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)

Monoclonal light chains (LCs) are responsible for a wide spectrum of renal and hepatic diseases, that above all include amyloid light-chain (AL) amyloidosis and light chain deposition disease (LCDD). Amyloid deposits stain for Congo red on light microscopy and have fibrillar aspect on electron microscopy, whereas deposits in LCDD are positive using monotypic LCs on immunofluorescence and have a granular aspect on electron microscopy. Sometimes fibrillar and granular deposits are observed in the same organ or in different organs of the same patient. Kidney and liver involvement is a frequent finding, both in primary amyloidosis (AL amyloidosis) or in LCDD. Renal manifestations include proteinuria, nephrotic syndrome, and progressive renal failure. End-stage renal disease requiring dialysis is observed in about 20% of patients with AL amyloidosis and in 70% of patients with LCDD. The mean survival time is about 12 to 18 months in AL amyloidosis and 34 months in LCDD. The most important prognostic factor is severe cardiac involvement, which reduces the mean survival to only 6 months. Hepatic manifestations include hepatomegaly, portal hypertension, ascites, intrahepatic cholostatic jaundice, and hepatic insufficiency. The mean survival of patients with liver damage is 14 months, but it is reduced to 5 months in patients with cholostatic jaundice. Contemporary kidney and liver involvement is usually observed on histologic examination, less frequently as clinical manifestation. No specific treatment exists for AL amyloidosis and LCDD, and the prognosis remains severe. The aim of treatment is to suppress proliferation of the abnormal clone of plasma cells and remove tissue deposits. The regimens, including melphalan-prednisone (MP) or vincristine-doxorubicin-dexamethasone (VAD), are used both in AL amyloidosis or in LCDD with some effectiveness. New approaches, especially the use of 4'-iodo-4'deoxydoxorubicin, could achieve better results. Dialysis seems to not worsen the outcome in both diseases because survival of patients on dialysis is not different from that of patients not reaching uremia. Also, kidney and liver transplantation is effective, though amyloidosis or LCDD may occur in transplanted organs. The most interesting therapeutic approach is autologous-blood stem-cell transplantation, which may produce a complete remission of the plasma-cell dyscrasia and a substantial improvement of clinical manifestations related to LC deposits.
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PMID:Kidney and liver involvement in monoclonal light chain disorders. 1211 97

Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelomas. Between September 1990 and November 2000, among 540 patients with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found high frequencies of female patients (62 percent), Bence Jones proteinuria (79 percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42 percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21 percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)-microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71 percent, respectively. Four patients were treated with vincristine, melphalan, cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine, adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2) plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other clinical characteristics were comparable among the three groups. Complete plus partial responses were achieved in one and six patients treated with VMCPA and M-80, respectively. All patients treated with VAD failed to respond to treatment. Patients receiving the M-80 regimen experienced higher platelet toxicity (P=0.05), vomiting (P<0.0003), and mucositis. Also, the need for red blood cell transfusions was higher in the M-80 group. Median overall survival was 60 days. Overall survival was better in patients achieving complete or partial response. In conclusion, our study illustrates that intermediate doses of melphalan plus dexamethasone are an effective chemotherapy regimen for this aggressive disease. Response to treatment is the only prognostic factor for survival in these patients.
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PMID:Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia. 1218 4

