Idiopathic mesangiocapillary glomerulonephritis: Comparison of types I and II in children and adults and long-term prognosis

Of 104 patients with idiopathic mesangiocapillary glomerulonephritis studied for at least two years, 69 patients had type I disease and 35 had type II. Forty-five patients were children, and 59 were adults. Type II mesangiocapillary glomerulonephritis was more common in children than in adults, but no other clinical feature distinguished the two types at onset. Complement studies revealed that patients with type II had lower serum C3 concentrations and more frequently showed C3-splitting activity (C3 nephritic factor) in the serum. Children had hypertension or a lowered gtomerular filtration rate less frequently at onset than did adults, but children had a higher incidence of a hematuric onset; C3 nephritic factor was also more frequent in the children.During a follow-up period of two to 21 years (mean eight years), only seven patients (five with type I and two with type II) showed clinical remission, whereas 38 percent of patients with type I and 49 percent of patients with type II died or required dialysis; a further 23 percent of patients with type I and 16 percent of patients with type II had continuing disease and reduced glomerular filtration rate. Only the presence and persistence of a nephrotic syndrome in type I predicted renal failure. In both types, the presence of sclerosis or crescents in the initial renal biopsy specimen was associated with a poorer prognosis, but no other feature was of major prognostic value.     

The nephrotic syndrome associated with neoplasia: An unusual paraneoplastic syndrome: Report of a case and review of the literature

The nephrotic syndrome complicating malignancy in the absence of renal vein thrombosis, amyloid or neoplastic infiltration of the kidney is an unusual occurrence. A case of diffuse, well differentiated, lymphocytic lymphoma and lipoid nephrosis documented by light microscopy, electron microscopy and immunofluorescent studies is reported. A review of the literature revealed 76 case reports in which the nephrotic syndrome was associated with neoplasia. The most frequently associated neoplasms are Hodgkin's disease, various carcinomas, nonHodgkin's lymphoma and leukemia in descending order. The most frequent renal lesion in patients with the nephrotic syndrome associated with various carcinomas is membranous glomerulonephritis (81 per cent) as opposed to patients with lymphomas or leukemias who have predominantly lipoid nephrosis (60 per cent). The evidence is reviewed suggesting that the lesions in membranous nephropathy are immunologically mediated by tumor or viral antigen-antibody complexes and in lipoid nephrosis perhaps by a defect in T-lymphocyte function.     

Long-term prognosis in lupus nephritis: relation to the renal biopsy data, therapy, and grade of remission

The relation between long term-prognosis and renal biopsy data or therapy were evaluated, and their contribution to remission was also considered. In total, 112 patients with new lupus nephritis who underwent renal biopsy and without other severe organ involvements were selected. These patients were divided into subgroups according to their renal biopsy data, and their clinical data were accumulated. Patients with World Health Organization (WHO) classification types III and IV had poor outcomes. Patients with mild lesions (WHO types I and II) had good outcomes when treated with low-dose steroid, while patients with severe lesions (WHO types III and IV) had better outcomes following medication with immunosuppressive agents. In particular, patients who received intravenous cyclophosphamide (IVCY) showed the best outcomes. Patients with WHO type III or IV classification without remission had poor outcomes, while those with complete remission had better outcomes. We conclude that renal biopsy data and course of therapy showed some relation in longterm prognosis, and the grade of remission was also related.     

Long-term prognosis in lupus nephritis: relation to the renal biopsy data,therapy, and grade of remission

Abstract

The relation between long term-prognosis and renal biopsy data or therapy were evaluated, and their contribution to remission was also considered. In total, 112 patients with new lupus nephritis who underwent renal biopsy and without other severe organ involvements were selected. These patients were divided into subgroups according to their renal biopsy data, and their clinical data were accumulated. Patients with World Health Organization (WHO) classification types III and IV had poor outcomes. Patients with mild lesions (WHO types I and II) had good outcomes when treated with low-dose steroid, while patients with severe lesions (WHO types III and IV) had better outcomes following medication with immunosuppressive agents. In particular, patients who received intravenous cyclophosphamide (IVCY) showed the best outcomes. Patients with WHO type III or IV classification without remission had poor outcomes, while those with complete remission had better outcomes. We conclude that renal biopsy data and course of therapy showed some relation in longterm prognosis, and the grade of remission was also related.     

