RESUMO
In this case report, a novel N-acetylgalactosaminyltransferase 3 homozygous mutation (c.782 G>A; p.R261Q) associated with hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome is described. The patient had elbow, pelvis, and lower limb pain and a hard mass in the hip and olecranon regions. Increased levels of inorganic phosphorus (Pi) and C-reactive protein were observed. After treating the patient with conventional drugs, we tested denosumab, which reduced but did not normalize the Pi.
Assuntos
Calcinose , Denosumab , Hiperfosfatemia , N-Acetilgalactosaminiltransferases , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/genética , Hiperfosfatemia/etiologia , Denosumab/uso terapêutico , Calcinose/genética , Calcinose/tratamento farmacológico , N-Acetilgalactosaminiltransferases/genética , Polipeptídeo N-Acetilgalactosaminiltransferase , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Mutação , Masculino , Hiperostose Cortical CongênitaRESUMO
BACKGROUND: Hyperphosphataemia is a common complication of kidney disease. Current dialysis techniques do not provide enough phosphorus clearance, hence the need to use phosphorus binders. Treatment options include calcium carbonate, calcium acetate, lanthanum carbonate, sevelamer hydrochloride and iron-based binders. Patients receiving peritoneal dialysis (PD) with sustained elevated ferritin levels exceeding 800 ng/mL are at a higher risk of death. We identify PD patients treated with iron-based binders and compare ferritin and risk of iron accumulation to patients treated with non-iron-based binders. METHODS: All records of patients receiving PD at Emory dialysis centres until 30 October 2021 were reviewed for phosphorus binders. Basic demographics and laboratory data were time-referenced to the days on treatment with a particular binder. Patients were followed until discontinuation of the phosphorus binder, death, transplant, transfer to another dialysis provider or censoring at 36 months after medication was started. RESULTS: Compared to calcium acetate and sevelamer, ferric citrate utilisation in PD patients resulted in a sustained increase in ferritin. The proportion of patients with a ferritin equal to or greater than 800 ng/dL and transferrin saturation greater than 40% increased over time in patients treated with ferric citrate and was higher during the second and third year of follow-up compared to baseline values and to patients treated with calcium acetate or sevelamer. Two patients (7%) treated with ferric citrate developed clinically significant haemosiderosis. CONCLUSIONS: Use of ferric citrated in PD resulted in significant iron accumulation as judged by ferritin levels.
Assuntos
Acetatos , Compostos Férricos , Hiperfosfatemia , Diálise Peritoneal , Humanos , Ferro/metabolismo , Sevelamer/uso terapêutico , Diálise Peritoneal/efeitos adversos , Diálise Renal , Fósforo/metabolismo , Fósforo/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Ferritinas/uso terapêutico , Biomarcadores , Fosfatos , Quelantes/efeitos adversos , Compostos de CálcioRESUMO
BACKGROUND Hyperphosphatemia is a complication of chronic renal failure (CRF) due to reduction in the glomerular filtration rate. Lanthanum carbonate is a commonly used phosphate binder for patients with CRF and hyperphosphatemia, but has adverse effects if patients are not monitored. This report is of a 47-year-old man with hyperphosphatemia due to CRF treated with lanthanum carbonate tablets who presented acutely with partial large bowel obstruction. The incidence of lanthanum carbonate causing intestinal obstruction is rare, and few cases in the literature have described the course of the disease in detail. CASE REPORT A 47-year-old man diagnosed with diabetic nephropathy underwent hemodialysis treatment and was prescribed 0.5 g/day of chewable lanthanum carbonate tablets. After taking lanthanum carbonate for 5 months, the patient experienced symptoms of decreased bowel movements and exhaustion, which progressively worsened. Abdominal computed tomography (CT) revealed multiple hyperdensities in the large bowel, indicating the presence of lanthanum deposition. Lanthanum carbonate was promptly discontinued. After undergoing enema and catharsis treatment, the large bowel obstruction was relieved, and the hyperdensities in the abdominal CT disappeared. The colonoscopy and histologic examination revealed ulcerations and inflammatory changes in the large bowel mucosa. CONCLUSIONS This report highlights the rare association between the use of lanthanum carbonate tablets and intestinal obstruction. Healthcare providers should enhance their vigilance regarding lanthanum carbonate-induced serious gastrointestinal adverse reactions and actively seek to detect lanthanum deposition by abdominal CT or radiography (X-ray). After the occurrence of lanthanum deposition, drug withdrawal and promotion of defecation are primary treatment methods.
