Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty-two patients with chronic renal failure undergoing hospital haemodialysis were given a single bolus dose of tinzaparin (Innohep, Leo Laboratories, UK) into the arterial side of the dialyser, for up to 43 consecutive dialyses. The mean tinzaparin dose at the beginning was 2,139 IU anti-Xa and at the end 2,186 IU anti-Xa. Overall, tinzaparin proved a satisfactory anticoagulant for 1,370 (96.0%) out of 1,427 dialyses. Significant clot formation was prevented in 1,326 (92.8%) out of 1,429 dialyses. The clinically effective dose was associated with a mean plasma anti-Xa activity 1 h after dosing of 0.4 IU/ml and suppressed fibrinopeptide A formation for up to 4 h. Bleeding, from the skin or mucous membranes, was recorded at 27 (1.9%) of 1,408 dialyses. Prolonged fistula bleeding on completion of dialysis was recorded on only 20 occasions. Other haemorrhagic events included haematemesis, bruising and subconjunctival haemorrhage (each in 1 patient) and epistaxis (2 patients). Three patients died during the study of causes considered unrelated to tinzaparin therapy, myocardial infarction (2 patients) and multiple myeloma. Other adverse events reported included vomiting (3 patients) and hypotension (3 patients). Three patients ceased treatment due to haematemesis, prolonged bleeding from fistula puncture and thrombosis of the arteriovenous access, respectively. A small, but statistically significant, increase within the normal reference range was recorded in the mean values for aspartate aminotransferase and alanine aminotransferase.
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PMID:Long-term use of the low molecular weight heparin tinzaparin in haemodialysis. 911 88

A retrospective analysis of survival time and causes of death has been undertaken in 109 patients treated for multiple myeloma (MM) at the Hematologic Clinic of the Russian Research Institute of Hematology and Transfusiology in 1979-1995. Group I included cases of mono- and group II-polychemotherapy (PCT). Survival in patients with MM increased significantly (from 27 to 43 months) after PCT. The main causes of death in MM patients of group I were chronic renal failure and infectious complications, while in group II-intoxication syndrome including blood toxicity, toxic hepatitis, etc. In cases of this grave disease, the effectiveness of therapy appeared to depend on both main and supporting treatment. Of great importance was profuse hydration using diuretics, active rheologic preparations, plasmapheresis and other counter-complication means. Following the administration of immunity correction drugs (thymaline, tactivin, immunoglobulin), infectious complication incidence in group II dropped from 22 to 8.3%. It is suggested that the effectiveness of MM therapy is determined by stage-by-stage approach, course cycling of PCT and adequate evaluation of its criteria. PCT courses should be supplemented with infusion detoxication measures, particularly, in cases of highly aggressive PCT schemes, and procedures of immunity correction, hemo-component therapy and plasmapheresis.
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PMID:[Effect of various chemotherapy regimens on survival and cause of death in patients with multiple myeloma (retrospective study)]. 924 97

An overview of constantly enlarging spectrum of renal lesions in monoclonal gammapathies and new insights in possible pathogenesis of renal disturbances is given. Between the different types of renal affections a predominant role is played by the "myeloma kidney", induced by the presence of casts, primary amyloidosis with light chains deposition and tubular dysfunctions. Case stories of 3 patients, affected by myeloma kidney (with acute and chronic renal failure) and primary amyloidosis (with pronounced nephrotic syndrome) in context of monoclonal gammapathy are presented. Clinical problems of patients necessitating intensive hematologic and nephrologic care are highlighted, as well as need of early diagnosis and complex care.
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PMID:[Clinical problems in kidney disorders associated with myeloma and other paraproteinemias]. 942 12

