Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer

2021 ◽  
pp. ASN.2020091340
Author(s):  
Elizabeth R. Stremke ◽  
Gretchen N. Wiese ◽  
Sharon M. Moe ◽  
Meryl E. Wastney ◽  
Ranjani N. Moorthi ◽  
...  
Keyword(s):  
Healthy Adults ◽  
Clinical Trial Registry ◽  
Apparent Lack ◽  
Content Type ◽  
Dihydroxyvitamin D ◽  
Phosphorus Absorption ◽  
Dietary Phosphorus ◽  
Registration Number ◽  
Moderate Chronic Kidney Disease

BackgroundReducing intestinal phosphorus absorption is a cornerstone in CKD-MBD management. Yet, knowledge gaps include how CKD pathophysiology affects intestinal phosphorus absorption. In vivo rodent studies suggest that intestinal phosphorus absorption remains inappropriately normal in early-moderate CKD, despite declining 1,25-dihydroxyvitamin D (1,25D). We measured intestinal phosphorus absorption in patients with moderate CKD versus healthy adults using a direct radiotracer method.MethodsPatients with CKD and healthy adults matched for age, sex, and race were enrolled in this 8-day controlled diet study: the first 6 days outpatient and the final 2 days inpatient. Oral and intravenous doses of 33P and serial blood and urine sampling determined intestinal phosphorus absorption during the final 2 days. Secondary outcomes included fasting biochemistries and 24-hour urine phosphorus (uP).ResultsIn total, n=8 patients with CKD (eGFR=29–55 ml/min per 1.73 m2) and n=8 matched healthy controls completed the study. On a controlled diet, no difference in fractional intestinal phosphorus absorption was detected between patients with CKD and healthy adults (0.69 versus 0.62, respectively; P=0.52), and this was similar for 24-hour uP (884 versus 935 mg/d, respectively; P=0.70). Fractional intestinal phosphorus absorption was not significantly related to 24-hour uP. Patients with CKD had higher serum intact PTH and intact FGF23 and lower 1,25D. The relationship between 1,25D and fractional intestinal phosphorus absorption was not statistically significant.ConclusionsIntestinal phosphorus absorption with typical dietary intake did not differ in patients with moderate CKD compared with controls, despite lower serum 1,25D levels. In this setting, a relationship between 24-hour uP and fractional or absolute intestinal absorption was not evident. Further investigation is needed to determine what factors influence intestinal phosphorus absorption in CKD and the apparent lack of compensation by the intestine to limit phosphorus absorption in the face of declining kidney function and reduced 1,25D. Whether this is evident across a range of dietary phosphorus intakes, as well as CKD severity, also needs to be determined.Clinical Trial registry name and registration number:Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease, NCT03108222

scholarly journals 3318 Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease

2019 ◽  
Vol 3 (s1) ◽  
pp. 51-51
Author(s):  
Elizabeth Stremke ◽  
Gretchen Wiese ◽  
Amy Wright ◽  
Sharon Moe ◽  
Ranjani Moorthi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Absorption Efficiency ◽  
Healthy Adults ◽  
Nutrition Intervention ◽  
Matched Pair ◽  
Dihydroxyvitamin D ◽  
Phosphorus Absorption ◽  
Moderate Chronic Kidney Disease ◽  
Fractional Absorption

OBJECTIVES/SPECIFIC AIMS: The aim of this study is to compare intestinal phosphorus absorption in healthy adults and moderate stage chronic kidney disease patients in the context of a controlled feeding study METHODS/STUDY POPULATION: Participants are 30-75 years old and include 10 healthy subjects and 10 moderate-staged CKD patients. Each subject pool will be enrolled in a 9-day study period including 7 days of controlled feeding of a 1500 mg phosphorus diet. Following the controlled feeding, two days of absorption tests will take place (oral and IV tests) utilizing radioisotopic phosphorus to calculate fractional absorption efficiency. RESULTS/ANTICIPATED RESULTS: Current enrollment has produced 7 total matched subject (current n = 14/20). Four of the 7 pairs of completed subjects are female and 3 of 7 are black. Preliminary kinetic modeling data from the first enrolled subject show a moderate CKD patient with fractional absorption of 0.375. With forthcoming analyses, we expect that this fractional absorption result will not be statistically different from this subject’s matched pair, nor will each groups average absorption be different from the other. Additionally, we expect absorption to be maintained even with changes in secondary outcomes measures in serum (FGF23, 1,25-dihydroxyvitamin D, parathyroid hormone, and total phosphorus) in CKD patients. DISCUSSION/SIGNIFICANCE OF IMPACT: Lack of statistical difference in fractional phosphorus absorption between gropus would support that intestinal phosphorus absorption is inappropriately normal in CKD patients compared to healthy adults, despite evidence of abnormal phosphorus homeostatic mechanisms. Future studies will consider the effect of dietary P restriction, the most common nutrition intervention in moderate stage CKD, on fractional absorption efficiency in CKD.

