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Query: UMLS:C0020437 (hypercalcemia)
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Multiple myeloma is a malignant disease characterized by plasmacytosis, paraprotein production, bone lesions, hypercalcemia, susceptibility to infections, and renal impairment. The underlying pathophysiologic phenomena of the clinical features include suppression of humoral- and cell-mediated immunity, elevation of IL-6, abnormalities of the bone marrow microenvironment, and increased osteoclastic activity. Overwhelming predictors of prognosis include albumin, beta2-microglobulin, and chromosomal karyotype. With modern, intensive therapy including autologous hematopoietic stem cell transplantation, the median survival is approximately 5 yr. The disease is incurable and eventually relapses; requiring salvage therapy. The development of newer agents such as thalidomide, bortezomib, and lenalidomide--drugs that interfere with several of the complex pathophysiologic steps--has improved the outlook of relapsed disease significantly. Current studies are directed at exploring the use of these novel agents earlier in the course of therapy, development of newer targeted therapies, and the use of gene expression profiling to individualize therapy.
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PMID:Multiple myeloma. 1769 65

We report three cases of urolithiasis associated with sarcoidosis and reviewed the Japanese published reports. All cases had hypercalcemia, hyperuricemia, hypercalciuria and renal dysfunction. A serum level of 1,25-(OH)2D3 was elevated and intact parathyroid hormone (PTH) was decreased. Stone components were predominantly calcium oxalate. Abnormal calcium metabolism is a well-known feature of sarcoidosis and the reported prevalence of urolithiasis in patients with sarcoidosis was 1.3-14.0% in the English published reports. However, urolithiasis associated with sarcoidosis is uncommon in Japan and we could find only 16 documented cases including ours. Abnormal calcium metabolism is caused by an increase in serum concentration of 1,25-(OH)2D3, which is derived from endogenous overproduction in the pulmonary macrophages. If patients with urolithiasis have abnormal calcium metabolism, renal impairment and suppression of PTH, the possibility of sarcoidosis should be considered for a differential diagnosis. Also, it should be emphasized that the presence or developing of urolithiasis is to be monitored during follow up of patients with sarcoidosis.
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PMID:Three cases of urolithiasis associated with sarcoidosis: a review of Japanese cases. 1788 Mar

Multiple myeloma accounts for approximately 1% of all new cancers and is characterized by abnormal plasma cell proliferation in the bone marrow. As a result, many patients develop bone lesions, hypercalcemia, anemia, and renal impairment. Although no cure exists for multiple myeloma, current treatments, such as oral melphalan and prednisone, can slow disease progression and prolong overall survival. Several new therapeutic options show promise: lenalidomide, thalidomide, liposomal doxorubicin, and bortezomib. Clinical research presented at the 2006 meeting of the American Society of Hematology, the 2007 meeting of the American Society of Clinical Oncology, and the 11th International Myeloma Workshop showed that newer therapeutic combinations were well tolerated and effective in patients with multiple myeloma. Oncology nurses, with their specialized knowledge of treatment administration and monitoring and their expertise in patient education, have an important role in the management of patients with multiple myeloma to help improve overall survival and quality of life. As newer regimens become available, oncology nurses must be aware of factors that optimize outcomes to help patients understand the benefits of treatment, how to manage side effects, and the importance of treatment adherence.
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PMID:Clinical updates and nursing considerations for patients with multiple myeloma. 1806 42