Assuntos
Hiperfosfatemia , Obstrução Intestinal , Falência Renal Crônica , Insuficiência Renal Crônica , Masculino , Humanos , Pessoa de Meia-Idade , Hiperfosfatemia/induzido quimicamente , Hiperfosfatemia/tratamento farmacológico , Lantânio/efeitos adversos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Comprimidos/uso terapêuticoRESUMO
Phosphate binders are the main treatment for hyperphosphatemia in patients with chronic kidney disease, and iron-based phosphate binders have been used with increasing frequency in recent years. This study examined the association of the use of iron-based, rather than non-iron-based, phosphate binders with the incidence of cardiovascular events, in a real-world setting. We used data from a cohort comprising representative adult patients on maintenance hemodialysis in Japan. The exposure of interest was the time-varying use of phosphate binders, classified into "iron-based", "only non-iron-based", and "no use". The primary outcome was a composite of cardiovascular events and all-cause deaths. A marginal structural Cox regression model was used to deal with possible time-dependent confounding. Of the 2247 patients from 58 hemodialysis facilities, iron-based and only non-iron-based phosphate binders were used in 328 (15%) and 1360 (61%), respectively, at baseline. Hazard ratios (95% confidence intervals) for iron-based and non-iron-based phosphate binders versus no use of phosphate binders were 0.35 (0.24, 0.52) and 0.44 (0.33, 0.58), respectively. The hazard ratio for iron-based relative to non-iron-based phosphate binders was 0.81 (0.58, 1.13), which was not statistically significant. Further studies are warranted to elucidate whether the use of iron-based phosphate binders reduces the event rate.
Assuntos
Doenças Cardiovasculares , Hiperfosfatemia , Adulto , Humanos , Ferro/uso terapêutico , Diálise Renal/efeitos adversos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , FosfatosRESUMO
Hyperphosphatemia is a well-known complication of kidney disease. Phosphate binders are a mainstay treatment, but despite the existence of several phosphate binders, there is no one best approach to manage hyperphosphatemia. Phosphate binders are calcium-based, non-calcium- based, and others. While calcium-based phosphate binders are used frequently, they may cause hypercalcemia. Conversely, lanthanum carbonate and sevelamer were not linked to hypercalcemia but are costlier. The most recently developed class of phosphate binders is the ironbased ferric citrate and sucroferric oxyhydroxide. These have an important role in controlling phosphate levels due to their ability to lower the phosphate while concurrently providing iron sources. This review provides pharmacological profiles of different phosphate binders and their clinical usages, and further elaborates on their place in hyperphosphatemia management.
Assuntos
Hipercalcemia , Hiperfosfatemia , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Ferro/uso terapêutico , Hipercalcemia/complicações , Hipercalcemia/tratamento farmacológico , Sevelamer/uso terapêutico , Fosfatos/uso terapêutico , Cálcio/uso terapêuticoRESUMO
Novel oral therapeutic agents based on inhibition or binding activity without adverse events in CKD patients are urgently needed. Here, 5/6 nephrectomy (NX) rats were used to construct a CKD model. Aminated cellulose (AC711), which is metal-free, non-absorbable, and low-volume expansive, was used as a novel oral therapeutic agent for hyperphosphataemia treatment in rats. The efficacy of AC711 on serum and urinary phosphate levels, the expression of type II sodium-dependent phosphate cotransporter (NPT2b), and type III Na-dependent phosphate cotransporter (PiT-1/2) was examined. Serum fibroblast growth factor-23 (FGF-23) levels, parathyroid hormone (PTH) levels, and the phenotypic transformation of vascular smooth muscle cell markers (smooth muscle 22 (SM22) and Runx2) are considered an adaptive response to elevated serum phosphate levels. A similar efficacy of AC711 was observed on serum and urinary phosphate levels when the same dose of AC711 and sevelamer was administered to 5/6 NX rats. The decreasing expression of NPT2b, PiT-1, and PiT-2 was examined in the AC711 groups in a dose-dependent manner. The sevelamer and AC711-MD groups for FGF-23 and PTH indicated no significant difference. The down-regulation of Runx2 expression and up-regulation of SM22 expression were seen in the AC711 groups in a dose-dependent manner. Two suppression mechanisms (binding and inhibiting activities) were observed in the gastrointestinal (GI) tract in the AC711 groups. A novel oral phosphate binder, AC711, showed both binding and inhibition characteristics. The low-volume expansion of AC711 following exposure to simulated intestinal fluid provides the potential therapeutic benefits with the advantage of moderate GI side effects.
