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BACKGROUND: Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. METHODS: The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. FINDINGS: Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, -1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, -1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.

Obesity has become a worldwide epidemic and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day will promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesityrelated glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased tenfold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating a healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

Obesity is a growing worldwide epidemic. It is one of the strongest risk factors for new-onset chronic kidney disease, and also for kidney stones and kidney cancer. This article is an accompaniment to World Kidney Day on 9 March 2017 to promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventative behaviours an affordable option.

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased bodyweight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long term. The incidence of obesity-related glomerulopathy has increased tenfold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating a healthy lifestyle and health policy measures that makes preventive behaviours an affordable option.

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease, and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased tenfold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle, and health policy measures that makes preventive behaviors an affordable option.

Obesity has become a worldwide epidemic and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day will promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesityrelated glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.

Obesity is a growing worldwide epidemic. It is one of the strongest risk factors for new-onset chronic kidney disease, and also for kidney stones and kidney cancer. This article is an accompaniment to World Kidney Day on 9 March 2017 to promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventative behaviours an affordable option.

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease. A high body mass index is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased bodyweight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long term. The incidence of obesity-related glomerulopathy has increased tenfold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating a healthy lifestyle and health policy measures that makes preventive behaviours an affordable option.

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased tenfold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating a healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease, and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased tenfold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle, and health policy measures that makes preventive behaviors an affordable option.

Background Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR. Methods To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years. Results Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%. Conclusions Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.

Background: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. Methods: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. Findings: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-P

BACKGROUND:The Systolic Blood Pressure Intervention Trial (SPRINT; ClinicalTrials.gov, NCT01206062) reported reduced cardiovascular events by intensive blood pressure (BP) control amongst hypertensive patients without diabetes. However, the risk-benefit profile of intensive BP control may differ across estimated glomerular filtration rate (eGFR) levels. METHODS:This is a post hoc analysis of the SPRINT. Nondiabetic hypertensive adults (n = 9361) with eGFR >20 mL per min per 1.73 m2 were enrolled from 102 US facilities between November 2010 and March 2013 and were followed up until August 2015 (median follow-up, 3.26 years). Patients were randomly assigned to either a systolic BP target of <120 or <140 mmHg (for intensive or standard treatment, respectively). The outcomes of interests were the development of (i) fatal and nonfatal major cardiovascular events and (ii) acute kidney injury (AKI). RESULTS:The cardiovascular benefit from intensive treatment was attenuated with lower eGFR (Pinteraction = 0.019), whereas eGFR did not modify the adverse effect on AKI (Pinteraction = 0.179). Amongst 891 participants with eGFR <45 mL per min per 1.73 m2 , intensive treatment did not reduce the cardiovascular outcome (54/446 vs. 54/445 events in the standard group, respectively; hazard ratio [HR], 0.92; 95% CI, 0.62-1.38) with an absolute rate difference (ARD) of -0.02 (95% CI, -0.07 to +0.03) per 100 patient-years, whereas it increased AKI (62/446 vs. 38/445 events in the standard group; HR, 1.73; 95% CI, 1.12-2.66) with an ARD of +1.93 (95% CI, +1.88 to +1.97) per 100 patient-years. CONCLUSIONS:Intensive BP control may provide little or no benefit and even be harmful for patients with moderate-to-advanced chronic kidney disease.

BACKGROUND:The Systolic Blood Pressure Intervention Trial (SPRINT; ClinicalTrials.gov, NCT01206062) reported reduced cardiovascular events by intensive blood pressure (BP) control amongst hypertensive patients without diabetes. However, the risk-benefit profile of intensive BP control may differ across estimated glomerular filtration rate (eGFR) levels. METHODS:This is a post hoc analysis of the SPRINT. Nondiabetic hypertensive adults (n = 9361) with eGFR >20 mL per min per 1.73 m2 were enrolled from 102 US facilities between November 2010 and March 2013 and were followed up until August 2015 (median follow-up, 3.26 years). Patients were randomly assigned to either a systolic BP target of <120 or <140 mmHg (for intensive or standard treatment, respectively). The outcomes of interests were the development of (i) fatal and nonfatal major cardiovascular events and (ii) acute kidney injury (AKI). RESULTS:The cardiovascular benefit from intensive treatment was attenuated with lower eGFR (Pinteraction  = 0.019), whereas eGFR did not modify the adverse effect on AKI (Pinteraction  = 0.179). Amongst 891 participants with eGFR <45 mL per min per 1.73 m2 , intensive treatment did not reduce the cardiovascular outcome (54/446 vs. 54/445 events in the standard group, respectively; hazard ratio [HR], 0.92; 95% CI, 0.62-1.38) with an absolute rate difference (ARD) of -0.02 (95% CI, -0.07 to +0.03) per 100 patient-years, whereas it increased AKI (62/446 vs. 38/445 events in the standard group; HR, 1.73; 95% CI, 1.12-2.66) with an ARD of +1.93 (95% CI, +1.88 to +1.97) per 100 patient-years. CONCLUSIONS:Intensive BP control may provide little or no benefit and even be harmful for patients with moderate-to-advanced chronic kidney disease.