Biologic and clinical significance of cryoglobulins. A report of 86 cases

Eighty-six patients with cryoglobulinemia repeatedly underwent complete immunochemical and clinical evaluation during the course of their disease. Immunochemical analysis of the purified cryoglobulins allowed us to classify them into three groups. Type I cryoglobulins are made of isolated monoclonal immunoglobulin: IgM (11 cases), IgG (7 cases), IgA (2 cases) or Bence Jones protein (1 case). Type II cryoglobulins are mixed cryoglobulins with a monoclonal component possessing antibody activity towards polyclonal IgG. These cryoglobulins were mainly IgM-IgG (19 cases), sometimes IgG-IgG (2 cases) or IgA-IgG (1 case). Type III cryoglobulins (43 cases) are mixed polyclonal cryoglobulins, i.e., composed of one or more classes of polyclonal immunoglobulins and sometimes nonimmunoglobulin molecules such as beta₁C or lipoprotein. Most of these type III cryoglobulins are also immunoglobulin-anti-immunoglobulin immune complexes. This classification enabled us to establish correlations between the biologic findings and the clinical features as well as the underlying diseases.Cutaneous and vasomotor symptoms were most severe in patients with type I and II cryoglobulins. The usual clinical picture in patients with type II or III cryoglobulins consisted of chronic vascular purpura and mild Raynaud's phenomenon. Renal and neurologic involvement were more frequent in patients with type II and III cryoglobulins, and were of major prognostic significance. In our series, immunoproliferative and autoimmune disorders were the most frequent diseases associated with cryoglobulinemia. The former were associated with type I or II cryoglobulins and the latter mainly with type III cryoglobulins. Of note is that idiopathic cryoglobulinemia accounted for nearly 30 per cent of the cases despite repeated careful clinical evaluation and a mean follow up of 9 years.In 10 per cent of the cases, acute and severe symptoms necessitated emergency treatment with plasmapheresis and chemotherapy which allowed a satisfactory initial remission in all but one patient. Conversely, no treatment was definitively effective in patients with chronic symptoms such as vascular purpura.     

Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization

The long-term course of 56 patients with systemic lupus erythematosus who had precisely defined renal histology and carefully assessed clinical status at the time of their initial renal biopsy prior to 1976 was evaluated and analyzed by life-table analysis. The average length of follow-up has now been greater than 10 years since initial biopsy. Patients with mesangial lesions (World Health Organization [WHO] classes IIA and IIB) had a more favorable renal and patient survival at five and 10 years than did patients in the other WHO classes (III, IV, and V). Individual renal histologic features of activity and chronicity when combined into an activity index and a chronicity index did not significantly predict renal survival in this population, nor did the presence of hypertension or renal dysfunction at the time of the initial renal biopsy significantly influence renal or patient survival. Patients with the nephrotic syndrome at initial biopsy had a poorer renal survival than did patients without the nephrotic syndrome. However, patients who experienced a remission of the nephrotic syndrome fared better in terms of both renal and patient survival than did those patients without a remission. By life-table analysis, patient survival was significantly better for patients in whom biopsy was performed after 1973 than for those in whom biopsy was performed prior to that time despite similar clinical features and WHO histology in each group interval. Our data suggest that improved survival for patients in recent studies may relate to better supportive care and more selective use of immunosuppressive therapy in patients with milder forms of lupus nephritis.     

