RESUMO
BACKGROUND: Optimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation. METHODS: We studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4-6 (2009-18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9-12 months on HD. RESULTS: The 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9-12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150-300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9-12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation. CONCLUSIONS: Increased PTH before HD start predicted a higher PTH level 9-12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients.
Assuntos
Biomarcadores/sangue , Hiperparatireoidismo Secundário/etiologia , Hormônio Paratireóideo/sangue , Fósforo/sangue , Diálise Renal/efeitos adversos , Idoso , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. RECENT FINDINGS: Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.
Assuntos
Osso e Ossos/metabolismo , Cálcio/metabolismo , Fraturas Ósseas/metabolismo , Osteoporose/metabolismo , Insuficiência Renal Crônica/metabolismo , Calcificação Vascular/metabolismo , Fraturas Ósseas/epidemiologia , Humanos , Osteoporose/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Calcificação Vascular/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVES: Achievement of mineral targets in patients receiving dialysis remains challenging. This study sought to evaluate outcomes for phosphorus, calcium, and parathyroid hormone when a dialysis population was switched from a predominantly active vitamin D analogue treatment regimen to a computerized algorithm incorporating both cinacalcet and active vitamin D as potential first-line therapies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This longitudinal prospective trial enrolled 92 patients undergoing maintenance hemodialysis. Baseline measures (the average of the 3 months before computerized algorithm implementation) were compared with the proportion of patients achieving the prespecified targets at 6 and 12 months. RESULTS: After 6 months there was a statistically significant improvement in the percentage of patients achieving the primary and secondary phosphorus targets (primary: phosphorus ≤ 5.5 mg/dl, increase from 41% to 75%, P<0.001; secondary: phosphorus 3.0-4.6 mg/dl, increase from 16% to 38%; P=0.005). These improvements were sustained at 12 months. There was a statistically significant improvement in the percentage of patients achieving all three prespecified secondary endpoints (an increase from 12.8% to 25.6% at 12 months; P=0.04); however, this was mainly driven by improved phosphorus control. The proportion of patients achieving the primary or secondary parathyroid hormone targets did not improve. CONCLUSIONS: A greater proportion of dialysis patients achieved improved phosphorus but not parathyroid hormone control by switching from a predominantly active vitamin D analogue-based treatment regimen for mineral and bone disorder to a computer-driven algorithm that incorporated cinacalcet and low-dose active vitamin D analogues as first-line therapy.
Assuntos
Algoritmos , Calcimiméticos/administração & dosagem , Quimioterapia Assistida por Computador , Falência Renal Crônica/terapia , Doenças Metabólicas/tratamento farmacológico , Naftalenos/administração & dosagem , Diálise Renal , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Idoso , Biomarcadores/sangue , Cálcio/sangue , Cinacalcete , Substituição de Medicamentos , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Estudos Longitudinais , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/etiologia , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Estudos Prospectivos , Diálise Renal/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Most patients with chronic kidney disease experience abnormalities in serum calcium, phosphorus, parathyroid hormone, and vitamin D metabolism. These can lead to vascular calcification (VC), which has been associated with increased risk for cardiovascular disease and mortality. Although hyperphosphatemia is believed to be a risk factor for mortality and VC, no randomized trial was ever designed to demonstrate that lowering phosphate reduces mortality. Nonetheless, binders have been used extensively, and the preponderance of evidence shows that sevelamer slows the development of VC whereas calcium salts do not. Four studies have demonstrated a slower progression of VC with sevelamer than with calcium-containing binders, although a fifth study showed nonsuperiority. Conversely, the results on mortality with sevelamer have been variable, and data on calcium-based binders are nonexistent. Improved survival with sevelamer was demonstrated in a small randomized clinical trial, whereas a larger randomized trial failed to show a benefit. In addition, preclinical models of renal failure and preliminary clinical data on hemodialysis patients suggest a potential benefit for bone with sevelamer. Meanwhile, several randomized and observational studies suggested no improvement in bone density and fracture rate, and a few noted an increase in total and cardiovascular mortality in the general population given calcium supplements. Although additional studies are needed, there are at least indications that sevelamer may improve vascular and bone health and, perhaps, mortality in hemodialysis patients, whereas data on calcium-based binders are lacking.
