Double-blind trial of oral 1,25-dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis (original) (raw)
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Nephro-Urology Monthly, 2017
Background: Secondary Hyperparathyroidism (sHPT) is an important feature of chronic renal failure and contributes to the development of renal osteodystrophy. This study was carried out to assess 25(OH)D status and its effect on sHPT in patients on hemodialysis (HD). Methods: A prospective experimental trial of 180 HD patients (F: 81, M: 99, age > 14year) participated in the study. At base line, levels of 25(OH)D, intact Parathyroid Hormone (iPTH), Calcium (Ca), Phosphorous (P), Alkaline phosphatase (Alk p), and albumin of serum were measured. Patients with 25(OH)D deficiency (< 30 ng/mL) were randomly divided to two groups: intervention (received 300,000 U/IM vitD3 at the beginning and after 2 months, if was necessary) and control (received placebo). After 2 and 4 months, the same biochemical markers were measured and efficacy of vitD3 on sHPT was assessed. Secondary Hyperthyroidism (sHPT) was defined as iPTH > 300 pg/mL. Results: Serum 25(OH)D levels were deficient in 87.8% (n: 158) of subjects, and normal in 12.2% (n: 22). The prevalence of sHPT, according to 25(OH)D levels, was 71.5% (n: 113)(< 30 ng/mL) and 40.9% (n: 9)(≥ 30), respectively. There were 57 intervention and 56 control subjects. In the intervention group, 2 months after injections, 25(OH)D increased from 13.85 ± 6.5 to 48.5 ± 20.7 (P < 0.001), iPTH was reduced from 567.2 ± 276.7 to 282.7 ± 183.6 (P < 0.001), calcium from 9.10 ± 0.5 to 8.76 ± 0.7 (P = 0.021), Alk p from 553.37 ± 495.6 to 393.4 ± 419.5 (P < 0.001), albumin from 3.87 ± 0.5 to 4.00 ± 0.4 (P = 0.06), and phosphorus from 4.90 ± 1.2 to 5.21 ± 1.3 (P = 0.12). Since all cases were under appropriate treatment for sHPT, there was a significant reduction on the levels of iPTH (P = 0.005) and Alk p (P = 0.049), and slight increase in 25(OH)D level (P = 0.08) in the control group. However, the amount of these changes was less than the intervention group. Conclusions: These findings showed that 25(OH)D insufficiency was highly prevalent in HD cases and higher amount of 25(OH)D levels prevent sHPT.
The Egyptian Journal of Hospital Medicine, 2015
Background: secondary hyperparathyroidism (SHPT), a complication of chronic kidney disease (CKD) and is characterized by not only increased serum levels of intact parathyroid hormone (iPTH), but also may cause skeletal and cardiovascular complications. Deficiency of calcitriol (1, 25-hydroxy vitamin D) caused by impaired renal function, a main factor in the pathogenesis and pathophysiology of secondary hyperparathyroidism (SHPT) is associated with poor outcomes in hemodialysis patients. Therapy with vitamin D receptor (VDR) activators, including calcitriol or the selective VDR activator paricalcitol, has been associated with improved survival in patients with CKD on hemodialysis. PATIENTS AND METHODS: single center cross over observational study of 28 patients on regular Hemodialysis in nephrology unit in Dubai hospital, the patient stopped all vitamin-D supplementations and calcium containing phosphate binder for 2 weeks prior to initiation and for the whole study period, non calcium based phosphate binder was continued. Initial dose of selective VDRA (PARICALCITOL) is 0.04 to 0.1 mcg/kg body weight (average total dose 2.8-7 mcg) administered as a bolus dose post hemodialysis twice to three times per week according to initial parathyroid hormone level Titration weekly dose (micrograms) calculated by dividing most recent i-PTH level (pg/ml)/80. RESULTS : analyzing the data at start and end of trial period 48 weeks showed that there was significant reduction of serum I-PTH from (491.210±144.690 pg/dl) at start of the trial to (142.610 ±41.519pg/dl) at 48 weeks with P-value (<0.001). Serum calcium increased from (8.343± 0.654mg/dl) at the start of the study to (8.629±0.534mg/dl) at 48 weeks but without statistical significance P-value (0.006), same occurred with serum phosphate which showed insignificant rise with phosphate level at start of the test(7.264±1.695mg/dl) and at 48 weeks (7.279±1.800mg/dl) with P-value(0.975). CONCLUSION: It could be concluded that use of intravenous vitamin D selective receptor activator (Paricalcitol) is effective in reducing serum I-PTH level in hemodialysis patients. Serum Ca++ and phosphorus levels were statistically insignificant.
Hemodialysis International, 2010
Secondary hyperparathyroidism (SHPT) is a frequent complication in chronic kidney disease, especially in hemodialysis (HD) patients. Treatments for SHPT include calcitriol analogues (CA), phosphate binders, cinacalcet (CC), and surgical parathyroidectomy (PTX). This study aimed to assess the incidence and prevalence of SHPT in a single center during the period when native vitamin D (N-VitD) supplementation and CC treatment became available. All incident and prevalent HD patients were prospectively recorded and compared using 3 periods from 2004 to 2005 (period 1), 2006 to 2007 (period 2), and 2008 to 2009 (period 3). SHPT was diagnosed with serum parathyroid hormone (PTH) levels 4300 pg/mL or the need for CA, CC, or PTX. Between periods 1 and 3, in incident patients (n= 120 and 101), N-VitD prescription increased from 11% to 68% (Po0.0001), CA prescription remained stable (40%), and patients with PTH4300 pg/mL decreased from 40% to 12% (Po0.0001). In prevalent HD patients (n= 235), N-VitD treatment increased from 55% to 91% (Po0.0001), whereas treatment with CA decreased from 67% to 17% (Po0.0001). Patients with serum PTH4300 pg/mL decreased from 38% to 13% (Po0.001), whereas patients with PTHo150 pg/mL remained stable (o30%). New CC prescriptions decreased from 45 to 3 (Po0.0001). Since 2004, SHPT has decreased drastically in incident and prevalent HD patients. The preventive role of N-VitD supplementation appears to be obvious and represents one more argument for its general recommendation in CKD patients.