Background - In the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care. Methods and Results - We compared all-cause mortality, incident coronary heart disease, and incident ischemic stroke using multivariable-adjusted Cox models in a nationwide cohort of 547 441 black and 2 525 525 white patients with baseline estimated glomerular filtration rate ≥60 mL·min-1·1.73 m-2 receiving care from the US Veterans Health Administration. In parallel analyses, we compared outcomes in black versus white individuals in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. After multivariable adjustments in veterans, black race was associated with 24% lower all-cause mortality (adjusted hazard ratio, 0.76; 95% confidence interval, 0.75-0.77; P<0.001) and 37% lower incidence of coronary heart disease (adjusted hazard ratio, 0.63; 95% confidence interval, 0.62-0.65; P<0.001) but a similar incidence of ischemic stroke (adjusted hazard ratio, 0.99; 95% confidence interval, 0.97-1.01; P=0.3). Black race was associated with a 42% higher adjusted mortality among individuals with estimated glomerular filtration rate ≥60 mL·min-1·1.73 m-2 in NHANES (adjusted hazard ratio, 1.42; 95% confidence interval, 1.09-1.87). Conclusions - Black veterans with normal estimated glomerular filtration rate and equal access to healthcare have lower all-cause mortality and incidence of coronary heart disease and a similar incidence of ischemic stroke. These associations are in contrast to the higher mortality experienced by black individuals in the general US population.

Background - In the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care. Methods and Results - We compared all-cause mortality, incident coronary heart disease, and incident ischemic stroke using multivariable-adjusted Cox models in a nationwide cohort of 547 441 black and 2 525 525 white patients with baseline estimated glomerular filtration rate ≥60 mL·min-1·1.73 m-2 receiving care from the US Veterans Health Administration. In parallel analyses, we compared outcomes in black versus white individuals in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. After multivariable adjustments in veterans, black race was associated with 24% lower all-cause mortality (adjusted hazard ratio, 0.76; 95% confidence interval, 0.75-0.77; P<0.001) and 37% lower incidence of coronary heart disease (adjusted hazard ratio, 0.63; 95% confidence interval, 0.62-0.65; P<0.001) but a similar incidence of ischemic stroke (adjusted hazard ratio, 0.99; 95% confidence interval, 0.97-1.01; P=0.3). Black race was associated with a 42% higher adjusted mortality among individuals with estimated glomerular filtration rate ≥60 mL·min-1·1.73 m-2 in NHANES (adjusted hazard ratio, 1.42; 95% confidence interval, 1.09-1.87). Conclusions - Black veterans with normal estimated glomerular filtration rate and equal access to healthcare have lower all-cause mortality and incidence of coronary heart disease and a similar incidence of ischemic stroke. These associations are in contrast to the higher mortality experienced by black individuals in the general US population.

Higher body mass index (BMI) appears paradoxically associated with better outcomes in patients with chronic kidney disease. Whereas higher BMI reflects both increased visceral and subcutaneous fat and/or muscle mass, a combined assessment of BMI and waist circumference may enable differentiation of visceral adiposity from muscle and/or nonvisceral fat mass. We examined the association of BMI and waist circumference with all-cause mortality in a prospective cohort of 993 kidney transplant recipients. Associations were examined in Cox models with adjustment for demographic and comorbid conditions and for inflammatory markers. Unadjusted death hazard ratios (95%CI) associated with one standard deviation higher BMI and waist circumference were 0.94 (0.78, 1.13), p = 0.5 and 1.20 (1.00, 1.45), p = 0.05, respectively. Higher BMI was associated with lower mortality after adjustment for waist circumference (0.48 [0.34, 0.69], p < 0.001), and higher waist circumference was more strongly associated with higher mortality after adjustment for BMI (2.18 [1.55-3.08], p < 0.001). The associations of waist circumference with mortality remained significant after additional multivariable adjustments. Higher BMI and waist circumference display opposite associations with mortality in kidney transplant recipients. Waist circumference appears to be a better prognostic marker for obesity than BMI.

