Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ig light chain-associated amyloidosis is a fatal plasma cell proliferative disorder that is characterized by fibril deposition in various organs. High-dose melphalan followed by autologous stem cell transplantation has been shown to improve organ dysfunction and survival. This study was undertaken to investigate factors that influence renal response. Patients who had AL amyloidosis with > or =1 g/d proteinuria and a minimum follow-up of 12 mo were recruited. Renal response was defined by >50% reduction in proteinuria with <25% decline in renal function. Hematologic response was defined as a 50% reduction in serum monoclonal protein or free light chains. Baseline characteristics were examined for relationship to renal response. Thirteen of the 135 patients were excluded for various reasons. Median follow-up was 45.4 mo. Hematologic and renal response was noted in 73 and 43.4% of the patients, respectively. Median response time for the kidney was 10 mo (1 to 40 mo). In univariate analysis, low cardiac troponin T (cTnT), higher albumin, lower proteinuria, and hematologic response were associated with renal response. In multivariate analysis, cTnT and proteinuria were predictive of renal response. Renal response was associated with a longer survival than hematologic response alone. This study showed that severe proteinuria and high cTnT negatively affected renal response after autologous stem cell transplantation. Achievement of renal response was associated with improved survival. These results suggest that early intervention with aggressive therapy is not only justified but recommended to achieve optimal response.
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PMID:Severity of baseline proteinuria predicts renal response in immunoglobulin light chain-associated amyloidosis after autologous stem cell transplantation. 1769 49

Amyloidosis is characterized by extracellular deposition of abnormal protein. There are six types: primary, secondary, hemodialysis-related, hereditary, senile, and localized. Primary (AL) amyloidosis is associated with monoclonal light chains in serum and/or urine with 15% of patients having multiple myeloma. Secondary (AA) amyloidosis is associated with inflammatory, infectious, and neoplastic diseases. The presentation is protean, including macroglossia, a dilated and atonic esophagus, gastric polyps or enlarged folds, and luminal narrowing or ulceration of the colon. Amyloid deposition in the gastrointestinal (GI) tract is greatest in the small intestine. The symptoms include diarrhea, steatorrhea, or constipation. Pseudo-obstruction carries a particularly grave prognosis, often not responding to pro-motility agents. Hepatic involvement is common, but the clinical manifestations are usually mild with hepatomegaly and an elevated alkaline phosphatase level. Biopsies to diagnose amyloidosis can be taken from the fat, kidney, intestine, or bone marrow. The safety of liver biopsies is controversial. With Congo Red stain, amyloid appears red in normal light and apple-green in polarized light. Treatment for AL amyloidosis is chemotherapy and stem cell transplantation; treatment for AA amyloidosis is control of the underlying disease. Amyloidosis should be considered in patients with proteinuria, cardiomyopathy, hepatomegaly (with mildly abnormal liver tests), peripheral and autonomic neuropathy, weight loss, and GI symptoms.
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PMID:Gastrointestinal manifestations of amyloidosis. 1972 11

Primary systemic (AL) amyloidosis involves vital organs from the early phase of illness, resulting in poor prognosis. Today, high-dose melphalan followed by autologous peripheral blood stem cell transplantation is an effective treatment for systemic AL amyloidosis. We report a patient with nephrotic syndrome due to systemic AL amyloidosis, who was successfully treated with autologous peripheral blood stem cell transplantation. At follow-up 36 months from ASCT, the patient showed a significant improvement in the signs of peripheral neuropathy and reduction in proteinuria without further organ involvement. Due to poor prognosis with conventional therapy, autologous stem cell transplantation should be considered for treatment in patients with systemic AL amyloidosis, and favorable outcome is ensured with achievement of renal response after ASCT.
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PMID:Successful treatment of nephrotic syndrome due to systemic AL amyloidosis after autologous stem cell transplantation: renal response is an important therapeutic end point. 1839 5

AL amyloidosis is a systemic disease characterized by extracellular amyloid deposition in tissues, causing progressive dysfunction of affected organs. The main clinical syndroms include nephrotic-range proteinuria with or without renal dysfunction, congestive heart failure, hepatomegaly and peripheral or autonomic neuropathy. The aim of therapy is the reduction of monoclonal light chains, by suppressing the underlying plasma cell dyscrasia. Recent therapeutic strategies involve intermediate-dose chemotherapy or high-dose melphalan supported by peripheral blood stem cell transplantation. Alternative therapeutic approaches include thalidomide, lenalidomide, iododoxorubicin, etanercept and rituximab. This paper reviews the pathogenesis, diagnosis and therapy of the AL amyloidosis, focusing on clinico-morphological symptoms of renal involvement, monitoring of treatment response and supportive therapy.
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PMID:[Advances in diagnosis and treatment of AL amyloidosis]. 1863 70

