PubMed Health⌕ Search

Biomedical subjects

F Llach

Publications and source records attributed to F Llach.

At least 19 recordsLinked to original sources
PubMed2006

Prostaglandin E1 increases in vivo and in vitro calcitriol biosynthesis in rabbits.

INTRODUCTION: Prostaglandins have an anabolic effect on bone. Possible mediation of this effect is via calcitriol. This study determines in vivo and in vitro effects of PGE(1) on calcitriol synthesis. METHODOLOGY: In vivo: rabbits received intravenous vehicle or prostaglandin E(1) (50 microg/day) for 20 days before measurements of serum total and ionic calcium, magnesium and phosphorus levels, total and bone-specific alkaline phosphatases, 25(OH)D(3), calcitriol, parathyroid hormone and calcitonin. In vitro: rabbit proximal renal tubules were incubated with 25(OH)D(3) (8 microM) together with PGE(1) (2.82 x 10(-6) M) and the prostaglandin receptor inhibitor AH6809 (10(-4) M) in selected samples. After 5 or 30 min incubation, calcitriol production was measured by radioimmunoassay and data analysed statistically. RESULTS: In vivo, in groups receiving PGE(1), levels of total Ca, Mg and calcitriol increased significantly and 25 dihydroxyvitamin D(3), parathyroid hormone and calcitonin remained unchanged. In vitro, PGE(1) increased calcitriol biosynthesis and the prostaglandin inhibitor AH6809 reduced calcitriol levels significantly after prolonged incubation. CONCLUSIONS: In vivo and in vitro results demonstrate that PGE(1) stimulates calcitriol synthesis. This study represent a major advancement in knowledge of bone metabolism.

Alprostadil↗
PubMed2001

Paricalcitol dosing according to body weight or severity of hyperparathyroidism: a double-blind, multicenter, randomized study.

Vitamin D therapy for patients with end-stage renal disease (ESRD) on hemodialysis therapy has relied on patient dry weight to determine the initial dose of medication. Obtaining a patient's dry weight can be difficult, and no correlation has been established between a patient's body weight and severity of secondary hyperparathyroidism. We conducted a double-blind, double-dummy, randomized, 12-week, multicenter trial to compare the incidence of hypercalcemia (single occurrence) between two dosing regimens: one regimen based on baseline intact parathyroid hormone (iPTH; PTH/80) level, and the other regimen based on patient body weight (0.04 microgram/kg). One hundred twenty-five adult patients with ESRD on maintenance hemodialysis therapy were enrolled at multiple sites. Before treatment, all patients were required to have PTH levels of 300 pg/mL or greater, calcium levels of 8.0 mg/dL or greater and 10.5 mg/dL or less, and a calcium x phosphorus (Ca x P) product of 70 or less. Patients were randomized to one of two regimens: the nonrandomized treatment was also administered as a placebo dummy. No incidence of hypercalcemia occurred in either treatment group during the study. Patients treated according to the formula iPTH/80 required fewer dose adjustments and achieved the first of four consecutive reductions from baseline PTH level of 30% or greater more rapidly than patients treated based on body weight (P = 0.0306). Incidences of elevated Ca x P product levels were similar between treatment groups. Treatment with paricalcitol injection based on degree of secondary hyperparathyroidism incurred no greater risk for hypercalcemia and achieved meaningful therapeutic results with fewer dose adjustments than dosing based on patient body weight.

Adolescent↗
PubMed2001

Secondary hyperparathyroidism in chronic renal failure: pathogenic and clinical aspects.

Secondary hyperparathyroidism occurs early in the course of chronic renal failure. Early in the course, a deficit of calcitriol and an abnormality in the calcium sensor receptor may be the important factors; later, with advanced renal failure, hyperphosphatemia becomes an additional important pathogenic factor. Important clinical problems in dialysis patients are as follows: (1) hyperphosphatemia, which contributes to high morbidity and mortality of dialysis patients (a clinical approach to maintaining a normal serum phosphorus is essential and is discussed in this review); (2) a high calcium X phosphorus product leading to coronary artery calcifications (factors leading to calcifications are also discussed); and (3) calciphylaxis, which has been observed with increasing frequency in these patients (an increase in the total calcium load may be the most important pathogenic factor leading to this syndrome). Therapeutic considerations regarding the use of new vitamin D analogues devoid of a hypercalcemic and/or a hyperphosphatemic effect are also mentioned.