Assuntos
Celulose , Hiperfosfatemia , Insuficiência Renal Crônica , Animais , Celulose/análogos & derivados , Celulose/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/metabolismo , Hiperfosfatemia/tratamento farmacológico , Hormônio Paratireóideo , Fosfatos/metabolismo , Ratos , Insuficiência Renal Crônica/tratamento farmacológico , SevelamerRESUMO
Hyperphosphatemic familial tumor calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and calcium and phosphorus crystal deposition. It occurs due to the loss of function of FGF23. Herein, we report a case of a 50-year-old woman diagnosed with HFTC (homozygous variant in the GALNT3 gene, c.803_804 C insertion) with a history of ectopic calcifications in the past 30 years. Laboratory tests on admission were as follows: phosphate (P) 7.1 mg/dL (Normal range (NR) 2.5-4.5 mg/dL), FGF23 c-terminal 2050 RU/mL (NR < 150 RU/mL), and intact FGF23 (iFGF23) 18.93 pg/mL (NR 12.0-69.0 pg/mL). Treatment with acetazolamide, sevelamer, and a phosphorus-restricted diet was started, but phosphatemia remained high and calcifications continued to progress. In an attempt to further decrease P, a 36-day cycle of teriparatide (TPTD) 20 mcg twice daily was added, decreasing P from 6.2 to 5.2 mg/dL and increasing the 1.25(OH)2 vitamin D by 34.2%. As urinalysis was not feasible at the end of the 36-day cycle, a second cycle was performed for another 28 days, producing a similar decrease in P (from 6.4 to 5.5 mg/mL) and an evident decrease in the rate of tubular reabsorption of P (from 97.2 to 85.3%), however, accompanied by a worrying increase in calciuria. The use of TPTD 20 mcg twice daily in a patient with genetic resistance to FGF23 (HFTC) was associated with consistent increase in phosphaturia and reduction in phosphatemia, in addition to an increase in calcitriol. The resulting hypercalciuria precludes the therapeutic use of TPTD in HFTC and suggests an important role of FGF23, not only in phosphate homeostasis but also in avoiding any excess of calcitriol.
Assuntos
Calcinose , Hiperfosfatemia , Hipofosfatemia Familiar , N-Acetilgalactosaminiltransferases , Neoplasias , Calcinose/tratamento farmacológico , Calcinose/genética , Calcitriol/uso terapêutico , Feminino , Fatores de Crescimento de Fibroblastos/genética , Humanos , Hiperostose Cortical Congênita , Hiperfosfatemia/diagnóstico , Hiperfosfatemia/tratamento farmacológico , Pessoa de Meia-Idade , N-Acetilgalactosaminiltransferases/genética , N-Acetilgalactosaminiltransferases/uso terapêutico , Fosfatos , Fósforo , Teriparatida/uso terapêuticoRESUMO
INTRODUCTION: Children with acute myeloid leukemia (AML) are at risk for serious electrolyte abnormalities. CASE REPORT: We reported a case of hyperphosphatemia in a child with acute myeloid leukemia who received liposomal amphotericin B (AMBL) for the treatment of an invasive fungal infection. The findings of this case suggest that cumulative dose accumulation due to long term AMBL treatment may result in late-onset hyperphosphatemia. MANAGEMENT AND OUTCOME: This is the first case report in the literature that of late-onset hyperphosphatemia (day 56) in a patient with low-dose AMBL treatment (3-5â mg/kg/day) and normal renal function. DISCUSSION: We highlight the importance of increasing awareness of AMBL related hyperphosphatemia among healthcare providers.
