CKD Populations Research Articles

Copeptin associates with major adverse cardiovascular events in patients on maintenance hemodialysis

BackgroundEnd-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. ObjectiveThis study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. MethodsESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. ResultsAmong 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. ConclusionElevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.

Adverse outcomes with left atrial appendage occlusion device implantation in chronic and end stage kidney disease: A systemic review and meta-analysis

BackgroundChronic kidney disease (CKD) and end stage renal disease (ESRD) are associated with increased risk of bleeding events, including hemorrhagic stroke, and periprocedural and gastrointestinal bleeding among patients with atrial fibrillation who are on anticoagulation. Safety of percutaneous left atrial appendage occlusion (LAAO) among this patient population has been uncertain with studies showing contradictory results. MethodsPubMed and Google Scholar databases were queried for studies comparing outcomes among patients with and without significant CKD, and with and without ESRD who underwent LAAO device implantation. Data on outcomes from the selected studies were extracted and analyzed using random effects model. Heterogeneity was assessed using I2 test. ResultsData from eleven studies with 61,724 patients with and without kidney disease were included in the final analyses. There was an increased risk of in-hospital mortality (OR 2.76, 95 % CI [1.15–6.64]; p = 0.02) and peri-procedural bleeding (1.51 [1.33–1.71]; p < 0.01) associated with kidney disease. There was no significant difference in risk of stroke (1.19 [0.70–2.03]; p = 0.53), pericardial effusion (1.22 [0.77–1.92]; p = 0.40), vascular complications (1.18 [0.92–1.52]; p = 0.20), or device related thrombus (1.13 [0.53–2.40]; p = 0.75). ConclusionsThis study shows an increased risk of complications among patients with kidney disease, who undergo LAAO device implantation. These findings suggest the need for studies with randomized control design specifically designed to compare outcomes with LAAO versus anticoagulation in the CKD and ESRD populations.

#2249 Morning blood pressure and heart rate surge in peritoneal dialysis patients

Abstract Background and Aims The increased surge of blood pressure (BP) early in the morning and the parallel increase of heart rate (HR) are risk factors for cardiovascular disease in general and CKD populations. Early morning changes in these parameters have not been investigated in peritoneal dialysis (PD) patients. The aim of the study is to correlate the morning fluctuations of BP and HR with left ventricular hypertrophy and cardiovascular risk. Method This was a cross-sectional study of PD patients followed-up in our Peritoneal Dialysis Unit (PDU). At their regular visit to our PDU, a 24-hour ambulatory BP measurement (Mobil-o-graph®) was performed. A diary was given to the patients in order to record the time they performed their evening exchange (continuous ambulatory peritoneal dialysis- CAPD) or connection to the automated peritoneal dialysis (APD) machine, the time they laid down, the time they approximately fell asleep, when they woke up in the morning, when they inclined from the bed and the time they performed the morning exchange or disconnection. The 24-hour BP recordings were analyzed in the available software and calculations were done based on the diary information; pre-awakening BP, HR surges, nocturnal dipping, weighted 24 h systolic BP and HR variability. Demographic, laboratory data and left heart hypertrophy parameters of the patients were also recorded. 35 patients were eligible for participation in the study; 2 denied participation, 1 was rejected due to ongoing cancer therapy and two patients were declined due to invalid BP measurements. Finally 30 patients (10 males and 20 females) were analyzed, 9 were on CAPD and 21 were on APD. Results The mean age of the patients was 60.5 ± 12.6 years old and the median PD vintage was 21.5 months (8.25-58) (Table 1). Left Ventricular Mass index (LVMi) was 99.01 ± 28 g/m2 (Table 1). The 24h systolic BP was 125.66 ± 10.9 mmHg and the diastolic BP was 79.59 ± 7.7 mmHg (Table 2). The mean pre-awaking Systolic BP surge was 10.76 ± 9.7 mmHg, the median non-dipping blood pressure 8.6 (IQR 1.11-12.86), the mean heart rate surge was 3.3 ± 4.7 /min and the mean non-dipping HR was 9.7 ± 5.9/min (Table 2). There was no statistically significant correlation of the parameters above with the LVMi. Patients with high cardiovascular risk (diabetes, coronary heart disease, heart failure) had statistically higher non-dipping BP (27 vs 12.3 mmHg, p = 0.034) and higher nighttime SPB (27 vs 20.74 mmHg, p = 0.024). When compared patients in CAPD vs APD, there were no differences in the pre-awaking BP or the rest of the measurements performed, although APD patients recorded interrupted sleep due to the alarms of the APD machine. Conclusion PD patients with high cardiovascular risk had higher nondipping BP and nighttime systolic BP compared with patients without cardiovascular disease. There were no correlations of BP and heart rate morning surge with left ventricular hypertrophy or PD mode.