scholarly journals Prevalence of Polymorphisms in Antifolate Drug Resistance Molecular Marker Genespvdhfrandpvdhpsin Clinical Isolates of Plasmodium vivax from Kolkata, India

2013 ◽  
Vol 58 (1) ◽  
pp. 196-200 ◽  
Author(s):  
Swagata Ganguly ◽  
Pabitra Saha ◽  
Moytrey Chatterjee ◽  
Ardhendu K. Maji
Keyword(s):  
Plasmodium Vivax ◽  
Therapeutic Efficacy ◽  
Point Mutations ◽  
Marker Genes ◽  
Clinical Trial Registry ◽  
Triple Mutant ◽  
Mutant Genotype ◽  
Content Type ◽  
Registration Number

ABSTRACTSulfadoxine-pyrimethamine has never been recommended for the treatment ofPlasmodium vivaxmalaria as the parasite is intrinsically resistant to pyrimethamine. The combination was introduced as a promising agent to treatPlasmodium falciparummalaria in many countries but was withdrawn after a few years due to development and spread of resistant strains. Presently, sulfadoxine-pyrimethamine is used as a partner drug of artemisinin-based combination therapy to treat uncomplicated falciparum malaria, and a combination of artesunate-sulfadoxine-pyrimethamine is currently in use in India. In countries like India, where bothP. vivaxandP. falciparumare equally prevalent, some proportion ofP. vivaxbacteria is exposed to sulfadoxine-pyrimethamine due to misdiagnosis and mixed infections. As reports on thein vivotherapeutic efficacy of sulfadoxine-pyrimethamine inP. vivaxare rare, the study of mutations in the marker genesP. vivaxdhfr(pvdhfr) andpvdhpsis important for predicting drug selection pressure and sulfadoxine-pyrimethamine resistance monitoring. We studied the prevalence of point mutations and haplotypes of both the genes in 80P. vivaxisolates collected from urban Kolkata, India, by the DNA sequencing method. Point mutation rates in both the genes were low. The double mutantpvdhfrA15N50R58N117I173(mutations are in boldface) and the single mutantpvdhpsgenotype S382G383K512A553V585were more prevalent, while 35% of the isolates harbored the wild-type genotype. The triple mutant ANRNI-SGKAV was found in 29.9% isolates. No quintuple mutant genotype was recorded. TheP. vivaxparasites in urban Kolkata may still be susceptible to sulfadoxine-pyrimethamine. Hence, a combination of antimalarial drugs like artesunate-sulfadoxine-pyrimethamine introduced forP. falciparuminfection might be effective inP. vivaxinfection also. Study of the therapeutic efficacy of this combination inP. vivaxis thus strongly suggested. (The study protocol was registered in the Clinical Trial Registry-India [CTRI] of the Indian Council of Medical Research under registration number CTRI/2011/09/002031.)

scholarly journals Reduction of dietary phosphorus absorption by phosphorus binders. A theoretical, in vitro, and in vivo study.

