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BACKGROUND: Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.METHODS: In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics.FINDINGS: We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m(2), adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m(2) and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m(2). Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR INTERPRETATION: Even mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease.FUNDING: American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

BackgroundThere is accumulating evidence that serum levels of non-high-density lipoprotein cholesterol (non-HDL-C) are a more accurate predictor of cardiovascular outcomes when compared with low-density lipoprotein cholesterol. However, we recently found that higher serum concentrations of triglycerides are associated with better outcomes in patients undergoing hemodialysis. Therefore, we hypothesized that the association of serum levels of non-HDL-C (which includes triglyceride-rich lipoproteins) with outcomes may also be different in patients undergoing hemodialysis when compared with other patient populations.Methods and resultsWe studied the association of baseline and time-dependent serum levels of non-HDL-C with all-cause and cardiovascular mortality using Cox proportional hazard regression models in a nationally representative cohort of 50118 patients undergoing incident hemodialysis from January 1, 2007, to December 31, 2011. In time-dependent models adjusted for case mix and surrogates of malnutrition and inflammation, a graded inverse association between non-HDL-C level and mortality was demonstrated with hazard ratios (95% confidence intervals) of the lowest (

Background Few studies evaluated associations of key measures of chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR) and albuminuria, with incident lower-extremity peripheral artery disease (PAD). Thus, we aimed to quantify the independent and joint associations of these two CKD measures with incident PAD. Methods In 21 cohorts (801,731 participants) free of PAD at baseline, we quantified associations of creatinine-based eGFR, urine albumin-to-creatinine ratio [ACR], and dipstick proteinuria with incident PAD (including PAD hospitalization, intermittent claudication, leg revascularization, and leg amputation). Discrimination improvement was assessed through c-statistics. Findings There were 17,852 PAD cases across cohorts (a median follow-up ranging from 2.0-15.8 years across cohorts). Both CKD measures were independently associated with incident PAD. Adjusted hazard ratios (HRs) at eGFR 45 and 15 (versus 95) ml/min/1.73m2 were 1.22 (95%CI, 1.14-1.30) and 2.06 (1.70-2.48), respectively. Adjusted HRs at ACR 30 and 300 (versus 5) mg/g were 1.50 (1.41-1.59) and 2.28 (2.12-2.44), respectively. ACR-amputation association was particularly strong (HR at ACR 300 mg/g 3.68 [3.00-4.52]). eGFR and ACR contributed multiplicatively (e.g., adjusted HR 5.76 [4.90-6.77] mg/g for incident PAD and 10.61 [5.70-19.77] for amputation in eGFR Interpretation Even mild to moderate CKD conferred increased risk of incident PAD, with remarkable albuminuria-amputation relationship. Clinical attention should be paid to the development of PAD symptoms and signs in persons with any stages of CKD.

Rationale & Objective Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m 2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD. © 2018. This is the authors’ accepted and refereed manuscript to the article. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ "