melphalan and Glomerulonephritis--Membranoproliferative

Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the non-amyloid deposition of monoclonal immunoglobulin fragments in the basement membranes. Heavy chain deposition disease (HCDD) is a type of MIDD. HCDD is an extremely rare disease, and only three cases have been reported in Japan up to the present. The prognosis of HCDD is very poor, and optimal treatment has not been established. Only a few cases of HCDD with favorable long-term renal prognosis have been reported to date.. The authors describe a 61-year-old woman who presented with massive proteinuria, progressive kidney impairment, and hypocomplementemia. Kidney biopsy was performed for a precise diagnosis. On light microscopy, glomerules were lobulated and presented with nodular sclerosing glomerulopathy with membranoproliferative glomerulonephritis-like features. Immunofluorescence studies were positive for IgG, C3, and C1q within the mesangial nodules and in a linear distribution along the capillary walls without associated deposition of light chains. Staining for IgG showed the presence of linear deposits along tubular basement membranes. The analysis of the IgG subclass stain demonstrated intense positivity for IgG3 only. Electron microscopy revealed non-organized electron-dense deposits in the expanded mesangial area and inner aspect of the glomerular basement membranes. In accordance with the histological findings, we diagnosed γ3-HCDD. There was no evidence of plasma cell dyscrasia as a result of bone marrow aspiration. Serum and urine monoclonal proteins were not detected by immunoelectrophoresis and immunofixation electrophoresis. The serum free light chain ratio was within normal range. At first, prednisolone was administrated at a dose of 40 mg/day. However, a therapeutic effect was not observed. Urinary protein was not decreased and renal function further deteriorated. Therefore, melphalan plus prednisolone (MP) therapy was initiated. After 4 courses of MP therapy, the clinical parameters, including proteinuria, serum creatinine, albumin, and complement level (C3 and C4) were ameliorated. To date, the patient has been followed for 28 months, and long-term renal survival has been observed.. In this case, hematologic disease such as multiple myeloma was not detected; however, MP therapy was effective. Recently, the novel concept of monoclonal gammopathy of renal significance (MGRS) has been reported. MIDD, which includes HCDD, is one category of MGRS. In MGRS, aggressive chemotherapy may induce favorable renal outcomes.

Topics: Drug Therapy, Combination; Female; Glomerulonephritis, Membranoproliferative; Heavy Chain Disease; Humans; Immunoglobulin G; Melphalan; Middle Aged; Prednisolone

To investigate the clinical characteristics and histopathological features of kidney disease in elderly patients.. We retrospectively analyzed the results of 4,185 consecutive renal biopsies, and 288 patients aged >60 years at the Second Hospital of Jilin University from January 1998 to December 2013 were finally included. All patients had been clinically and histologically diagnosed with kidney disease.. Nephrotic syndrome was the main clinical indication for biopsy. Twenty-four patients (8.33 %) experienced a minor complication related to their biopsy procedure. Among patients diagnosed as primary glomerulonephritis (GN), membranous nephropathy (MN) was the most frequent subclassification (24.7 %), followed by mesangioproliferative glomerulonephritis (MsPGN, 11.1 %) and IgA nephropathy (IgAN, 8.0 %). Amyloidosis (8.7 %) was the most common secondary GN, followed by antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune GN (5.2 %) and diabetic nephropathy (DN, 3.8 %). Based on renal biopsies results, 143/288 patients received immunosuppressive therapy and showed an overall remission rate (complete plus partial remissions) of 74.1 %. Among 71 MN patients, 29 patients received steroids plus cyclophosphamide and showed a remission rate of 79.3 %, while 42 patients received steroids and tacrolimus and showed a remission rate of 90.5 %. Among 25 patients with amyloidosis, 22 cases received melphalan plus dexamethasone and showed a remission rate of 40.9 %, while three patients received vincristine, adriamycin, and dexamethasone and showed a remission rate of 66.7 %.. Making an accurate pathologic diagnosis by renal biopsy is crucial for selecting the proper treatment for elderly patients with kidney disease.

