Effects of Oral Paricalcitol and Calcitriol Treatment on Peritoneal Membrane Characteristics of Peritoneal Dialysis Patients — A Pilot Study

2018 ◽  
Vol 38 (3) ◽  
pp. 220-228 ◽  
Author(s):  
Karima Farhat ◽  
Andrea W.D. Stavenuiter ◽  
Marc G. Vervloet ◽  
Pieter M. ter Wee ◽  
Robert H.J. Beelen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Peritoneal Dialysis ◽  
Parathyroid Hormone ◽  
Pilot Study ◽  
Peritoneal Membrane ◽  
Transport Parameters ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Markers Of Inflammation ◽  
Peritoneal Transport

BackgroundLong-term peritoneal dialysis (PD) is frequently complicated by technique failure preceded by peritoneal remodeling. Vitamin D has potent immunomodulatory characteristics: anti-inflammatory, anti-angiogenic, anti-fibrotic properties, and influences on the macrophage phenotype. Little is known about the relation between pleiotropic effects attributed to vitamin D3and the peritoneal membrane and what is the most appropriate vitamin D sterol in prevention of peritoneal remodeling in PD patients. Animal studies have suggested that paricalcitol has advantageous effects: decrease in plasma markers of inflammation, less peritoneal fibrosis, less pronounced PD-induced omental angiogenesis, and prevention of loss of ultrafiltration. We investigated whether paricalcitol is advantageous over calcitriol in PD patients.MethodA multicenter open-label 1:1 randomized non-blinded clinical pilot study enrolled prevalent continous ambulatory PD (CAPD) patients for a period of 6 months comparing paricalcitol with calcitriol. All patients were treated with biocompatible PD fluids. The primary endpoint was peritoneal transport parameters, exploratory endpoints were biomarkers of peritoneal damage and cell analysis (including M1/M2 macrophages), and safety endpoints were metabolic parameters.ResultsTwenty-seven patients were included. Fourteen were randomized to treatment with paricalcitol. There was no difference in peritoneal transport parameters between the groups. We found similar Kt/V, D/P creatinine, D/D0 glucose, ultrafiltration, residual renal function and 24-h urine volume during the study. There was no difference in biomarker concentrations in peritoneal effluents, and no difference in leucocyte differentiation or mesothelial cells between the groups at any time point. Parathyroid hormone (PTH) levels decreased after administration of calcitriol after 12 and 24 weeks compared with baseline ( p = 0.001; p = 0.025). Parathyroid hormone levels in the paricalcitol group did not change significantly.ConclusionIn this pilot study we investigated the effect of active vitamin D in PD patients. We found no specific benefit of active vitamin D3in vitamin D3-sufficient PD patients. Additional studies in preferably incident patients, with an adequate PTH suppression in the intervention groups and during a longer period, are required to test the beneficial effects of active vitamin D3over no treatment and to investigate whether in 25(OH)D3-deficient PD patients the type of active vitamin D3matters.

scholarly journals Dynamic changes in calcium and phosphate plasma concentrations in the patients on peritoneal dialysis

2006 ◽  
Vol 63 (1) ◽  
pp. 27-30
Author(s):  
Natasa Jovanovic ◽  
Mirjana Lausevic ◽  
Biljana Stojimirovic
Keyword(s):  
Vitamin D ◽  
Renal Failure ◽  
Peritoneal Dialysis ◽  
End Stage Renal Disease ◽  
Calcium Concentration ◽  
Phosphate Binders ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Stage Renal Disease ◽  
End Stage

Background/Aim. The disturbances of active forms of vitamin D synthesis and disturbances in calcium and posphate metabolism develop early in chronic renal failure, when creatinine clearance is about 30 ml/min. Chronic hemodialysis and peritoneal dialysis only partially correct the biochemical environment of patients on chronic renal replacement therapy because of end-stage renal disease. These dialysis modalities can?t significantly affect the endocrine disturbances of chronic renal failure and they have minimal modulatory effect. The management of disturbed calcium (Ca) and phosphate (P) metabolism and the maintainance of Ca ? P product below 4.4 mmol/l thanks to the use of dialysate solutions with the appropriate calcium concentration and the careful dosage of phosphate binders, calcium and active vitamin D metabolits, are extremely important for the prevention of renal osteodystrophy, secondary hyperparathyroidism as well as low-bone turnover disease. The aim of the study was to analyze the plasma levels of calcium, phosphate, albumin, alkaline phosphatase and parathormon (PTH) in 58 patients who were treated with continuous ambulatory peritoneal dialysis (CAPD) from March to August 2003. The use of phosphate binders and the substitution with active vitamin D metabolits were also analyzed. Methods. We examined 58 patients, 30 males and 28 female, mean-age 52 years (range, 26-78 years), affected by end-stage renal disease of the different leading cause. The average time on peritoneal dialysis program was 20 months (2-66 months). Most of the patients were treated by CAPD, while only few of them performed automatic, cyclic or intermittent peritoneal dialysis. Most of the patients used a dialysate with 1.75 mmol/l calcium concentration. Results. The study showed that our patients on chronic CAPD program during several months had normal calcemia, phosphatemia and the level of alkaline phosphatase, and that they had Ca ? P product in the recommended range. PTH serum level ranged from 16 to 490 pg/l in our patients. Conclusion. The study showed that a balanced diet and a correct dosage of phosphate binders, as well as a careful substitution with active vitamin D metabolits render a good control of calcium and phosphate serum balance, as well as an effective prevention of renal osteodystrophy development in the patients on chronic peritoneal dialysis treatment.

