Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non‐genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25‐hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions

Prevalence of chronic kidney disease in women of reproductive age and observed birth rates

INTRODUCTION: Women of reproductive age with chronic kidney disease (CKD) are recognised to have decreased fertility and a higher risk of adverse pregnancy outcomes. How often CKD afflicts women of reproductive age is not well known. This study aimed to evaluate the burden of CKD and associated birth rates in an entire region.METHODS: This was a retrospective cohort study including women of childbearing age in Stockholm during 2006-2015. We estimated the prevalence of "probable CKD" by the presence of an ICD-10 diagnosis of CKD, a single estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73 m2 or history of maintenance dialysis. By linkage with the Swedish Medical Birth Register we identified births during the subsequent three years from study inclusion and evaluated birth rates.RESULTS: We identified 817,730 women in our region, of whom 55% had at least one creatinine measurement. A total of 3938 women were identified as having probable CKD, providing an age-averaged CKD prevalence of 0.50%. Women with probable CKD showed a lower birth rate 3 years after the index date (35.7 children per 1000 person years) than the remaining women free from CKD (46.5 children per 1000 person years).CONCLUSION: As many as 0.50% of individuals in this cohort had probable CKD, defined on the basis of at least one eGFR&lt;60 ml/min1.73 m2 test result, dialysis treatment (i.e. CKD stages 3-5) or an ICD-10 diagnosis of CKD. This prevalence is lower than previous estimates. Women with probable CKD, according to a study mainly capturing CKD 3-5, had a lower birth rate than those without CKD, illustrating the challenges of this population to successfully conceive.</p

Net Endogenous Acid Excretion and Kidney Allograft Outcomes

BACKGROUND AND OBJECTIVES: High dietary acid load may accelerate a decline in kidney function. We prospectively investigated whether dietary acid load is associated with graft outcomes in kidney transplant recipients, and whether venous bicarbonate mediates this association. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used data from 642 kidney transplant recipients with a functioning graft ≥1 year after transplantation. Net endogenous acid production was estimated using food frequency questionnaires and, alternatively, 24-hour urinary urea and potassium excretion to estimate net endogenous acid production. We defined the composite kidney end point as a doubling of plasma creatinine or graft failure. Multivariable Cox regression analyses, adjusted for potential confounders, were used to study the associations of dietary acid load with the kidney end point. We evaluated potential mediation effects of venous bicarbonate, urinary bicarbonate excretion, urinary ammonium excretion, titratable acid excretion, and net acid excretion on the association between net endogenous acid production and the kidney end point. RESULTS: The median net endogenous acid production using food frequency questionnaires and net endogenous acid production using urinary excretion were 40 (interquartile range, 35-45) and 54 (interquartile range, 44-66) mEq/day, respectively. During a median follow-up of 5.3 years (interquartile range, 4.1-6.0), 121 (19%) participants reached the kidney end point. After multivariable adjustment, net endogenous acid production using food frequency questionnaires and net endogenous acid production using urinary excretion (per SD higher) were independently associated with higher risk for kidney end point (hazard ratio, 1.33; 95% confidence interval, 1.12 to 1.57, P=0.001 and hazard ratio, 1.44; 95% confidence interval, 1.24 to 1.69, P<0.001, respectively). Baseline venous bicarbonate mediated 20% of the association between net endogenous acid production using food frequency questionnaires and the kidney end point. Baseline venous bicarbonate, urinary ammonium excretion, and net acid excretion mediated 25%, -14%, and -18%, respectively, of the association between net endogenous acid production using urinary excretion and the kidney end point. CONCLUSIONS: Higher dietary acid load was associated with a higher risk of doubling of plasma creatinine or graft failure, and this association was partly mediated by venous bicarbonate, urinary ammonium, and net acid excretion

Optimization of injection parameters to obtain selected properties on foamed PP with hollow glass microspheres and thermally expandable microspheres using Taguchi method

Se utilizó un sistema de espumación compuesto por microesferas de vidrio huecas (HGM) y microesferas térmicamente expandibles (EM) para lograr un equilibrio entre las propiedades seleccionadas de polipropileno (PP) espumado mediante moldeo por inyección, combinando las mayores propiedades de flexión y menor densidad requeridas en las piezas interiores de los automóviles. El L16 de Taguchi (44.23) se empleó para el plan experimental y la relación señal/ruido (S/N) para la optimización del sistema planteado. Los dos parámetros importantes de moldeo por inyección que afectan a las propiedades seleccionadas fueron la temperatura de la masa fundida y del molde. El efecto más importante efecto sobre el módulo de flexión fue la cantidad de HGM, y para la densidad la cantidad de EM.Ministerio de Economía, Industria y Competitividad (project MAT2017-85101-C2-1-R

Economic and environmental strategic water management in the shale gas industry: Application of cooperative game theory

In this work, a mixed‐integer linear programming (MILP) model is developed to address optimal shale gas‐water management strategies among shale gas companies that operate relatively close. The objective is to compute a distribution of water‐related costs and profit among shale companies to achieve a stable agreement on cooperation among them that allows increasing total benefits and reducing total costs and environmental impacts. We apply different solution methods based on cooperative game theory: The Core, the Dual Core, the Shapley value, and the minmax Core. We solved different case studies including a large problem involving four companies and 207 wells. In this example, individual cost distribution (storage cost, freshwater withdrawal cost, transportation cost, and treatment cost) assigned to each player is included. The results show that companies that adopt cooperation strategies improve their profits and enhance the sustainability of their operations through the increase in recycled water.The authors gratefully acknowledge the financial support by the Ministry of Economy, Industry, and Competitiveness from Spain, under the projects CTQ2016-77968-C3-1-P and CTQ2016-77968-C3-2-P (AEI/FEDER, UE)

