A case of nephrotic syndrome associated with bronchogenic carcinoma]

A 58-year-old fisherman was admitted because of an abnormal chest X-ray shadow on the right side. Bronchoscopic examination revealed tumor of right B7. Transbronchial biopsy showed squamous cell carcinoma. He was treated with four courses of CDDP and PEP. Two years later, he developed nephrotic syndrome and relapse of lung cancer. Proteinuria and pedal edema continued. Renal biopsy revealed the characteristic light and immunofluorescent microscopic features of membranous nephropathy. Oral administration of low dose etoposide resulted in reduction of the carcinomatous lung lesion and a decrease in proteinuria as well as pedal edema.     

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.     

The nephrotic syndrome in the elderly: clinico-pathological correlations in 317 patients

We have used the Medical Research Council's Glomerulonephritis (GN) registry to review the clinicopathological findings in a large group (317) of patients over 60 years of age and presenting with the nephrotic syndrome. A wide variety of histological appearances were seen to underlie this clinical diagnosis with the most frequent being membranous nephropathy (36.6%), minimal change nephrotic syndrome (11.0%) and renal amyloid (10.7%). Clinical parameters measured at the time of biopsy were unhelpful in distinguishing between the individual histological groups. A secondary cause for the nephrotic syndrome was identified in 103 (32%) patients, and a malignancy was known to be present at the time of biopsy in 15 patients. As confusion currently surrounds the treatment of these patients (particularly those with membranous nephropathy) and as histology cannot be predicted by clinical parameters, we believe that renal biopsy is an important investigation in the management of elderly adults with the nephrotic syndrome.     

A case of cervical cancer-related membranous nephropathy treated with radiation therapy

Paraneoplastic nephropathy is a rare complication of malignant disease. We present a case of cervical cancer with biopsy-proven membranous nephropathy and associated nephrotic syndrome. Irradiation to the specific neoplasm site and to the metastatic paraaortic lymph node tissues lead to regression of the nephrotic syndrome without causing severe adverse events. Radiation therapy can be the first choice in the treatment of paraneoplastic nephrotic syndrome if the primary neoplasm is unresectable. Invasiveness of intervention and patient prognosis should be carefully deliberated in the management of the two diseases.     

Membranous nephropathy and crescentic glomerulonephritis

The most frequent causes of glomerular diseases whose main clinical syndrome are nephrotic syndrome and acute renal failure may have several causes: acute tubular necrosis, thrombosis of renal veins, acute tubulointerstitial nephritis. Infrequently, the association between primary glomerular disease (membranous nephropathy and others) and crescentic glomerulonephritis can cause this clinical picture. We describe a young woman without systemic disease with nephrotic syndrome and acute renal failure secondary to membranous nephropathy and superimposed crescentic glomerulonephritis. She received steroids and cyclophosphamide with stabilization of renal function after two months of follow-up.     

Paraneoplastic glomerular diseases and malignancies

Paraneoplastic glomerulopathies are rare manifestations of neoplastic disease to be distinguished from iatrogenic renal damage. Solid tumors are preferentially associated with membranous nephropathy, whereas Hodgkin's lymphomas are associated with minimal change disease. The most common neoplasia associated with paraneoplastic glomerular disease are carcinomas of the lung and of the gastrointestinal tract. Nephrotic syndrome is the most frequent presentation of paraneoplastic glomerulopathy and the most critical glomerular disease regarding prognosis and patient care. Renal biopsy is recommended in patients with glomerular proteinuria or nephrotic syndrome and cancer, depending on life expectancy and therapeutic options. The primary treatment must be directed at the cancer in all cases. Symptomatic treatment of the nephrotic syndrome with diuretics and ACE inhibitors is justified. Prevention of nephrotic syndrome complications, i.e. thromboses and infections, should also be addressed and systematic regular renal follow-up is warranted. All treatments should be regularly reviewed to avoid toxicity, associated renal function loss or low albumin levels for patients receiving albumin-binding drugs. Epidemiologic studies have low evidence-based value. There is no widely accepted experimental model of the association of glomerulopathy and cancer. Thus, epidemiologic and mechanistic studies are needed to determine the true prevalence of paraneoplastic glomerulopathies and investigate new pathophysiologic approaches.     