Association of dietary total antioxidant capacity with all-cause and cardiovascular mortality in patients with chronic kidney disease: based on two retrospective cohort studies of NHANES

Background The relationship between dietary total antioxidant capacity (DTAC) and death risk among CKD populations remains unclear. Methods Based on vitamin C equivalent antioxidant capacity (VCEAC) and the component dietary antioxidant index (CDAI) indices, we analyzed two cohorts to investigate the association of DTAC with all-cause and CVD mortality in CKD patients using data from National Health and Nutrition Examination Survey (2007–2018). VCEAC (n = 6330) and CDAI (n = 6300) cohorts with mortality follow-up data available through 2018 were included. Cox models with restricted cubic splines was used to model the nonlinear association between VCEAC/CDAI and outcomes in CKD patients. Results Our results showed L-shaped associations of DTAC with all-cause mortality among individuals with CKD stages 1–2 in both cohorts. Compared to the lowest quartile, higher dietary total antioxidant intake was associated with lower all-cause mortality risks among CKD stages 1–2 after adjustment for covariates, with HRs (95%CI) of 1.00, 0.91 (0.71,1.17), 0.69 (0.53,0.90), and 0.70 (0.54,0.91) in VCEAC, and similar respective estimate trends in CDAI. After sensitivity and subgroup analyses, there were no benefits for patients with stage 3–5 CKD or albuminuria. Mediation analysis revealed that the proportions mediated in both cohorts were less consistent. Conclusions Moderate dietary total antioxidants intake has potential benefits for early-stage CKD patients. However, further evidence is needed to confirm whether patients with worsening CKD can benefit in the long term.

Evaluation of Variation in the Performance of GFR Slope as a Surrogate End Point for Kidney Failure in Clinical Trials that Differ by Severity of CKD.

The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope. We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1.73 m2/yr) and those of the clinical end point (doubling of serum creatinine, GFR <15 ml/min per 1.73 m2, or kidney failure, expressed as a log-hazard ratio), where models allow interaction with variables defining disease severity. We evaluated three measures (baseline GFR in 10 ml/min per 1.73 m2, baseline urine albumin-to-creatinine ratio [UACR] per doubling in mg/g, and CKD progression rate defined as the control arm chronic slope, in ml/min per 1.73 m2/yr) and defined strong evidence for modification when 95% posterior credible intervals for interaction terms excluded zero. There was no evidence for modification by disease severity when evaluating 3-year total slope (95% credible intervals for the interaction slope: baseline GFR [-0.05 to 0.03]; baseline UACR [-0.02 to 0.04]; CKD progression rate [-0.07 to 0.02]). There was strong evidence for modification in evaluations of chronic slope (95% credible intervals: baseline GFR [0.02 to 0.11]; baseline UACR [-0.11 to -0.02]; CKD progression rate [0.01 to 0.15]). These analyses indicate consistency of the performance of total slope over 3 years, which provides further evidence for its validity as a surrogate end point in RCTs representing varied CKD populations.

Sleep-related breathing disorders and cardiometabolic risk factors in pediatric kidney transplant recipients.

