RESUMO
Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum ß-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type â N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.
Assuntos
Conservadores da Densidade Óssea , Doenças Ósseas , Denosumab , Hipocalcemia , Mieloma Múltiplo , Ácido Zoledrônico , Humanos , Ácido Zoledrônico/administração & dosagem , Denosumab/efeitos adversos , Denosumab/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Doenças Ósseas/etiologia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Hipocalcemia/induzido quimicamente , Hipocalcemia/etiologia , Masculino , Feminino , Resultado do Tratamento , Pessoa de Meia-Idade , IdosoRESUMO
PURPOSE: Denosumab is used to treat patients with bone metastasis from solid tumors, but sometimes causes severe hypocalcemia, so careful clinical management is important. This study aims to externally validate our previously developed risk prediction model for denosumab-induced hypocalcemia by using data from two facilities with different characteristics in Japan and to develop an updated model with improved performance and generalizability. METHODS: In the external validation, retrospective data of Kameda General Hospital (KGH) and Miyagi Cancer Center (MCC) between June 2013 and June 2022 were used and receiver operating characteristic (ROC)-AUC was mainly evaluated. A scoring-based updated model was developed using the same data set from a hospital-based administrative database as previously employed. Selection of variables related to prediction of hypocalcemia was based on the results of external validation. RESULTS: For the external validation, data from 235 KGH patients and 224 MCC patients were collected. ROC-AUC values in the original model were 0.879 and 0.774, respectively. The updated model consisting of clinical laboratory tests (calcium, albumin, and alkaline phosphatase) afforded similar ROC-AUC values in the two facilities (KGH, 0.837; MCC, 0.856). CONCLUSION: We developed an updated risk prediction model for denosumab-induced hypocalcemia with small interfacility differences. Our results indicate the importance of using data from plural facilities with different characteristics in the external validation of generalized prediction models and may be generally relevant to the clinical application of risk prediction models. Our findings are expected to contribute to improved management of bone metastasis treatment.
Assuntos
Bases de Dados Factuais , Denosumab , Hipocalcemia , Humanos , Hipocalcemia/induzido quimicamente , Hipocalcemia/epidemiologia , Hipocalcemia/diagnóstico , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Feminino , Masculino , Idoso , Medição de Risco , Estudos Retrospectivos , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/efeitos adversos , Japão/epidemiologia , Curva ROC , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Idoso de 80 Anos ou mais , Fatores de RiscoAssuntos
Conservadores da Densidade Óssea , Denosumab , Hipocalcemia , Recidiva , Insuficiência Renal Crônica , Humanos , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Hipocalcemia/induzido quimicamente , Hipocalcemia/diagnóstico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Resultado do Tratamento , Feminino , Cálcio/sangue , Idoso , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure. CONCLUSIONS: Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.
Assuntos
Conservadores da Densidade Óssea , Doenças do Cão , Glucocorticoides , Hipercalcemia , Hipocalcemia , Pamidronato , Animais , Cães , Pamidronato/uso terapêutico , Hipocalcemia/veterinária , Hipocalcemia/induzido quimicamente , Masculino , Hipercalcemia/induzido quimicamente , Hipercalcemia/veterinária , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêuticoAssuntos
Conservadores da Densidade Óssea , Denosumab , Hipocalcemia , Falência Renal Crônica , Diálise Renal , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Cálcio/sangue , Cálcio/uso terapêutico , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Hipocalcemia/induzido quimicamente , Hipocalcemia/tratamento farmacológico , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapiaAssuntos
Conservadores da Densidade Óssea , Denosumab , Hipocalcemia , Falência Renal Crônica , Diálise Renal , Humanos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Hipocalcemia/induzido quimicamente , Falência Renal Crônica/complicações , Falência Renal Crônica/terapiaRESUMO
BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.
Assuntos
Hipocalcemia , Humanos , Estudos de Coortes , Hipocalcemia/induzido quimicamente , Hipocalcemia/epidemiologia , Japão/epidemiologia , Difosfonatos/efeitos adversos , RimRESUMO
BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements. CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine. CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.
Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Hipocalcemia , Feminino , Humanos , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Hipocalcemia/induzido quimicamente , Lapatinib/efeitos adversos , Denosumab/efeitos adversos , Cálcio/uso terapêutico , Neoplasias Ósseas/secundárioRESUMO
An 81-year-old Caucasian man who had commenced thrice weekly hemodialysis (HD) three months earlier, presented with a hip fracture, two vertebral fractures and a bone mineral density T-score of -3.6. He had received weekly iron sucrose infusions for 6 weeks and alphacalcidol on dialysis days. Although he suffered from coeliac disease and cirrhosis, he was fully ambulatory and well-nourished. He was normocalcaemic with a marginally low plasma phosphate and the PTH was 11.8 pmol/L (<2-times the upper range of the assay). In view of his severe osteoporosis, it was decided to treat him with denosumab (dmab). Laboratory assessment 2 weeks post dmab showed severe hypophosphatemia and hypocalcemia; phosphate 0.11 mmol/L and ionized calcium 0.83 mmol/L, and he was admitted for intravenous phosphate infusion. Three months later he remained on a phosphate supplement. The case illustrates that, in addition to the risks of hypocalcemia in patients with kidney failure and high bone turnover, kidney failure patients without evidence of high bone turnover, can also be at risk of hypocalcemia and severe hypophosphatemia requiring acute hospitalization and phosphate infusion. The potential role of compromised phosphate absorption versus increased deposition will be discussed. We recommend a cautious approach to dmab therapy in patients on dialysis, with evaluation of bone turnover and serum phosphate levels prior to initiation of treatment.
Assuntos
Conservadores da Densidade Óssea , Hipocalcemia , Hipofosfatemia , Insuficiência Renal , Humanos , Masculino , Idoso de 80 Anos ou mais , Denosumab/efeitos adversos , Hipocalcemia/induzido quimicamente , Hipofosfatemia/induzido quimicamente , Diálise Renal/efeitos adversos , Fosfatos , Insuficiência Renal/induzido quimicamente , Conservadores da Densidade Óssea/efeitos adversos , Densidade ÓsseaRESUMO
Deviations of calcium, phosphate, parathyroid hormone, and vitamin D levels are the basis for the diagnosis of calcium-phosphate metabolism disorders. The plasma concentration of the biologically active form known as free calcium is regulated in a harmonious manner by its exchange in the bones and reabsorption by the kidneys. These steps take place under the control of parathyroid hormone and calcitriol. In the process of chronic kidney disease, the kidney cannot synthesize adequate calcitriol, and the resulting hypocalcemia and hyperphosphatemia cause the development of secondary hyperparathyroidism. Osteoporosis is a metabolic bone disease and is essentially the consequence of osteoclastogenesis-induced bone resorption that exceeds bone formation. Osteoporosis is common after kidney transplant. However, hypocalcemia following kidney transplant is rare. The hungry bone syndrome after parathyroidectomy is often responsible for this condition in the pretransplant period. Denosumab is a human monoclonal antibody developed against the receptor activator of nuclear factor kappa-B ligand (known as RANKL). Denosumab exerts an antiresorptive effect on bones by reducing differentiation into osteoclasts. It is an effective treatment option for osteoporosis in the general population. There is insufficient scientific data regarding the use of denosumab in kidney transplant patients. Here, we present the case of a kidney transplant recipient who developed severe hypocalcemia (serum calcium 4.7 mg/dL) after denosumab treatment for osteoporosis.
Assuntos
Hipocalcemia , Transplante de Rim , Osteoporose , Humanos , Hipocalcemia/induzido quimicamente , Hipocalcemia/diagnóstico , Hipocalcemia/tratamento farmacológico , Denosumab/efeitos adversos , Calcitriol/efeitos adversos , Cálcio , Transplante de Rim/efeitos adversos , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Hormônio Paratireóideo , FosfatosRESUMO
BACKGROUND: Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment. METHODS: We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr Ë80), moderate (30 ≤ Ccr Ë50), and severe (Ccr Ë30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis. RESULTS: Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia. CONCLUSIONS: Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.
Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Hipocalcemia , Nefropatias , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hipocalcemia/induzido quimicamente , Hipocalcemia/prevenção & controle , Denosumab/efeitos adversos , Cálcio/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Estudos Retrospectivos , Neoplasias Ósseas/tratamento farmacológico , Albuminas/efeitos adversos , Nefropatias/induzido quimicamenteRESUMO
INTRODUCTION: Hydroxychloroquine and azathioprine have been routinely used to control and treat primary and secondary Sjögren's syndrome, which potentially triggered some overdoses by these drugs. Toxicity from hydroxychloroquine and azathioprine manifests in the form of cardiac conduction abnormalities, nausea, vomiting, and muscle weakness. Recognizing these unique drug overdoses and management of these toxicities is important. This case report aims to expand our current understanding of these drug overdoses and their management and also underscores the importance of anticipating and identifying fewer common complications, such as hypocalcemia. CASE REPORT: A 34-year-old Persian woman with a history of Sjögren's syndrome presented to the emergency department 3.5-4 hours after an intentional overdose of hydroxychloroquine and azathioprine and severe hypotension and loss of consciousness. Although the patient was regularly taking other medications, such as fluoxetine, naproxen, and prednisolone, she explicitly clarified that these were not the substances involved in her overdose. Early investigations showed hypokalemia (2.4 mEq/L), hypocalcemia (7.5 mg/dL), and hypoglycemia (65 mg/dL). She was also diagnosed with metabolic acidosis and respiratory alkalosis. The electrocardiogram showed changes in favor of hypokalemia; other lab tests were run on the patient. Supportive treatments were applied, including rapid intravenous fluid dextrose 5%, normal saline, potassium chloride 30 mEq, and calcium gluconate 100 mg. The patient was managed and monitored overnight in the emergency room and recovered without residual side effects. CONCLUSION: Hydroxychloroquine and azathioprine toxicity are considered rare, but it is likely to increase in frequency given the prevalence and increase in autoimmune diseases and the increasing usage of these drugs in treating such diseases. We found hypocalcemia as the presentation to this patient, which needs further investigation into the probable mechanism. Clinicians need to consider the unique effects of hydroxychloroquine and azathioprine poisoning and initiate appropriate emergency interventions to improve the outcomes in similar patients.
Assuntos
Overdose de Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipocalcemia , Hipopotassemia , Síndrome de Sjogren , Feminino , Humanos , Adulto , Hidroxicloroquina/uso terapêutico , Azatioprina/uso terapêutico , Hipocalcemia/induzido quimicamente , Síndrome de Sjogren/complicações , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/diagnóstico , Hipopotassemia/tratamento farmacológico , Overdose de Drogas/tratamento farmacológicoAssuntos
Conservadores da Densidade Óssea , Hipocalcemia , Osteoporose Pós-Menopausa , Insuficiência Renal Crônica , Humanos , Feminino , Denosumab/efeitos adversos , Hipocalcemia/induzido quimicamente , Hipocalcemia/diagnóstico , Hipocalcemia/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
Importance: Dialysis-dependent patients experience high rates of morbidity from fractures, yet little evidence is available on optimal treatment strategies. Chronic kidney disease-mineral and bone disorder is nearly universal in dialysis-dependent patients, complicating diagnosis and treatment of skeletal fragility. Objective: To examine the incidence and comparative risk of severe hypocalcemia with denosumab compared with oral bisphosphonates among dialysis-dependent patients treated for osteoporosis. Design, Setting, and Participants: Retrospective cohort study of female dialysis-dependent Medicare patients aged 65 years or older who initiated treatment with denosumab or oral bisphosphonates from 2013 to 2020. Clinical performance measures including monthly serum calcium were obtained through linkage to the Consolidated Renal Operations in a Web-Enabled Network database. Exposures: Denosumab, 60 mg, or oral bisphosphonates. Main Outcomes and Measures: Severe hypocalcemia was defined as total albumin-corrected serum calcium below 7.5 mg/dL (1.88 mmol/L) or a primary hospital or emergency department hypocalcemia diagnosis (emergent care). Very severe hypocalcemia (serum calcium below 6.5 mg/dL [1.63 mmol/L] or emergent care) was also assessed. Inverse probability of treatment-weighted cumulative incidence, weighted risk differences, and weighted risk ratios were calculated during the first 12 treatment weeks. Results: In the unweighted cohorts, 607 of 1523 denosumab-treated patients and 23 of 1281 oral bisphosphonate-treated patients developed severe hypocalcemia. The 12-week weighted cumulative incidence of severe hypocalcemia was 41.1% with denosumab vs 2.0% with oral bisphosphonates (weighted risk difference, 39.1% [95% CI, 36.3%-41.9%]; weighted risk ratio, 20.7 [95% CI, 13.2-41.2]). The 12-week weighted cumulative incidence of very severe hypocalcemia was also increased with denosumab (10.9%) vs oral bisphosphonates (0.4%) (weighted risk difference, 10.5% [95% CI, 8.8%-12.0%]; weighted risk ratio, 26.4 [95% CI, 9.7-449.5]). Conclusions and Relevance: Denosumab was associated with a markedly higher incidence of severe and very severe hypocalcemia in female dialysis-dependent patients aged 65 years or older compared with oral bisphosphonates. Given the complexity of diagnosing the underlying bone pathophysiology in dialysis-dependent patients, the high risk posed by denosumab in this population, and the complex strategies required to monitor and treat severe hypocalcemia, denosumab should be administered after careful patient selection and with plans for frequent monitoring.
