diagnosed with glomerular endothelial injury associated with takotsubo cardiomyopathy. A second biopsy was performed two years later because of persistent proteinuria despite renin-angiotensin system inhibition. This biopsy indicated non-immune-complex-mediated MPGN, but a mesangial and subendothelial substance of a higher electron density than that in the first biopsy was detected, suggesting the possibility of glomerular disease with non-immune deposits rather than endothelial injury. Finally, she was diagnosed with fibronectin nephropathy. Although rare, fibronectin glomerulopathy should be considered in non-immune-complex-mediated MPGN.     

Renal involvement in patients with hepatosplenic Schistosomiasis mansoni.

In a prospective study of renal involvement in 100 consecutively hospitalized patients with hepatosplenic schistosomiasis mansoni, 15 exhibited persistent proteinuria of varying degree, which in 6 instances was accompanied by hypertension. Nine patients had the nephrotic syndrome. The most common glomerular lesion in this group was membrano-proliferative glomerulonephritis. Surgical biospy obtained during splenectomy in 15 patients without clinical evidence of renal involvement showed glomerular lesions in 6 instances. Focal proliferative glomerulonephritis was the most common lesion in this group. The detection of silent glomerular lesions in patients with Schistosoma mansoni infection suggests that the glomerular alterations may precede clinical manifestations of renal disease.     

Evaluation of recurrent glomerulonephritis in kidney allografts

The clinical records and biopsy and nephrectomy specimens from 320 patients treated at the Duke University Medical Center between 1965 and 1977 were examined to determine the type and incidence of recurrent glomerulonephritis in the allograft. The diagnosis of recurrent disease required that the histopathologic features of the transplanted kidney resemble those of the diseased native kidney by immunofluorescence and light and electron microscopy. Of 204 patients with tissue available for evaluation from both the native and the transplanted kidney, 117 had some form of chronic glomerulonephritis. Of the 117, there were 61 whose disease could be subclassified further. Idiopathic membranous glomerulonephritis was documented in seven patients, IgA nephropathy in five, focal glomerular sclerosis in 20, type 1 membranoproliferative glomerulonephritis in 16, type 2 membranoproliferative glomerulonephritis in two, proliferative glomerulonephritis in five, crescentic proliferative glomerulonephritis in four and anti-glomerular basement membrane disease in two. In this group of 61, there were 19 patients with 21 allografts in which there was evidence of recurrent glomerulonephritis including four each with idiopathic membranous glomerulonephritis and focal glomerular sclerosis, seven with type 1 membranoproliferative glomerulonephritis, two each with type 2 membranoproliferative glomerulonephritis and anti-glomerular basement membrane disease and one each with IgA nephropathy and crescentic proliferative glomerulonephritis. There were 104 living related donor kidneys grafted into patients with chronic glomerulonephritis, and 78 had tissue available for evaluation. In this group, 15 patients had 16 grafts with recurrent glomerulonephritis. There were 55 cadaveric donor kidneys transplanted into patients with chronic glomerulonephritis, and 39 had tissue available for evaluation. In this group, there were five examples of recurrent glomerulonephritis. Thus, recurrent glomerulonephritis can occur in a variety of histologic subtypes, and in this study population, recurrent glomerulonephritis was more common in allografts from living related donors.     

Mesangial proliferative glomerulonephritis associated with multiple myeloma

IgA lambda multiple myeloma was diagnosed in a 58-year-old white woman after the onset of nephrotic syndrome. Serial renal histology demonstrated progressive mesangial proliferative glomerulonephritis. Electron microscopy revealed subepithelial electron dense deposits. Immunofluorescence microscopy demonstrated granular staining of peripheral capillary loops with IgG and C3. No IgA was present. No evidence of deposition of the myeloma protein in the glomeruli was found. The temporal relationship of occurrence of the two diseases and the progression of glomerular disease suggest that multiple myeloma be added to the list of malignancies causing immune complex glomerulonephritis.     

