A numerical model for the prediction of radon flux from uranium mill tailings at Jaduguda, India.

Solid process fine waste or tailings of a uranium mill is a potential source of release of radiologically significant gaseous radon (222Rn). A number of variables such as radium (226Ra) content, porosity, moisture content, and tailings density can affect the extent of emanation from the tailings. Further, if a cover material is used for remediation purposes, additional challenges due to changes in the matrix characteristics in predicting the radon flux can be anticipated. The uranium mill tailings impoundment systems at Jaduguda have been in use for the long-term storage of fine process waste (tailings). A pilot-scale remediation exercise of one of the tailings ponds has been undertaken with 30 cm soil as a cover material. For the prediction of the radon flux, a numerical model has been developed to account for the radon exhalation process at the remediated site. The model can effectively be used to accommodate both the continuous and discrete variable inputs. Depth profiling and physicochemical characterization for the remediated site have been done for the required input variables of the proposed numerical model. The predicted flux worked out is well below the reference level of 0.74 Bq m-2 s-1 IAEA (2004).

Potassium-Enriched Salt Substitutes: A Review of Recommendations in Clinical Management Guidelines.

Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives, efforts to control hypertension by improving dietary intake have largely failed because the changes required are mostly too hard to implement. Consistent recent data from randomized controlled trials show that potassium-enriched, sodium-reduced salt substitutes are an effective option for improving consumption levels and reducing blood pressure and the rates of cardiovascular events and deaths. Yet, salt substitutes are inconsistently recommended and rarely used. We sought to define the extent to which evidence about the likely benefits and harms of potassium-enriched salt substitutes has been incorporated into clinical management by systematically searching guidelines for the management of hypertension or chronic kidney disease. We found incomplete and inconsistent recommendations about the use of potassium-enriched salt substitutes in the 32 hypertension and 14 kidney guidelines that we reviewed. Discussion among the authors identified the possibility of updating clinical guidelines to provide consistent advice about the use of potassium-enriched salt for hypertension control. Draft wording was chosen to commence debate and progress consensus building: strong recommendation for patients with hypertension-potassium-enriched salt with a composition of 75% sodium chloride and 25% potassium chloride should be recommended to all patients with hypertension, unless they have advanced kidney disease, are using a potassium supplement, are using a potassium-sparing diuretic, or have another contraindication. We strongly encourage clinical guideline bodies to review their recommendations about the use of potassium-enriched salt substitutes at the earliest opportunity.

Patterns of multimorbidity among a community-based cohort in rural India.

Background: Multimorbidity estimates are expected to increase in India primarily due to the population aging. However, there is a lack of research estimating the burden of multimorbidity in the Indian context using a validated tool. We estimated the prevalence and determinants of multimorbidity amongst the adult population of the rural Uddanam region, Andhra Pradesh. Methods: This community-based cross-sectional study was conducted as a part of an ongoing research program. Multistage cluster sampling technique was used to select 2419 adult participants from 40 clusters. Multimorbidity was assessed using Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC) tool, collecting information on 13 chronic diseases. Patient Health Questionnaire (PHQ-12) was used to screen for depression. Multiple logistic regression was conducted to identify the strongest determinants of multimorbidity. Results: Of the 2419 participants, 2289 completed the MAQ-PC tool. Mean age (standard deviation) of participants was 48.1 (13.1) years. The overall prevalence of multimorbidity was 58.5% (95% CI 56.5-60.6); with 30.7%, 15.6%, and 12.2% reporting two, three, and four chronic conditions, respectively. Acid peptic disease-musculoskeletal disease (44%) and acid peptic disease-musculoskeletal disease-hypertension (14.9%) were the most common dyad and triad. Among metabolic diseases, diabetes-hypertension (28.3%) and diabetes-hypertension-chronic kidney disease (7.6%) were the most common dyad and triad, respectively. Advancing age, female gender, and being obese were the strongest determinates of the presence of multimorbidity. Depression was highly prevalent among the study population, and participants with higher PHQ-12 score had 3.7 (2.5-5.4) greater odds of having multimorbidity. Conclusions: Our findings suggest that six of 10 adults in rural India are affected with multimorbidity. We report a higher prevalence of multimorbidity as compared with other studies conducted in India. We also identified vulnerable groups which would guide policy makers in developing holistic care packages for individuals with multimorbidity.