Idiopathic membranous nephropathy associated with anti-calcineurin toxicity. Prognosis and other immunosuppressive treatments

A 32-year-old male patient was admitted at our department presenting microhematuria and full nephrotic syndrome in April 1995. A percutaneous kidney biopsy showed a stage I-lI membranous nephropathy and an eight-week course with oral prednisone was initiated without response. Then, oral cyclosporine A (3.5 mg/kg/day) was given and after 5 weeks of treatment, remission of the nephrotic syndrome was observed but creatinine raised to 1.6 mg/dl, normalizing after reducing the dose of cyclosporine A. We discuss the settings, prognostic and therapeutic alternatives for idiopathic membranous nephropathy.     

Membranous Nephropathy Associated with Donor Lymphocyte Infusion following Allogeneic Bone Marrow Transplantation

Nephrotic syndrome after hematopoietic stem cell transplantation (HSCT) followed by donor lymphocyte infusion (DLI) has never been described. We report the case of a myelodysplastic syndrome (MDS) patient who developed nephrotic syndrome with membranous nephropathy 18 months after allogeneic HSCT and 4 months after DLI. A 50-year-old woman with MDS underwent allogeneic bone marrow transplantation from her HLA-matched brother. MDS relapsed 55 days after transplantation, donor lymphocytes were infused as adoptive immunotherapy, and complete remission was achieved. Four months after the third DLI, the patient developed nephrotic syndrome with proteinuria up to 9 g/day. Renal biopsy revealed granular deposits of immunoglobulin G along the glomerular basement membrane, and subepithelial electron-dense deposits. A diagnosis of membranous nephropathy was made. For maintenance of the immunotherapeutic effect of DLI, minimum doses of immunosuppressive therapy for decreasing proteinuria were administered, and improvement of nephrotic syndrome and persistent complete remission of MDS were achieved.     

Nephrotic syndrome associated with adenocarcinoma of the breast

Although the nephrotic syndrome has been reported in association with a wide variety of neoplastic diseases, it has only rarely been noted as a complication of breast carcinoma. We describe a patient who presented with the nephrotic syndrome and who was subsequently found to have carcinoma of the breast. The findings on renal biopsy were indicative of membranous nephropathy with positive immunofluorescent staining for immunoglobulin G (IgG) and the third component of complement (C3). The nephrotic syndrome completely resolved following successful treatment of the cancer. We have now followed this patient for over two years and there has been no recurrence of tumor or 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.     

Nephrotic syndrome in childhood

Childhood nephrotic syndromes are most commonly caused by one of two idiopathic diseases: minimal-change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS). A third distinct type, membranous nephropathy, is rare in children. Other causes of isolated nephrotic syndrome can be subdivided into two major categories: rare genetic disorders, and secondary diseases associated with drugs, infections, or neoplasia. The cause of idiopathic nephrotic syndrome remains unknown, but evidence suggests it may be a primary T-cell disorder that leads to glomerular podocyte dysfunction. Genetic studies in children with familial nephrotic syndrome have identified mutations in genes that encode important podocyte proteins. Patients with idiopathic nephrotic syndrome are initially treated with corticosteroids. Steroid-responsiveness is of greater prognostic use than renal histology. Several second-line drugs, including alkylating agents, ciclosporin, and levamisole, may be effective for complicated and steroid-unresponsive MCNS and FSGS patients. Nephrotic syndrome is associated with several medical complications, the most severe and potentially fatal being bacterial infections and thromboembolism. Idiopathic nephrotic syndrome is a chronic relapsing disease for most steroid-responsive patients, whereas most children with refractory FSGS ultimately develop end-stage renal disease. Research is being done to further elucidate the disorder's molecular pathogenesis, identify new prognostic indicators, and to develop better approaches to treatment.     

A case of progressive systemic sclerosis with Sj?gren's syndrome complicated by nephrotic syndrome caused by bucillamine

A 53-year-old woman was admitted with complaints of edema in the lower legs. The patient had developed polyarthralgia in 1982 and had been treated with D-penicillamine and prednisolone under the diagnosis of rheumatoid arthritis. She then had developed sclerosis of skin as well as dry eyes and dry mouth. In November 1987, bucillamine treatment had started and proteinuria had appeared in February 1988. Her blood showed hypoproteinemia and was positive for anti-Scl-70 antibody test and for anti-SS-A antibody test. The skin biopsy and labial salivary gland biopsy revealed the increased collagen fibers in the subcutaneous tissue and the round cell infiltration around the salivary ducts. We diagnosed her as progressive systemic sclerosis (PSS) with Sj?gren's syndrome (SjS) complicated by nephrotic syndrome. Subsequently a renal biopsy was performed. There were the granular deposition of IgG and complements in the glomerular capillary wall and electron dense deposits in the subepithelial region. These findings suggested that she had membranous nephropathy. Since such a renal lesion was rarely observed in PSS and SjS, it was highly probable that bucillamine induced the nephropathy. The bucillamine treatment was discontinued about 2 months after the nephrotic syndrome had developed. However, the nephrotic syndrome has continued for additional 8 months. Thus it is concluded that the renal damage is one of the important side effect caused by bucillamine.     