A male with angioimmunoblastic T-cell lymphoma and proliferative glomerulonephritis

In this article we present the case report of a 67-year-old male with a nephrotic syndrome due to a proliferative glomerulonephritis, associated with an angioimmunoblastic T-cell lymphoma. Diagnosis was made on an axillary lymph node biopsy and showed expanded T-cell areas with multiple blood vessels, small mature lymphocytes, eosinophils, and plasma cells. A kidney biopsy was suggestive for a proliferative glomerulonephritis with intra- and extracapillary proliferation. Hypercellular glomeruli were seen, as well as multiple floride crescents. Interstitial edema and fibrosis were absent. Immunohistochemical reactions were negative; there was some mesangial reaction with IgM in the glomeruli. Treatment with high-dose corticosteroids was initiated, with clinical improvement, and was immediately followed by therapy with cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP), which induced complete remission with a follow-up of 1 year. To our knowledge, the association of angioimmunoblastic T-cell lymphoma and proliferative glomerulonephritis has only been described twice. It concerned elderly men who developed acute renal failure a couple of months after the diagnosis of an angioimmunoblastic T-cell lymphoma. In both, immunoglobulin-containing dense deposits within glomeruli were observed, which was not the case in our patient, where only some mesangial colorization of the IgM in the glomeruli was seen.     

IS THERE AN IgM NEPHROPATHY?

Recent reports have suggested that there is a specific form of mesangial proliferative glomerulonephritis (GN) characterised by a diffuse and generalised mesangial deposition of IgM. The study included 149 consecutive patients with primary GN, who had adequate renal tissue for detailed light and immunofluorescent microscopy. Forty of these 149 patients had glomerular deposition of IgM. Of those 40, 20 had small and isolated focal deposits of IgM in sclerotic areas, but other immunoglobulins were predominant. The remaining 20 patients had IgM as the sole (16) or predominant (4) immunoglobulin deposited. Only one of these, however, fulfilled the published criteria of a mesangial proliferative GN with a diffuse and generalised mesangial deposition of IgM. The frequency of this entity in published series varies considerably, and there is a suspicion that in some studies patients with focal and segmental sclerosis and hyalinosis may have been included. More prospective studies are necessary to confirm whether there is a separate entity of IgM nephropathy.     

Glomerulonephropathy associated with hepatitis B virus (HBV) infection

Forty-seven renal biopsies of glomerulonephropathy with persistent Australian antigenaemia (HBsAg is mostly positive) were studied with light microscope, electron microscope and direct immunofluorescence. Immunohistochemical method (ABC method) was used to examine HBsAg, HBeAg and HBcAg deposits in renal tissue. In addition 20 cases of idiopathic membranous nephropathy (MN) were studied for comparison. These 47 cases included 19 children and 28 adults. The results indicated that Australian antigens diffusely deposited in glomeruli in 14 cases (29.7%), with HBsAg in 7 cases (50.0%), HBeAg in 13 cases (92.8%) and HBcAg in 2 cases (14.3%). The 14 positive cases included 11 children and 3 adults. The pathologic types were membranous nephropathy in 12 and membranoproliferative glomerulonephritis in 2 cases. The membranous type was characterized by irregular thickening of capillary wall and double contour, bubble-like appearance and spike formation of glomerular basement membrane (GBM); immune complexes and electron dense deposits may be present in different sites of glomeruli. Coarse granular deposits of IgG and C3 along GBM were the principal pattern, but IgA, IgM and C1q were often present. Among the 20 idiopathic MN, 2 were found to have HBeAg deposition along GBM, one was a child and the other an adult IgG, IgA, IgM, C3 and C1q with HBeAg deposits were present in glomeruli.     

Case Report: Acute Cerebellar Thrombosis in an Adult Patient with IgM Nephropathy

IgM nephropathy is a relatively rare cause of idiopathic nephrotic syndrome.1 It was initially described by van de Putte,2 then by Cohen and Bhasin in 1978, as a distinctive feature of mesangial proliferative glomerulonephritis.2 It is typically characterized by diffuse IgM deposits on the glomeruli and diffuse mesangial hypercellularity. Little is known about the pathogenesis and treatment of this disease.1,3 We describe a patient who presented with nonspecific symptoms of epigastric pain, nausea, and early satiety. Abdominal imaging and endoscopies were unremarkable. She was found to have significant proteinuria (6.4 g/24 hours), hyperlipidemia, and edema consistent with a diagnosis of nephrotic syndrome. Kidney biopsy was performed and confirmed an IgM nephropathy. Less than 2 weeks after her diagnosis of IgM nephropathy, she presented with an acute cerebellar stroke. Thrombophilia is a well-known complication of nephrotic syndrome, but a review of the literature failed to show an association between IgM nephropathy and acute central nervous system thrombosis.     