Animals↗
PubMed2001

Paricalcitol in dialysis patients with calcitriol-resistant secondary hyperparathyroidism.

Paricalcitol was evaluated for the treatment of secondary hyperparathyroidism (SHPT) in a long-term, prospective, open-label study of 37 patients with end-stage renal failure resistant to intravenous calcitriol. All patients had an intact parathyroid hormone (iPTH) level of 600 pg/mL or greater before being converted from calcitriol to paricalcitol therapy. Paricalcitol therapy was initiated at a 1:4 calcitriol to paricalcitol dose conversion ratio for the initial 14 patients and a 1:3 dose ratio for the next 23 patients. Subsequent dosing was based on iPTH, calcium, and phosphorus determinations. All patients underwent hemodialysis three times weekly and received structured nutritional counseling. Mean iPTH level (baseline, 901 +/- 58 pg/mL) decreased rapidly during the initial 2 months and was 165 +/- 24 pg/mL at 16 months. Alkaline phosphatase levels decreased from 280 +/- 27 IU at baseline to 65 +/- 12 IU at 16 months. Mean calcium and phosphorus levels did not change significantly over the 16 months of paricalcitol therapy. The baseline mean calcium level of 9.4 +/- 0.2 mg/dL increased to 9.7 +/- 0.2 mg/dL (P = 0.86), and phosphorus level decreased from 6.1 +/- 0.2 to 5.8 +/- 0.2 mg/dL (P = 0.77). The greater paricalcitol doses afforded by the initial dose conversion ratio of 1:4 produced unacceptably rapid iPTH suppression and subsequent hypercalcemia. Mean doses of paricalcitol decreased six- to sevenfold throughout the course of therapy while maintaining acceptable iPTH suppression. Eight patients developed hypercalcemia, which successfully managed by dietary counseling, phosphate-binder adjustment, and paricalcitol dose reduction. Six patients developed hyperphosphatemia; 3 patients responded adequately to dietary manipulation and phosphate binders, but 3 patients had repeated episodes. Three patients did not respond adequately to paricalcitol therapy and required parathyroidectomy. In summary, paricalcitol was successful at controlling SHPT in patients resistant to calcitriol therapy with minimal impact on calcium and phosphorus homeostasis. The 1:3 initial dose conversion provided the smoothest iPTH control with only a single episode of hypercalcemia in patients treated with this initial dose. Doses of paricalcitol decreased over time.

Calcitriol↗
PubMed2000

Current medical management of secondary hyperparathyroidism.

The treatment of secondary hyperparathyroidism (HPT) in patients with chronic renal disease has improved markedly in recent years. The skeletal pain, disabling fractures, tendon ruptures, and myriad other symptoms associated with HPT can now be avoided, and the quality of life of patients with end-stage renal disease is improved. Control of hyperphosphatemia, maintenance of normocalcemia, and appropriate dosing of vitamin D analogues can prevent HPT in many cases. Palatable, nutritious diets should be followed; serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone should be monitored; and treatment regimens should be adjusted accordingly. If prevention fails, and even if severe HPT develops, many of these patients can still be controlled medically with correction of hyperphosphatemia and high doses of intravenous calcitriol. In our experience, only a few patients require surgical parathyroidectomy (usually noncompliant patients or patients whose HPT has been poorly managed from early uremia). The essence to medical management is to correct the two most important pathogenetic factors of HPT, hyperphosphatemia, and calcitriol deficiency. We present the current approach to the management of HPT, with highlights of recent advances.

Acetates↗
PubMed1999

Hyperphosphatemia in end-stage renal disease patients: pathophysiological consequences.

A study of 6407 end-stage renal disease (ESRD) patients has shown that hyperphosphatemia is increasingly important as a risk for mortality. Half of the patients showed serum phosphorus levels of over 6.0 mg/dl; at the same time, an elevated calcium x phosphorus product indicated increased risk of mortality. These observations lead to questions regarding the mechanisms at work in both the observed phenomena and the way in which they affect mortality. To answer these questions, an understanding of the pathophysiological consequences of hyperphosphatemia is necessary.