SRBDs have been shown to increase the risk of cardiovascular disease, which is a significant cause of mortality in kidney transplant recipients. Few studies have investigated the association between SRBDs and cardiometabolic risk factors in pediatric kidney transplant recipients. This was a cross-sectional study of pediatric kidney transplant recipients using baseline cardiometabolic data from a previous clinical trial (NCT01007994). Parents/guardians of pediatric kidney transplant recipients filled out 22-item PSQ. A score greater than 33% was defined as a diagnosis of a SRBD. Fisher's exact test, Mann-Whitney U test, and regressions were used to determine associations. Among the 58 transplant recipients enrolled, 14.80% (n=8) of participants identified as Black and 40.7% (n=22) were male. The median age was 13 (IQR 8.25, 17) years and median number of years post-transplant for participants was 2 (IQR 1, 4). The prevalence of SRBDs was 26% (n=14). The presence of a SRBD was associated with abnormalities in multiple cardiometabolic risk factors including total cholesterol level (β=23.63; 95% CI 3.58-43.67), LDL level (β=24.94; 95% CI 6.37-43.50), triglyceride level (β=54.62; 95% CI 8.74-100.50), and LVH (OR=5.12; 95% CI 1.12-23.45) when adjusted for age, sex, and race. Similar to associations reported in the general pediatric and general CKD populations, SRBD is associated with increased cardiometabolic risk in pediatric kidney transplant recipients.

Early Menopause May Associate With a Higher Risk of CKD and All-Cause Mortality in Postmenopausal Women: An Analysis of NHANES, 1999-2014.

BackgroundChronic kidney disease (CKD) in women is often accompanied by hormone disorders such as sex hormones, and most women with CKD are in the post-menopausal age group. Due to the close relationship between menopause and sex hormones, we aimed to explore the association between early menopause and CKD in post-menopausal women, and the influence of early menopause on longevity in the CKD population.MethodsInformation regarding 4,945 post-menopausal women was extracted from the database of the National Health and Nutrition Examination Survey (NHANES) 1999–2014, and then divided into 4 groups according to the type of menopause (natural or surgical) and early menopause (menopause at age <45) or not. The association between early menopause and CKD prevalence was examined using multivariable logistic regression, while we used multivariable Cox proportional hazards models to investigate the possible relationship between early menopause and all-cause mortality in CKD and non-CKD populations. The differences in the levels of sex hormones between women with and without CKD were also explored.ResultsCompared with women with natural menopause at age ≥45, women experiencing early natural menopause had a higher risk of CKD [OR = 1.26 (1.01–1.56)]. Similarly, as compared to women with surgical menopause at age ≥ 45, women in the early surgical menopause group were more likely to have CKD [OR = 1.38 (1.05–1.81)]. In addition, early surgical menopause was associated with higher mortality in the non-CKD group [HR = 1.62 (1.06–2.49)], but not in the CKD group. Women with CKD had a higher level of luteinizing hormone and follicle-stimulating hormone, combined with a lower level of testosterone and estradiol than the non-CKD women.ConclusionBoth early natural and surgical menopause were associated with a higher risk of CKD. Early surgical menopause was a hazard factor for survival in the non-CKD group, but not in the CKD group. Further research is required to understand the mechanisms.

Risk Prediction Models for Atherosclerotic Cardiovascular Disease in Patients with Chronic Kidney Disease: The CRIC Study.

Individuals with CKD may be at high risk for atherosclerotic cardiovascular disease (ASCVD). However, there are no ASCVD risk prediction models developed in CKD populations to inform clinical care and prevention. We developed and validated 10-year ASCVD risk prediction models in patients with CKD that included participants without self-reported cardiovascular disease from the Chronic Renal Insufficiency Cohort (CRIC) study. ASCVD was defined as the first occurrence of adjudicated fatal and nonfatal stroke or myocardial infarction. Our models used clinically available variables and novel biomarkers. Model performance was evaluated based on discrimination, calibration, and net reclassification improvement. Of 2604 participants (mean age 55.8 years; 52.0% male) included in the analyses, 252 had incident ASCVD within 10 years of baseline. Compared with the American College of Cardiology/American Heart Association pooled cohort equations (area under the receiver operating characteristic curve [AUC]=0.730), a model with coefficients estimated within the CRIC sample had higher discrimination (P=0.03), achieving an AUC of 0.736 (95% confidence interval [CI], 0.649 to 0.826). The CRIC model developed using clinically available variables had an AUC of 0.760 (95% CI, 0.678 to 0.851). The CRIC biomarker-enriched model had an AUC of 0.771 (95% CI, 0.674 to 0.853), which was significantly higher than the clinical model (P=0.001). Both the clinical and biomarker-enriched models were well-calibrated and improved reclassification of nonevents compared with the pooled cohort equations (6.6%; 95% CI, 3.7% to 9.6% and 10.0%; 95% CI, 6.8% to 13.3%, respectively). The 10-year ASCVD risk prediction models developed in patients with CKD, including novel kidney and cardiac biomarkers, performed better than equations developed for the general population using only traditional risk factors.

Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD.

Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.

Stressors and Resilience: An Integrative Model for Understanding Chronic Kidney Disease

Stressors and Resilience: An Integrative Model for Understanding Chronic Kidney Disease

The LIFT trial: study protocol for a double-blind, randomised, placebo-controlled trial of K+-binder Lokelma for maximisation of RAAS inhibition in CKD patients with heart failure

BackgroundCKD is common in heart failure (HF) and associated with morbidity and mortality, yet life-prolonging medications such as renin-angiotensin-aldosterone inhibitors (RAASi) are underused due to risk of hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is a potassium-binding medication that has been shown to reduce incidence of hyperkalaemia in CKD, non-CKD, and HF populations, which we propose will support maximisation of RAASi therapy.MethodsWe propose a 1:1 randomised, double-blind, placebo-controlled trial in which participants will receive either SZC or placebo. We will up-titrate participants’ RAASi therapy while monitoring their serum potassium levels and adjusting their SZC dose if necessary. Participants with CKD and HF will be recruited from CKD and HF clinics at St George’s Hospital. The total study period will be 18 months; 130 participants will be enrolled for approximately two months each following screening. Our primary outcome will be the proportion of participants who achieve maximum RAASi dose while maintaining normokalaemia. Secondary outcomes include participants reaching maximum RAASi dose without severe hyperkalaemia; time from randomisation to hyperkalaemia; time from randomisation to severe hyperkalaemia; number of RAASi dose escalations per participant; final doses of RAASi therapy; changes in quality of life score, eGFR, ACR, serum sodium, troponin T; number and duration of hospital admissions; and within-participant change in serum potassium compared to baseline.DiscussionThis trial will be the first to examine the use of SZC for the maximisation of RAASi dosing in patients with advanced CKD and HF. We will assess the impact of achieving target RAASi dosing on hospital admission rates and duration of stay, with the hope that optimum RAASi treatment will translate into reduced morbidity and improved QoL. If clinical benefit is demonstrated, we hope that the joint multidisciplinary CKD-HF approach will be expanded.Trial registrationEudraCT number 2020–002946-18. Registered on 08 June 2020. Online record pending.

FC 007CKD DERIVED MUSCLE CELLS RETAIN PHENOTYPIC CHARACTERISTICS OF UREIC SARCOPENIA: THE NEXT STEP IN CELLULAR MODELLING FOR THERAPEUTIC SCREENING