Nephrotic syndrome as a clinical manifestation of systemic sclerosis

We have described the unusual case of coexistence of membranous nephropathy resulting in nephrotic syndrome with systemic sclerosis. A 60-year-old patient was admitted to the Department of Nephrology with marked proteinuria and oedema. The renal biopsy specimen disclosed the features characteristic of membranous glomerulonephritis. The patient was treated with chlorambucil for 1 month followed by prednisone for 1 month. However, her condition still did not improve. Therefore, the other causes of nephrotic syndrome were investigated. Once anti-Scl-70 antibody was detected the patient was transferred to the Department of Rheumatology and Connective Tissue Diseases. Physical examination revealed Raynaud phenomenon, sclerodactylia, thickened skin of the chest and back. The patient was diagnosed with diffuse systemic sclerosis. The cyclophosphamide therapy was instituted and the patient’s condition improved.     

老年肾病综合征肾活检病理类型及血清抗M型磷脂酶A2受体IgG水平的研究

目的探讨老年肾病综合征肾活检病理类型及血清M型磷脂酶A2受体(PLA2R)IgG水平,为老年肾病综合征肾脏病理类型的非肾活检诊断提供依据。方法回顾分析2009年1月至2019年6月在中日友好医院肾内科诊断为肾病综合征,并住院期进行肾穿刺活检的老年患者临床数据和肾活检资料。结果共纳入研究对象250例,年龄平均(65.85±4.68)岁,其中男152例,女98例。(1)常见肾活检病理类型:膜性肾病154例(61.6%),微小病变性肾小球病31例(12.4%),局灶节段性肾小球硬化症20例(8.0%),IgA肾病11例(4.4%);继发性肾小球疾病中,糖尿病肾病11例(4.4%),乙型肝炎病毒相关性膜性肾病5例(2.0%),淀粉样变性肾损害5例(2.0%)。(2)对比前后5年间肾活检病理谱变化,膜性肾病(由61.11%增至62.36%)、微小病变性肾小球病(由9.72%增至13.48%)、糖尿病肾病(由4.17%增至4.49%)所占比例略有增加,IgA肾病(由11.11%降至1.69%),局灶节段性肾小球硬化症(由11.11%降至7.30%)所占比例显著下降。近5年来,膜性肾病和肾小球微小病变病两者所占比例达到了75.9%。(3)86例原发膜性肾病检测了血清PLA2R抗体水平,其中44例(51.2%)阳性,肾小球微小病变病和局灶节段性肾小球硬化症患者血清PLA2R抗体均阴性。结论老年肾病综合征中以膜性肾病最常见,其次是肾小球微小病变病,且所占比例有增多趋势。血清PLA2R抗体检测对老年肾病综合征中原发性膜性肾病诊断具有参考意义。     

Therapy of the idiopathic nephrotic syndrome with alternate day steroids

Eighty-one adult patients with the idiopathic nephrotic syndrome were treated with prednisone, 60 to 120 mg, on alternate days. Treatment was continued with diminishing drug doses for up to 10 years. Biopsy specimens were categorized as showing lipoid nephrosis 36 per cent, focal sclerosis 12 per cent, diffuse proliferative 22 per cent and membranous nephropathy 30 per cent. Patients with systemic causes of the nephrotic syndrome were excluded.     

Treatment with Candesartan Combined with Angiotensin-Converting Enzyme Inhibitor for Immunosuppressive Treatment—Resistant Nephrotic Syndrome after Allogeneic Stem Cell Transplantation