Effect of Vitamin D Supplementation on Serum Hepcidin Levels in Non-Diabetic Chronic Kidney Disease Patients.

Introduction: Vitamin D deficiency and anemia frequently coexist. Moreover, vitamin D deficiency is found to play a role in chronic kidney disease (CKD)-associated anemia. We investigated the effect of cholecalciferol on serum hepcidin levels in vitamin D-deficient, non-diabetic individuals with CKD in a randomized, double-blind, placebo-controlled trial. Methods: This study was performed on stored samples of our previously published randomized, double-blind, placebo-controlled trial of cholecalciferol supplementation in non-diabetic patients with stage III-IV CKD and vitamin D deficiency. Stable patients of either sex, aged 18-70 years, with non-diabetic stage III-IV CKD (estimated glomerular filtration rate between 15 and 60 ml/min/1.73 m2), and having serum 25-hydroxyvitamin D3 [25(OH) D] levels ≤20 ng/ml were included. Participants received either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and at eight weeks. Follow-up was done at 16 weeks. Serum hepcidin levels were analyzed at baseline and at 16 weeks. Results: A total of 120 CKD patients were enrolled. Serum 25(OH) D levels were similar in the placebo and cholecalciferol groups at baseline (13.21 ± 4.78 ng/ml and 13.40 ± 4.42 ng/ml; P = 0.88). After 16 weeks, the serum 25(OH) D levels were found to be increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change 23.40 ng/ml; 95% CI: 19.76 to 27.06; P < 0.001). Serum hepcidin levels were similar at baseline (median [IQR]: 33.6 [8.6-77.8] ng/ml vs. 24.6 [9.3-70.7] ng/ml, P = 0.903) and did not vary between groups at 16 weeks (median [IQR]: 41.5 [10.9-75.0] ng/ml vs. 34.8 [12.3-63.75] ng/ml, P = 0.703). Conclusion: Our study provides preliminary data based on which a larger adequately powered clinical trial can be conducted to conclusively assess the impact of vitamin D supplementation on hepcidin levels and anemia in patients with CKD and vitamin D deficiency.

Cholecalciferol supplementation and angiogenic markers in chronic kidney disease.

Vitamin D plays an important role in proliferation and differentiation of cells and deficiency of vitamin D disturbs angiogenic balance. Previous studies in animal models have reported an association between serum levels of vitamin D and balance between pro- and anti-angiogenic factors. There is insufficient evidence about the effect of vitamin D on mediators of angiogenesis in patients with CKD. We investigated the effect of cholecalciferol supplementation on serum levels of angiogenic markers in non-diabetic patients with CKD stage 3-4. In this secondary analysis on stored samples of our previously published randomized, double-blind, placebo-controlled trial, stable patients of either sex, aged 18-70 years, with non-diabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in brachial artery flow-mediated dilatation at 16 weeks. Changes in levels of serum angiogenesis markers (angiopoietin-1, angiopoietin-2, VEGF-A, VEGEF-R, and Tie-2) between groups over 16 weeks were compared. A total 120 patients were enrolled. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21±4.78 ng/ml and 13.40±4.42 ng/ml; p = 0.888). At 16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change:23.40 ng/ml; 95% CI, 19.76 to 27.06; p<0.001). Serum levels of angiogenic markers were similar at baseline. At 16 weeks, angiopoietin-2 level decreased in cholecalciferol group (mean difference:-0.73 ng/ml, 95%CI, -1.25 to -0.20, p = 0.002) but not in placebo group (mean difference -0.46 ng/ml, 95%CI, -1.09 to 0.17, p = 0.154), however there was no between-group difference at 16 weeks (between-group difference in mean change: -0.27 ng/ml, 95%CI, -1.09 to 0.55, p = 0.624). Serum angiopoietin-1 level increased [mean change: 5.63 (0.51 to 10.75), p = 0.018] and VEGF-R level decreased [mean change: -87.16 (-131.89 to -42.44), p<0.001] in placebo group but did not show any change in cholecalciferol group. Our data shows the changes in Ang-1, Ang-2 and Ang-1/Ang-2 ratio after high dose oral cholecalciferol supplementation in patients with non-diabetic G3-4 CKD. The data suggests changes in circulating levels of angiogenic markers which needs to be confirmed through an adequately powered study.

Assessing Global Kidney Nutrition Care.