The number of newly diagnosed cases of multiple myeloma in the Czech Republic is about 3-4 per 100 000 persons per year. In the higher age groups, the incidence increases. Multiple myeloma is an illness that reacts well to treatment which can result in periods of remission lasting for years. Some of the patients are even able to return to work. A pre-requisite for successful treatment is early diagnosis and this is usually in the hands of first line physicians. This is the reason why the Czech Myeloma Group, in conjunction with neurologists, orthopedicians and radio diagnosticians has issued the following recommendations for first line physicians containing a more detailed description of the symptoms and the diagnostic pitfalls of the disease. This disease reminds a chameleon for the variety of its symptoms. For the sake of clarification, we shall divide multiple myeloma symptoms into five points, each of which is reason enough to warrant an examination to confirm or rule out a malignant cause of health problems (a negative result does not automatically mean exclusion). If any of the recommended examinations results positive, the diagnostic process must be continued, in which case a general practitioner refers the patient to a specialist health centre. Observing these recommendations should minimize the number of cases of late diagnosis. 1. Bone destruction symptoms. - Unexplained backache for more than one month in any part of spine even without nerve root irritability or without pain in other part of skeleton (ribs, hips, or long bones). - Pain at the beginning of myeloma disease is very similar to benigne common discopathy, however the intensity of backache is decreasing within one months in benigne disease. In the case of malignant process the intensity of bone pain is steadily increasing. - Immediate imaging and laboratory investigation are indicated by resting and night pain in spinal column or in any part of skeleton. - Backache with the sign of spinal cord or nerve compression should be sent for immediate X Ray, and focussed CT/MRI followed by acute surgery if needed. - Osteoporosis especially in men and premenopausal women. 2. Features of changed immunity or bone marrow function. Persistent and recurrent infection, typical is normochromic anaemia, with leucopenia and trombocytopenia. 3. Raised erythrocyte sedimentation rate even increase concentration of total plasma protein. 4. Impaired renal function. Increased level of creatinin or proteinuria, nephrotic syndrome with bilateral legs oedema. 5. Hypercalcemia with typical clinical symptoms (polyuria with dehydratation, constipation, nausea, low level conscience, coma). Every one from these points has to be reason for general medical doctor to start battery of tests: -X-ray of bones focused to painful area (mandatory before physiotherapy, local anaesthesia or other empiric therapy). If plain X-ray does not elucidate pain and symptoms are lasting more than one month, please consider all circumstances and results from laboratory investigation. This patient needs referral to the centre with MRI/CT facilities (CT or MRI is necessary investigation in case of nerve root or spine compression). -Investigation of erythrocyte sedimantion rate (high level of sedimentation of erythrocyte can indicate multiple myeloma). -Full blood count. -Basic biochemical investigation serum and urine: serum urea, creatinin, ionts including calcium, total protein, and albumin CRP (high concentration of total protein indicates myeloma, low level of albumin indicates general pathological process, similary increased concentration of fibrinogen, impaired renal function indicates myeloma kidney, however hypercalcemia is typical for highly aggressive myeloma). -Quantitative screening for IgG, IgM and IgA in serum (isolated raised level one of immunoglobulin with decreased level of the others indicates myeloma). -Common electrophoresis of serum is able to detect monoclonal immunoglobulin level at few gramm concentration. If all the laboratory investigation are in normal level the possibility that the current problems are multiple myeloma origine is smaller, but it does not exclude one of rare variant--non secretory myeloma (undifferentiated plasmocyt lost characteristic feature to produce monoclonal immunoglobulin). If any of tests indicate the possibility of myeloma, patient require urgent specialist referral to department with possibility to make diagnosis of malignant myeloma.
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PMID:[Recommendations for early identification of damage to the skeleton by malignant processes, and for early diagnosis of multiple myeloma]. 1817 27

Sarcoidosis is one of the granulomatus disorders affecting many organ systems of the body. Renal impairment in sarcoidosis is rare and occurs usually as a result of long standing hypercalcemia or hypercalciuria with nephrocalcinosis or renal stones. Sarcoid glomerulopathy and tubulo-interstitial granulomatus involvement have been described. We report two cases of sarcoidosis, the first with interstitial nephritis and anterior uveitis without evidence of granuloma. The patient was normocalcemic and normocalciuric. The second case presented with nephritic range proteinuria and severe renal insufficiency with a history of recurrent parotid swelling seven years before diagnosis. Renal biopsy showed non-caseating granulomas in the tubulo-interstitial region. Both patients showed good response to steroid therapy, however, there is still residual renal insufficiency six months after therapy. In conclusion, renal sarcoidosis although a rare presentation, should be considered in the presence of extra-renal manifestation of sarcoidosis as it is amenable to treatment.
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PMID:Sarcoidosis with partial reversibility of renal failure: two case reports with review of literature. 1840 17

Renal failure is a frequent complication in patients with multiple myeloma (MM) that causes significant morbidity. In the majority of cases, renal impairment is caused by the accumulation and precipitation of light chains, which form casts in the distal tubules, resulting in renal obstruction. In addition, myeloma light chains are also directly toxic on proximal renal tubules, further adding to renal dysfunction. Adequate hydration, correction of hypercalcemia and hyperuricemia and antimyeloma therapy should be initiated promptly. Recovery of renal function has been reported in a significant proportion of patients treated with conventional chemotherapy, especially when high-dose dexamethasone is also used. Severe renal impairment and large amount of proteinuria are associated with a lower probability of renal recovery. Novel agents, such as thalidomide, bortezomib and lenalidomide, have significant activity in pretreated and untreated MM patients. Although there is limited experience with thalidomide and lenalidomide in patients with renal failure, data suggest that bortezomib may be beneficial in this population. Clinical studies that have included newly diagnosed and refractory patients indicate that bortezomib-based regimens may result in rapid reversal of renal failure in up to 50% of patients and that full doses of bortezomib can be administered without additional toxicity.
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PMID:Pathogenesis and treatment of renal failure in multiple myeloma. 1852 26

Multiple myeloma (MM) is characterized by the presence of osteolytic bone disease, renal impairment, anemia, and immune dysfunction. Adequate supportive care is considered an essential part of anti-myeloma therapy. The administration of bisphosphonates has been shown to reduce skeletal related events and hypercalcemia. Bisphosphonates are well tolerated, but preventive steps should be taken to avoid renal impairment and osteonecrosis of the jaw (ONJ). Adequate pain control is of crucial importance for the quality of life of MM patients. Local radiotherapy may rapidly ameliorate symptoms of painful MM bone lesions, and vertebroplasty and kyphoplasty are able to control symptoms and restore the original height of vertebral fractures. Symptomatic chemotherapy-induced anemia should preferentially be treated with erythropoietic growth factors, but further studies are required to confirm the long-term safety of this approach. Light-chain-induced renal impairment should be treated without delay with a highly effective anti-myeloma regimen consisting of novel drugs. Prophylaxis of infections should be considered particularly in patients with poorly controlled disease and documented infections should be treated aggressively as they contribute significantly to morbidity and mortality. The concerted action of these supportive therapies can significantly improve the quality of life of MM patients during the different phases of their disease.
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PMID:Management of complications in multiple myeloma. 1938 1