Small cell anaplastic carcinoma of the lung with mesangial proliferative glomerulonephritis

Mesangial proliferative glomerulonephritis is an uncommon manifestation of renal injury associated with neoplastic disease. A 50-year-old woman with small cell anaplastic cancer of the lung and nephrotic syndrome had renal biopsy findings that were consistent with diffuse mesangial cell proliferation. Electron microscopic evaluation of renal tissue demonstrated numerous intramesangial and paramesangial dense deposits. Resolution of the nephrotic syndrome with improvement in renal function was noted after a response of the patient's tumor to combination chemotherapy.     

肾脏病肾间质中淋巴细胞亚群浸润的意义

本文报告286例各种肾脏病肾间质中淋巴细胞亚群的分析结果.正常肾间质散在分布少量CD_4~+细胞、CD_~+细胞及B~+细胞.局灶节段硬化肾炎、膜增肾炎、IgA肾病、狼疮肾炎、结节性多动脉炎及多种间质小管疾病间质中CD_4~+细胞、CD_~+细胞及B~+细胞数量著增多,CD_4~+/CD_~+细胞比值在狼疮肾炎一般<1,IgA肾病大都>1;系膜增殖肾炎、糖尿病肾病及内皮系膜增殖肾炎的CD_4~+细胞、CD_~+细胞及B~+细胞轻度增加;遗传肾炎、原发肾炎的轻微病变、IgM肾病、膜性肾病及高血压肾损害者等其CD_4~+细胞、CD_~+细胞及B~+细胞数量接近正常.间质中的T细胞数量与小管萎缩、间质纤维化程度以及血清肌酐值呈正相关.结果表明,分析肾间质淋巴细胞亚群可能有助于肾脏病的诊断,有助于判断病情的严重程度.细胞免疫可能参与间质小管损伤.     

Benign primary hematuria. Clinicopathologic study of 65 patients.

Renal biopsy specimens were examined in a group of 65 patients with primary hematuria who met the following criteria: urine protein excretion under 1 g in 24 hours or a negative Albustix^® in a concentrated specimen, absence of hypertension and normal renal function. The median age at discovery of the disease was 13 years, and the median duration of the hematuria at biopsy was two years. Recurrent gross hematuria was present in 38 instances. Thirty of the 65 renal biopsy specimens showed mesangial proliferative glomerulonephritis and in 44 there were red blood cells in the tubules. Mesangial deposits of a variety of immunoglobulins and/or third component of complement (C3) were identified in 30 of the 44 biopsy specimens examined. Immunoglobulin M (IgM) was the predominant immunoglobulin. Electron dense mesangial deposits were identified only in 12 cases; however, ultrastructural study of the biopsy specimens led to the detection of one patient who was probably suffering from Alport's syndrome. There was a poor correlation between histologic lesions and immunohistochemical findings. Thirty-nine patients were followed for a median period of four years without evidence of any deterioration of renal or any other manifestation of renal or systemic disease, although half of these patients still showed bleeding in the last urinalysis. Thus, the name benign primary hematuria appears appropriate to designate this clinical syndrome. The use of pathologic terms such as focal glomerulonephritis or immunoglobulin A (IgA) nephropathy (Berger's disease) has been a cause of ambiguity since there is not a consistent correlation between these lesions and clinical manifestations. Because the discrete mesangial changes may be predicted virtually from the clinical presentation, kidney biopsy may not seem to be indicated in the majority of these patients unless there is an increase in urinary protein excretion or other manifestations of renal, genitourinary or systemic disease appear.     