Renal vein thrombosis and the nephrotic syndrome. Report of two cases with successful treatment of one

A nephrotic syndrome and bilateral renal vein thrombosis developed in two women. One suffered low back pain, the other oliguric renal failure. Both suffered pulmonary emboli and had exhibited edema, proteinuria and hypertension during pregnancies several years before. Results of thrombectomy and anticoagulant therapy were successful in one patient, although she suffered serious hemorrhage at the biopsy site during anticoagulant therapy. The other patient died of pulmonary embolism. Renal interstitial changes usually associated with renal vein thrombosis were found in both, but neither showed membranous nephropathy (membranous glomerulonephritis). This study suggests that (1) although membranous nephropathy is frequently associated with renal vein thrombosis, it is probably not the result of that condition nor invariably associated with it. (2) Prognosis in renal vein thrombosis with nephrotic syndrome may be partially dependent upon underlying renal disease. (3) Renal biopsy is useful for diagnosis and assaying prognosis. (4) Treatment should consist of thrombectomy and anticoagulants. However, serious hemorrhage may occur in patients recently subjected to biopsy.     

Membranous glomerulopathy associated with captopril therapy

Two cases of nephrotic syndrome and biopsy-proved membranous glomerulopathy (membranous glomerulonephritis) were encountered during captopril treatment of 53 hypertensive subjects in our institution. Both patients had impaired renal function before treatment and were treated with 600 mg per day. Discontinuation of captopril led to transient partial remission of proteinuria but was followed by a recurrent, fluctuating course over one year later. Repeat biopsies, eight and 12 months after discontinuation of the drug, demonstrated persistent subepithelial deposits in the glomerular basement membrane. There has been a decline in glomerular filtration rate since discontinuation of the drug, apparently due to arterionephrosclerosis. These studies suggest that glomerular basement membrane deposits in captopril-associated membranous glomerulonephritis are not readily reversible and may be associated with persistent proteinuria, contrary to some previous reports.     

The prognostic and therapeutic implications of DNA:anti-DNA immune complexes in systemic lupus erythematosus (SLE).

Serum samples serially obtained from 50 patients with systemic lupus erythematosus (SLE) were studied for antibody to deoxyribonucleic acid (DNA) and circulating DNA:anti-DNA complexes during the active and inactive phases of their disease. The patients were divided into four categories: Group I: six patients without clinical evidence of central nervous system (CNS) or renal involvement. Group II: three patients with CNS lupus. Group III: nine patients with normal urinalyses and glomerular filtration rates, but morphologic evidence of glomerular disease. Group IV: 32 patients with overt lupus nephritis. Elevated anti-DNA levels were observed in 16 of 18 patients (88 per cent) in groups I, II and III during active disease. This persisted in 14 (77 per cent) during remission. DNA:anti-DNA complexes were demonstrated in four of 18 (22 per cent) during active disease and disappeared in all but one patient with progressive disease. In 30 of the 32 patients (94 per cent) in group IV, DNA binding was increased during active disease; this persisted in 21 (70 per cent) despite remission. Complexes were observed in 25 of the patients in group IV (78 per cent) with active disease. In six of these patients, complexes have persisted; two have died, one has progressed to renal failure and the remaining three patients continue to manifest active disease. This study suggests that measurement of DNA:anti-DNA complexes provides a valuable additional index of disease activity and prognosis in SLE.     

Unilateral renal vein thrombosis and nephrotic syndrome: Report of a case with protein selectivity and antithrombin III clearance studies

A case of the nephrotic syndrome with unilateral renal vein thrombosis is reported. The patient, an 18 year old man, presented with a six month history of edema and the recent development of a left-sided varicocele. An enlarged left kidney and a thrombus in the left renal vein were demonstrated roentgenographically. A biopsy specimen of the right kidney was interpreted as membranous glomerulonephritis. Selective renal function studies showed nearly identical creatinine excretion, and similar total protein excretion and protein selectivity from each kidney. Thus, the thrombus in the left renal vein did not influence glomerular filtration rate or quantitative or qualitative protein excretion. A high urinary output and a decreased serum level of antithrombin III were measured. These findings suggest a mechanism to explain the increased thrombotic tendency seen in this and other patients with the nephrotic syndrome.     