1989 ◽  
Vol 83 (1) ◽  
pp. 66-73 ◽  
Author(s):  
M S Sheikh ◽  
J A Maguire ◽  
M Emmett ◽  
C A Santa Ana ◽  
M J Nicar ◽  
...  
Keyword(s):  
In Vivo Study ◽  
Phosphorus Absorption ◽  
Dietary Phosphorus

scholarly journals Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

2013 ◽  
Vol 304 (3) ◽  
pp. E310-E320 ◽  
Author(s):  
Stephen J. Quinn ◽  
Alex R. B. Thomsen ◽  
Jian L. Pang ◽  
Lakshmi Kantham ◽  
Hans Bräuner-Osborne ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Fibroblast Growth Factor 23 ◽  
Threshold Level ◽  
Serum Levels ◽  
Serum Phosphorus ◽  
Dihydroxyvitamin D ◽  
Dietary Phosphorus ◽  
Calcium Phosphorus ◽  
Calcium And Phosphorus

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range.

scholarly journals In VivoTherapeutic Efficacy of Chloroquine Alone or in Combination with Primaquine against Vivax Malaria in Kolkata, West Bengal, India, and Polymorphism inpvmdr1andpvcrt-oGenes

2012 ◽  
Vol 57 (3) ◽  
pp. 1246-1251 ◽  
Author(s):  
Swagata Ganguly ◽  
Pabitra Saha ◽  
Subhasish K. Guha ◽  
Sonali Das ◽  
Dilip K. Bera ◽  
...  
Keyword(s):  
Clinical Trial Registry ◽  
Content Type ◽  
Sequencing Method ◽  
Life Threatening ◽  
Group A ◽  
Mutation Pattern ◽  
Group B ◽  
Parasitological Response

ABSTRACTPlasmodium vivaxmalaria, though benign, has now become a matter of concern due to recent reports of life-threatening severity and development of parasite resistance to different antimalarial drugs. The magnitude of the problem is still undetermined. The present study was undertaken to determine thein vivoefficacy of chloroquine (CQ) and chloroquine plus primaquine inP. vivaxmalaria in Kolkata and polymorphisms in thepvmdr1andpvcrt-ogenes. A total of 250 patients withP. vivaxmonoinfection were recruited and randomized into two groups, A and B; treated with chloroquine and chloroquine plus primaquine, respectively; and followed up for 42 days according to the WHO protocol of 2009. Data were analyzed using per-protocol analyses. We assessed polymorphisms of thepvmdr1 and pvcrt-ogenes by a DNA-sequencing method. Out of the 250 patients recruited, 204 completed a 42-day follow-up period, 101 in group A and 103 in group B. In group A, the non-PCR-corrected efficacy of CQ was 99% (95% confidence interval [CI], 0.944 to 1.00), and in group B, all cases were classified as adequate clinical and parasitological response (ACPR). Day 3 positivity was observed in 11 (5.3%) cases. No specific mutation pattern was recorded in thepvcrt-ogene. Eight nonsynonymous mutations were found in thepvmdr1gene, three of which were new. The Y976F mutation was not detected in any isolate. Chloroquine, either alone or in combination with primaquine, is still effective againstP. vivaxmalaria in the study area. (The study protocol was registered in CTRI [Clinical Trial Registry-India] of the Indian council of Medical Research under registration no. CTRI/2011/09/002031.)

scholarly journals Safety and Pharmacokinetics of CD101 IV, a Novel Echinocandin, in Healthy Adults

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Taylor Sandison ◽  
Voon Ong ◽  
Jonathan Lee ◽  
Dirk Thye
Keyword(s):  
Adverse Events ◽  
Vital Signs ◽  
High Plasma ◽  
Primary Objective ◽  
Healthy Adults ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Content Type

ABSTRACT CD101 IV is a novel echinocandin with distinctive pharmacokinetic properties that is being developed as a once-weekly treatment for candidemia and invasive candidiasis. CD101 has potent in vitro activity and in vivo efficacy against a broad range of Candida and Aspergillus species. The primary objective of two randomized, double-blind, placebo-controlled, dose-escalation studies in healthy adults was to determine the safety and tolerability of CD101 IV. Sequential cohorts of 8 subjects (n = 6, active; n = 2, placebo) were administered single (50, 100, 200, 400 mg) or multiple once-weekly (100 mg given once weekly for two weeks [×2], 200 mg ×2, 400 mg ×3) doses of CD101 IV infused over 1 h. There were no deaths, serious adverse events (SAEs), severe adverse events (AEs), or withdrawals from the study due to an AE. The majority of AEs were mild, and all completely resolved. There was a higher incidence of total AEs and mild transient infusion reactions in the 400-mg ×3 dose group. There were no clinically meaningful trends in postbaseline laboratory abnormalities and no safety issues related to electrocardiograms, vital signs, or physical exams. CD101 showed dose-proportional plasma exposures, minor accumulation (30% to 55%), low apparent clearance (<0.28 liter/h), long half-life (t 1/2) (>80 h), and minimal urine excretion. CD101 IV was safe and well tolerated at single and multiple doses of up to 400 mg given once weekly for 3 weeks and exhibited a long t 1/2, minimal accumulation over several weeks, negligible renal excretion, and high plasma exposures enabling once-weekly dosing.