BACKGROUND AND OBJECTIVES: Nutrition intervention is an essential component of kidney disease management. This study aimed to understand current global availability and capacity of kidney nutrition care services, interdisciplinary communication, and availability of oral nutrition supplements. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The International Society of Renal Nutrition and Metabolism (ISRNM), working in partnership with the International Society of Nephrology (ISN) Global Kidney Health Atlas Committee, developed this Global Kidney Nutrition Care Atlas. An electronic survey was administered among key kidney care stakeholders through 182 ISN-affiliated countries between July and September 2018. RESULTS: Overall, 160 of 182 countries (88%) responded, of which 155 countries (97%) answered the survey items related to kidney nutrition care. Only 48% of the 155 countries have dietitians/renal dietitians to provide this specialized service. Dietary counseling, provided by a person trained in nutrition, was generally not available in 65% of low-/lower middle-income countries and "never" available in 23% of low-income countries. Forty-one percent of the countries did not provide formal assessment of nutrition status for kidney nutrition care. The availability of oral nutrition supplements varied globally and, mostly, were not freely available in low-/lower middle-income countries for both inpatient and outpatient settings. Dietitians and nephrologists only communicated "sometimes" on kidney nutrition care in ≥60% of countries globally. CONCLUSIONS: This survey reveals significant gaps in global kidney nutrition care service capacity, availability, cost coverage, and deficiencies in interdisciplinary communication on kidney nutrition care delivery, especially in lower-income countries.

Increased serum catalytic iron may mediate tissue injury and death in patients with COVID-19.

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients-mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.

Preventing the Next Pandemic: The Case for Investing in Circulatory Health - A Global Coalition for Circulatory Health Position Paper.

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.

Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases.

With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of metabolic diseases come together to identify the challenges and provide perspectives on building a framework for a virtual primary care-driven, patient-centred, multidisciplinary model to deliver holistic care for patients with metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. We focus on clinical care and innovative trial design for metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. This work represents a call to action to promote collaboration and partnerships between stakeholders for improving the lives of people with, or at risk of, metabolic dysfunction-associated fatty liver disease and associated metabolic diseases.

Strategic plan for integrated care of patients with kidney failure.

There is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5-10 years.

Sobol sensitivity analysis for risk assessment of uranium in groundwater.

The exposure to uranium (U) in the natural environment is primarily through ingestion (eating contaminated food and drinking water) and dermal (skin contact with U powders/wastes) pathways. This study focuses on the dose assessment for different age-groups using the USEPA model. A total of 156 drinking water samples were tested to know U level in the groundwater of the study region. Different age-groups were selected to determine the human health impact due to uranium exposure in the residing populations. To determine the relative importance of each input, a variance decomposition technique, i.e., Sobol sensitivity analysis, was used. Furthermore, different sample sizes were tested to obtain the optimal Sobol sensitivity indices. Three types of effects were evaluated: first-order effect (FOE), second-order effect (SOE) and total effect. The result of analysis revealed that 17% of the samples had U concentration above 30 µg l-1 of U, which is the recommended level by World Health Organization. The mean hazard index (HI) value for younger age-group was found to be less than 1, whereas the 95th percentile value of HI value exceeded for both age-groups. The mean annual effective dose of U for adults was found to be slightly higher than the recommended level of 0.1 m Sv year-1. This result signified that adults experienced relatively higher exposure dose than the children in this region. Sobol sensitivity analysis of FOE showed that the concentration of uranium (Cw) is the most sensitive input followed by intake rate (IR) and exposure frequency. Moreover, the value of SOE revealed that interaction effect of Cw - IR is the most sensitive input parameter for the assessment of oral health risk. On the other hand, dermal model showed Cw - F as the most sensitive interaction input. The larger value of SOE was also recorded for older age-group than for the younger group.

Insight into the impact of vitamin D on cardiovascular outcomes in chronic kidney disease.

Patients with chronic kidney disease (CKD) experience excess cardiovascular morbidity and mortality that is unexplained by traditional cardiovascular risk factors. Vitamin D deficiency is highly prevalent in CKD and is associated with increased cardiovascular mortality in both the general population and in CKD patients. Vitamin D supplementation is a reasonably safe and simple intervention and meta-analyses of observational studies have suggested that vitamin D supplementation in CKD improves cardiovascular mortality. However, randomized controlled trials examining the impact of vitamin D supplementation in improving surrogate markers of cardiovascular structure and function remain inconclusive. This review investigates the impact of vitamin D supplementation on surrogate end-points and cardiovascular events from trials in CKD; and discusses why results have been heterogenous, particularly critiquing the effect of different dosing regimens and the failure to take into account the implications of vitamin D supplementation in study participants with differing vitamin D binding protein genotypes.