Assuntos
Conservadores da Densidade Óssea , Hipocalcemia , Osteoporose , Estados Unidos , Humanos , Idoso , Feminino , Hipocalcemia/induzido quimicamente , Hipocalcemia/sangue , Denosumab/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Cálcio/uso terapêutico , Estudos Retrospectivos , Diálise Renal , Medicare , Osteoporose/tratamento farmacológico , Difosfonatos/efeitos adversosRESUMO
A 15-year-old male neutered mixed breed dog weighing 28 kg presented to a referral center after developing severe tremors and altered mentation. There was hypocalcemia and hypernatremia after oral administration of sodium phosphate as a bowel cleansing agent in preparation for colonoscopy. The dog was treated intravenously with low sodium fluids and calcium gluconate. Neurologic status and electrolyte derangements normalized over the next 12 hours. Oral administration of sodium phosphate appeared to cause clinical electrolyte derangements in this dog.
Assuntos
Doenças do Cão , Hipernatremia , Hipocalcemia , Masculino , Cães , Animais , Hipocalcemia/induzido quimicamente , Hipocalcemia/veterinária , Hipernatremia/induzido quimicamente , Hipernatremia/veterinária , Fosfatos/efeitos adversos , Administração Oral , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológicoRESUMO
PURPOSE: This study investigated the clinical risk factors for peripheral neuropathy induced by docetaxel and albumin-bound paclitaxel (AP) in patients with breast cancer. METHODS: This prospective observational study recruited 268 patients between March 2019 and December 2020. Patient information was obtained through the query system for laboratory test results, patient consultations, and scale evaluations. Neuropathic symptoms were followed up throughout and until 3 months after taxane chemotherapy. Univariate and multivariate analyses were used to find the risk factors for overall and moderate-severe taxane-induced peripheral neuropathy (TIPN). RESULTS: Cumulative dose (odds ratio [OR] = 3.533, 95% confidence interval [CI]: 1.797-6.944, p < 0.001), body mass index (BMI) (OR = 2.926, 95% CI: 1.621-5.281, p < 0.001), body surface area (BSA) (OR = 1.724, 95% CI: 1.011-2.941, p = 0.045), and hypocalcemia (OR = 4.899, 95% CI: 1.518-15.811, p = 0.008) all increased the risk of TIPN. Only cumulative dose (OR = 2.577, 95% CI: 1.161-5.719, p = 0.020) and BSA (OR = 2.040, 95% CI: 1.073-3.877, p = 0.030) were independent risk factors for moderate-severe TIPN. CONCLUSION: Cumulative dose, BMI, BSA, and hypocalcemia are all risk factors for overall TIPN, whereas cumulative dose and BSA are risk factors for moderate-severe TIPN. Patients with breast cancer who have high BMI, large BSA, hypocalcemia, and large cumulative dose may be at risk of TIPN, and intervention measures must be actively carried out for them.
Assuntos
Neoplasias da Mama , Hidrocarbonetos Aromáticos com Pontes , Hipocalcemia , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Hipocalcemia/induzido quimicamente , Paclitaxel/efeitos adversos , Taxoides/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Fatores de RiscoRESUMO
We assessed the prevalence of hypocalcemia after denosumab injections in a real-world cohort routinely monitored for calcium during up to 7.5 years of treatment. Among 1096 injections in 242 patients, 6.3% resulted in hypocalcemia, and was independent of the injection number. Severe hypocalcemia was rare (1%). PURPOSE: To assess the prevalence of and risk factors for hypocalcemia after administration of denosumab in a patient cohort routinely monitored for ionized calcium after each dose. METHODS: In this retrospective observational study, we analyzed denosumab-induced hypocalcemia in a real-world cohort who were routinely followed up with ionized calcium pre- and post-injection (within 31 days after injection) during the period 2011 to 2020. RESULTS: In total, we included data from 1096 denosumab injections in 242 individuals (1-15 injections per patient). The mean age for the first injection was 74 ± 10 years, and 88% were female. Post-injection hypocalcemia occurred after 6.3% of all injections (4.6% mild, 0.6% moderate, and 1.1% severe) and was independent of the number of injections (rate of hypocalcemia varied from 3-8%). Risk factors for hypocalcemia were male sex, severe renal failure, pre-injection hypocalcemia, hypomagnesemia, hypophosphatemia, and vitamin D insufficiency. Furthermore, older age was not associated with an increased hypocalcemia risk. CONCLUSIONS: Denosumab-induced hypocalcemia is a prevalent adverse event, which occurs independently of the number of injections. However, severe hypocalcemia is a rare occurrence, and severe renal failure and nutritional status appear to be important predictive factors. Magnesium and phosphate might add value in the pre-injection risk assessment; however, this observation needs to be confirmed in larger cohorts.