Comparison of Iron Dosing Strategies in Patients Undergoing Long-Term Hemodialysis

2021 ◽  
Vol 16 (10) ◽  
pp. 1512-1521
Author(s):  
Bernhard Bielesz ◽  
Matthias Lorenz ◽  
Rossella Monteforte ◽  
Thomas Prikoszovich ◽  
Michaela Gabriel ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Transferrin Saturation ◽  
Iron Sucrose ◽  
Ferric Carboxymaltose ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Content Type ◽  
Registration Number ◽  
Dosing Strategies

Background and objectivesWhether iron supplementation in patients on hemodialysis could be delivered by less frequent but higher single doses compared with the currently more common higher-frequency schedules of lower single iron doses is unknown.Design, setting, participants, & measurementsWe carried out an open-label, randomized, controlled noninferiority trial over 40 weeks in patients on prevalent hemodialysis (n=142). We administered in total 2 g iron as 100 mg iron sucrose biweekly in a continuous (20 × 100 mg) fashion or 500 mg ferric carboxymaltose every 10 weeks in a periodic (4 × 500 mg) fashion. The primary end point was the change in hemoglobin at week 40 from baseline with a noninferiority margin of −0.8 g/dl. Secondary end points were changes in ferritin, transferrin, transferrin saturation, and erythropoiesis-stimulating agent use.ResultsIn total, 108 patients completed the study. At 40 weeks, hemoglobin changed by −0.27 g/dl (95% confidence interval, −0.64 to 0.09) in the iron sucrose arm and by −0.74 g/dl (95% confidence interval, −1.1 to −0.39) in the ferric carboxymaltose arm compared with baseline. Noninferiority was not established in the per-protocol population as hemoglobin changes compared with baseline differed by −0.47 g/dl (95% confidence interval, −0.95 to 0.01) in the ferric carboxymaltose arm compared with the iron sucrose arm. Proportional changes from baseline to week 40 differed by −31% (98.3% confidence interval, −52 to −0.1) for ferritin, by 1% (98.3% confidence interval, −7 to 10) for transferrin, and by −27% (98.3% confidence interval, −39 to −13) for transferrin saturation in the ferric carboxymaltose arm compared with the iron sucrose arm. Erythropoiesis-stimulating agent dosing did not differ between groups. The overall number of adverse events was similar; however, more infections were observed in the iron sucrose arm.ConclusionsAn equal cumulative dose of ferric carboxymaltose administered less frequently did not meet noninferiority for maintaining hemoglobin levels compared with iron sucrose administered more frequently.Clinical Trial registry name and registration number:Comparison Study of Two Iron Compounds for Treatment of Anemia in Hemodialysis Patients (COPEFER), NCT02198495

scholarly journals Oxycodone versus morphine for analgesia after laparoscopic endometriosis resection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lijun Niu ◽  
Lihong Chen ◽  
Yanhua Luo ◽  
Wenkao Huang ◽  
Yunsheng Li
Keyword(s):  
Respiratory Depression ◽  
Visceral Pain ◽  
Deep Infiltrating Endometriosis ◽  
Trial Registry ◽  
Clinical Trial Registry ◽  
Morphine Group ◽  
Registration Number ◽  
To Receive ◽  
Registry Record ◽  
Infiltrating Endometriosis