Multiple myeloma is the most frequent dysproteinemia leading to nephropathy. The aim of the study was to analyse this complication in patients treated in nephrological departments. The study was performed in 83 patients (45 M, 38 F) aged 47-82 years in whom a diagnosis of multiple myeloma was based on clinical manifestation (weakness, subfebrile states, bone aches, loss of body weight, recurrent infections of urinary and respiratory tracts), increased number of plasmocytes in bone-marrow, presence of monoclonal protein in serum and/or urine and lesions in bone system. In a significant number of the studied patients the disease was revealed while diagnosing proteinuria as well as searching for a reason of elevated erythrocyte sedimentation rate or proteinogram abnormalities. The obtained results indicate that signs of nephropathy in the course of multiple myeloma may be the first visible symptoms of the disease. Proteinuria was observed in 79.5% of the studied patients. Bence-Jones protein was found in 41% of individuals and features of renal failure in different stages of development in 67%. Dialysis therapy was started in 3 patients with acute and 7 patients with chronic renal failure.
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PMID:[Selected renal complications during the course of multiple myeloma]. 959 50

Monoclonal gammapathies are detected because of clinical symptoms and biological tests confirm their presence. Wishing to investigate these diseases, we carried out a series of biochemical tests on 14 patients from October 1995 to July 1996: protein, cryoglobulin, electrophoresis of proteins, proteinuria of BENCE JONES, C-reactive protein, weight measuring of immunoglobulins (Ig), immunofixation of Ig, creatinine and calcium. The results we obtained confirmed the presence of 14 cases of myeloma with: -9 IgG myelomas with 6 kappa light chains and 3 lambda light chains -4 IgA myelomas with 2 kappa light chains and 2 lambda light chains -1 IgG kappa, Ig lambda biclonal gammapathy united to a cryoglobulin of class I. We observed a predominance of the IgG over the others Ig and the kappa over the alpha light chains. The proteinuria of BENCE JONES was present among 3 patients, hypercalcemia among 4 patients and hypercreatininemia in 1 patient with chronic renal failure.
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PMID:[Laboratory diagnosis of monoclonal gammopathies. Prospective study of 14 cases in Dakar, Senegal]. 977 1

A 45-year-old white woman was found to have microscopic hematuria during her annual physical examination. After a negative urologic workup, she returned 5 months later with nephrotic syndrome, renal insufficiency, and hypocomplementemia. Renal biopsy showed a nodular sclerosing glomerulopathy that could not be further characterized because of inadequate tissue for immunofluorescence. The patient returned 8 months later with chronic renal failure. A repeat renal biopsy showed deposits composed of immunoglobulin G (IgG) heavy chain and complement components C3 and C1 along glomerular, tubular, and vascular basement membranes, with negativity for kappa and lambda light chains, findings consistent with heavy chain deposition disease (HCDD). The heavy chain subclass was exclusively IgG3. Staining with monoclonal antibodies to epitopes of the constant domains of IgG heavy chain showed a CH1 deletion, indicating a truncated heavy chain. On review of the previously reported cases of HCDD, common clinical presentations include nephrotic syndrome, renal insufficiency, hematuria, and, in some cases, hypocomplementemia. In most patients, the hematologic disorder is mild, without overt myeloma. Light microscopy shows a nodular sclerosing glomerulopathy, and heavy chain deposits are detectable within basement membranes throughout the kidney by immunofluorescence and electron microscopy. There is no effective treatment for this condition, and virtually all patients progress to chronic renal failure.
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PMID:Heavy chain deposition disease: the disease spectrum. 1021 55

Renal impairment is a common complication of multiple myeloma occuring in 50% of patients at some stage in their disease. Pathogenesis is multifactorial. Nephrotoxic manifestations of monoclonal immunoglobulin overexpression include the 'myeloma kidney', light chain deposition disease, AL amyloid, plasma cell infiltration and glomerulonephritis. Other factors, such as hypercalcaemia, hyperuricaemia, infection, hyperviscocity and nephrotoxic drugs can precipitate or exacerbate acute and chronic renal failure. Aggressive treatment has dramatically improved outcome in patients who present with acute or acute-on-chronic renal failure. Dialysis has become an accepted treatment acutely and in end stage renal disease due to myeloma. Conventional therapy with melphalan and prednisolone is still advocated for elderly patients. However, renal failure is not a contraindication to aggressive cytoreduction, stem cell collection, double hemibody radiotherapy and autologous transplantation in those otherwise fit to tolerate these procedures. Prognosis is primarily determined by the response of the myeloma clone to chemotherapy. Outcome in chemosensitive patients approaches that of patients with equivalent disease stage without renal dysfunction.
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PMID:Renal failure and multiple myeloma: pathogenesis and treatment of renal failure and management of underlying myeloma. 1041 44