Assuntos
Hiperfosfatemia , Leucemia Mieloide Aguda , Anfotericina B/uso terapêutico , Antifúngicos/efeitos adversos , Criança , Humanos , Hiperfosfatemia/induzido quimicamente , Hiperfosfatemia/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológicoRESUMO
Calciphylaxis is a potencially disorder in patients with hyperphosphatemic familial tumoral calcinosis (HFTC). Patients commonly present livedo racemosa and retiform purpura, which may progress to necrosis and very painful ulcers. Treatment with sodium thiosulfate provides good results; however, intralesional and intravenous treatment can be limited by its adverse effects. Topical sodium thiosulfate has been successfully reported for cutaneous calcification associated with connective tissue diseases and calciphylaxis in patients with chronic kidney disease. We provide a case report of a patient with HFTC and calciphylaxis who was treated with topical sodium thiosulfate with a rapid and complete response with no side effects.
Assuntos
Antioxidantes/uso terapêutico , Calcinose/tratamento farmacológico , Calciofilaxia/tratamento farmacológico , Hiperostose Cortical Congênita/tratamento farmacológico , Hiperfosfatemia/tratamento farmacológico , Tiossulfatos/uso terapêutico , Idoso , Humanos , MasculinoRESUMO
Chronic kidney disease (CKD) leads to alterations of iron metabolism, which contribute to the development of anemia and necessitates iron supplementation in patients with CKD. Elevated hepcidin accounts for a significant iron redistribution in CKD. Recent data indicate that these alterations in iron homeostasis coupled with therapeutic iron supplementation have pleiotropic effects on many organ systems in patients with CKD, far beyond the traditional hematologic effects of iron; these include effects of iron on inflammation, oxidative stress, kidney fibrosis, cardiovascular disease, CKD-mineral and bone disorder, and skeletal growth in children. The effects of iron supplementation appear to be largely dependent on the route of administration and on the specific iron preparation. Iron-based phosphate binders exemplify the opportunity for using iron for both traditional (anemia) and novel (hyperphosphatemia) indications. Further optimization of iron therapy in patients with CKD may inform new approaches to the treatment of CKD complications and potentially allow modification of disease progression.
Assuntos
Anemia , Hiperfosfatemia , Insuficiência Renal Crônica , Anemia/etiologia , Criança , Eritropoese , Feminino , Hepcidinas , Humanos , Hiperfosfatemia/tratamento farmacológico , Ferro/metabolismo , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismoRESUMO
Tumoral calcinosis (TC) is a rare disease characterized by periarticular soft tissue calcification. Some cases were reported in Africa and the Middle East. We report an 11-year-old Chinese girl presenting with recurrent multiple subcutaneous masses around the right elbow and hip regions. Although we found abnormalities in FGF23, a protein associated with phosphate metabolism, no positive results were observed in gene sequencing and analysis. The imaging features, laboratory examination, and pathology results confirmed our diagnosis. By using oral phosphorus-lowering drugs (acetazolamide) combined with complete surgical excision, good results were achieved, and no recurrence was reported during the follow-up of 18 months. We report a case of primary hyperphosphatemic TC. The combined use of oral phosphorus-lowering drugs (acetazolamide) and complete surgical excision produced good results, and no recurrence was reported during the follow-up of 18 months.
Assuntos
Calcinose , Hiperostose Cortical Congênita , Hiperfosfatemia , Calcinose/diagnóstico por imagem , Criança , Feminino , Fatores de Crescimento de Fibroblastos , Humanos , Hiperfosfatemia/tratamento farmacológicoRESUMO
PURPOSE: Iron-based phosphate binders, including ferric citrate hydrate (FCH) and sucroferric oxyhydroxide (SFOH), have been used for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. However, the long-term efficacy and safety of these agents have not yet been clearly elucidated. METHODS: Laboratory data of 56 hemodialysis patients who had been prescribed either FCH (n = 33) or SFOH (n = 23) were retrospectively examined. RESULTS: We showed that both FCH and SFOH significantly and consistently decreased serum phosphate concentrations in the patients undergoing maintenance hemodialysis during the 36-month observation period. Serum levels of calcium, intact parathyroid hormone, as well as hemoglobin levels were unaltered. No overshoot of parameters of iron metabolism, such as transferrin saturation and serum ferritin levels, was observed, and serum ferritin level remained under 300 ng/mL in most patients. A trend towards decrease in the doses of erythropoiesis-stimulating agents used and frequency of intravenous iron use was observed in both treatment groups. No severe adverse drug reactions were observed in either the patients receiving FCH or SFOH. CONCLUSION: The results of the present study suggest that the iron-based phosphate binders, FCH and SFOH, decrease serum phosphate concentrations consistently and are safe to use over the long-term in maintenance hemodialysis patients.