Assuntos
Compostos de Cálcio/uso terapêutico , Quelantes/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Nefropatias/terapia , Fosfatos/metabolismo , Poliaminas/uso terapêutico , Diálise Renal , Animais , Biomarcadores/sangue , Remodelação Óssea/efeitos dos fármacos , Calcinose/etiologia , Calcinose/metabolismo , Calcinose/prevenção & controle , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Doença Crônica , Progressão da Doença , Medicina Baseada em Evidências , Humanos , Hiperfosfatemia/etiologia , Hiperfosfatemia/metabolismo , Hiperfosfatemia/mortalidade , Nefropatias/complicações , Nefropatias/metabolismo , Nefropatias/mortalidade , Sevelamer , Resultado do TratamentoRESUMO
OBJECTIVE: This study was designed to evaluate the efficacy of magnesium carbonate as a phosphate binder in hemodialysis patients. DESIGN: This study was a prospective, randomized, open-label trial comparing magnesium carbonate/calcium carbonate versus calcium acetate as a sole phosphate binder. SETTING: This study involved outpatient hemodialysis. PARTICIPANTS: We recruited 30 stable hemodialysis patients without a history of frequent diarrhea. INTERVENTION: After receiving informed consent, we randomized patients 2:1 to magnesium carbonate versus calcium acetate. The dose of each binder was titrated to achieve the Kidney Disease Outcomes Quality Initiative (K/DOQI) phosphate target of <5.5 mg/dL. MAIN OUTCOME MEASURE: The efficacy-phase serum phosphorus concentration and the percentage of patients meeting K-DOQI targets for phosphorus, along with the daily elemental calcium intake, were the primary outcome measures. RESULTS: Magnesium carbonate provided equal control of serum phosphorus (70.6% of the magnebind group and 62.5% of the calcium acetate group had their average serum phosphorus within the K-DOQI target during the efficacy phase), while significantly reducing daily elemental calcium ingestion from phosphate binders (908 +/- 24 vs. 1743 +/- 37 mg/day, P < .0001). CONCLUSION: Magnesium carbonate was generally well-tolerated in this selected patient population, and was effective in controlling serum phosphorus while reducing elemental calcium ingestion.
Assuntos
Cálcio da Dieta/administração & dosagem , Magnésio/farmacologia , Fosfatos/metabolismo , Distúrbios do Metabolismo do Fósforo/tratamento farmacológico , Fósforo/sangue , Diálise Renal , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal/efeitos adversos , Resultado do TratamentoRESUMO
Magnesium is predominantly an intracellular cation that plays a critical role in cellular physiology. Serum levels are often slightly elevated in patients on chronic hemodialysis and older reports suggests that total body stores may also be increased, based on bone biopsies in patients treated with higher dialysate magnesium levels than are currently in use today. Several studies have shown that magnesium, particularly in the form of magnesium carbonate, is an effective phosphate binder and can decrease patients' exposure to calcium. Retrospective studies suggest that magnesium may prevent vascular calcification in dialysis patients, although this remains controversial and has not been evaluated prospectively. Magnesium may reduce arrhythmias postoperatively and, while it may theoretically reduce arrhythmic death in dialysis patients, this hypothesis has never been tested. While short-term or adjuvant use of magnesium carbonate appears safe and effective as a phosphate binder, more studies are needed to evaluate the long-term effects on vascular calcification, bone histology, and mortality.