Assuntos
Conservadores da Densidade Óssea , Hipocalcemia , Insuficiência Renal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hipocalcemia/induzido quimicamente , Hipocalcemia/epidemiologia , Cálcio/uso terapêutico , Denosumab/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Prevalência , Estudos Retrospectivos , Insuficiência Renal/complicaçõesRESUMO
BACKGROUND: Calcimimetics are widely used in hemodialysis patients and influence serum calcium levels. Although the Kidney Disease: Improving Global Outcomes guidelines argued that low calcium levels induced by calcimimetics may be harmless, large observational studies investigating the association between hypocalcemia and mortality are scarce. We investigated the association between serum calcium levels and cardiovascular mortality in calcimimetics users using the nationwide Japanese registry for dialysis patients. METHODS: In this 9-year prospective cohort study, the baseline data were collected at the end of 2009. We enrolled patients on maintenance hemodialysis or hemodiafiltration. We employed three models (baseline, time-dependent and time-averaged) to conduct Cox proportional hazard regression analyses. RESULTS: Cinacalcet was prescribed to 12.7% (N = 22 853) at baseline. The median observation period was 98 (interquartile range 40-108) months and 108 (interquartile range 59-108) months in the whole cohort (N = 180 136) and in cinacalcet users, respectively. Three-quarters of survivors at the end of 2019 had continued calcimimetic therapy for 10 years, corresponding to a mean annual dropout rate of 2.9%. Hypocalcemia was not associated with cardiovascular mortality in the baseline or time-averaged model. In the time-dependent model, however, the lowest calcium decile (corrected calcium <8.4 mg/dL) was significantly associated with higher cardiovascular mortality than the reference (corrected calcium 8.7-8.9 mg/dL) in both cinacalcet users and all patients [hazard ratio (95% confidence interval) 1.32 (1.00, 1.75) and 1.15 (1.05, 1.26), respectively]. Hypocalcemia was especially associated with sudden death and death due to hemorrhagic stroke, heart failure and ischemic heart disease. Higher rate of fatal and non-fatal cardiovascular events was observed in hypocalcemic patients regardless of cinacalcet usage. CONCLUSIONS: Our findings suggest that transient hypocalcemia was associated with an increased risk of cardiovascular death independent of cinacalcet usage. We should pay attention to hypocalcemia transiently induced by cinacalcet.
Assuntos
Insuficiência Cardíaca , Hiperparatireoidismo Secundário , Hipocalcemia , Humanos , Cinacalcete , Hipocalcemia/induzido quimicamente , Cálcio , Estudos Prospectivos , Diálise Renal/efeitos adversos , Hormônio Paratireóideo , Hiperparatireoidismo Secundário/etiologia , Calcimiméticos , Insuficiência Cardíaca/etiologiaRESUMO
PURPOSE OF REVIEW: Continuous renal replacement therapy (CRRT) is a vital medical intervention used in critically ill patients with acute kidney injury (AKI). One of the key components of adequate clearance with CRRT is the use of anticoagulants to prevent clotting of the extracorporeal circuit. Regional citrate anticoagulation is the most often recommended modality. The term 'citrate toxicity' is used to describe potential adverse effects of accumulation of citrate and subsequent hypocalcemia. However, citrate is itself not inherently toxic. The term and diagnosis of citrate toxicity are questioned in this review. RECENT FINDINGS: Citrate is being increasingly used for regional anticoagulation of the CRRT circuit. Citrate accumulation is infrequent and can cause hypocalcemia and metabolic alkalosis, which are potential adverse effects. Citrate itself, however, is not a toxic molecule. The term 'citrate toxicity' has been used to denote hypocalcemia and metabolic acidosis. However, citrate administration is well known to cause systemic and urinary alkalinization and under certain circumstances, metabolic alkalosis, but is not associated itself with any 'toxic' effects.We review the existing literature and debunk the perceived toxicity of citrate. We delve into the metabolism and clearance of citrate and question current data suggesting metabolic acidosis occurs as the result of citrate accumulation. SUMMARY: In conclusion, this article calls into question prevailing concerns about 'citrate toxicity'. We emphasize the need for a more nuanced understanding of its safety profile. We recommend discarding the term 'citrate toxicity' in favor of another frequently used, but more meaningful term: 'citrate accumulation'.