Assuntos
Hiperfosfatemia , Ferro , Combinação de Medicamentos , Compostos Férricos , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Ferro/metabolismo , Fosfatos , Diálise Renal/efeitos adversos , Estudos Retrospectivos , SacaroseRESUMO
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) both influence blood phosphate levels by regulating urinary phosphate reabsorption. Clinical data suggest that adequate renal phosphate handling requires the presence of both FGF23 and PTH, but robust evidence is lacking. To investigate whether the phosphaturic effects of PTH and FGF23 are interdependent, 11 patients with hypoparathyroidism, which features high blood phosphate in spite of concomitant FGF23 elevation, and 1 patient with hyperphosphatemic familial tumoral calcinosis (HFTC), characterized by deficient intact FGF23 action and resulting hyperphosphatemia, were treated with synthetic human PTH 1-34 (hPTH 1-34). Biochemical parameters, including blood phosphate, calcium, intact FGF23 (iFGF23), nephrogenic cAMP, 1,25(OH)2 vitamin D (1,25D), and tubular reabsorption of phosphate (TRP), were measured at baseline and after hPTH 1-34 treatment. In patients with hypoparathyroidism, administration of hPTH 1-34 increased nephrogenic cAMP, which resulted in serum phosphate normalization followed by a significant decrease in iFGF23. TRP initially decreased and returned to baseline. In the patient with HFTC, hPTH 1-34 administration also increased nephrogenic cAMP, but this did not produce changes in phosphate or TRP. No changes in calcium were observed in any of the studied patients, although prolonged hPTH 1-34 treatment did induce supraphysiologic 1,25D levels in the patient with HFTC. Our results indicate that PTH and FGF23 effects on phosphate regulation are interdependent and both are required to adequately regulate renal phosphate handling. Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
Assuntos
Hiperfosfatemia , Hipoparatireoidismo , Calcinose , Fatores de Crescimento de Fibroblastos , Humanos , Hiperostose Cortical Congênita , Hiperfosfatemia/tratamento farmacológico , Hipoparatireoidismo/tratamento farmacológico , Hipoparatireoidismo/genética , Hormônio Paratireóideo/farmacologia , Hormônio Paratireóideo/uso terapêutico , FosfatosRESUMO
Circulating phosphate levels are tightly controlled within a narrow range in mammals. By using a novel small-molecule inhibitor, we show that the enzymatic activity of inositol hexakisphosphate kinases (IP6K) is essential for phosphate regulation in vivo. IP6K inhibition suppressed XPR1, a phosphate exporter, thereby decreasing cellular phosphate export, which resulted in increased intracellular ATP levels. The in vivo inhibition of IP6K decreased plasma phosphate levels without inhibiting gut intake or kidney reuptake of phosphate, demonstrating a pivotal role of IP6K-regulated cellular phosphate export on circulating phosphate levels. IP6K inhibition-induced decrease in intracellular inositol pyrophosphate, an enzymatic product of IP6K, was correlated with phosphate changes. Chronic IP6K inhibition alleviated hyperphosphataemia, increased kidney ATP, and improved kidney functions in chronic kidney disease rats. Our results demonstrate that the enzymatic activity of IP6K regulates circulating phosphate and intracellular ATP and suggest that IP6K inhibition is a potential novel treatment strategy against hyperphosphataemia.