Background/aimsHyperphosphatemia is associated with higher mortality and increased incidence of end-stage renal disease in patients with non-dialysis dependent CKD (NDD-CKD), but there has not been a concomitant assessment of mortality and progressive kidney disease that would also account for cumulative effects of hyperphosphatemia.MethodsIn order to account for the cumulative effects of abnormal serum phosphorus we examined associations of not only baseline, but also time-averaged serum phosphorus levels with all-cause mortality, the composite of mortality or ESRD and the slopes of estimated glomerular filtration rate (eGFR), by using Cox models and mixed effects models in a contemporary cohort of 713 males with moderate and advanced NDD-CKD.ResultsHigher baseline and time-averaged serum phosphorus were both associated with mortality and with the composite outcome. A 1 mg/dl higher time-averaged serum phosphorus was associated with a multivariable adjusted hazard ratio of all-cause mortality (95% CI) of 1.56 (1.19 - 2.05), p = 0.001. Higher serum phosphorus was associated with a steeper slope of eGFR in unadjusted analyses, but this association became non-significant after multivariable adjustments.ConclusionThe cumulative burden of hyperphosphatemia is associated with increased mortality in patients with moderate and advanced NDD-CKD. Clinical trials are needed to determine if lowering serum phosphorus can result in improved mortality in this population.

Higher body mass index (BMI) appears paradoxically associated with better outcomes in patients with chronic kidney disease. Whereas higher BMI reflects both increased visceral and subcutaneous fat and/or muscle mass, a combined assessment of BMI and waist circumference may enable differentiation of visceral adiposity from muscle and/or nonvisceral fat mass. We examined the association of BMI and waist circumference with all-cause mortality in a prospective cohort of 993 kidney transplant recipients. Associations were examined in Cox models with adjustment for demographic and comorbid conditions and for inflammatory markers. Unadjusted death hazard ratios (95%CI) associated with one standard deviation higher BMI and waist circumference were 0.94 (0.78, 1.13), p = 0.5 and 1.20 (1.00, 1.45), p = 0.05, respectively. Higher BMI was associated with lower mortality after adjustment for waist circumference (0.48 [0.34, 0.69], p < 0.001), and higher waist circumference was more strongly associated with higher mortality after adjustment for BMI (2.18 [1.55-3.08], p < 0.001). The associations of waist circumference with mortality remained significant after additional multivariable adjustments. Higher BMI and waist circumference display opposite associations with mortality in kidney transplant recipients. Waist circumference appears to be a better prognostic marker for obesity than BMI.

Background/aimsHyperphosphatemia is associated with higher mortality and increased incidence of end-stage renal disease in patients with non-dialysis dependent CKD (NDD-CKD), but there has not been a concomitant assessment of mortality and progressive kidney disease that would also account for cumulative effects of hyperphosphatemia.MethodsIn order to account for the cumulative effects of abnormal serum phosphorus we examined associations of not only baseline, but also time-averaged serum phosphorus levels with all-cause mortality, the composite of mortality or ESRD and the slopes of estimated glomerular filtration rate (eGFR), by using Cox models and mixed effects models in a contemporary cohort of 713 males with moderate and advanced NDD-CKD.ResultsHigher baseline and time-averaged serum phosphorus were both associated with mortality and with the composite outcome. A 1 mg/dl higher time-averaged serum phosphorus was associated with a multivariable adjusted hazard ratio of all-cause mortality (95% CI) of 1.56 (1.19 - 2.05), p = 0.001. Higher serum phosphorus was associated with a steeper slope of eGFR in unadjusted analyses, but this association became non-significant after multivariable adjustments.ConclusionThe cumulative burden of hyperphosphatemia is associated with increased mortality in patients with moderate and advanced NDD-CKD. Clinical trials are needed to determine if lowering serum phosphorus can result in improved mortality in this population.