Abstract Background and Aims Skeletal muscle wasting and dysfunction is a debilitating co-morbidity for people who suffer from kidney disease. To date research has sought to understand the mechanisms by which this occurs, in order to inform the prescription of required interventions in order to counteract such effects. Though progress has been made through in-vivo physiology research, the lack of an in-vitro translational model which replicates the phenotype noted in this patient group has hindered progression. The aim of the work presented was to systematically define a human derived skeletal muscle model with cells derived from people with kidney disease, in order to provide a test bed for the future screening of novel therapeutics and the investigation of the dynamic processes involved in the unwanted characteristics observed in this population. Method Skeletal muscle biopsies were taken from the vastus lateralis of non-dialysis dependent CKD patients (CKD; n=12) and Controls (CON; n=12), matched for age, sex, ethnicity and physical activity levels. Biopsy samples were subject to an enzymatic digestion method to enable the isolation of the muscle derived cells required for cellular experimentation. Once taken through the cell cycle, cells were plated into experimental wells and proliferated for 5 days or until confluent. Once confluent cells were differentiated through serum restriction to form mature myotubes (muscle fiber like structures) for a minimum of 7 days. Sampling time points were taken throughout to allow for the analysis of markers of proliferation, myogenic capacity, maturation, inflammation, protein synthesis and protein degradation. Further experiments were conducted on mature myotubes, where myotubes from both donor groups were exposed to either 0.4nM or 100nM of IGF-1 and p-Akt and protein synthesis quantified to investigate the presence of anabolic resistance in CKD derived cells. Results We report here that muscle cells derived from CKD patients have significantly higher levels of markers of proliferation (p = 0.041) and myogenic capacity (p = 0.034). Regarding myotube maturity, lower ratios of mature Myosin Heavy Chains were noted in CKD derived cells in comparison with CON derived cells (p = 0.012). On analysis of rates of protein synthesis and degradation in mature myotubes, no differences were noted in the rate of protein synthesis or the p-Akt in basal conditions (p &amp;gt; 0.05), however, significant elevations were noted in both protein degradation rates (p = 0.014) and the mRNA gene expression levels of E3-ligases (p = 0.016). On analysis of the experimentation investigating anabolic resistance, a degree of anabolic resistance was noted with inhibited p-Akt (p = 0.019) and protein synthesis (p ≤ 0.001) noted in cells derived from CKD cells in comparison to CON cells, when exposed to both doses of IGF-1. Conclusion Here we describe for the first time a human derived, disease specific model of uremic sarcopenia with many of the phenotypic traits noted in this population being maintained, such as elevated protein degradation and anabolic inhibition. This work not only provides a translational mechanistic insight into the cellular underpinnings of uremic sarcopenia but will allow for the future screening of novel therapeutics, in order manipulate the dynamic processes which lead to the debilitations noted in CKD populations.

POS-226 BIOELECTRICAL IMPEDANCE ANALYSIS AND RENAL FUNCTION IN NIGERIANS

Volume overload occurs early in CKD resulting in increased cardiovascular morbidity and mortality. Bioelectrical impedance analysis (BIA) is a quick, non-invasive and reproducible technique for the assessment of fluid overload. However, there is paucity of data for BIA in both healthy and CKD populations in Nigeria.We performed a cross-sectional study of BIA in 363 Nigerians (including 150 CKD patients and 213 controls) to assess the association between BIA-derived measurements and renal function.

Serum Uric Acid and Mortality in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Background: Existing studies suggested conflicting relationships between serum uric acid (SUA) and mortality in CKD patients. The present meta-analysis aimed to determine whether SUA can be a predictor for mortality in CKD cohorts. Method: A systematical search was conducted on PubMed, EMBASE, and The Cochrane Library to identify studies reporting the relationship between SUA level and all-cause and cardiovascular mortality in CKD populations. In addition, random-effects models were adopted to calculate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results: On the whole, 29 studies were involved. In the present meta-analysis, patients exhibiting the maximum SUA level showed an association with a significantly higher risk for all-cause mortality (HR, 1.30; 95% CI, 1.06–1.59) compared with patients exhibiting the minimum SUA level. As revealed from the meta-analysis of 8 studies, low level of SUA was another predictor for all-cause mortality in patients with CKD (HR, 1.36; 95% CI, 1.20–1.54). No significant relationship was identified between SUA and cardiovascular mortality. Conclusions: Higher and lower SUA levels are both associated with significantly increased risk of all-cause mortality in patients with CKD. A appreciate dose of treatment of lowering SUA agents should be confirmed.