Animals↗
PubMed1998

Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2.

In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level > 300 pg/mL) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then randomized to treatment for 4 weeks with either paricalcitol or placebo. Overall, there was a clinically and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo (P = 0.006). The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH level for 75% of the patients receiving paricalcitol per dosing group. The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH for 75% of patients receiving paricalcitol per dosing group. Sixty-eight percent (15 of 22) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 microg/kg). Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point. Only two patients receiving placebo attained the iPTH end point. There were no clinically relevant differences in serum calcium (Ca) or phosphorus (P) levels between the group treated with paricalcitol and that treated with placebo. Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the final-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625). Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point. Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point, with iPTH reductions of 83% to 98%. There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions. These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT.

Adolescent↗
PubMed1998

Is there a lesser hyperparathyroidism in diabetic patients with chronic renal failure?

Diabetic patients on dialysis have lower levels of parathyroid hormone (PTH); however, there is no data regarding PTH levels with different degrees of chronic renal failure (CRF). We compared 58 diabetic patients with different degrees of CRF with 268 non-diabetic patients with CRF (serum creatinine >1.2 mg/dl). In both groups, we investigated the main biochemical parameters together with plasma calcium, phosphorus, magnesium, PTH and calcitriol. Diabetic patients showed lower levels of PTH than non-diabetics (P=0.003). The differences were observed in patients with creatinine clearance <70ml/min. We also observed differences in phosphorus, magnesium and tubular resorption of phosphate. In the group of diabetic patients, serum glucose correlated inversely with PTH. Our study suggests that poor control of diabetes (hyperglycaemia) may play a role in the pathogenesis of the hypoparathyroidism observed in patients with diabetes and CRF.

Adult↗
PubMed1997

The importance of dietary calcium and phosphorous in the secondary hyperparathyroidism of patients with early renal failure.

Secondary hyperparathyroidism (HPT) was evaluated in 157 patients with chronic renal failure (CRF). It was noted that HPT developed early in CRF at a time when plasma calcium and phosphorous were within normal limits. As creatinine clearance decreased below 80 mL/m, there was a significant decrease in plasma calcitriol and a slow and progressive significant increment in plasma parathyroid hormone (PTH). The effect of dietary intake of calcium and phosphorous was evaluated in these patients with early renal failure (ERF). They were divided into two groups. Group A was placed on a protein- and phosphorous-restricted diet (10 days) followed by a daily phosphorous-load diet (10 days). Group B had similar sequential diets plus a calcium supplement throughout the study. Dietary protein and phosphorous restriction resulted in an amelioration of the HPT only in the group of patients receiving calcium supplementation. The phosphate-load diet resulted in worsening of HPT in both groups. In summary, a deficit of calcitriol occurs early in CRF, which in turn leads to a significant increase in PTH. Phosphorous restriction, together with calcium supplementation, ameliorated the HPT of patients with ERF.

Adolescent↗
PubMed1996

A deficit of calcitriol synthesis may not be the initial factor in the pathogenesis of secondary hyperparathyroidism.

Secondary hyperparathyroidism (HPT) develops early in chronic renal failure (CRF) at a time when plasma calcitriol levels are normal. At this time, PTH are higher than normal controls and serum phosphorous levels are lower. A decrement in total serum Ca is noted, after an oral phosphate load, only in patients with ERF. These data suggest that factors, other than a decrease in calcitriol synthesis, may be involved in the pathogenesis of HPT. A hypothesis is forwarded suggesting that an alteration in the newly cloned calcium sensor receptor may be the earliest abnormality in the HPT, preceding a decrease in plasma calcitriol levels.

Adolescent↗
PubMed1996

Guidelines for dosing of intravenous calcitriol in dialysis patients with hyperparathyroidism.