Restless legs syndrome is a common sleep disorder, but there is a paucity of large cohort studies examining the association of restless legs syndrome with clinical outcomes, including all-cause mortality, incident coronary heart disease, stroke and chronic kidney disease. From a nationally representative prospective cohort of over 3 million US veterans [93% male, median follow-up time of 8.1 years (interquartile range: 7.0-8.5 years)] with baseline estimated glomerular filtration rate ≥60 mL min-1 1.73 m-2, a propensity-matched cohort of 7392 patients was created, and the association between incident restless legs syndrome and the following was examined: (1) all-cause mortality; (2) incident coronary heart disease; (3) incident strokes; and (4) incident chronic kidney disease defined as estimated glomerular filtration rate <60 mL min-1 1.73 m-2. Associations were examined using Cox models. The mean ± SD age of the propensity-matched cohort at baseline was 59 ± 12 years; 89 and 8% of patients were white and black, respectively; 31% of the patients were diabetic; and the mean baseline estimated glomerular filtration rate was 83.9 ± 15.1 mL min-1 1.73 m-2. Propensity matching resulted in a balanced cohort, with the disappearance in baseline differences in comorbidities. Compared with restless legs syndrome-negative patients, incident restless legs syndrome was associated with 88% higher mortality risk [hazard ratio and 95% confidence interval: 1.88 (1.70-2.08)], and almost four times higher risk of coronary heart disease and stroke [hazard ratio: 3.97 (3.26-4.84) and 3.89 (3.07-4.94), respectively]. The risk of incident chronic kidney disease was also significantly higher in incident restless legs syndrome patients [hazard ratio: 3.17 (2.74-3.66)] compared with restless legs syndrome-negative counterparts. In this large and contemporary cohort of US veterans, incident restless legs syndrome was associated with higher risk of mortality, incident coronary heart diseas

Restless legs syndrome is a common sleep disorder, but there is a paucity of large cohort studies examining the association of restless legs syndrome with clinical outcomes, including all-cause mortality, incident coronary heart disease, stroke and chronic kidney disease. From a nationally representative prospective cohort of over 3 million US veterans [93% male, median follow-up time of 8.1 years (interquartile range: 7.0-8.5 years)] with baseline estimated glomerular filtration rate ≥60 mL min-1 1.73 m-2, a propensity-matched cohort of 7392 patients was created, and the association between incident restless legs syndrome and the following was examined: (1) all-cause mortality; (2) incident coronary heart disease; (3) incident strokes; and (4) incident chronic kidney disease defined as estimated glomerular filtration rate <60 mL min-1 1.73 m-2. Associations were examined using Cox models. The mean ± SD age of the propensity-matched cohort at baseline was 59 ± 12 years; 89 and 8% of patients were white and black, respectively; 31% of the patients were diabetic; and the mean baseline estimated glomerular filtration rate was 83.9 ± 15.1 mL min-1 1.73 m-2. Propensity matching resulted in a balanced cohort, with the disappearance in baseline differences in comorbidities. Compared with restless legs syndrome-negative patients, incident restless legs syndrome was associated with 88% higher mortality risk [hazard ratio and 95% confidence interval: 1.88 (1.70-2.08)], and almost four times higher risk of coronary heart disease and stroke [hazard ratio: 3.97 (3.26-4.84) and 3.89 (3.07-4.94), respectively]. The risk of incident chronic kidney disease was also significantly higher in incident restless legs syndrome patients [hazard ratio: 3.17 (2.74-3.66)] compared with restless legs syndrome-negative counterparts. In this large and contemporary cohort of US veterans, incident restless legs syndrome was associated with higher risk of mortality, incident coronary heart diseas

Replacement of activated vitamin D has been the cornerstone of therapy for secondary hyperparathyroidism (SHPT). Recent findings from several large observational studies have suggested that the benefits of vitamin D receptor activators (VDRA) may extend beyond the traditional parathyroid hormone (PTH)-lowering effect, and could result in direct cardiovascular and metabolic benefits. The advent of several new analogs of the activated vitamin D molecule has widened our therapeutic armamentarium, but has also made therapeutic decisions more complicated. Treatment of SHPT has become even more complex with the arrival of the first calcium-sensing receptor (CSR) agonist (cinacalcet hydrochloride) and with the uncovering of novel mechanisms responsible for SHPT. We provide a brief overview of the physiology and pathophysiology of SHPT, with a focus on vitamin D metabolism, and discuss various practical aspects of VDRA therapy and its reported association with survival in recent observational studies. A detailed discussion of the available agents is aimed at providing the practicing physician with a clear understanding of the advantages or disadvantages of the individual medications. A number of open questions are also analyzed, including the present and future roles of CSR agonists and 25(OH) vitamin D replacement.