Patients with multiple myeloma (MM) and chronic renal failure have generally been excluded from myeloablative therapy programs followed by hematopoietic stem cell support because of the potential increase in transplant-related morbidity and mortality. We here report our experience treating six MM patients with moderate to severe renal insufficiency, with autologous stem cell transplantation. One of these patients required chronic hemodialysis since the diagnosis of MM was made. Peripheral blood stem cell collection was performed with either cyclophosphamide 5.5-7 g/m2 + G-CSF, 5 microg/kg/day (patients 1-3, 5 and 6) or G-CSF, 15 microg/kg/day alone (patient No. 4). Four patients (Nos 1-4) received autotransplant as front-line therapy, while the last two patients were treated in relapse, which occurred following prior autologous stem cell transplantation in support of melphalan, 200 mg/m2 (No. 5) or maintainance therapy with alpha-interferon (No. 6). High-dose chemotherapy administered as preparation to transplant included busulfan 12 mg/kg + melphalan 80 mg/m2 (patients 1-3 and 6) or melphalan 80 mg/m2 alone (patients 4 and 5) in order to reduce mucosal damage. Following transplant, prompt and sustained recovery of hematopoiesis was documented in all the patients; 500 PMN/microI and 20000 platelets/microI were reached after a median of 13 and 14 days, respectively. None of the patients suffered from WHO grade 3-4 infectious complications. Transplant-related toxicity included grade 3-4 oral mucositis (patients 1, 4 and 5) and veno-occlusive disease (patient No. 3). Renal function either improved or remained stable throughout the transplant period. All the patients but one responded to therapy, three of them are progression free after 2, 15 and 26 months; two relapsed after 16 and 4 months and one died from cholangiocarcinoma 7 months after transplant, while still in remission. Although our experience is limited so far, these results appear promising and support the investigational use of myeloablative therapy in MM patients with chronic renal failure.
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PMID:Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure. 1091 57

Although the kidney is frequently involved in malignant monoclonal gammopathy, the clinical outcome of the patients varies considerably. We retrospectively assessed the clinical course in seventeen patients with acute and chronic renal failure suffering from multiple myeloma, and analyzed their case history focusing on the therapeutic management, the possible clinical improvement as well as the patients' outcome. Treatment included chemotherapy (n = 17), forced diuresis (n = 3), hemodialysis (n = 11, 7 chronic, 4 intermittent) and plasmapheresis (n = 3). Renal function improved in five patients, and was stabilized compensated in four. Seven patients developed end-stage renal disease, one refused further treatment and was lost for follow up. In addition to renal failure, the most frequent complications included local bone destruction (all), anemia (n = 12), low platelet count (n = 11), and bacterial infections (n = 9). One year survival rate after admission to the nephrology department was 76 percent. Chemotherapy in combination with renal replacement therapy may improve the clinical course even in MM patients with serum creatinine levels above 3.0 mg/dL or end-stage renal disease.
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PMID:Management of renal complications in patients with advanced multiple myeloma. 1095 72

Cast nephropathy, or myeloma kidney, is a potentially reversible cause of chronic renal failure. In this condition, filtered light chains bind to a common site on Tamm-Horsfall protein (THP), which is produced by cells of the thick ascending limb of the loop of HENLE: Subsequent aggregation of these proteins produces casts that obstruct tubule fluid flow and results in renal failure. In the present study, we used the yeast two-hybrid system to determine the site of interaction of light chains with THP. The third complementarity-determining region (CDR3) of both kappa and lambda light chains interacted with THP. These findings were confirmed in a series of competition studies using a synthetic peptide that corresponded to the CDR3 region and purified THP and light chains. Variations in the CDR3 sequence of the light chain affected binding. Thus, the current studies increase our understanding of the process of cast formation and provide an opportunity to develop strategies that may inhibit this interaction and prevent the clinical manifestations of myeloma kidney.
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PMID:Mapping the binding domain of immunoglobulin light chains for Tamm-Horsfall protein. 1133 84


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