Intravenous calcitriol has not been used appropriately in the treatment of secondary hyperparathyroidism (HPT) of dialysis patients. Initiation of calcitriol therapy late in severe HPT and inappropriate dosing of calcitriol are common causes of inadequate use of calcitriol. This paper gives general guidelines on the use of intravenous calcitriol and emphasizes the importance of appropriate control of serum phosphorous. The issue of dosing of calcitriol commensurate with the severity of the HPT are highlighted as essential for the complexion of a successful therapeutic attempt. In addition, maintenance dose of calcitriol varies according to the severity of the HPT at the time of initiation of therapy.

Calcitriol↗
PubMed1995

The importance of dosing intravenous calcitriol in dialysis patients with severe hyperparathyroidism.

The current study evaluates the use of intravenous (IV) calcitriol in 10 patients with severe hyperparathyroidism (HPTH). Patients with parathyroid hormone (PTH) > 1,200 pg/m and serum P < 6.5 mg/dL were studied. Ten patients with a mean PTH of 1,826 +/- 146 pg/mL were treated for a mean of 48 weeks with a dose of IV calcitriol commensurate to the level of PTH. The initial calcitriol dose had to be increased in seven patients. The mean maximum dose of calcitriol was 3.8 micrograms thrice weekly. There was a dramatic decrease in PTH levels, and by the end of the study it was 211 +/- 48 pg/mL. Alkaline phosphatase decreased from 582 +/- 3 to 120 +/- 12 IU/L. Serum Ca and P remained unchanged in most patients. There were three episodes of hyperphosphatemia in one patient, and another had a hypercalcemic episode. In conclusion, patients with severe HPTH respond very well to IV calcitriol, provided that dosing of calcitriol is commensurate to PTH levels, and hyperphosphatemia is kept under control.

Adult↗
PubMed1995

Secondary hyperparathyroidism in renal failure: the trade-off hypothesis revisited.

Our understanding of the mechanism responsible for secondary hyperparathyroidism (HPTH) has advanced significantly since the "trade-off" hypothesis was formulated. It appears that in early renal failure a deficit of calcitriol synthesis is an important factor. However, additional factors, such as a defect of the vitamin D receptor or the newly cloned calcium sensor receptor (BoPCaR1), may be present in the parathyroid cells. As renal failure progresses, the lack of calcitriol becomes more pronounced, inducing HPTH. With advanced chronic renal failure, hyperphosphatemia is an additional important factor in worsening HPTH. In addition, resistance of the parathyroids to calcitriol due to a reduced density of calcitriol receptors also may contribute to HPTH. Finally, uremia per se not only may cause a receptor abnormality in the parathyroid but at the level of the bone it may aggravate the impaired calcemic response to PTH. In conclusion, after reviewing the "trade-off" hypothesis, although some of the original concepts may have been simplistic, most of the factors postulated 30 years ago are still operative in the pathogenesis of secondary HPTH in renal failure.

Calcitriol↗
PubMed1994

Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat.

Secondary hyperparathyroidism (2 degree HPT) develops as a result of renal failure. Hypocalcemia, phosphorus retention, calcitriol deficiency and skeletal resistance to the calcemic action of parathyroid hormone (PTH) are closely interrelated pathogenic factors important for the development of 2 degrees HPT in renal failure. Since previous studies have mainly focused on advanced renal failure, only limited data are available in early renal failure. The goal of the present study was to evaluate how alterations in the dietary calcium and phosphorus composition affect the factors known to contribute to the genesis of 2 degrees HPT in early and more advanced renal failure. To achieve this goal, graded differences in renal function were surgically induced in 453 rats while the dietary content of calcium and phosphorus was varied. Three different diets were used: (1) a high phosphorus diet (HPD), to induce phosphorus retention and stimulate 2 degrees HPT; (2) a high calcium diet (HCaD), to inhibit calcitriol synthesis; and (3) a moderate calcium-moderate phosphorus diet (MCaPD), to separate the effects of high dietary phosphorus and calcium. Based on the serum creatinine (SCr) concentration rats were assigned to one of four different groups: (1) normal renal function (SCr < or = 0.3 mg/dl); (2) mild renal failure (SCr 0.4 to 0.6 mg/dl); (3) moderate renal failure (SCr 0.7 to 0.8 mg/dl); or (4) advanced renal failure (SCr > or = 0.9 mg/dl). As the severity of renal failure increased, progressive 2 degrees HPT developed in each of the dietary groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