Secondary hyperparathyroidism is associated with mortality in patients undergoing maintenance dialysis treatment. We studied 515 male US veterans with chronic kidney disease, who were not yet on dialysis, to see what outcomes were associated with secondary hyperparathyroidism in this population. Relationships between intact parathyroid hormone levels and all-cause mortality along with the composite of mortality or incidence of dialysis were measured in unadjusted and adjusted Cox models for case-mix and laboratory variables. Elevated parathyroid hormone levels above the upper limit compared to the lower limit of the normal range were significantly associated with mortality after adjustments. Higher intact parathyroid hormone levels in the upper limit of normal were significantly associated with higher mortality overall and showed similar trends in subgroups of patients with stage 3 and stage 4-5 chronic kidney disease and with higher and lower serum calcium and phosphorus levels. Similar associations were found with the composite outcome of mortality or dialysis. Our study shows that secondary hyperparathyroidism is independently associated with higher mortality in patients with chronic kidney disease but not yet on dialysis.

Iron is an essential micronutrient that is indispensable for erythropoesis. Correct assessment of iron stores is needed both for the diagnosis of iron deficiency and to direct iron replacement therapies. Serum ferritin is a commonly employed measure to assess iron stores, yet there are caveats that influence its accuracy as a diagnostic tool. While low ferritin levels are specific for iron deficiency, high levels can be the result of inflammation, liver disease, or malignancies and could be independent of iron stores. Optimal anemia management involves administration of adequate amounts of iron. The right dose of iron that allows optimal erythropoesis yet avoids oxidative stress is a matter of ongoing debate, especially when using imperfect diagnostic tools such as serum ferritin to direct therapy. Data from hemodialysis patients are presented to illustrate the challenges one faces when trying to achieve the best possible therapeutic benefit from iron-replacement therapy. © 2008 Sage Publications.

Iron is an essential micronutrient that is indispensable for erythropoesis. Correct assessment of iron stores is needed both for the diagnosis of iron deficiency and to direct iron replacement therapies. Serum ferritin is a commonly employed measure to assess iron stores, yet there are caveats that influence its accuracy as a diagnostic tool. While low ferritin levels are specific for iron deficiency, high levels can be the result of inflammation, liver disease, or malignancies and could be independent of iron stores. Optimal anemia management involves administration of adequate amounts of iron. The right dose of iron that allows optimal erythropoesis yet avoids oxidative stress is a matter of ongoing debate, especially when using imperfect diagnostic tools such as serum ferritin to direct therapy. Data from hemodialysis patients are presented to illustrate the challenges one faces when trying to achieve the best possible therapeutic benefit from iron-replacement therapy. © 2008 Sage Publications.

Replacement of activated vitamin D has been the cornerstone of therapy for secondary hyperparathyroidism (SHPT). Recent findings from several large observational studies have suggested that the benefits of vitamin D receptor activators (VDRA) may extend beyond the traditional parathyroid hormone (PTH)-lowering effect, and could result in direct cardiovascular and metabolic benefits. The advent of several new analogs of the activated vitamin D molecule has widened our therapeutic armamentarium, but has also made therapeutic decisions more complicated. Treatment of SHPT has become even more complex with the arrival of the first calcium-sensing receptor (CSR) agonist (cinacalcet hydrochloride) and with the uncovering of novel mechanisms responsible for SHPT. We provide a brief overview of the physiology and pathophysiology of SHPT, with a focus on vitamin D metabolism, and discuss various practical aspects of VDRA therapy and its reported association with survival in recent observational studies. A detailed discussion of the available agents is aimed at providing the practicing physician with a clear understanding of the advantages or disadvantages of the individual medications. A number of open questions are also analyzed, including the present and future roles of CSR agonists and 25(OH) vitamin D replacement.