Vitamin D deficiency, endothelial function and bone biomarkers in post-kidney transplantation patients from North India.

PURPOSE: CKD patients after kidney transplantation continue to suffer from elevated CV events which may be related to low vitamin D and its adverse impact on vascular function. The prevalence of vitamin D deficiency in North Indian kidney transplantation patients and its impact on vascular and bone biomarkers is unknown which this study investigated. METHODS: Non-diabetic, stable, > 6 months post-kidney transplantation patients, not on vitamin D supplementation, were recruited after informed consent. Data on demographics, anthropometrics and treatment were collected. Blood samples were stored at - 80 °C until analysis for bone and endothelial cell biomarkers using standard ELISA techniques. RESULTS: The clinical characteristics were: age 37.4 ± 9.9 years, 80% men, 27% ex-smokers, BP 125.5 ± 15.7/78.6 ± 9.7 mmHg, cholesterol 172.0 ± 47.8 mg/dL, hemoglobin 12.6 ± 2.3 g/dL, calcium 9.5 ± 0.6 mg/d and iPTH 58.4 ± 32.9 ng/mL and vitamin D 36.5 ± 39.8 nmol/L. Patients with vitamin D < 37.5 nmol/L (66%) had similar age, serum creatinine, serum phosphate, iPTH, blood pressure but lower calcium (9.3 ± 0.7 vs. 9.6 ± 0.5 mg/dL; p = 0.024), lower FGF23 (median 18.8 vs. 80.0 pg/mL; p = 0.013) and higher E-selectin (15.8 ± 7.9 vs. 13.0 ± 5.5 ng/mL; p = 0.047). On Univariate analysis, E-selectin (r = - 0.292; p = 0.005), FGF23 (r = 0.217; p = 0.036) and calcium (r = 0.238; p = 0.022) were significantly correlated with vitamin D levels. On stepwise multiple regression analysis, only E-selectin was associated with vitamin D levels (ß = - 0.324; p = 0.002). CONCLUSION: Vitamin D deficiency was common in kidney transplant recipients in North India, associated with low FGF23 and high E-selectin. These findings suggest further investigations to assess the role of vitamin D deficiency-associated endothelial dysfunction, its implications and reversibility in kidney transplantation recipients.

Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney disease.

Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤ 20 ng/ml [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At baseline, serum levels of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml, IQR;140-260 pg/ml and placebo - median;180 pg/ml, IQR; 140-240 pg/ml, p = 0.67). 16 weeks after cholecalciferol supplementation, there was no change in level of sclerostin (mean change;1.10 pg/ml, 95%CI; -27.34 to 29.34 pg/ml, p = 0.25). However, a significant decrease in sclerostin level was noted in the placebo group (mean change; -31.94 pg/ml, 95%CI; -54.76 to -9.13 pg/ml, p = 0.002). Change (Δ) in sclerostin level at 16 weeks correlated negatively with Δ eGFR (r = -0.20, p = 0.03) and positively with Δuric acid (r = 0.37, p < 0.001) but not with Δ25(OH) D (r = 0.06, p = 0.54), Δ iPTH (r = - 0.03, p = 0.78) ΔFGF23 (r = - 0.08, p = 0.38) and Δ125 (OH)2 D (r = - 0.04, p = 0.65). In conclusion, high dose cholecalciferol supplementation did not change sclerostin levels in non-diabetic stage 3-4 CKD subjects.

Vascular function and cholecalciferol supplementation in CKD: A self-controlled case series.