Mutations in the fibrinogen A alpha-chain gene are the most common cause of hereditary renal amyloidosis in the United Kingdom. Previous reports of fibrinogen A alpha-chain amyloidosis have been in isolated kindreds, usually in the context of a novel amyloidogenic mutation. Here, we describe 71 patients with fibrinogen amyloidosis, who were prospectively studied at the UK National Amyloidosis Centre. Median age at presentation was 58 yr, and renal involvement led to diagnosis in all cases. Even after a median follow-up of 4 yr, clinically significant extra-renal disease was rare. Renal histology was characteristic: striking glomerular enlargement with almost complete obliteration of the normal architecture by amyloid deposition and little or no vascular or interstitial amyloid. We discovered four amyloidogenic mutations in fibrinogen (P552H, E540V, T538K, and T525fs). A family history of renal disease was frequently absent. Median time from presentation to ESRD was 4.6 yr, and the estimated median patient survival from presentation was 15.2 yr. Among 44 patients who reached ESRD, median survival was 9.3 yr. Twelve renal transplants survived for a median of 6.0 (0-12.2) yr. Seven grafts had failed after median follow up from transplantation of 5.8 yr, including three from recurrent amyloid after 5.8, 6.0, and 7.4 yr; three grafts failed immediately for surgical reasons and one failed from transplant glomerulopathy after 5.8 yr with no histological evidence of amyloid. At censor, the longest surviving graft was 12.2 yr. In summary, fibrinogen amyloidosis is predominantly a renal disease characterized by variable penetrance, distinctive histological appearance, proteinuria, and progressive renal impairment. Survival is markedly better than observed with systemic AL amyloidosis, and outcomes with renal replacement therapy are comparable to those for age-matched individuals with nondiabetic renal disease.
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PMID:Diagnosis, pathogenesis, treatment, and prognosis of hereditary fibrinogen A alpha-chain amyloidosis. 1907 21

IgM-associated AL amyloidosis is rare and may represent a distinct entity. Sixty (7%) of 868 consecutive AL patients referred to our center had an IgM monoclonal protein. They were significantly older than non-IgM patients (median, 67 years vs. 62 years), had a higher frequency of lymph-node involvement (25% vs. 2%) and significantly lower median proteinuria (1.2 g/24h vs. 3.4 g/24h), N-terminal pro-natriuretic peptide type-B (1177 ng/L vs. 2135 ng/L) and troponin I (0.02 ng/mL vs. 0.05 ng/mL). In IgM patients, kappa light-chains were more frequent (42% vs. 23%) and the involved free light-chain concentration was lower (median 63 mg/L vs. 182 mg/L). Serum albumin and NT-proBNP were independent prognostic determinants. Response to treatment improved survival. The 14 patients who received melphalan/dexamethasone showed a 64% hematologic (complete remissions, 29%) and a 43% organ response rate. IgM-associated AL amyloidosis is a distinct entity, with less advanced organ dysfunction. Treatment with melphalan/ dexamethasone might be effective in these patients.
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PMID:AL amyloidosis associated with IgM monoclonal protein: a distinct clinical entity. 1936 81

We report a 58-year-old Japanese man with primary systemic AL amyloidosis who achieved disappearance of proteinuria including Bence-Jones protein (lambda-type) after two courses of VAD therapy (vincristine, doxorubicin, and dexamethasone) and subsequent high-dose melphalan, followed by autologous peripheral blood stem cell transplantation. Because this patient did not have any apparent amyloidosis-related heart or liver damage and met all of the eligibility criteria for this therapy, this treatment was performed. Both proteinuria and M-protein disappeared completely, and he is doing well clinically at 19 months after treatment. However, amyloid deposits were still found in the kidneys, including the glomeruli and tubulointerstitium, when renal biopsy was done at 8 months after treatment. In the future, we may reach a time when clinical remission corresponds to histological remission.
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PMID:Successful treatment of primary AL amyloidosis by VAD therapy, high-dose melphalan, and autologous peripheral stem cell transplantation. 1949 80

Amyloidosis results from the deposition of amyloid proteins in organ and tissues. It can be systemic or localized. Localized primary amyloidosis in renal allograft is an extremely rare clinical condition. We describe here a 46-year-old man who developed proteinuria and re-renal failure 5 years after receiving deceased renal allograft and proved to be a case of isolated primary AL amyloidosis in renal allograft confirmed by clinical investigations and renal biopsy.
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PMID:Unusual cause of proteinuria and re-renal failure after kidney transplantation: de novo localized AL amyloidosis in renal allograft. 1975 36

This study reports on a 67-year-old man, suffering from type 2 diabetes mellitus for 11 years along with arterial hypertension and autoimmune thyroiditis, in whom nephrotic proteinuria was detected together with a mild reduction in GFR. No autoantibodies or monoclonal proteins were detected in blood and urine. Renal biopsy material examined by light microscopy, immunofluorescence and electron microscopy showed AL amyloidosis. This case underlines the role of renal biopsy in patients with type 2 diabetes mellitus, in whom renal diseases other than diabetic nephropathy may occur frequently.
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PMID:[Nephrotic proteinuria with type 2 diabetes mellitus and autoimmune thyroiditis]. 1980 8

A 55-year-old woman with primary Immunoglobulin light chain (AL) systemic amyloidosis died due to spontaneous rupture of her liver following treatment with high-dose melphalan and autologous stem cell transplant (HDM/SCT). She was first diagnosed after developing nephrotic-range proteinuria. Spontaneous rupture of her liver occurred 10 days after treatment with HDM/SCT and was complicated by septic shock. She was not eligible for surgical intervention and died shortly after. Amyloid fibrils were extracted from the autopsied liver sample (05-135L) and the biochemical nature of the fibrils was analyzed using electrophoretic and immunohistochemical techniques. Our testing showed that the fibrils were composed of immunoglobulin lambda light chains that were not glycosylated. While the liver is often involved in AL amyloidosis, this is the first documented case of a spontaneous hepatic rupture in a patient during treatment with HDM/SCT. A literature review of spontaneous liver rupture in patients with amyloidosis is presented.
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PMID:Spontaneous rupture of the liver in a patient with systemic AL amyloidosis undergoing treatment with high-dose melphalan and autologous stem cell transplantation: a case report with literature review. 2053 4


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