Light chain nephropathy

In 13 specimens of renal tissue from 11 patients, deposits of monoclonal immunoglobulin light chains and continuous granular electron-dense material within tubular basement membranes and in association with the glomerular basement membrane were identified. All but one patient were men in the fifth to seventh decades of life, and each presented with azotemia and features of glomerular rather than tubulointerstitial disease. Osteolytic bone lesions occurred in only three patients, and a bone marrow plasmacytosis >30 percent consistent with plasma cell myeloma was identified in only four patients.Light chain distribution in the nephron was confirmed with immunoelectron microscopy and was not associated with deposition of other serum proteins such as immunoglobulin heavy chains, complement, transferrin, alpha₂ macroglobulin and albumin. The electron dense deposits differed in distribution and character from those associated with membranoproliferative glomerulonephritis type II (dense deposit disease), amyloidosis, cryoglobulinemla, macroglobulinemia and benign monoclonal gammopathy. Serum from six of these patients did not bind to normal human or rat renal parenchyma in vitro. Kappa light chain nephropathy was characterized by predominant linear tubular basement membrane κ deposits, and nodular mesangial and linear glomerular basement membrane κ immunostaining. Lambda light chain nephropathy was characterized by linear λ glomerular basement membrane and tubular basement membrane immunostaining.Manifestations of glomerular dysfunction dominated the clinical presentation of light chain nephropathy, and most patients did not have typical features of multiple myeloma. The diagnosis was predicated upon thorough immunohistologic assessment of renal biopsy material.     

Vasculitis with mesangial IgA deposits complicating relapsing polychondritis

The authors report the case of a patient presenting with cutaneous, renal and neurologic vasculitis in the course of relapsing polychondritis (RPC). A 78-year-old man presented with a palpable purpura of the lower limbs, high fever arthralgias, delirium, and nephrotic syndrome. He had a history of relapsing polychondritis treated by corticosteroids. Renal biopsy showed diffuse endo- and extracapillary proliferative glomerulonephritis with mesangial IgA deposits. A spectacular regression of the symptoms was observed in response to pulse intravenous methylprednisolone. Relapsing polychondritis is complicated by vasculitis in 25% of the cases. This vasculitis is characterized by cutaneous, neurologic and renal manifestations, usually occurring in elderly patients. Renal involvement is characterized by segmental and focal or diffuse necrotizing glomerulonephritis. The mesangial IgA deposits observed in our patient are rarely present in the course of RPC. Renal manifestations identify severe forms of RPC, justifying systematic screening for renal complications.     

Predictors of prognosis in IgA nephropathy

IgA nephropathy (nephropathy with mesangial IgA and IgG deposits, so-called Berger's disease) is the most common primary chronic glomerulonephritis worldwide, and was first described in 1968. Histopathologically, IgA nephropathy is characterized by expansion of the glomerular mesangial matrix with mesangial cell proliferation and/or mononuclear cell infiltration. Glomeruli typically contain generalized-diffuse granular mesangial deposits of IgA (mainly IgA1), IgG and C3. This disease, therefore, is considered to be an immune-complex-mediated glomerulonephritis although the antigenic agents are still obscure. Clinically, patients with IgA nephropathy show microscopic and macroscopic hematuria and/or proteinuria. Although the clinical course is generally gradual in patients with IgA nephropathy, progression to renal hypertension, renal anemia, and end-stage kidney disease is not as rare as originally thought. Since pathogenesis and radical treatment for IgA nephropathy are still not established, it is necessary to study them using various clinical findings.     

对拉米夫定治疗无应答或变异的乙型肝炎病毒相关性肾炎的治疗

目的探讨对拉米夫定治疗无应答或变异的乙型肝炎病毒相关性肾炎(HBV-GN)的治疗方法。方法 2005年1月至2009年1月南京军区福州总医院诊治的HBV-GN且对拉米夫定治疗无应答或变异的患者共9例。采用恩替卡韦(0.5 mg/d)为主方案治疗9例对拉米夫定治疗无应答或变异的HBV-GN且蛋白尿>1.5 g/d、血HBV-DNA≥1.0×108拷贝/L的患者,观察其疗效及血HBV-DNA的变化。结果 9例患者肾病综合征(NS)7例、蛋白尿伴血尿2例,其中系膜增生性肾炎3例,膜性肾病3例,膜增生性肾炎、IgA肾病及局灶节段系膜增生性肾炎各1例。拉米夫定治疗(14.1±10.3)个月(其中6例联合激素治疗),5例部分缓解(PR)、4例无效(均为NS),改用恩替卡韦治疗后,治疗12个月时7例完全缓解(CR)、1例PR、1例NR,7例检测血清HBV-DNA水平患者中5例降至正常,随访观察了19～27个月,平均(23.7±3.0)个月,至随访结束,完全缓解(CR)7例,NR 2例,均停用激素。未见副反应。结论恩替卡韦为主的治疗对对拉米夫定治疗无应答或变异的HBV-GN是安全有效的,疗程以1年半为宜。     