Vitamin D deficiency is common and associated with mortality in chronic kidney disease (CKD) patients. Cardiovascular disease (CVD) is the commonest cause of mortality in CKD patients. In a randomized, double blind, placebo controlled trial, we have recently reported favorable effects of vitamin D supplementation on vascular & endothelial function and inflammatory biomarkers in vitamin D deficient patients with non-diabetic stage 3-4 CKD (J Am Soc Nephrol 28: 3100-3108, 2017). Subjects in the placebo group who had still not received vitamin D after completion of the trial received two oral doses 300,000 IU of oral cholecalciferol at 8 weeks interval followed by flow mediated dilatation (FMD), pulse wave velocity (PWV), circulating endothelial and inflammatory markers (E-Selectin, vWF, hsCRP and IL-6), 125 (OH)2D, iPTH and iFGF-23 assessment at 16 weeks. 31 subjects completed this phase of the study. Last values recorded in the preceding clinical trial were taken as baseline values. Serum 25(OH)D and 1,25(OH)2D increased and FMD significantly improved after cholecalciferol supplementation [mean change in FMD%: 5.8% (95% CI: 4.0-7.5%, p < 0.001]. Endothelium independent nitroglycerine mediated dilatation, PWV, iPTH, iFGF-23 and IL-6 also showed favorable changes. The data further cement the findings of beneficial effects of correction of vitamin D deficiency on vascular function.

The Effect of Vitamin D Supplementation on Bone Metabolic Markers in Chronic Kidney Disease.

Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo-controlled trial investigating the effect of cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3-G4 and vitamin D ≤20 ng/mL (Clinical Trials Registry of India: CTRI/2013/05/003648). Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At 16 weeks, the serum 25(OH)D and 1,25(OH)2 D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change: 23.40 ng/mL; 95% CI, 19.76 to 27.06; p < 0.001, and 14.98 pg/mL; 95% CI, 4.48 to 27.18; p = 0.007, respectively). Intact parathyroid hormone (iPTH) decreased in the cholecalciferol group (between-group difference in mean change -100.73 pg/mL (95% CI, -150.50 to -50.95; p < 0.001). Serum total and bone-specific alkaline phosphatase (SAP, BAP) and serum C-terminal cross-linked collagen type I telopeptides (CTX-1) were significantly reduced in cholecalciferol group (between group difference for change in mean: -20.25 U/L; 95% CI, -35.14 to -5.38 U/L; p = 0.008 for SAP; -12.54 U/L; 95% CI, -22.09 to -2.98 U/L; p = 0.013 for BAP; and -0.21 ng/mL; 95% CI, -0.38 to -0.05 ng/mL; p = 0.05 for CTX-1). Correlation analysis showed significant correlation of Δ25(OH)D with ΔiPTH (r = -0.409, p < 0.0001), Δ1,25(OH)2 D (r = 0.305, p = 0.001), ΔSAP (r = -0.301, p = 0.002), ΔBAP (r = -0.264, p = 0.004), and ΔCTX-1 (r = -0.210, p = 0.0230). Cholecalciferol supplementation corrects vitamin D deficiency and is effective in lowering serum intact parathyroid hormone and bone turnover markers in early stages of CKD. © 2017 American Society for Bone and Mineral Research.

Fibroblast growth factor 23 in untreated nephrotic syndrome.

AIM: Despite its importance in bone and cardiovascular disease in subjects with kidney disease, there are no data on fibroblast growth factor 23 (FGF23) perturbations in nephrotic syndrome. We evaluated FGF23 and markers of mineral bone metabolism in subjects with untreated NS. METHODS: In this cross-sectional study, we measured circulating levels of FGF23, 25-hydroxy vitamin D [25(OH)D], 1,25 di-hydroxy vitamin D [1,25(OH)2 D], serum albumin, serum calcium, phosphorus, creatinine and intact parathyroid hormone (iPTH) in 101 patients with adults onset NS and 40 healthy controls. We examined the correlation between FGF23 and markers of mineral bone metabolism. RESULTS: Compared to healthy controls, subjects with NS showed reduced levels of 25(OH)D (21.76 ± 10.18 vs 35.74 ± 40.27 nmol/L, P = 0.001), 1,25(OH)2 D (median; 37.80 vs 73.13 pmol/L, P = 0.0001) and FGF23 (37.81 ± 20.42 vs 48.20 ± 11.60 pg/mL, P = 0.004) levels. Serum phosphorus levels were marginally, but significantly higher in subjects with nephrotic syndrome compared to healthy controls (P = 0.004). Serum iPTH levels were significantly higher in subjects with NS compared to healthy controls (52.24 ± 39.58 vs 37.90 ± 14.60 pg/mL, P = 0.028). CONCLUSIONS: We conclude that FGF23 is reduced in subjects with NS compared to healthy controls. The reduced levels of Vitamin D, and urinary losses may contribute to lower levels of FGF23 in NS.