Nephrology Dialysis Transplantation, 2008
Background. Adequate control of all four KDOQI TM biochemical targets for chronic kidney disease, bone and mineral disorder (CKD-MBD), which include parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and Ca × P, remains difficult and is accomplished in <6% of patients receiving haemodialysis. The objective of the current study was to determine whether treatment with cinacalcet combined with low doses of vitamin D sterols improves control of both PTH and Ca × P among haemodialysis patients with secondary hyperparathyroidism (sHPT).
American Journal of Kidney Diseases, 2001
Most reports on the effectiveness and side effects of oral versus parenteral calcitriol or alfacalcidol in hemodialysis patients with secondary hyperparathyroidism show no advantage of parenteral treatment. The efficacy and safety of intravenous doxercalciferol (1␣D 2 ) were studied in hemodialysis patients with secondary hyperparathyroidism (plasma intact parathyroid hormone [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were compared with those of a previous trial using intermittent oral 1␣D 2 ; the same 70 patients were entered onto both trials, and 64 patients completed both trials per protocol. Twelve weeks of open-label treatment in both trials were preceded by identical 8-week washout periods. Degrees of iPTH suppression from baseline were similar in the two trials, with iPTH level reductions less than 50% in 89% and 78% of patients during oral and intravenous treatment, respectively. Grouping patients according to entry iPTH levels (<750 and >750 pg/mL) showed similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer treatment and larger doses were required by the high-iPTH groups. Highest serum calcium levels averaged 9.82 ؎ 0.14 and 9.67 ؎ 0.11 mg/dL during oral and intravenous 1␣D 2 treatment, respectively (P ؍ not significant [NS]). Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively (P < 0.001). Highest serum phosphorus levels during oral and intravenous treatment averaged 5.82 ؎ 0.21 and 5.60 ؎ 0.21 mg/dL, respectively (P ؍ NS). The percentage of increments in serum phosphorus levels during oral treatment exceeded that during intravenous treatment during 5 of 12 treatment weeks. Thus, intermittent oral and intravenous therapy with 1␣D 2 reduced iPTH levels effectively and similarly, hypercalcemia was less frequent, and serum phosphorus levels increased less during intravenous than oral 1␣D 2 therapy, suggesting that intravenous 1␣D 2 therapy may be advantageous in patients prone to hypercalcemia or hyperphosphatemia.
International Journal of Nephrology and Renovascular Disease
Secondary hyperparathyroidism (sHPT) represents the adaptive and very often, finally, maladaptive response of the organism to control the disturbed homeostasis of calcium, phosphorus, and vitamin D metabolism caused by declining renal function in chronic kidney disease (CKD). sHPT leads to cardiovascular and extravascular calcifications and is directly linked to an increased risk of cardiovascular morbidity and mortality as well as excess all-cause mortality. Vitamin D plays an important role in the development of sHPT. CKD patients are characterized by a high prevalence of hypovitaminosis D. Supplementation with both vitamin D prohormones cholecalciferol and ergocalciferol enables the achievement and maintenance of a normal vitamin D status when given in adequate doses over an appropriate treatment period. In patients with earlier stages of CKD, sHPT is influenced by and can be successfully treated with vitamin D prohormone supplementation, whereas in patients with very late stages of CKD and those requiring dialysis, treatment with prohormones seems to be of limited efficacy. This review gives an overview of the pathogenesis of sHPT, summarizes vitamin D metabolism, and discusses the existing literature regarding the role of vitamin D prohormone in the treatment of sHPT in patients with CKD.
Intermittent Doxercalciferol (1α-Hydroxyvitamin D 2) Therapy for Secondary Hyperparathyroidism
American Journal of Kidney Diseases, 2000
Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1␣-hydroxyvitamin D 2 [1␣D 2 ]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1␣D 2 use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1␣D 2 treatment (16 weeks), and randomized, double-blinded treatment with 1␣D 2 or placebo (8 weeks). Oral 1␣D 2 was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 ؎ 52 [SE] pg/mL) decreased by 20% ؎ 3.4% by week 1 (P < 0.001) and by 55% ؎ 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1␣D 2 treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 ؎ 0.84 (SD) to 9.7 ؎ 1.05 mg/dL and 5.4 ؎ 1.10 to 5.9 ؎ 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1␣D 2 than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1␣D 2 and placebo, respectively (P < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1␣D 2 therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia.
Nephrology Dialysis Transplantation, 2013
Background. Treatment with cinacalcet improves the control of secondary hyperparathyroidism (SHPT) and the achievement of calcium and phosphorus targets. Most data come from subjects receiving cinacalcet after several years of dialysis treatment. We therefore compared the efficacy of treatment with cinacalcet and low doses of active vitamin D to flexible doses of active vitamin D alone for the management of SHPT in patients recently initiating haemodialysis.