Secondary hyperparathyroidism is associated with mortality in patients undergoing maintenance dialysis treatment. We studied 515 male US veterans with chronic kidney disease, who were not yet on dialysis, to see what outcomes were associated with secondary hyperparathyroidism in this population. Relationships between intact parathyroid hormone levels and all-cause mortality along with the composite of mortality or incidence of dialysis were measured in unadjusted and adjusted Cox models for case-mix and laboratory variables. Elevated parathyroid hormone levels above the upper limit compared to the lower limit of the normal range were significantly associated with mortality after adjustments. Higher intact parathyroid hormone levels in the upper limit of normal were significantly associated with higher mortality overall and showed similar trends in subgroups of patients with stage 3 and stage 4-5 chronic kidney disease and with higher and lower serum calcium and phosphorus levels. Similar associations were found with the composite outcome of mortality or dialysis. Our study shows that secondary hyperparathyroidism is independently associated with higher mortality in patients with chronic kidney disease but not yet on dialysis.

Hypercholesterolemia has been implicated as a risk factor for atherosclerosis by numerous observational studies in the general population. Observational studies in patients suffering from various chronic illnesses and in individuals with advanced age have indicated an inverse association between cholesterol level and mortality, suggesting that the classical Framingham paradigm may not apply to these groups. It is yet unclear what the reasons for these paradoxically inverse associations are. We present a summary of the descriptive studies that have examined the association between cholesterol levels and outcomes in a variety of patient groups. The various possible mechanisms behind the observed "lipid paradox" and the potential implications of reverse epidemiology of hypercholesterolemia in clinical medicine and public health are discussed. Copyright © 2007 Termedia & Banach.

Hypercholesterolemia has been implicated as a risk factor for atherosclerosis by numerous observational studies in the general population. Observational studies in patients suffering from various chronic illnesses and in individuals with advanced age have indicated an inverse association between cholesterol level and mortality, suggesting that the classical Framingham paradigm may not apply to these groups. It is yet unclear what the reasons for these paradoxically inverse associations are. We present a summary of the descriptive studies that have examined the association between cholesterol levels and outcomes in a variety of patient groups. The various possible mechanisms behind the observed "lipid paradox" and the potential implications of reverse epidemiology of hypercholesterolemia in clinical medicine and public health are discussed. Copyright © 2007 Termedia & Banach.

Anemia is a common complication of chronic kidney disease (CKD), but the outcomes associated with lower hemoglobin (Hgb) levels in patients with CKD not yet on dialysis are not well characterized. Analyses exploring outcomes associated with a single baseline Hgb value also do not account for the longitudinal variation of this measure. After collecting all Hgb measurements (N=17 194, median (range): 12 (1-168)) over a median follow-up period of 2.1 years in a historical prospective cohort of 853 male US veterans with CKD Stages 3-5 not yet on dialysis, we examined the association of time-averaged Hgb levels with predialysis all-cause mortality, end-stage renal disease (ESRD), and a composite end point of both. Kaplan-Meier survival analysis and Cox models adjusted for age, race, body mass index, smoking status, blood pressure, diabetes mellitus, cardiovascular disease, categories of estimated glomerular filtration rate, serum concentrations of albumin and cholesterol, and proteinuria were examined. Lower time-averaged Hgb was associated with significantly higher hazard of the composite end point (hazard ratio (95% confidence interval) in the adjusted model for time-averaged Hgb of <110, 111-120 and 121-130, compared to >130 g/l: 2.57 (1.85-3.58), 1.97 (1.45-2.66), 1.19 (0.86-1.63), P(trend)<0.001). Lower time-averaged Hgb was associated with both significantly higher pre-dialysis mortality and higher risk of ESRD, when analyzed separately. Anemia (especially time-averaged Hgb <120 g/l) is associated with both higher mortality and increased risk of ESRD in male patients with CKD not yet on dialysis.