Assuntos
Fosfatos/sangue , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Homeostase/efeitos dos fármacos , Humanos , Hiperfosfatemia/tratamento farmacológico , Fosfatos de Inositol/metabolismo , Mamíferos , Fosfatos/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/antagonistas & inibidores , Ratos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Virais/genética , Receptores Virais/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Receptor do Retrovírus Politrópico e XenotrópicoRESUMO
OBJECTIVES: Familial hyperphosphatemic tumoral calcinosis is a rare disorder characterized by hyperphosphatemia with recurrent ectopic periarticular calcifications, in addition to other visceral and vascular manifestations, without any inflammatory or neoplastic disorder. The available treatment strategies are limited. Here we report an eight year old female patient with recurrent lesions under the chin, and bilateral hips which are painful and improving of the size of the lesions and hyperphosphatemia. CASE PRESENTATION: The patient was started to the treatment with peroral acetazolamide however the lesion did not regress but a new lesion appeared then we added sevelamer and topical sodium thiosulfate treatment for three months. After the three months of the combination treatment the lesions, there were no pain, no hyperphospahtemia regression/disappearance of the lesions. CONCLUSIONS: This combination treatment or topical sodium thiosulfate use only may be a novel treatment strategy for the patients prospective controlled trials are needed.
Assuntos
Acetazolamida/uso terapêutico , Calcinose/tratamento farmacológico , Hiperfosfatemia/tratamento farmacológico , Sevelamer/uso terapêutico , Tiossulfatos/administração & dosagem , Administração Tópica , Anticonvulsivantes/uso terapêutico , Antioxidantes/administração & dosagem , Calcinose/complicações , Calcinose/patologia , Quelantes/uso terapêutico , Criança , Quimioterapia Combinada , Feminino , Humanos , Hiperfosfatemia/complicações , Hiperfosfatemia/patologia , PrognósticoRESUMO
PURPOSE: A study was conducted to determine whether iron-based phosphate binders (IBPBs) need to be preferred for hyperphosphatemia and anemia management in patients on dialysis. METHODS: For this meta-analysis, we searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials that evaluated the efficacy and safety of IBPBs in decreasing phosphate and correcting anemia in dialysis patients. RESULTS: Nineteen trials comprising 4719 participants were included. Compared with placebo, serum phosphate decreased significantly after treatment with ferric citrate (FC), fermagate (one study), and SBR759 (one study). Hemoglobin increased significantly after treatment with FC and sucroferric oxyhydroxide (PA21). In addition, FC and PA21 reduced serum intact parathyroid hormone (iPTH) and increased ferritin and transferrin saturation, but SBR759 did not. Compared with active treatment, the non-inferiority of IBPBs in reducing serum phosphate and iPTH was demonstrated. FC significantly improved serum hemoglobin and iron-related parameters and decreased the use of intravenous iron and erythropoiesis-stimulating agent, whereas PA21 did not increase serum hemoglobin level. The incidences of infection and hospitalization were similar between the two groups, with FC having a higher risk of diarrhea than the placebo and active treatments. CONCLUSION: FC was associated with the control of hyperphosphatemia and the improvement of anemia. However, PA21 did not show superiority for alleviating anemia compared with the active treatment. Other IBPBs, such as fermagate and SBR759, remained poorly understood due to the limited number of studies. Further trials are required to assess the effect of IBPBs on the risk of cardiovascular events and all-cause mortality.
Assuntos
Anemia/tratamento farmacológico , Carbonatos/uso terapêutico , Compostos Férricos/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Ferro/uso terapêutico , Magnésio/uso terapêutico , Diálise Renal , Amido/uso terapêutico , Sacarose/uso terapêutico , Combinação de Medicamentos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges. METHODS: We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment. RESULTS: The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1; P=0.006). This effect was pronounced in older (aged 65-74 years) versus younger (aged 20-64 years) participants (P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores. CONCLUSIONS: Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048.
Assuntos
Calcinose/sangue , Calcinose/etiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/etiologia , Fosfatos/sangue , Diálise Renal/efeitos adversos , Adulto , Idoso , Calcinose/prevenção & controle , Doença da Artéria Coronariana/prevenção & controle , Progressão da Doença , Combinação de Medicamentos , Feminino , Compostos Férricos/efeitos adversos , Compostos Férricos/uso terapêutico , Humanos , Hiperfosfatemia/complicações , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/prevenção & controle , Lantânio/efeitos adversos , Lantânio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Sequestrantes/efeitos adversos , Sequestrantes/uso terapêutico , Sacarose/efeitos adversos , Sacarose/uso terapêutico , Adulto JovemRESUMO
Tumor lysis syndrome (TLS) is an oncologic emergency due to massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation. Clinical presentation is characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia. Acute kidney injury due to tumor lysis is potentiated by the precipitation of uric acid and calcium phosphate as well as renal vasoconstriction. Early recognition of tumor lysis can help prevent cardiac arrhythmias, seizures, and death. Management includes intravenous hydration to maintain urine flow, medications targeting hyperuricemia including rasburicase and allopurinol and in severe cases renal replacement therapy may be required.