Renal artery dysplasia in a patient with membranoproliferative glomerulonephritis.

A 27 year old man with nephrotic syndrome due to membranoproliferative glomerulonephritis had multifocal stenoses of the renal and intestinal arteries. The arterial lesions demonstrated by angiograhy closely resembled those of medial fibromuscular dysplasia. The dysplasia progressed over a five year period to involve both renal arteries from their extrarenal segments through their interlobar branches. Low serum levels of complement components C3 and C4, focal reduplication of the glomerular basement membrane on light microscopy, and the patterns of glomerular localization of IgG and C3 by immunofluorescence were characteristic of type I membranoproliferative glomerulonephritis. The development of the arterial dysplasia in a patient with chronic glomerulonephritis suggests a common immunologic pathogenesis of both disorders.     

Hepatitis-B-associated glomerulonephritis: pathology, pathogenesis, and clinical course

Hepatitis-B-associated glomerulonephritis (HBGN) is a distinct entity occurring frequently in hepatitis-B-prevalent areas of the world. The disease affects both adults and children who are chronic hepatitis-B-virus (HBV) carriers with or without a history of overt liver disease. The diagnosis is established by serologic evidence of HBV antigens/antibodies, presence of an immune complex glomerulonephritis, immunohistochemical localization of 1 or more HBV antigens, and pertinent clinical history, when available. In this study we present clinicopathologic and follow-up findings in 12 patients (7 children, 5 adults) with hepatitis-B-associated glomerulonephritis. Twelve patients provided 15 renal biopsies and 1 specimen of kidney tissue, obtained at autopsy; these were examined by light microscopy, electron microscopy, and immunohistochemical methods. Membranous glomerulonephritis (MGN) with or without mesangial proliferation was noted in 7 biopsies, mesangiocapillary (membranoproliferative) glomerulonephritis (MCGN) in 5 biopsies, and proliferative glomerulonephritis with or without membranous changes in 2 biopsies. Tubulointerstitial changes were minimal except in 3 adults, in whom they were attributable to arterionephrosclerosis. Ultrastructural findings included the presence of considerable amounts of focal or diffuse granular electron-dense deposits in the glomeruli, in the subepithelial, subendothelial, and mesangial locations, occasionally destroying or replacing the lamina densa of the basement membrane. Variable mesangial proliferation was also observed, with interposition, with focal irregular reduplication of the basement membranes and rare clusters of spherical particles, probably representing viral particles in the deposits. In addition, granular deposits along tubular basement membranes were seen in 1 case. The glomerular deposits stained for 2 or more immunoglobulins, the predominant one being IgG, and variably also for complement components (C3, C4 and C1q). Hepatitis B viral antigens (HBsAg, HBcAg, HBeAg) were demonstrated using acid elution techniques in the deposits in all biopsies where frozen tissue was available, singly or in a variety of combinations and intensities. There were deposits of IgG, C3, C1q, and HBsAg along the tubular basement membranes in 1 case. Follow-up biopsies in 2 cases, 2 and 5 years apart, showed a transformation from a diffuse MGN to MCGN with segmental membranous features. Follow-up biopsy after 3 years in the third patient, who went into clinical remission, revealed partially resolving glomerular lesions. Renal lesions secondary to chronic liver disease, parasitic diseases, certain tropical nephropathies, and lupus nephritis are some of the diseases that may morphologically resemble HBGN. Recognition and differentiation of HBGN from other entities may have significant prognostic and therapeutic implications.(ABSTRACT TRUNCATED AT 400 WORDS)