Association between potassium level and outcomes in heart failure with reduced ejection fraction: a cohort study from the Swedish Heart Failure Registry

AimsHyperkalaemia and hypokalaemia are common in heart failure and associated with worse outcomes. However, the optimal potassium range is unknown. We sought to determine the optimal range of potassium in patients with heart failure and reduced ejection fraction (5.0- mmol/L. Potassium 5.0- mmol/L were more common with lower estimated glomerular filtration rate and heart failure of longer duration and greater severity. The potassium level associated with the lowest hazard risk for mortality at 30- days, 12 months, and maximal follow- up was 4.2- mmol/L, and there was a steep increase in risk with both higher and lower potassium levels. In adjusted strata analyses, lower potassium was independently associated with all- cause mortality at 12 months and maximal follow- up, while higher potassium levels only increased risk at 30- days.ConclusionIn this nationwide registry, the relationship between potassium and mortality was U- shaped, with an optimal potassium value of 4.2- mmol/L. After multivariable adjustment, hypokalaemia was associated with increased long- term mortality but hyperkalaemia was associated with increased short- term mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/3/EJHF1757-sup-0001-APPS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/2/ejhf1757_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162724/1/ejhf1757.pd

Effects of HCV Eradication on Bone mineral density in HIV/HCV Coinfected Patients

Little is known about the effects of eradication of HCV on bone mineral density (BMD) and biomarkers of bone remodeling in HIV/HCV coinfected patients. We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization (WHO) BMD categories at both sites, and plasma concentrations of soluble receptor activator of nuclear factor-kappaβ ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. A total of 238 patients were included, median age 49.5 years, 76.5% males, 48.3% with cirrhosis, 98.3% on antiretroviral therapy, median CD4+ cell count 527 cells/mm 3, 86.6% with HIV-1 RNA < 50 copies/mL. The prevalence of osteoporosis at baseline at the lumbar spine (LS) and femoral neck (FN) was 17.6% and 7.2%, respectively. Anti-HCV therapy comprised pegylated interferon and ribavirin (PegIFN-RBV) plus one direct-acting antiviral in 53.4%, PegIFN-RBV in 34.5%, and sofosbuvir/RBV in 12.2%. A total of 145 (60.9%) patients achieved sustained viral response (SVR). No significant effect of SVR was observed on sBMD for the interaction between time and SVR either in the LS (P=0.801) or the FN (P=0.911). Likewise, no significant effect of SVR was observed in plasma levels of sRANKL (P=0.205), OPG (P=0.249), and sRANKL/OPG ratio (P=0.123) for the interaction between time and SVR. No significant correlation was found between fibrosis by transient elastography, and LS and FN sBMD, at baseline, and week 96. SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.This study was supported by Instituto de Salud Carlos III (ISCII), grant numbers PI11/01556, PI14/01094, PI14/01581, and PI14CIII/00011, and by Ministerio de Sanidad, Servicios Sociales e Igualdad, grant number EC11-241. The study was also funded by the RD16/0025/0017, RD16/0025/0018 and RD16CIII/0002/0002 projects as part of the Plan Nacional R + D + I and cofunded by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER).S

Albuminuria Testing in Hypertension and Diabetes:An Individual-Participant Data Meta-Analysis in a Global Consortium

Albuminuria is an under-recognized component of chronic kidney disease definition, staging, and prognosis. Guidelines, particularly for hypertension, conflict on recommendations for urine albumin-to-creatinine ratio (ACR) measurement. Separately among 1 344 594 adults with diabetes and 2 334 461 nondiabetic adults with hypertension from the chronic kidney disease Prognosis Consortium, we assessed ACR testing, estimated the prevalence and incidence of ACR ≥30 mg/g and developed risk models for ACR ≥30 mg/g. The ACR screening rate (cohort range) was 35.1% (12.3%-74.5%) in diabetes and 4.1% (1.3%-20.7%) in hypertension. Screening was largely unrelated to the predicted risk of prevalent albuminuria. The median prevalence of ACR ≥30 mg/g across cohorts was 32.1% in diabetes and 21.8% in hypertension. Higher systolic blood pressure was associated with a higher prevalence of albuminuria (odds ratio [95% CI] per 20 mm Hg in diabetes, 1.50 [1.42-1.60]; in hypertension, 1.36 [1.28-1.45]). The ratio of undetected (due to lack of screening) to detected ACR ≥30 mg/g was estimated at 1.8 in diabetes and 19.5 in hypertension. Among those with ACR/g, the median 5-year incidence of ACR ≥30 mg/g across cohorts was 23.9% in diabetes and 21.7% in hypertension. Incident albuminuria was associated with initiation of renin-angiotensin-aldosterone system inhibitors (incidence-rate ratio [95% CI], diabetes 3.09 [2.71-3.53]; hypertension 2.87 [2.29-3.59]). In conclusion, despite similar risk of albuminuria to those with diabetes, ACR screening in patients with hypertension was low. Our findings suggest that regular albuminuria screening should be emphasized to enable early detection of chronic kidney disease and initiation of treatment with cardiovascular and renal benefits