Assuntos
Quelantes/uso terapêutico , Falência Renal Crônica/complicações , Magnésio/uso terapêutico , Distúrbios do Metabolismo do Fósforo/tratamento farmacológico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Calcinose/etiologia , Calcinose/prevenção & controle , Quelantes/administração & dosagem , Humanos , Magnésio/metabolismo , Distúrbios do Metabolismo do Fósforo/etiologia , Diálise Renal , Doenças Vasculares/etiologia , Doenças Vasculares/prevenção & controleRESUMO
Achieving the K/DOQI targets for bone and mineral metabolism has proven difficult with the use of vitamin D analogues and phosphate binders. The introduction of cinacalcet HCl provided a new tool with a novel therapeutic mechanism of action. The purpose of this study was to evaluate the effect of the introduction of combination algorithm for managing secondary hyperparathyroidism (SHPT) on phosphorus, calcium, and biointact parathyroid hormone (PTH). The 61 patients who dialyzed in the facility from January 2004 (baseline) and who remained in the facility as of April 2005 (follow-up) were included in the study. In the baseline period, 37 (61%) of the patients received paricalcitol at some time during the 3-month observation period. In the follow-up period, 19% or 31% of the patients received cinacalcet HCl. Of those not receiving cinacalcet HCl, 67% had PTH at or below target, 17% were felt to be noncompliant with oral meds, 7% had low calcium, and 10% either could not get the medication or were not switched to the combination pathway. Compared with the baseline period, the percent of patients who met the PTH target increased from 19.7% to 37.7%, p<0.05. The percent of patients meeting all 4 targets increased from 14.8% to 24.6%, although this did not reach statistical significance. The introduction of cinacalcet HCl into a treatment algorithm for management of SHPT resulted in a significant increase in the percentage of patients achieving the PTH target while maintaining the other mineral metabolism targets.
Assuntos
Osso e Ossos/metabolismo , Cálcio/metabolismo , Hiperparatireoidismo Secundário/prevenção & controle , Falência Renal Crônica/terapia , Naftalenos/uso terapêutico , Fósforo/metabolismo , Diálise Renal/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Osso e Ossos/efeitos dos fármacos , Cinacalcete , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. METHODS: We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. RESULTS: During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). CONCLUSIONS: The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.
Assuntos
Acetatos/metabolismo , Calcinose/metabolismo , Carbonato de Cálcio/metabolismo , Vasos Coronários/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Hipoparatireoidismo/metabolismo , Diálise Renal , Acetatos/uso terapêutico , Calcinose/tratamento farmacológico , Calcinose/terapia , Cálcio/sangue , Carbonato de Cálcio/uso terapêutico , Compostos de Cálcio/metabolismo , Compostos de Cálcio/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Hipoparatireoidismo/tratamento farmacológico , Hipoparatireoidismo/terapia , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Fósforo/sangue , Poliaminas/uso terapêutico , SevelamerRESUMO
BACKGROUND: Hemodialysis patients are at increased risk for progressive coronary artery calcification; however, the development and progression of this disease process in patients new to hemodialysis is unknown. METHOD: One hundred and twenty-nine patients new to hemodialysis were randomized to receive calcium containing phosphate binders or the noncalcium phosphate binder sevelamer hydrochloride. Subjects underwent electron beam computed tomography scanning (EBCT) at entry into the study and again at 6, 12, and 18 months. RESULTS: One hundred and nine patients underwent baseline and at least one additional assessment of coronary calcification. At baseline, 37% of sevelamer treated and 31% of calcium treated patients had no evidence of coronary calcification. No subject with a zero coronary artery calcium score (CACS) at baseline progressed to a CACS >30 over 18 months. Subjects with a CACS > 30 at baseline showed progressive increases in CACS in both treatment arms (P < 0.05 for each time point in both groups). Subjects treated with calcium containing phosphate binders showed more rapid and more severe increases in CACS when compared with those receiving sevelamer hydrochloride (P= 0.056 at 12 months, P= 0.01 at 18 months). CONCLUSION: New hemodialysis patients with no evidence of coronary calcification showed little evidence of disease development over 18 months independent of phosphate binder therapy. However, subjects with evidence of at least mild coronary calcification had significant progression at 6, 12, and 18 months. Use of calcium containing phosphate binders resulted in more rapid progression of coronary calcification than did use of sevelamer hydrochloride.