Assuntos
Hiperfosfatemia , Hiperuricemia , Síndrome de Lise Tumoral , Alopurinol/uso terapêutico , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/terapia , Hiperuricemia/tratamento farmacológico , Terapia de Substituição Renal , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/etiologia , Síndrome de Lise Tumoral/terapia , Urato Oxidase/uso terapêuticoRESUMO
BACKGROUND: Hyperphosphataemia is a common complication of chronic kidney disease (CKD). PT20 (ferric iron oxide adipate) is an investigational molecule engineered to offer enhanced phosphate-binding properties relative to other phosphate binders. METHODS: In this double-blind, parallel-group, placebo-controlled, dose-ranging study (ClinicalTrials.gov identifier NCT02151643), the efficacy and safety of 28 days of oral PT20 treatment were evaluated in patients with dialysis-dependent CKD. Participants were randomly assigned in an 8:8:8:13:13 ratio to receive PT20 (400, 800, 1600 or 3200 mg) or placebo three times daily. RESULTS: Among 153 participants, 129 completed treatment [7 discontinued because of adverse events (AEs), 2 because of hyperphosphataemia and 15 for other reasons]. PT20 treatment for 28 days resulted in a statistically significant and dose-dependent reduction in serum phosphate concentration. There were no statistically significant effects of PT20 treatment on changes in haemoglobin or ferritin concentrations or transferrin saturation between Days 1 and 29. The incidence of treatment-emergent AEs was broadly similar across the PT20 and placebo groups (42-59% versus 44%). The most common PT20 treatment-related AEs were gastrointestinal, primarily diarrhoea (13-18%) and discoloured faeces (3-23%). No serious AEs were considered to be related to study treatment. There were no clinically significant changes in laboratory results reflecting acid/base status or increases in ferritin that could indicate the absorption of components of PT20. CONCLUSIONS: In this first study investigating the efficacy and safety of PT20 in patients with hyperphosphataemia and dialysis-dependent CKD, PT20 significantly lowered serum phosphate concentrations and was generally well tolerated.
Assuntos
Hiperfosfatemia , Insuficiência Renal Crônica , Método Duplo-Cego , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Ferro , Fosfatos , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapiaRESUMO
AIMS: Phosphate-lowering effects of ferric citrate were reported in several clinical trials, but mostly in small-scale studies. The aim of this meta-analysis was to investigate the efficacy and safety of ferric citrate in controlling hyperphosphataemia and iron-deficiency anaemia in chronic kidney disease (CKD) patients. METHODS: PubMed, Embase and Cochrane Library were searched for clinical trials that enrolled CKD patients receiving ferric citrate for hyperphosphataemia. Two investigators performed systematic literature search to identify eligible studies, evaluated risk of bias and extracted relevant data. RESULTS: Sixteen studies were included in the meta-analysis. Phosphate-lowering effects of ferric citrate were greater compared to no active treatment (standardized mean difference [SMD] = -1.15; P < 0.001) and comparable to other phosphate binders (SMD = 0.03; P = 0.61). Calcium concentrations post ferric citrate treatment did not differ compared to no active treatment (SMD = 0.15; P = 0.21) but were significantly lower compared to other phosphate binders (SMD = -0.14; P = 0.01). These led to significant reductions in calcium-phosphorus product with ferric citrate versus no active control (SMD = -1.02; P < 0.001) but no difference versus active control (SMD = -0.01; P = 0.93). Intact parathyroid hormone showed no substantial between-group difference in both comparison against no active and active controls. Ferric citrate improved iron stores and anaemia parameters, but increased risk of diarrhoea, abdominal pain and discoloured faeces. CONCLUSION: Ferric citrate was effective in lowering phosphorus and phosphorus-calcium product versus no active treatment and had comparable effects versus other phosphate binders. Calcium levels were significantly lower with ferric citrate than with other phosphate-lowering treatment. Ferric citrate had additive effects on iron repletion and anaemia control and was associated with mostly gastrointestinal side effects.