P0820EMERGENCY DEPARTMENT UTILIZATION BY PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE AND DIALYSIS: A POPULATION BASED STUDY

Abstract Background and Aims Chronic Kidney Disease (CKD) is a potent risk factor for kidney failure, cardiovascular events and all cause hospitalizations. In addition to higher outpatient resource use, patients with CKD may present more frequently to the emergency department (ED) and may be more likely to be admitted for hospitalization. In Manitoba, we previously demonstrated an 8-fold increase in the frequency of ED presentations by patients on dialysis as compared to a non-dialysis population. Comparable data on ED visits remain sparse for patients with CKD G3-G5, not on dialysis. Here, we aim to describe the frequency of ED visits and highlight differences in reasons for visit in patients with CKD stages G3-G5 and Those on dialysis when compared to a non-renal population. Method We performed a retrospective cohort study using administrative health data from the Winnipeg Regional Health Authority, Canada. We included all adults (≥ 18 years) with CKD stages G3-G5 and patients undergoing dialysis between January 1st, 2010 and December 31, 2014. Secular trends in the in the rates of ED visits were calculated for those with CKD, those on dialysis and in the non-renal population. Results Over the study period, patients undergoing dialysis had the highest incidence of ED visits, followed by patients with CKD and those with normal kidney function (150 vs 106 vs 34 per 100 persons per year respectively). These rates were stable over the period studied. Among the non-renal population, the most common reasons for an ED visit were musculoskeletal complaints (25.6%), followed by gastrointestinal (11.04%) and cardiovascular complaints (10.26%). In the CKD and dialysis cohort, ED visits were more commonly secondary to cardiovascular complaints (21.54% and 18.99% respectively), followed by respiratory and gastrointestinal complaints. Admission to hospital was higher in CKD and dialysis populations than in the non-renal population (29.56%, 26.07% vs 10.61%, respectively). Conclusion Patients with CKD present frequently to the ED, and are often admitted after presentation. Cardiovascular and respiratory complaints are more common in the CKD population.

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease.

BackgroundChronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with non-cardiovascular death in CKD populations are lacking.MethodsThe main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n = 2185 CKD patients).ResultsAfter 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG + rs2283368 CC/CT + rs2320762 GG). Among the patients with the three SNPs genotyped (n = 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA + rs2283368 TT + rs2320762 GT/TT). All the other combinations [n = 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher {hazard ratio [HR] 3.28 [confidence interval (CI) 1.51–7.12]} and lower [HR 6 × 10−6 (95% CI 3.3 × 10−7–1.1 × 10−5)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination.ConclusionsDetermination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD.

Impact of prior stroke on major clinical outcome in chronic kidney disease: the Salford kidney cohort study

BackgroundChronic kidney disease (CKD) is an independent risk factor for stroke in the general population. The impact of prior stroke on major clinical outcomes in CKD populations is poorly characterised.MethodsThe Salford Kidney Study is a UK prospective cohort of more than 3000 patients recruited since 2002 and followed until March 2018. Multivariable Cox regression examined associations of stroke at two time points; cohort inception, and at dialysis initiation, with risks of death, non-fatal cardiovascular events (NFCVE) and end stage renal disease (ESRD).Results277 (9.1%) of 3060 patients suffered a prior stroke and this was associated with mortality, ESRD and future NFCVE after cardiovascular risk factor adjustments. Median survival for prior stroke patients was 40 months vs 77 months in patients without a stroke. Prior stroke was independently associated with mortality (HR 1.20 95%CI 1.0–1.43, p = 0.05). Of 579 patients who reached ESRD and commenced dialysis, a prior stroke (N = 48) was independently associated with mortality. Median survival for the prior stroke group was 29 months compared with 50 months for the non-stroke group. Only 70 and 75% of patients who had suffered an ischaemic stroke were prescribed antiplatelets or statins respectively.ConclusionsA diagnosis of stroke is strongly and independently associated with several adverse clinical outcomes for patients with CKD. Prior stroke profoundly alters cardiovascular risk in CKD patients. Greater attention to primary and secondary preventive strategies is warranted which may improve these outcomes.

Predictive value of quantitative ultrasound parameters in individuals with chronic kidney disease: A population-based analysis of CARTaGENE.