Venous thrombophilia is the result of clotting changes namely of a hypercoagulable state together with blood flow and vessel wall changes. There is no need for all these components to be present in order for thrombosis to occur. As the matter of fact, thrombosis may occur even if only one of these conditions is present. In clinical practice a combination of factors is usualy seen. In comparison with arterial thrombophilia, clotting changes and blood flow seen to play a major role in venous thrombosis. Venous thrombophilia may remain asynptomatic or may result in a series of clinical syndromes. The commonest of these are: 1. Superficial vein thrombosis, 2. Deep vein thrombosis of legs, 3. Deep vein thrombosis of arms, 4. Caval veins thrombosis, 5. Portal vein thrombosis, 6. Hepatic veins thrombosis, 7. Renal vein thrombosis, 8. Cerebral sinuses thrombosis, 9. Right heart thrombosis, 10. Miscellaneous (ovarian, adrenal veins thrombosis, etc.). Since the first two are widely and easily recognized, these is no need for an extensive discussion. Deep vein thromboses of upper limbs are not as frequent as those of lower limbs or of superficial phlebitis but they can still be recognized on clinical grounds and non invasive techniques. The remaining 7 syndromes are less common and therefore less frequently suspected and recognized. Of particular interest, among these less common manifestations of venous thrombophilia are hepatic vein and renal vein thrombosis. Hepatic veins thrombosis, sometimes part of inferior vena cava thrombosis is most frequently due to an isolated occlusion of hepatic veins thereby causing a form of venocclusive disease. Occasionally diagnosis may be difficult because of slow onset of symptoms (hepatomegaly, right flank pain, fever, ascites etc.). The same is true for renal vein thrombosis which may also be of difficult diagnosis since it causes proteinuria and flank pain. The proteinuria is often interpreted as due to a nephrotic syndrome which, incidentally, may cause by its turn renal vein thrombosis. Portal vein thrombosis and cerebral sinuses thrombosis on the contrary are more easily suspected because of ascites, adominal pain, jaundice or headache, eye proptosis, vomiting. Right heart thrombosis should be suspected in cases of recurrent pulmonary embolization. Ovarian or adrenal veins thrombosis are rare. The competent physician should always consider, given certain congenital or acquired conditions, the possibility to be facing a special form of venous thrombosis or a venous thrombosis in unusual sites. An early diagnosis, as often in medicine, is of paramount importance for a prompt treatment and a satisfactory outcome.
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PMID:Clinical aspects of venous thrombophilia. 1367 53

The liver is a common site of amyloid deposition in primary systemic amyloidosis. We reviewed the clinical features and natural history of patients with primary systemic amyloidosis and biopsy-proven hepatic involvement who were evaluated at Mayo Clinic from January 1, 1975, to December 31, 1997. The median age of the study group (68 men; 30 women) was 58.5 years. Seventy-one patients (72%) had involuntary weight loss. Hepatomegaly was found in 79 patients (81%). Eighty-two patients (89%) had proteinuria, and 81 patients (86%) had elevated serum alkaline phosphatase levels. Seventy-six patients (83%) had either a serum or urine monoclonal protein. Before liver biopsy, clinicians considered amyloidosis in the differential diagnosis for only 14 patients (26%). None of our patients experienced hepatic rupture or death due to liver biopsy, and only 4 (4%) bled after liver biopsy. The median survival of the 98 patients was 8.5 months. Predictors of a poor prognosis were congestive heart failure, elevated concentrations of bilirubin, and a platelet count greater than 500 x 109/L. In conclusion, clinicians should consider the diagnosis of primary hepatic amyloidosis in patients who present with involuntary weight loss or hepatomegaly. Other clues to the diagnosis include an unexplained elevated serum alkaline phosphatase level, proteinuria, and evidence for hyposplenism (for example, Howell-Jolly bodies on peripheral blood smear). Liver biopsy was safe. Some patients benefit from systemic chemotherapy.
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PMID:Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. 1453 Jul 78

In this Grand Round we present a 32-yr-old African man who became severely ill after a 5-month history of weight loss, pyrexia, arthralgia, sweats and rash. He went on to develop pericarditis, pericardial effusion with tamponade, hepatomegaly with abnormal liver function tests, lymphadenopathy, massive proteinuria and required ventilatory, circulatory and renal support. The differential diagnosis was adult onset Still's disease, systemic lupus erythematosus (SLE), infection and lymphoma. Primary infection and lymphoma were excluded and he was treated, with dramatic success, with intravenous immunoglobulins (i.v.IG). Subsequent renal biopsy excluded SLE but confirmed collapsing glomerulopathy. The proteinuria improved dramatically following treatment with mycophenolate mofetil. We discuss some of the difficult diagnostic and management issues raised by this patient and the different uses and mechanisms of action of i.v.IG.
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PMID:Adult onset Still's disease and collapsing glomerulopathy: successful treatment with intravenous immunoglobulins and mycophenolate mofetil. 1503 97

