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ImportanceThe benefit of vitamin D treatment for coronavirus disease 2019 (COVID-19) remains unclear. ObjectiveTo investigate the effect of raising serum total 25-hydroxyvitamin D (25D) to 50-100 ng/mL with oral extended-release calcifediol (ERC) on time to symptom resolution in mild to moderate COVID-19. Design, Setting, and ParticipantsA multicenter, randomized, double-blind, placebo-controlled study evaluated treatment of 160 outpatients with COVID-19 diagnosed between November 2020 and October 2021. InterventionsPatients were treated for 4 weeks with ERC (30 mcg/capsule; 300 mcg on Days 1-3 and 60 mcg on Days 4-27) or placebo. Outcome MeasuresPrimary endpoints were raising serum 25D to [≥]50 ng/mL at Day 14 and resolution time for five aggregated symptoms. Secondary endpoints included resolution time for aggregated and individual symptoms as a function of serum 25D and changes in clinical biomarkers. Results171 subjects randomized, 160 treated and 134 (65 ERC and 69 placebo) retained. Average age was 43 (range: 18-71); 59% female, 92% White, 80% Hispanic, 7% African-American, 1% Other, 76% overweight, 40% obese, 26% comorbidities, mean baseline 25D of 37{+/-}1 (SE) ng/mL. ERC increased mean 25D to 82{+/-}4 ng/mL (p<0.001) by Day 7; 88% of subjects attained a level [≥]50 ng/mL; the placebo group trended lower. Resolution time for five aggregated symptoms was unchanged by ERC given that two composite non-respiratory symptoms responded poorly. Prespecified analyses showed that respiratory symptoms tended to resolve earlier when serum 25D levels reached [≤]50 ng/mL, but statistical significance was limited by small sample size and non-compliance: 25D increased in seven placebo subjects (unauthorized supplementation) and none occurred in five ERC subjects (failure to dose). A post-hoc composite of three respiratory symptoms (trouble breathing, chest congestion and dry or hacking cough) resolved 3.0 days faster when 25D was elevated at Days 7 and 14 (p<0.05); chest congestion resolved 4.0 days faster with 25D increases of [≥]25 ng/mL (p<0.05). Safety concerns including hypercalcemia were absent with ERC treatment. Conclusions and RelevanceERC was effective in increasing serum 25D in outpatients with COVID-19, which may have accelerated resolution of respiratory symptoms suggesting mitigation of COVID-19 pneumonia risk, findings which warrant further study.
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High dietary protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration, which in the long-term can lead to de novo or aggravating preexisting chronic kidney disease (CKD). Hence, a low protein diet (LPD, 0.6 to 0.8 g/kg/day) is recommended for the management of CKD. There are evidences that dietary protein restriction mitigate progression of CKD and retard the initiation of dialysis or facilitate incremental dialysis. LPD is also helpful to control metabolic derangements in CKD such as metabolic acidosis and hyperphosphatemia. Recently, a growing body of evidence has emerged on the benefits of plant-dominant low-protein diet (PLADO), which composed of > 50% plant-based sources. PLADO is considered to be helpful for relieving uremic burden and metabolic complications in CKD compared to animal protein dominant consumption. It may also lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation along with reducing cardiovascular risk. Alleviation of constipation in PLADO may minimize the risk of hyperkalemia. A balanced and individualized dietary approach for good adherence to LPD utilizing various plant-based sources as patients’ preference should be elaborated for the optimal care in CKD. Periodic nutritional assessment under supervision of trained dietitians should be warranted to avoid protein-energy wasting.
RESUMO
High dietary protein intake may lead to increased intraglomerular pressure and glomerular hyperfiltration, which in the long-term can lead to de novo or aggravating preexisting chronic kidney disease (CKD). Hence, a low protein diet (LPD, 0.6 to 0.8 g/kg/day) is recommended for the management of CKD. There are evidences that dietary protein restriction mitigate progression of CKD and retard the initiation of dialysis or facilitate incremental dialysis. LPD is also helpful to control metabolic derangements in CKD such as metabolic acidosis and hyperphosphatemia. Recently, a growing body of evidence has emerged on the benefits of plant-dominant low-protein diet (PLADO), which composed of > 50% plant-based sources. PLADO is considered to be helpful for relieving uremic burden and metabolic complications in CKD compared to animal protein dominant consumption. It may also lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation along with reducing cardiovascular risk. Alleviation of constipation in PLADO may minimize the risk of hyperkalemia. A balanced and individualized dietary approach for good adherence to LPD utilizing various plant-based sources as patients’ preference should be elaborated for the optimal care in CKD. Periodic nutritional assessment under supervision of trained dietitians should be warranted to avoid protein-energy wasting.
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Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic??hematologic, (6) inflammatory-oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 microg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.