Cinacalcet hydrochloride (cinacalcet) is a calcimimetic approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) receiving dialysis and for the treatment of hypercalcaemia in patients with parathyroid carcinoma. Following oral administration, peak plasma concentrations of cinacalcet occur within 2-6 hours. The absolute bioavailability is 20-25%, and administration of cinacalcet with low- or high-fat meals increases exposure (area under the plasma concentration-time curve from time zero to infinity [AUC(infinity)]) 1.5- to 1.8-fold. Cinacalcet has no significant interaction with calcium carbonate or sevelamer hydrochloride, phosphate binders commonly used in the treatment of patients with CKD receiving dialysis. The terminal elimination half-life is 30-40 hours, and steady-state concentrations are achieved within 7 days. The pharmacokinetics of cinacalcet are dose proportional over the dose range of 30-180 mg. The pharmacokinetic profile of cinacalcet is not notably affected by varying degrees of renal impairment. The pharmacokinetics of cinacalcet are comparable between healthy subjects, patients with primary hyperparathyroidism and patients with secondary hyperparathyroidism with reduced renal function (including those patients with secondary hyperparathyroidism receiving dialysis). Additionally, the pharmacokinetics of cinacalcet are similar in patients with secondary hyperparathyroidism receiving haemodialysis and patients with secondary hyperparathyroidism receiving peritoneal dialysis. Mild hepatic impairment does not affect the pharmacokinetics of cinacalcet, whereas moderate or severe hepatic impairment increases the exposure (AUC(infinity)) by approximately 2- and 4-fold, respectively. Age, sex, bodyweight and race do not notably affect the pharmacokinetics of cinacalcet. Cinacalcet is extensively metabolized by multiple hepatic cytochrome P450 (CYP) enzymes (primarily 3A4, 2D6 and 1A2) with <1% of the parent drug excreted in the urine. Dose adjustments of cinacalcet may be necessary, and parathyroid hormone (PTH) and serum calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g. ketoconazole, erythromycin, itraconazole). Cinacalcet is a strong inhibitor of CYP2D6; therefore, dose adjustment of concomitant medications that are predominantly metabolized by CYP2D6 and have a narrow therapeutic index (e.g. flecainide, vinblastine, thioridazine and most tricyclic antidepressants) may be required. Cinacalcet does not appreciably inhibit or induce the activities of CYP3A4, 1A2, 2C9 or 2C19. An inverse relationship exists between plasma PTH and cinacalcet concentrations. PTH concentrations are greatest before dose administration when the cinacalcet concentration is lowest (24 hours after the previous day's dose). Nadir PTH levels occur approximately 2-3 hours after dosing.
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PMID:Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. 1956 13

While in some patients, renal failure is the only, isolated sign of multiple myeloma, other patients have further simultaneous symptoms (signs of bone destruction, hypercalcaemia, cytopenia). Therefore, differential diagnosis of renal failure should always include monoclonal gametopathy-associated nephropathy. Renal damage is caused dominantly by free light chains. Elevated early mortality reaches 30% during the first 3 months and complicates treatment of patients with multiple myeloma with renal failure. More serious the renal damage caused by monoclonal immunoglobulin is, less likely is the improvement of renal function following treatment. Early diagnosis at the time when renal impairment is still reversible is extremely important for the patient's prognosis. Treatment regimens with high-dose glucocorticoids form the basis of treatment. Combined treatments with new, highly effective drugs (bortezomib or thalidomide) with high-dose glucocorticoids and an alkylating cytostatic agent, or with doxorubicin, have the fastest onset of action and thus provide the highest likelihood that haematological treatment response will be followed by improved renal function. High-dose chemotherapy is recommended in patients with persisting renal failure, particularly in the subgroup of patients with chemotherapy-sensitive disease; melphalan dose should not exceed 140 mg/m2.
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PMID:[The treatment of renal failure in multiple myeloma]. 1966 89

Multiple myeloma is the second most common hematological malignancy in the United States. The disease is characterized by an accumulation of clonal plasma cells. Clinically, patients present with anemia, lytic bone lesions, hypercalcaemia, or renal impairment. The genome of the malignant plasma cells is extremely unstable and is typically aneuploid and characterized by a complex combination of structure and numerical abnormalities. The basis of the genomic instability underlying myeloma is unclear. In this regard, centrosome amplification is present in about a third of myeloma and may represent a mechanism leading to genomic instability in myeloma. Centrosome amplification is associated with high-risk features and poor prognosis. Understanding the underlying etiology of centrosome amplification in myeloma may lead to new therapeutic avenues.
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PMID:Centrosomes and myeloma; aneuploidy and proliferation. 1973 37


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