Most cases of nephrotic syndrome following stem cell transplantation (SCT) occur 6 months after SCT. The patients are treated with immunosuppressive therapies; however, in some cases treatment is not effective. We used enalapril, an angiotensin-converting enzyme inhibitor (ACEI) and candesartan, an angiotensin II receptor blocker (ARB), for the control of proteinuria in a case of immunosuppressive treatment (IST)-resistant nephrotic syndrome. A 15-year-old boy with acute lymphoblastic leukemia underwent allogeneic peripheral blood SCT from a completely HLA-matched sibling after completion of a conditioning regimen composed of 12-Gy doses of total-body irradiation, 600 mg/m2 thiotepa, and 140 mg/m2 melphalan. Twenty-eight months after SCT, minimal-change nephrotic syndrome was diagnosed on the basis of biopsy findings. Although neither cyclosporine (trough level, 100-150 ng/mL) nor corticosteroid was effective, proteinuria disappeared 2 months after the beginning of treatment with tacrolimus (trough level, 13-20 ng/mL), and remission was maintained for 23 months. Nephrotic syndrome recurred, however, and was resistant to tacrolimus. Findings at the second renal biopsy revealed membranous nephropathy. An ARB (candesartan, 4 mg/ day) in combination with an ACEI (enalapril, 5 mg/day) was started. Proteinuria improved within 2 weeks. We suggest that ARB combined with ACEI can be used to control proteinuria in patients with IST-resistant nephrotic syndrome after SCT.     

Extramembranous glomerulopathy in chronic B lymphoid leukemia. 5 years' follow-up

A nephrotic syndrome due to membranous nephropathy and B chronic lymphocytic leukemia were simultaneously discovered in a 52 year old patient. Proteinuria was significantly reduced with chlorambucil therapy and nephrotic syndrome disappeared. Treatment withdrawal for 5 months resulted in a significant lowering of serum albumin level, while blood lymphocyte count increased. These observations indicate a probable causal relationship between the lymphoproliferative disease and the onset of the glomerulopathy which is supported by the efficacy of the chemotherapy on the evolution of the nephrotic syndrome.     

Spontaneous Remission of Thrombospondin Type-1 Domain-Containing-Associated Membranous Nephropathy

Membranous nephropathy often achieves spontaneous remission. However, there are scarce reports of spontaneous remission of thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy. A 64-year-old female presented with nephrotic syndrome and edema of the lower extremities. We diagnosed membranous nephropathy by kidney biopsy and confirmed positive THSD7A on immunofluorescence using frozen sections; serum THSD7A antibodies were also detected. Thirty-four months after the initial diagnosis, she achieved a spontaneous complete remission without immunosuppressive therapy. With the complete remission, no serum THSD7A levels were detected. In this study, we describe serial examinations of kidney biopsies and serum THSD7A antibodies.     

Primary Sjögren's syndrome with minimal change disease--a case report

Glomerular involvement in patients with primary Sj?gren's syndrome (pSS) has rarely been reported. Among them, membranoproliferative glomerulonephritis and membranous nephropathy are the more common types. We report a middle-aged female presenting concurrently with nephrotic syndrome and microscopic hematuria, and her pSS was diagnosed by positive anti-Ro (SSA)/anti-La (SSB) autoantibodies, dry mouth, severely diffuse impaired function of both bilateral parotid and submandibular glands, and a positive Schirmer test. Renal pathology revealed minimal change disease and thin basement membrane nephropathy. The patient's nephrotic syndrome resolved after treatment with corticosteroids. To our knowledge, this is the first report of minimal change disease in a patient with pSS.     

Collapsing focal segmental glomerulosclerosis in a patient with oral cavity cancer: A case report

Rationale:Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases, leading to end-stage renal disease. Among the 5 variants of FSGS, the collapsing variant is rare and has the worst prognosis. Solid and hematologic malignancies are associated with glomerular diseases, such as membranous nephropathy, minimal change disease, and FSGS. However, squamous cell carcinoma of the oral cavity is rarely associated with nephrotic syndrome, especially FSGS.Patient concerns:A 55-year-old woman diagnosed with oral cavity cancer presented with generalized edema with heavy proteinuria and renal dysfunction after neoadjuvant chemotherapy and wide surgical excision.Diagnosis:Renal biopsy shows segmental or global collapse of glomerular capillaries with marked hyperplasia and swelling of overlying epithelial cells, suggesting a collapsing variant of FSGS.Interventions:After the renal biopsy, we prescribed oral prednisolone at a dose of 1 mg/kg/day. Despite immunosuppressive treatment, renal function deteriorated, and hemodialysis was started.Outcomes:After 23 sessions of hemodialysis and high-dose oral glucocorticoid treatment, renal function gradually improved, and oral glucocorticoid therapy was discontinued after 8 months. Currently, this patient is in a cancer-free state and has normal renal function without proteinuria.Lessons:Unusual collapsing FSGS might be associated with neoadjuvant chemotherapy and wide surgical excision in patients with oral cavity cancer. Proper diagnostic workup, such as renal biopsy and high-dose glucocorticoid therapy, might have helped recover from nephrotic syndrome and acute renal injury in cancer patients.