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

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

An increase in albuminuria is associated with a higher incidence of malignancies

Background. A single albuminuria measurement is reported to be an independent predictor of cancer risk. Whether change in albuminuria is also independently associated with cancer is not known. Methods. We included 64 303 subjects of the Stockholm CREAtinine Measurements( SCREAM) project without a history of cancer and with at least two urine albumin-creatinine ratio( ACR) tests up to 2 years apart. Albuminuria changes were quantified by the fold-change in ACR over 2 years, and stratified into the absence of clinically elevated albuminuria( i.e. never) , albuminuria that remained constant, and albuminuria that increased or decreased. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidences. Results. During a median follow-up of 3.7( interquartile range 3.6-3.7) years, 5126 subjects developed de novo cancer. After multivariable adjustment including baseline estimated glomerular filtration rate and baseline ACR, subjects with increasing ACR over 2 years had a 19%( hazard ratio 1.19; 95% confidence interval 1.08-1.31) higher risk of overall cancer compared with those who never had clinically elevated ACR. No association with cancer risk was seen in the groups with decreasing or constant ACR. Regarding site-specific cancer risks, subjects with increasing ACR or constant ACR had a higher risk of developing urinary tract and lung cancer. No other associations between 2-year ACR changes and site-specific cancers were found. Conclusions. Increases in albuminuria over a 2-year period are associated with a higher risk of developing overall, urinary tract and lung cancer, independent of baseline kidney function and albuminuria. These data add important weight to the link that exists between albuminuria and cancer incidence.</p

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

An increase in albuminuria is associated with a higher incidence of malignancies

Background. A single albuminuria measurement is reported to be an independent predictor of cancer risk. Whether change in albuminuria is also independently associated with cancer is not known. Methods. We included 64 303 subjects of the Stockholm CREAtinine Measurements( SCREAM) project without a history of cancer and with at least two urine albumin-creatinine ratio( ACR) tests up to 2 years apart. Albuminuria changes were quantified by the fold-change in ACR over 2 years, and stratified into the absence of clinically elevated albuminuria( i.e. never) , albuminuria that remained constant, and albuminuria that increased or decreased. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidences. Results. During a median follow-up of 3.7( interquartile range 3.6-3.7) years, 5126 subjects developed de novo cancer. After multivariable adjustment including baseline estimated glomerular filtration rate and baseline ACR, subjects with increasing ACR over 2 years had a 19%( hazard ratio 1.19; 95% confidence interval 1.08-1.31) higher risk of overall cancer compared with those who never had clinically elevated ACR. No association with cancer risk was seen in the groups with decreasing or constant ACR. Regarding site-specific cancer risks, subjects with increasing ACR or constant ACR had a higher risk of developing urinary tract and lung cancer. No other associations between 2-year ACR changes and site-specific cancers were found. Conclusions. Increases in albuminuria over a 2-year period are associated with a higher risk of developing overall, urinary tract and lung cancer, independent of baseline kidney function and albuminuria. These data add important weight to the link that exists between albuminuria and cancer incidence.</p

Albuminuria and the risk of cancer:the Stockholm CREAtinine Measurements (SCREAM) project

Background:Studies investigating the association of chronic kidney disease and cancer have focused on estimated glomerular filtration (eGFR) rather than on albuminuria. This study aimed to examine whether albuminuria is associated with cancer incidence, and whether this association is independent of eGFR. Methods:We included subjects of the Stockholm Creatinine Measurements (SCREAM) project without a history of cancer—250 768 subjects with at least one urine albumin–creatinine ratio (ACR) test (primary cohort) and 433 850 subjects with at least one dipstick albuminuria test (secondary cohort). Albuminuria was quantified as KDIGO albuminuria stages. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidence rates. Multivariable Cox proportional hazards regression models adjusted for confounders including eGFR to calculate hazard ratios and 95% confidence intervals (HRs, 95% CIs). Results:During a median follow-up of 4.3 (interquartile range 2.0–8.2) years, 21 901 subjects of the ACR cohort developed de novo cancer. In multivariable analyses, adjusting among others for eGFR, subjects with an ACR of 30–299 mg/g or ≥300 mg/g had a 23% (HR 1.23; 95% CI 1.19–1.28) and 40% (HR 1.40; 95% CI 1.31–1.50) higher risk of developing cancer, respectively, when compared with subjects with an ACR &lt;30 mg/g. This graded, independent association was also observed for urinary tract, gastrointestinal tract, lung and hematological cancer incidence (all P &lt; .05). Results were similar in the dipstick albuminuria cohort. Conclusions:Albuminuria was associated with the risk of cancer independent of eGFR. This association was primarily driven by a higher risk of urinary tract, gastrointestinal tract, lung and hematological cancers.</p

Albuminuria and the risk of cancer:the Stockholm CREAtinine Measurements (SCREAM) project

Background:Studies investigating the association of chronic kidney disease and cancer have focused on estimated glomerular filtration (eGFR) rather than on albuminuria. This study aimed to examine whether albuminuria is associated with cancer incidence, and whether this association is independent of eGFR. Methods:We included subjects of the Stockholm Creatinine Measurements (SCREAM) project without a history of cancer—250 768 subjects with at least one urine albumin–creatinine ratio (ACR) test (primary cohort) and 433 850 subjects with at least one dipstick albuminuria test (secondary cohort). Albuminuria was quantified as KDIGO albuminuria stages. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidence rates. Multivariable Cox proportional hazards regression models adjusted for confounders including eGFR to calculate hazard ratios and 95% confidence intervals (HRs, 95% CIs). Results:During a median follow-up of 4.3 (interquartile range 2.0–8.2) years, 21 901 subjects of the ACR cohort developed de novo cancer. In multivariable analyses, adjusting among others for eGFR, subjects with an ACR of 30–299 mg/g or ≥300 mg/g had a 23% (HR 1.23; 95% CI 1.19–1.28) and 40% (HR 1.40; 95% CI 1.31–1.50) higher risk of developing cancer, respectively, when compared with subjects with an ACR &lt;30 mg/g. This graded, independent association was also observed for urinary tract, gastrointestinal tract, lung and hematological cancer incidence (all P &lt; .05). Results were similar in the dipstick albuminuria cohort. Conclusions:Albuminuria was associated with the risk of cancer independent of eGFR. This association was primarily driven by a higher risk of urinary tract, gastrointestinal tract, lung and hematological cancers.</p

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)