Generalized lipodystrophy is characterized by adipose tissue absence, hypoleptinemia, hypertriglyceridemia, insulin resistance, diabetes, hepatomegaly, and nonalcoholic steatohepatitis. In the course of recruiting patients for treatment with recombinant leptin, we were struck by the frequency and severity of proteinuria. We evaluated 25 patients with generalized lipodystrophy. Eighteen were treated with recombinant leptin, and we have followed 15 on leptin for 4-36 months. We followed renal parameters at baseline and during follow-up visits. Renal biopsies were performed as clinically indicated. At baseline, 22 of 25 patients (88%) had elevated urine albumin excretion (>30 mg/24 h), 15 (60%) had macroalbuminuria (>300 mg/24 h), and five (20%) had nephrotic-range proteinuria (>3500 mg/24 h). Twenty-three (92%) had elevated creatinine clearance (>125 ml/min.1.73 m(2)). Eleven of 15 patients (73%) treated with recombinant leptin exhibited reduction in proteinuria, associated with reduction of hyperfiltration. Four patients who did not improve are discussed individually. Renal biopsy findings were remarkable for focal segmental glomerulosclerosis in four patients, membranoproliferative glomerulonephritis in two patients, and diabetic nephropathy in one patient. In conclusion, generalized lipodystrophy is associated with proteinuria and unique renal pathologies, including focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis. The majority treated with recombinant leptin demonstrated reduction in proteinuria and hyperfiltration.
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PMID:Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: baseline characteristics and course during recombinant leptin therapy. 1524 May 93

Amyloidosis is the term for specific pathological peptide deposits in various tissues. Amyloid substances may be the manifestation of the following nosological units: AL-amyloidosis, AA-amyloidosis, ATTR-amyloidosis, beta2-microglobulin amyloidosis and possibly othr familiar forms of amyloidosis. The most frequent symptoms of amyloidosis are: 1. proteinuria with nephrotic syndrome, 2. cardiac failure with restrictive cardiomyopathy, 3. unexplicable hepatomegaly, 4. idiopathic peripheral polyneuropathy, 5. haemorrhagic manifestations and symptoms of increased fragility of the capillaries while the number of thrombocytes is normal, 6. periorbital haematomas and 7. macroglossia. Diagnostic and therapeutic procedures differ according to the type of amyloidosis and are analyzed in detail in the text.
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PMID:[Clinical manifestations of AL-amyloidosis and some other types of amyloidosis]. 1563 67

Idiopathic myelofibrosis is characterized by bone marrow fibrosis, anemia, leukoerythroblastosis, and extramedullary hematopoiesis in many organs. Renal abnormalities in idiopathic myelofibrosis have been rarely described in the literature and include extramedullary hematopoiesis in the pararenal or retroperitoneal areas resulting in obstructive uropathy and hemtopoietic cell infiltration in tubulointerstitial area and urolithiasis. These lead to azotemia or acute renal failure, which may respond well to radiotherapy and adjuvant chemotherapy. To our knowledge, there has been only one case report of nephrotic syndrome associated with glomerulonephritis in a myelofibrosis patient; however, no effective treatment was described. Herein, we report the case of a patient with idiopathic myelofibrosis who initially presented with hepatomegaly, anemia, and leukoerythroblastosis. A nephrotic syndrome developed 7 years after initial diagnosis. Renal biopsy disclosed the unique pathological finding of simultaneous mesangial proliferative glomerulonephritis, renal extramedullary hematopoiesis, and gouty nephropathy. Despite treatment with busulfan, proteinuria persisted that implied irreversible glomerular injury and a terminal prognosis. We focus on the unusual pathological finding and the association between nephrotic syndrome and idiopathic myelofibrosis.
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PMID:Idiopathic myelofibrosis associated with renal extramedullary hematopoiesis and nephrotic syndrome: case report. 1564 Dec 21