The use of calcaneal quantitative ultrasound (QUS) to predict fractures has not been well studied in early CKD populations. We compared the association of QUS with incidental fractures and its predictive properties in non-CKD and CKD individuals. Analysis of a prospective population-based survey of 40- to 69-year-old individuals recruited between 2009 and 2010. QUS parameters (stiffness index [SI], speed of sound [SOS], broadband attenuation [BUA]) were measured at baseline. Renal function was measured using baseline creatinine and was classified into CKD stages (non-CKD, stage 2, stage 3). Fracture incidence at any site or at major osteoporotic fracture sites for up to 7 years of follow-up was identified in administrative databases using a validated algorithm. The association (age-adjusted hazard ratio per standard deviation decrease in Cox models), discrimination (c-statistic) and calibration (standardized incidence ratio [SIR]) of QUS parameters with fracture outcomes was computed in each CKD stratum. We included 18,306 individuals (9,011 non-CKD; 8,595 CKD stage 2; 700 CKD stage 3). During a median follow-up of 70 months, we identified 782 fractures at any site and 326 major osteoporotic fractures. Although all QUS parameters (SI, SOS and BUA) were associated with any or major fracture incidence in non-CKD and CKD patients, the magnitude of these associations was lower for any fracture and for BUA. QUS parameters moderately discriminated incidental fractures across CKD strata but underestimated fracture incidence in CKD stage 3 even after adjustment for demographics and clinical risk factors. At a given QUS value, CKD stage 3 patients had higher fracture risk than non-CKD and CKD stage 2 patients. QUS parameters are associated with fracture incidence in both non-CKD and CKD but underestimate fracture incidence in individuals with early CKD.

Metabolites related to eGFR: Evaluation of candidate molecules for GFR estimation using untargeted metabolomics

BackgroundMetabolomics can be used to identify novel metabolites related to renal function and that could therefore be used for estimating GFR. We evaluated metabolites replicated and related to eGFR in 3 studies (CKD and general population). MethodsMetabolomics was performed by GC–MS. The Progredir Cohort (n = 454, class 3 and 4 CKD) was used as the derivation study and adjusted linear regression models on eGFR-CKDEPI were built. Bonferroni correction was applied for selecting metabolites to be independently validated in the Diabetic Nephropathy Study (n = 56, macroalbuminuric DN) and in the Baependi Heart Study (BHS, n = 1145, general population). ResultsIn the Progredir Cohort, 72 metabolites where associated with eGFR. Of those, 11 were also significantly associated to eGFR in the DN Study and 8 in the BHS. Four metabolites were replicated and significantly associated to eGFR in all 3 studies: d-threitol, myo-inositol, 4-deoxierythronic acid and galacturonic acid. In addition, pseudouridine was strongly correlated to eGFR only in the 2 CKD populations. ConclusionsOur results demonstrate metabolites that are potential biomarkers of renal function: d-threitol, myo-inositol, 4-deoxierythronic acid, galacturonic acid and pseudouridine. Further investigation is needed to determine their performance against otherwise gold-standard methods, most notably among those with normal eGFR.

Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification.

Phosphate is essential for life but its accumulation can be detrimental. In end-stage renal disease, widespread vascular calcification occurs as a result of chronic phosphate load. The accumulation of phosphate is likely to occur long before the rise in serum phosphate above the normal range since several observational studies in both general population and early-stage CKD patients have identified the relationship between high-normal serum phosphate and adverse cardiovascular outcomes. Consumption of food high in phosphate increases both fasting and postprandial serum phosphate and habitual intake of high phosphate diet is associated with aging, cardiac hypertrophy, endothelial dysfunction, and subclinical atherosclerosis. The decline in renal function and dietary phosphate load can increase circulating fibroblast growth factor-23 (FGF-23) which may have a direct impact on cardiomyocytes. Increased FGF-23 levels in both CKD and general populations are associated with left ventricular hypertrophy, congestive heart failure, atrial fibrillation, and mortality. Increased extracellular phosphate directly affects endothelial cells causing cell apoptosis and vascular smooth muscle cells (VSMCs) causing transformation to osteogenic phenotype. Excess of calcium and phosphate in the circulation can promote the formation of protein-mineral complex called calciprotein particles (CPPs). In CKD, these CPPs contain less calcification inhibitors, induce inflammation, and promote VSMC calcification.