scholarly journals A Pilot Study of Active Vitamin D Administration and Insulin Resistance in African American Patients Undergoing Chronic Hemodialysis

2013 ◽  
Vol 23 (3) ◽  
pp. 185-193 ◽  
Author(s):  
Adriana M. Hung ◽  
Mary B. Sundell ◽  
Natalia E. Plotnikova ◽  
Aihua Bian ◽  
Ayumi Shintani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
African American ◽  
Pilot Study ◽  
Chronic Hemodialysis ◽  
Active Vitamin ◽  
Active Vitamin D

Calcium homeostasis

2015 ◽  
Author(s):  
Francesco Trepiccione ◽  
Giovambattista Capasso
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Calcium Homeostasis ◽  
Calcineurin Inhibitors ◽  
Blood Levels ◽  
Active Vitamin ◽  
Active Vitamin D

Ca2+ homeostasis is achieved through a fine balance among three main organs: the intestine, the kidney, and bone. Blood levels of Ca2+ are accurately tuned through the Ca2+ sensing receptors and regulated by several hormones, including parathyroid hormone (PTH), active vitamin D, and calcitonin. The most recent findings in Ca2+ handling are described. The role of the Ca2+ sensing receptor, as well as Klotho, a new player participating in Ca2+ homeostasis, are described. Finally, the effects of diuretics, calcineurin inhibitors, and the link between hypertension and Ca2+ metabolism are reviewed.

Risk Factors for Peritoneal Dialysis–Associated Peritonitis: The Role of Oral Active Vitamin D

2010 ◽  
Vol 30 (5) ◽  
pp. 541-548 ◽  
Author(s):  
Michael Rudnicki ◽  
Julia Kerschbaum ◽  
Johann Hausdorfer ◽  
Gert Mayer ◽  
Paul König
Keyword(s):  
Risk Factors ◽  
Vitamin D ◽  
Peritoneal Dialysis ◽  
Lower Risk ◽  
Concomitant Medication ◽  
Mortality Data ◽  
Active Vitamin ◽  
Baseline Serum ◽  
Laboratory Parameters ◽  
Active Vitamin D

BackgroundPeritonitis is a major complication of peritoneal dialysis (PD), being associated with hospitalization, catheter loss, technique failure, and increased mortality. Data on various risk factors for peritonitis are inconsistent, and no association with concomitant therapy has been shown.MethodsWe performed a retrospective analysis of all incident and prevalent PD patients ( n = 55) treated in Innsbruck, Austria, between 2000 and 2007. Data consisted of 1291 patient–months and 55 episodes of peritonitis. Patient demographic data, comorbidities, concomitant medication, laboratory parameters, and microbiology results were obtained from the medical records and from the hospital's electronic database.ResultsThe mean peritonitis incidence rate was 0.51 episodes/patient–year (range: 0.24 – 0.73 episodes/patient–year) or 1 episode every 23.5 months (range: 16 – 50 months). In a primary analysis including demographic characteristics, comorbidities, laboratory parameters, and concomitant medication, only treatment with oral active vitamin D was associated with a significantly lower risk of peritonitis. Adjusted for time on PD and baseline serum albumin, oral active vitamin D therapy was associated with an 80% reduced relative risk of peritonitis [hazard ratio (HR): 0.20; 95% confidence interval (CI): 0.06 to 0.64; p = 0.007)]. The risk reduction was comparable in patients who received 0.25 μg or more of vitamin D daily (HR: 0.18; 95% CI: 0.05 to 0.65; p = 0.008) and in those who received less than 0.25 μg vitamin D daily (HR: 0.21; 95% CI: 0.06 to 0.77; p = 0.018).ConclusionsTreatment with oral active vitamin D might be associated with a lower risk of peritonitis in PD patients.

scholarly journals The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation

2020 ◽  
Vol 36 (1) ◽  
pp. 160-169
Author(s):  
Nahid Tabibzadeh ◽  
Angelo Karaboyas ◽  
Bruce M Robinson ◽  
Philipp A Csomor ◽  
David M Spiegel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Secondary Hyperparathyroidism ◽  
Patient Characteristics ◽  
Risk Difference ◽  
First Year ◽  
Active Vitamin ◽  
Adjusted Risk ◽  
Active Vitamin D ◽  
Dialysis Outcomes

Abstract 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.

scholarly journals Leukaemic Secretion of Calcitriol: A Novel Mechanism of Hypercalcaemia in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5098-5098
Author(s):  
Joshua Misha Lewis Casan ◽  
Sarah Ghotb ◽  
Sue Morgan ◽  
Stephen B Ting
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Calcium ◽  
Rare Complication ◽  
Kidney Injury ◽  
Active Vitamin ◽  
Normal Range ◽  
Lymphoid Malignancies ◽  
Active Vitamin D ◽  
Upper Limit

Abstract Introduction: Whilst relatively common in lymphoid malignancies, hypercalcaemia is an extremely rare complication of acute myeloid leukaemia (AML). Previous case reports have described ectopic parathyroid hormone secretion, leukaemic bony invasion and the release of boneresorptivemediators as causes of hypercalcaemia in AML (GewirtzAM et al. Br JHaematology1983;31(12):1590,ZidarBL, et al.NEJM.1976;295:692). We describe a case of severe hypercalcaemia with acute kidney injury (AKI) accompanying a new diagnosis of AML, subsequently demonstrated to be secondary to leukaemic blast production of active vitamin D (calcitriol) with gross over-expression of vitamin D related genes. This represents a novel pathogenic mechanism causing hypercalcaemia in a myeloid malignancy. Case Report: AA, a 68 year old male presenting with fatigue and found to have circulating blasts was subsequently diagnosed with acutemyelomonocyticleukaemia(78% blasts on bone marrow biopsy). Additionally, he had marked hypercalcaemia (calcium 3.3mmol/L, normal range 2.1-2.6mmol/L) and AKI (creatinine 263umol/L, normal range 60-110umol/L). Given the rarity of AML-associated hypercalcaemia, extensive investigations were undertaken to elucidate the cause. In search of a second concurrent malignancy, AA underwent computed tomography and positron emission tomography scanning, with subsequent biopsy of FDG avid vocal cord nodules; but only benign pathology could be demonstrated. Parathyroid hormone (PTH) levels were appropriately suppressed (0.9pmol/L, normal range 1.6-6.9pmol/L) and levels of PTH-related peptide and serum ACE were normal (<2pmol/L, and 37units/L, normal range 20-70units/L, respectively). Inactive vitamin D, (calcidiol or 25(OH)D3) levels were also normal (88nmol/L, normal range 50-250nmol/L). However, the active vitamin D (calcitriol or 1,25(OH)2D3) level was grossly elevated beyond the upper limit of assay (>500pmol/L, upper limit of normal: 190pmol/L). Both the hypercalcaemia and kidney injury proved refractory to multiple therapeutic strategies including aggressive hydration with an average of over 2.5L of crystalloid per day, as well as intravenouspamidronate. However, as depicted in Figure 1, there was a precipitous response following the initiation of chemotherapy (idarubicinandcytarabine, 7+3 regimen). Within several days, AA's serum calcium levels returned to normal levels, and his kidney function followed a similar pattern of improvement shortly thereafter. The rapid resolution of serum calcium levels also mirrored peripheral blast clearance, and repeat testing of calcitriol levels showed progressive improvement towards a normal concentration. AA achieved complete remission following induction chemotherapy and remains leukaemia free after consolidation chemotherapy and current maintenanceazacitidine. His hypercalcaemia has not recurred and his renal function remains normal. Having excluded other causes of hypercalcaemia and given the dramatic response to chemotherapy, we hypothesised that AA's AML blasts were secreting calcitriol. Accordingly, quantitative PCR was performed on AA's stored leukaemic cells for genes essential to vitamin D metabolism: the vitamin-D receptor (VDR), CYP24A1, and CYP27B1 (1-α-hydroxylase). RNA was extracted from AML cells using the QIAGEN RNeasykit. cDNAwas synthesised from 400ng of RNA using the Roche First Strand cDNASynthesis Kit. Gene expression was assessed by quantitative real-time PCR, relative to the housekeeping gene GAPDH. AA's leukaemia cells demonstrated markedly elevated expression of these vitamin-D related genes compared to healthy control CD34+ cells and four other independent primary AML cells (Figure 2, labelled AML 1-4), which were selected for absence of patient hypercalcaemia from our institution's tissue bank (Figure 2). Conclusion: Hypercalcaemia secondary to secretion of calcitriol can be a manifestation of lymphoid malignancies, however our case is the first documented occurrence of this phenomenon in a myeloid cancer. The PCR studies demonstrated striking overexpression of vitamin D related genes in leukaemia cells, resulting in the patient's hypercalcaemia and AKI. This finding represents a novel mechanism for a rare complication in AML. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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