Topics: Aged; Aged, 80 and over; Amyloidosis; Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antineoplastic Agents, Alkylating; Autoimmune Diseases; Biopsy; Cyclophosphamide; Dexamethasone; Diabetic Nephropathies; Female; Glomerulonephritis, IGA; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kidney; Kidney Diseases; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Retrospective Studies; Tacrolimus; Treatment Outcome

A 38-year-old man was admitted to the hospital for the evaluation of proteinuria, microscopic hematuria, and monoclonal IgA-kappa gammopathy. The initial renal pathological findings showed mesangial proliferative glomerulonephritis with endocapillary proliferation, a necrotizing lesion, and cellular crescent formation accompanied by IgA1-kappa deposition in the mesangium. Neither typical immune-complex deposits nor organized-structure deposits were detected. We diagnosed the patient with monoclonal immunoglobulin deposition disease (MIDD) associated with monoclonal IgA (mIgA). After the initiation of a monthly treatment with melphalan and predonisolone (MP therapy), the patient's serum IgA levels declined, and clinical remission was ultimately achieved. The follow-up renal biopsy showed reduced IgA-kappa staining, and both the endocapillary proliferation and the necrotizing lesion had disappeared. To elucidate the mechanism of IgA deposition, we investigated the glycan profile of the patient's serum mIgA using a mass spectrometry technique. The results revealed an unusual N-glycan profile compared to that of another patient with circulating mIgA lacking renal involvement and that of a healthy control. mIgA deposition in the mesangial area is a rare disease, and the glycan profiling of MIDD with renal involvement has not been reported previously. Thus, the present case suggests that any variation in Ig glycosylation may be a step in the pathogenesis of MIDD with renal involvement and/or contribute to some cases of IgA nephropathy.

Topics: Adult; Drug Therapy, Combination; Glomerular Mesangium; Glomerulonephritis, Membranoproliferative; Glucocorticoids; Glycosylation; Humans; Immunoglobulin A; Immunoglobulin kappa-Chains; Male; Mass Spectrometry; Melphalan; Paraproteinemias; Polysaccharides; Prednisolone; Protein Processing, Post-Translational; Treatment Outcome

We report a case of light and heavy chain deposition disease (LHCDD), a rather rare monoclonal immunoglobulin deposition disease (MIDD) with successful therapeutic effect. A 58-year-old woman suffered from proteinuria and renal insufficiency (serum creatinine 1.0 mg/dl, creatinine clearance 49.2 ml/min) in February 2003. In serum and urine samples, monoclonal IgG-kappa was detected. A bone marrow aspiration showed a slightly hypocellular marrow and plasma cell population was increased to 7.0%. Renal histological findings revealed lobulated glomeruli with nodular lesions on light microscopy, characteristic findings of MIDD. Intense deposition of IgG heavy chains in the linear pattern in the glomerular and tubular basement membranes was observed. Immunohistochemistry revealed both kappa and lambda light chain depositions in glomeruli. Electron-microscopic examination revealed fine granular electron-dense deposits accompanied by microfibrils. Based on these findings, this patient was diagnosed as LHCDD. She received three courses of melphalan and prednisone chemotherapy, resulting in disappearance of proteinuria, prevention of renal functional deterioration and the decrease of monoclonal immunoglobulin. This case clearly demonstrates that the earlier and accurate diagnosis and initiation of chemotherapy at the early stage with serum creatinine level below 4.0 mg/dl are necessary to improve renal and patient outcome.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerulonephritis, Membranoproliferative; Heavy Chain Disease; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Immunohistochemistry; Kidney Glomerulus; Melphalan; Microscopy, Electron; Middle Aged; Prednisolone

Topics: Aged; Biopsy; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Drug Therapy, Combination; Glomerulonephritis, Membranoproliferative; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Melphalan; Paraproteinemias; Paraproteins; Plasmapheresis; Postoperative Complications; Prednisolone; Recurrence; Transplantation; Transplantation, Homologous