We here report a case of a 50-year-old man who showed histologically evident resolution of primary amyloidosis by melphalan and prednisolone. The patient was admitted to our hospital for further evaluation of nephrotic syndrome and remarkable hepatomegaly with refractory ascites, on September 11, 1998. Laboratory tests at presentation showed nephrotic syndrome with slight renal impairment and elevation of the enzymes of the biliary system. Monoclonal light chains were not detected in the serum or urine by immunoelectrophoresis. A renal biopsy revealed global deposition of amyloid in all glomeruli, interstitium and blood vessels. Immunofluorescence staining was positive for kappa light chains. Liver biopsy specimens showed extensive deposition of amyloid along sinusoid walls. Bone marrow aspiration contained 7% plasma cells but no clusters or abnormal cells. Based on these findings, systemic AL- (amyloid light chain) amyloidosis was diagnosed, and the treatment with combinations of melphalan and prednisolone was started from October 1998 at intervals of 4-6 weeks. Renal impairment progressed, resulting in the initiation of maintenance hemodialysis in February 1999. Reinfusion of ascitic fluid into the hemodialysis circuit had been performed from March 1999 for refractory ascites, and ascites disappeared in July 1999. Furthermore, urinary output increased after 14 courses of chemotherapy. Renal function gradually ameliorated with a concomitant reduction in the enzymes of biliary system, and finally hemodialysis was discontinued in April 2001. Sixteen courses of chemotherapy were administered by April 2001. Proteinuria was negative in August 2001. A second renal biopsy was performed on November 20, 2001, which showed markedly decreased amyloid deposition and a proliferation of mesangial cells and increase in matrix in various degrees. We report a case of a patient with primary amyloidosis who was successfully treated by melphalan and prednisolone, resulting in marked resolution of renal amyloidosis.
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PMID:Resolution of primary amyloidosis by melphalan and prednisolone: a case report. 1578 23

We analyzed the clinical features and prognostic factors for transformation of immunoglobulin Mrelated disorders (IgM-RDs) to malignant lymphoproliferative disease (MLD) in 83 patients with IgM-RDs. We studied 19 patients with type I cryoglobulinemias, 56 patients with type II cryoglobulinemias, 5 patients with peripheral neuropathies (PNs), and 3 patients with idiopathic thrombocytopenic purpuras. Fourteen patients with cryoglobulinemias presented with mild to moderate hepatomegaly with or without splenomegaly. Fourteen patients with type II cryoglobulinemias had arthralgias and/or vascular purpura (12 receiving corticosteroids), and 7 presented with PN. These latter patients and those with PNs without cryoglobulinemia were treated with steroids, cyclophosphamide, or polychemotherapy with/without plasma-exchange. Cumulative probability of evolution to MLD at 5 years was 15% (95% CI; 5%-25%). At a median of 62 months (12-195 months), 8 cases of IgM-RDs (8.4%) evolved to overt Waldenstrom's macroglobulinemia (n = 6), 1 case to non-Hodgkin's lymphoma, and 1 case to B-cell chronic lymphocytic leukemia. At univariate analysis, male sex (P = 0.02), IgM level > or = 3 g/dL (P < 0.0001), detectable Bence Jones proteinuria (P = 0.0005), lymphocytosis (P = 0.049), and high erythrocyte sedimentation rate (P = 0.003) significantly correlated with the evolution risk. Age, blood cell counts, b2-microglobulin level, degree of marrow lymphoplasmacytic infiltration, type of cryoglobulinemia, and hepatitis C virus positivity did not correlate with transformation. Although IgM-RDs represent a distinct clinical entity frequently requiring treatment in view of the IgM-related symptoms, their evolution probability and prognostic factors for malignant transformation seem to widely overlap those described for asymptomatic IgM monoclonal gammopathies.
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PMID:Clinical characteristics and outcome of immunoglobulin M-related disorders. 1579 61


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