The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol

Background. Lanthanum carbonate and sevelamer carbonate are non-calcium-based phosphate binders used to manage hyperphosphataemia in patients with chronic kidney disease (CKD). Patients with CKD may require intravenous or oral active vitamin D. We investigated the effects of lanthanum carbonate and sevelamer carbonate on the bioavailability of oral calcitriol

Comparison of total parathyroidectomy without autotransplantation and without thymectomy versus total parathyroidectomy with autotransplantation and with thymectomy for secondary hyperparathyroidism: TOPAR PILOT-Trial

<p>Abstract</p> <p>Background</p> <p>Secondary hyperparathyroidism (sHPT) is common in patients with chronic renal failure. Despite the initiation of new therapeutic agents, several patients will require parathyroidectomy (PTX). Total PTX with autotransplantation of parathyroid tissue (TPTX+AT) and subtotal parathyroidectomy (SPTX) are currently considered as standard surgical procedures in the treatment of sHPT. Recurrencerates after TPTX+AT or SPTX are between 10% and 12% (median follow up: 36 months).</p> <p>Recent retrospective studies demonstrated a lower rate of recurrent sHPT of 0–4% after PTX without autotransplantation and thymectomy (TPTX) with no higher morbidity when compared to the standard procedures. The observed superiority of TPTX is flawed due to different definitions of outcomes, varying follow up periods and different surgical treatment strategies (with and without thymectomy).</p> <p>Methods/Design</p> <p>Patients with sHPT (intact parathyroid hormone > 10 times above the upper limit of normal) on long term dialysis (>12 months) will be randomized either to TPTX or TPTX+AT and followed for 36 months. Outcome parameters are recurrence rates of sHPT, frequencies of reoperations due to refractory hypoparathyroidism or recurrent/persistent hyperparathyroidism, postoperative morbidity and mortality and quality of life. 50 patients per group will be randomized in order to obtain relevant frequencies of outcome parameters that will form the basis for a large scale confirmatory multicentred randomized controlled trial.</p> <p>Discussion</p> <p>sHPT is a disease with a high incidence in patients with chronic renal failure. Even a small difference in outcomes will be of clinical relevance. To assess sufficient data about the rate of recurrent sHPT after both methods, a multicentred, randomized controlled trial (MRCT) under standardized conditions is mandatory.</p> <p>Due to the existing uncertainties the calculated number of patients necessary in each treatment arm (n > 4000) makes it impossible to perform this study as a confirmatory trial. Therefore estimates of different outcomes are performed using a pilot MRCT comparing 50 versus 50 randomized patients in order to establish a hypothesis that can be tested thereafter.</p> <p>If TPTX proves to have a lower rate of recurrent sHPT, no relevant disadvantages and no higher morbidity than TPTX+AT, current surgical practice may be changed.</p> <p>Trial registration</p> <p>International Standard Randomized Controlled Trial Number Registration (ISRCTN86202793)</p

Vitamin D Levels in Asymptomatic Adults-A Population Survey in Karachi, Pakistan

Background: It is well established that low levels of 25(OH) Vitamin D (/dL) are a common finding world over, affecting over a billion of the global population. Our primary objective was to determine the prevalence of vitamin D deficiency and insufficiency in the asymptomatic adult population of Karachi, Pakistan and the demographic, nutritional and co-morbidity characteristics associated with serum vitamin D levels. Methods: A cross-sectional population survey was conducted at two spaced out densely populated areas of the city. Serum levels of 25OH vitamin D were measured and GFR as renal function was assessed by using 4 variable MDRD formula. Results: Our sample of 300 had a median age of 48(interquartile range 38-55) years. The median level of serum vitamin D was 18.8 (IQ range 12.65-24.62) ng/dL. A total of 253 (84.3%) respondents had low levels (/dL) of 25OH vitamin D. Serum PTH and vitamin D were negatively correlated (r = -0.176, p = 0.001). The median PTH in the vitamin D sufficiency group was 38.4 (IQ range28.0-48.8)pg/mL compared with 44.4 (IQ range 34.3-56.8) pg/mL in the deficiency group (p = 0.011).The median serum calcium level in the sample was 9.46(IQ range 9.18-9.68) ng/dL. Low serum levels of vitamin D were not associated with hypertension (p = 0.771) or with an elevated spot blood pressure (p = 0.164).In our sample 75(26%) respondents had an eGFR corresponding to stage 2 and stage 3 CKD. There was no significant correlation between levels of vitamin D and eGFR (r = -0.127, p-value = 0.277). Respondents using daily vitamin D supplements had higher 25 OH vitamin D levels (p-value = 0.021). Conclusion: We observed a high proportion of the asymptomatic adult population having low levels of vitamin D and subclinical deterioration of eGFR. The specific cause(s) for this observed high prevalence of low 25OH vitamin D levels are not clear and need to be investigated further upon

Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease

BACKGROUND: Elevated intact parathyroid hormone (iPTH) levels can contribute to morbidity and mortality in children with chronic kidney disease (CKD). We evaluated the pharmacokinetics, efficacy, and safety of oral paricalcitol in reducing iPTH levels in children with stages 3-5 CKD.METHODS: Children aged 10-16 years with stages 3-5 CKD were enrolled in two phase 3 studies. The stage 3/4 CKD study characterized paricalcitol pharmacokinetics and compared the efficacy and safety of paricalcitol with placebo followed by an open-label period. The stage 5 CKD study evaluated the efficacy and safety of paricalcitol (no comparator) in children with stage 5 CKD undergoing dialysis.RESULTS: In the stage 3/4 CKD study, mean peak plasma concentration and area under the time curve from zero to infinity were 0.13 ng/mL and 2.87 ng•h/((or ng×h/))mL, respectively, for 12 children who received 3 μg paricalcitol. Thirty-six children were randomized to paricalcitol or placebo; 27.8% of the paricalcitol group achieved two consecutive iPTH reductions of ≥30% from baseline versus none of the placebo group (P = 0.045). Adverse events were higher in children who received placebo than in those administered paricalcitol during the double-blind treatment (88.9 vs. 38.9%; P = 0.005). In the stage 5 CKD study, eight children (61.5%) had two consecutive iPTH reductions of ≥30% from baseline, and five (38.5%) had two consecutive iPTH values of between 150 and 300 pg/mL. Clinically meaningful hypercalcemia occurred in 21% of children.CONCLUSIONS: Oral paricalcitol in children aged 10-16 years with stages 3-5 CKD reduced iPTH levels and the treatment was well tolerated. Results support an initiating dose of 1 μg paricalcitol 3 times weekly in children aged 10-16 years.</p

Pathogenesis of vascular calcification in chronic kidney disease

Background Hyperphosphatemia and hypercalcemia are independent risk factors for higher incidence of cardiovascular events in patients with chronic kidney disease. In addition to increased calcium-phosphate product, hyperphosphatemia accelerates the progression of secondary hyperparathyroidism with the concomitant bone loss, possibly linked to vascular calcium-phosphate precipitation. Results The control of serum phosphate levels reduces vascular calcification not only by decreasing the degree of secondary hyperparathyroidism and calcium-phosphate product, but also by reducing the expression of proteins responsible for active bone mineral deposition in cells of the vasculature. The calcium and aluminum-free phosphate-binders provide a new and effective therapeutic tool in preventing vascular calcifications in chronic kidney disease in animal models and in hemodialysis patients. Conclusion Additional investigations are necessary to examine the benefits of different phosphate-binders in reducing mortality from cardiovascular disease