Membranes nephropathy associated with renal cell carcinoma. Evidence against a role of renal tubular or tumor antibodies in pathogenesis

A patient with the nephrotic syndrome due to membranous nephropathy was found to have renal cell carcinoma. Since membranous nephropathy in patients with malignancies has been attributed to a tumor antigen-antibody complex form of glomerulonephritis, an attempt was made to implicate tumor antigens and/or renal tubular epithelial antigens in the pathogenesis of membranous nephropathy in our patient with renal cell carcinoma. Antibodies directed against tumor antigens and renal tubular antigens and renal tubular eipthelial antigens were sought in his serum and in eluates of his glomeruli; no such antibodies were found. The concurrence of the two renal lesions may have been fortuitous in this patient. However, their association temporally suggests that they were related, and our immunologic studies demonstrate that tumor antigen-antibody complexes are not invariably involved in the pathogenesis of malignancy-associated membranous nephropathy.     

环孢霉素A治疗Ⅴ型狼疮性肾炎的研究

目的Ⅴ型狼疮性肾炎(WHO分型LN-V型)主要表现为蛋白尿或肾病综合征,本文分析环孢霉素A(CsA)对LN-V型的疗效。方法分析16例经肾活检明确诊断为LN-V型患者CsA治疗的近期及远期的治疗反应。16例患者治疗前均处于肾病综合征状态。治疗方法CsA 5 mg／(kg·d)诱导治疗3个月,以后每月减1mg／(kg·d)直至2mg／(kg·d)维持,CsA治疗同时采用强的松维持。总疗程12～24月,随访时间18月～4年。结果诱导期CsA平均血药谷浓度为185±30.8μg／L。经CsA治疗3个月后,4例(25％)缓解,6例(37.5％)部分缓解。治疗6个月,平均尿蛋白为0.3±0.4g／24h,血清白蛋白为40.7±4.9g／L。12例(75％)缓解,3例(18.7％)部分缓解,1例(6.3％)无效,总有效率达93.7％。8例伴有镜下血尿者有6例血尿消失,血清学指标也有所改善。CsA停药两年后有5例(41.7％)复发。CsA治疗1月内81.2％患者(13／16)血尿素氮和肌酐有一过性升高。其它副作用有血压升高(6／16),少数患者出现多毛及齿龈增生。3例重复肾活检未见条索状间质纤维化或典型CsA导致的小动脉病变。结论本研究证实CsA治疗降低V型LN蛋白尿短期内疗效肯定,且CsA≤5mg／(kg·d)用于肾功能正常LN患者未出现严重肾毒性。但停用CsA后复发率高。CsA治疗V型LN的长期疗效及安全性有待严格的临床对照研究和随访。     

Primary glomerular diseases in the elderly Glomerulonephritis in the elderly

Recent studies have pointed out that the incidence of primary glomerular diseases is similar in the elderly and in younger populations. However the clinical characteristics of the different subtypes may be different in the advanced age. Minimal change nephropathy responds favorably to corticosteroids and/or cyclophosphamide, but many untreated or non-responder patients progress to end-stage renal disease or die from nephrotic complications. Focal and segmental glomerulosclerosis also has a severe prognosis in older patients but some 50% of patients may attain remission of the nephrotic syndrome with a prolonged corticosteroid treatment. The responders tend to maintain normal renal function over time. Membranoproliferative glomerulonephritis and IgA nephritis have a severe prognosis and do not respond to treatment. The clinical presentation and the outcome of membranous nephropathy are similar in the elderly and in younger adults. Corticosteroids are of little benefit while a 6-month treatment with chlorambucil and methylprednisolone may obtain remission of the nephrotic syndrome in about 2/3 of older patients. Crescentic glomerulonephritis has an ominous prognosis in older patients but some patients may improve if treatment with methylprednisolone pulses is started early. Acute postinfectious glomerulonephritis is often associated with renal failure in older patients. The prognosis may be severe.     

Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids

OBJECTIVE: Rituximab, an anti-CD20 monoclonal antibody, has been used in lupus nephritis and membranous idiopathic nephropathy and has proved effective in non-renal manifestations of type II mixed cryoglobulinaemia (MC) syndrome. We investigated the possible efficacy and safety of rituximab in the treatment of cryoglobulinaemic nephritis. METHODS: Five patients with active, biopsy-proven, glomerulonephritis in hepatitis C virus (HCV)-related type II MC syndrome were treated with four weekly infusions of rituximab (375 mg/m2) in monotherapy, without steroids whenever possible. Rituximab was the first-line therapy in three cases. RESULTS: A rapid and sustained renal response was observed in all patients, in one of them without retreatment up to the last follow-up (month 21+). Renal biopsy was repeated after 6 months in one patient and histopathological improvement was documented. Three patients relapsed, at months +5, +7 and +12 of follow-up, respectively. Two of them were then retreated with rituximab and again presented a rapid improvement in renal function. Maintenance therapy with rituximab was performed in two patients: nephritis remission was maintained in both. Fc-gamma receptor 3a (FcgammaRIIIa) genotype characterization was consistent with the clinical response observed. Rituximab also proved effective against other active MC manifestations, when present. No major side-effects occurred and steroids were not required in the follow-up. CONCLUSIONS: Rituximab may provide effective and safe therapy in type II MC-related glomerulonephritis, possibly as first-line therapy, avoiding steroids and hazardous immunosuppressive treatment.     

Membranous Glomerulonephritis Associated with Sarcoidosis*

Summary: Two patients with sarcoidosis involving pulmonary hilar lymph nodes developed the nephrotic syndrome. Renal biopsy in both cases showed membranous glomerulonephritis. In one patient, there was an associated renal vein thrombosis.     

Membranous Glomerulonephritis Associated with Sarcoidosis*

Summary: Two patients with sarcoidosis involving pulmonary hilar lymph nodes developed the nephrotic syndrome. Renal biopsy in both cases showed membranous glomerulonephritis. In one patient, there was an associated renal vein thrombosis.     

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.     

Nondiabetic renal disease in patients with diabetes mellitus

Renal diseases other than diabetic nephropathy were found in 10 of 122 diabetic patients who underwent renal biopsy between 1960 and 1982. These diseases included lupus glomerulonephritis, acute post-streptococcal glomerulonephritis, membranoproliferative glomerulonephritis (type I), focal glomerulosclerosis, idiopathic membranous nephropathy, and nonspecific immune complex glomerulonephritides. Because some of these disorders can alter the management and prognosis of renal disease in diabetic patients, the appearance of urinary abnormalities or deterioration in renal function inconsistent with the natural history of diabetic nephropathy raises the possibility of a nondiabetic renal disease and should lead to a more detailed evaluation.     

Rapidly progressive glomerulonephritis. A clinical and pathologic study.

Twenty-nine cases of rapidly progressive glomerulonephritis were reviewed. In all cases there was less than three months between the onset of renal symptoms and renal biopsy. The serum creatinine was greater than 2.5 mg/100 ml at the time of biopsy, and the histology showed a 50 per cent or greater incidence of crescents in the glomeruli. Infectious or febrile episodes were present in 21 cases, microscopic hematuria was noted in 15 and proteinuria exceeding 2.5 g/24 hours in eight. Oliguria less than 500 ml/24 hours was present in 20 cases and dialysis was required in 22. In 10 cases there was sustained improvement; in the remainder the disease progressed or the patient died. The prognosis was related to the number and size of the glomerular crescents. Histologically cases fell into two main groups, one with predominantly extracapillary proliferation and the other with endo- and extracapillary proliferation. In the first group the disease was histologically and clinically more severe, and Immunofluorescence histology was heterogeneous and often non-specific except for three cases in which there were linear immunoglobulin deposits. In the second group the lesions were less severe and immunoglobulin deposits were common. Electron microscopy in 14 cases was confirmatory, and also demonstrated capillary rupture and necrosis of podocytes in some loops. Transition from group I to group II was observed in serial biopsy specimens in one case. The histologic and immunofluorescent heterogeneity suggest that rapidly progressive glomerulonephritis is the end result of several different pathogenetic mechanisms.     

Membranous glomerulonephritis in rheumatoid arthritis unassociated with gold or penicillamine treatment.

A 16 year old girl with rheumatoid arthritis who had not received gold or penicillamine developed a nephrotic syndrome. Her renal biopsy specimen showed membranous glomerulonephritis by light, electron, and immunofluorescence microscopy.