Anemia is a common complication of chronic kidney disease (CKD), but the outcomes associated with lower hemoglobin (Hgb) levels in patients with CKD not yet on dialysis are not well characterized. Analyses exploring outcomes associated with a single baseline Hgb value also do not account for the longitudinal variation of this measure. After collecting all Hgb measurements (N=17 194, median (range): 12 (1-168)) over a median follow-up period of 2.1 years in a historical prospective cohort of 853 male US veterans with CKD Stages 3-5 not yet on dialysis, we examined the association of time-averaged Hgb levels with predialysis all-cause mortality, end-stage renal disease (ESRD), and a composite end point of both. Kaplan-Meier survival analysis and Cox models adjusted for age, race, body mass index, smoking status, blood pressure, diabetes mellitus, cardiovascular disease, categories of estimated glomerular filtration rate, serum concentrations of albumin and cholesterol, and proteinuria were examined. Lower time-averaged Hgb was associated with significantly higher hazard of the composite end point (hazard ratio (95% confidence interval) in the adjusted model for time-averaged Hgb of <110, 111-120 and 121-130, compared to >130 g/l: 2.57 (1.85-3.58), 1.97 (1.45-2.66), 1.19 (0.86-1.63), P(trend)<0.001). Lower time-averaged Hgb was associated with both significantly higher pre-dialysis mortality and higher risk of ESRD, when analyzed separately. Anemia (especially time-averaged Hgb <120 g/l) is associated with both higher mortality and increased risk of ESRD in male patients with CKD not yet on dialysis.

Background In the general population, low serum magnesium levels are associated with poor outcomes and death. While limited data suggest that low baseline magnesium levels may be associated with higher mortality in hemodialysis (HD) patients, the impact of changes in magnesium levels over time is unknown. Study Design We examined the association of time-varying serum magnesium levels with all-cause mortality using multivariable time-varying survival models adjusted for clinical characteristics and other time-varying laboratory measures. Setting & Participants 9,359 maintenance HD patients treated in a large dialysis organization between 2007 and 2011. Predictor Time-varying serum magnesium levels across 5 magnesium increments (<1.8, 1.8-<2.0, 2.0-<2.2, 2.2-<2.4, and ≥2.4 mg/dL). Outcome All-cause mortality. Results 2,636 individuals died over 5 years. Time-varying serum magnesium levels < 2.0 mg/dL were associated with higher mortality after adjustment for demographics and comorbid conditions, including hypertension, diabetes, and malignancies (reference: magnesium, 2.2-<2.4 mg/dL): adjusted HRs for serum magnesium level < 1.8 and 1.8 to <2.0 mg/dL were 1.39 (95% CI, 1.23-1.58; P < 0.001) and 1.20 (95% CI, 1.06-1.36; P = 0.004), respectively. Some associations were attenuated to the null after incremental adjustment for laboratory test results, particularly serum albumin. However, among patients with serum albumin measurements, low albumin level (<3.5 g/dL) and magnesium level < 2.0 mg/dL were associated with an additional death risk (adjusted HR, 1.17; 95% CI, 1.05-1.31; P = 0.004), whereas patients with high serum albumin levels (≥3.5 g/dL) exhibited low death risk (adjusted HRs of 0.53 and 0.53 [P ≤ 0.001] for magnesium < 2.0 and ≥2.0 mg/dL, respectively; reference: albumin < 3.5 g/dL and magnesium ≥ 2.0 mg/dL). Limitations Causality cannot be determined, and residual confounding cannot be excluded given the observationa

A significant number of dietary restrictions are imposed traditionally and uniformly on maintenance dialysis patients, whereas there is very little data to support their benefits. Recent studies indicate that dietary restrictions of phosphorus may lead to worse survival and poorer nutritional status. Restricting dietary potassium may deprive dialysis patients of heart-healthy diets and lead to intake of more atherogenic diets. There is little data about the survival benefits of dietary sodium restriction, and limiting fluid intake may inherently lead to lower protein and calorie consumption, when in fact dialysis patients often need higher protein intake to prevent and correct protein-energy wasting. Restricting dietary carbohydrates in diabetic dialysis patients may not be beneficial in those with burnt-out diabetes. Dietary fat including omega-3 fatty acids may be important caloric sources and should not be restricted. Data to justify other dietary restrictions related to calcium, vitamins, and trace elements are scarce and often contradictory. The restriction of eating during hemodialysis treatment is likely another incorrect practice that may worsen hemodialysis induced hypoglycemia and nutritional derangements. We suggest careful relaxation of most dietary restrictions and adoption of a more balanced and individualized approach, thereby easing some of these overzealous restrictions that have not been proven to offer major advantages to patients and their outcomes and which may in fact worsen patients' quality of life and satisfaction. This manuscript critically reviews the current paradigms and practices of recommended dietary regimens in dialysis patients including those related to dietary protein, carbohydrate, fat, phosphorus, potassium, sodium, and calcium, and discusses the feasibility and implications of adherence to ardent dietary restrictions and future research.