Abstract Background The objective of this study was to compare the analgesic potency of oxycodone versus morphine after laparoscopic deep infiltrating endometriosis resection. Methods Fifty patients undergoing laparoscopic deep infiltrating endometriosis resection were randomized to receive oxycodone or morphine intravenous-PCA after surgery. The primary outcome was opioid consumption during the 24 h after surgery. Secondary outcomes included time to first request for analgesia, the number of bolus, pain, sedation, nausea, vomiting, respiratory depression, and bradycardia. The prominent pain that caused patients to press the analgesic device was also recorded. Results Oxycodone consumption (14.42 ± 2.83) was less than morphine consumption (20.14 ± 3.83). Compared with the morphine group, the total number of bolus (78 vs 123) was less and the average time to first request for analgesia (97.27 ± 59.79 vs 142.17 ± 51) was longer in the oxycodone group. The incidence of nausea was higher in the morphine group than in the oxycodone group at 0–2 h (45.45% vs 17.19%), 2–4 h (50% vs 17.19%),12–24 h (40.91% vs 13.04%) and 0–24 h (39.17% vs 19.13%). The overall incidence of vomiting was higher in the morphine group (27.27% vs 13.92%). There was no difference in visual analogue scale score, the incidence of respiratory depression, and bradycardia between groups. Of the three types of pain that prompted patients to request analgesia, the incidence of visceral pain was highest (59.9%, P < 0.01). Conclusion Oxycodone was more potent than morphine for analgesia after laparoscopic endometriosis resection, and oxycodone has fewer side effects than morphine. Name of the registry: Chinese Clinical Trial Registry Trial registration number: ChiCTR1900021870 URL of trial registry record:http://www.chictr.org.cn/edit.aspx?pid=35799&htm=4 Date of registration: 2019/3/13 0:00:00

scholarly journals MetR-Regulated Vibrio cholerae Metabolism Is Required for Virulence

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Ryan W. Bogard ◽  
Bryan W. Davies ◽  
John J. Mekalanos
Keyword(s):  
Amino Acid ◽  
Vibrio Cholerae ◽  
Virulence Factor ◽  
Current Knowledge ◽  
Intestinal Colonization ◽  
Wild Type ◽  
Pathogenic Potential ◽  
Content Type ◽  
Mouse Intestine

ABSTRACTLysR-type transcriptional regulators (LTTRs) are the largest, most diverse family of prokaryotic transcription factors, with regulatory roles spanning metabolism, cell growth and division, and pathogenesis. Using a sequence-defined transposon mutant library, we screened a panel ofV. choleraeEl Tor mutants to identify LTTRs required for host intestinal colonization. Surprisingly, out of 38 LTTRs, only one severely affected intestinal colonization in the suckling mouse model of cholera: the methionine metabolism regulator, MetR. Genetic analysis of genes influenced by MetR revealed thatglyA1andmetJwere also required for intestinal colonization. Chromatin immunoprecipitation of MetR and quantitative reverse transcription-PCR (qRT-PCR) confirmed interaction with and regulation ofglyA1, indicating that misregulation ofglyA1is likely responsible for the colonization defect observed in themetRmutant. TheglyA1mutant was auxotrophic for glycine but exhibited wild-type trimethoprim sensitivity, making folate deficiency an unlikely cause of its colonization defect. MetJ regulatory mutants are not auxotrophic but are likely altered in the regulation of amino acid-biosynthetic pathways, including those for methionine, glycine, and serine, and this misregulation likely explains its colonization defect. However, mutants defective in methionine, serine, and cysteine biosynthesis exhibited wild-type virulence, suggesting that these amino acids can be scavenged in vivo. Taken together, our results suggest that glycine biosynthesis may be required to alleviate an in vivo nutritional restriction in the mouse intestine; however, additional roles for glycine may exist. Irrespective of the precise nature of this requirement, this study illustrates the importance of pathogen metabolism, and the regulation thereof, as a virulence factor.IMPORTANCEVibrio choleraecontinues to be a severe cause of morbidity and mortality in developing countries. Identification ofV. choleraefactors critical to disease progression offers the potential to develop or improve upon therapeutics and prevention strategies. To increase the efficiency of virulence factor discovery, we employed a regulator-centric approach to multiplex our in vivo screening capabilities and allow whole regulons inV. choleraeto be interrogated for pathogenic potential. We identified MetR as a new virulence regulator and serine hydroxymethyltransferase GlyA1 as a new MetR-regulated virulence factor, both required byV. choleraeto colonize the infant mouse intestine. Bacterial metabolism is a prerequisite to virulence, and current knowledge of in vivo metabolism of pathogens is limited. Here, we expand the known role of amino acid metabolism and regulation in virulence and offer new insights into the in vivo metabolic requirements ofV. choleraewithin the mouse intestine.

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