eGFR Categories Research Articles

Baseline liver function tests and full blood count indices and their association with progression of chronic kidney disease and renal outcomes in Aboriginal and Torres Strait Islander people: the eGFR follow- up study

BackgroundDetermination of risks for chronic kidney disease (CKD) progression could improve strategies to reduce progression to ESKD. The eGFR Study recruited a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, aiming to address the heavy CKD burden experienced within these communities.MethodsUsing data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR < 60 mL/min/1.73 m2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs.ResultsOf 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8–3.6) years. Annual decline in eGFR was associated with low serum albumin (p < 0.001) and haemoglobin (p = 0.007). After adjustment for age, gender, urine albumin/creatinine ratio, diabetes, BMI, CRP, WHR, alcohol consumption, cholesterol and triglycerides, low serum albumin (p < 0.001), haemoglobin (p = 0.012) and bilirubin (p = 0.011) were associated with annual decline in eGFR.Renal outcomes were inversely associated with serum albumin (p < 0.001), bilirubin (p = 0.012) and haemoglobin (p < 0.001) and directly with GGT (p = 0.007) and ALP (p < 0.001). Other FBC indices and LFTs were not associated with annual decline in eGFR or renal outcomes.ConclusionsGGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.

Comparison of the Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration Equations for Detection of Cardiovascular Risk: Tehran Lipid and Glucose Study.

ObjectivesThe study aimed to compare the Modification of Diet in Renal Disease Study (MDRD) and the Epidemiology Collaboration (CKD-EPI) equations for the detection of cardiovascular risk.MethodsData of 9,970 Tehranian participants aged ≥ 20 years were analyzed. The prevalence of cardiovascular disease (CVD), its risk factors, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were compared across the categories of glomerular filtration rate based on the MDRD and CKD-EPI equations. Chronic kidney disease (CKD) was defined as the estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73 m2 according to each equation.ResultsThe prevalence of CKD weighted to the 2016 Tehranian urban population was 11.0% (95% confidence interval: 10.3 - 11.6) and 9.7% (9.1 - 10.2) according to the MDRD and CKD-EPI equations, respectively. Besides, 8.3% and 1.5% of the participants with CKDMDRD and non-CKDMDRD were reclassified to non-CKDCKD-EPI and CKDCKD-EPI categories, respectively. Participants with CKDCKD-EPI but without CKDMDRD were more likely to be male and older, and more frequently had diabetes, hypertension, dyslipidemia, and CVD, when compared to those without CKD according to both equations; they were also more likely to be male, older, and smokers, and had less dyslipidemia and more CVD, when compared to those with CKD by using both equations. In multivariate logistic regression analysis, compared to CKDMDRD, the odds of CKDCKD-EPI were significantly higher for older age and lower for the female gender.ConclusionsCompared to MDRD, the CKD-EPI equation provides more appropriate detection of cardiovascular risk, which is caused by the reclassification of older individuals and fewer females into lower eGFR categories.

Abstract 13474: Rivaroxaban Reduces Major Cardiovascular and Limb Events in Patients With the High-risk Triad of Chronic Kidney Disease, Peripheral Artery Disease and Recent Lower Extremity Revascularization: Insights From VOYAGER PAD

Introduction: Chronic kidney disease (CKD) is common among patients undergoing lower extremity revascularization (LER) for peripheral artery disease (PAD) and identifies a population at high risk for adverse outcomes. The VOYAGER PAD trial demonstrated the efficacy of rivaroxaban in PAD patients after LER on a composite of cardiovascular (CV) and limb ischemic events (HR 0.85 vs placebo, 95% CI 0.76-0.96; p=0.009); this analysis examines the prespecified subgroup of patients with CKD. Methods: VOYAGER PAD (NCT02504216) was a double-blind, placebo-controlled trial which randomized PAD patients with recent LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. The primary endpoint was a composite of acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke or CV death. The primary safety endpoint was TIMI major bleeding. Analysis of the intention-to-treat population utilized Kaplan Meier estimates and Cox proportional-hazards models. Results: Among 6319 VOYAGER patients with baseline estimated glomerular filtration rate (eGFR), 21% were &lt;60 (mostly CKD stage 3) and 79% were ≥60 ml/min/1.73m 2 . During 28-month (median) follow up, patients with CKD had a higher rate of major CV and limb events: placebo group 10.0 events/100 patient-years (95% CI 8.5, 11.8) for eGFR &lt;60 vs 7.4 (95% CI 6.7, 8.2) for eGFR ≥60. Rivaroxaban reduced primary outcome events with no heterogeneity by eGFR category (Figure, p for interaction 0.62). Acute limb ischemia and major amputation were significantly reduced among patients with eGFR&lt;60 (HR 0.55, 95% CI 0.36, 0.86) as well as ≥60 (HR 0.77, 95% CI 0.63, 0.94). TIMI major bleeding was numerically more frequent among patients with CKD with no heterogeneity by treatment group (Figure, p for interaction 0.37). Conclusions: Rivaroxaban reduced major CV and limb events in patients with PAD undergoing LER, including those with CKD, a particularly high-risk population.

Outcomes of a Clinician-Directed Protocol for Discontinuation of Complement Inhibition Therapy in Atypical Hemolytic Uremic Syndrome

Introduction : Terminal complement inhibition with a C5 inhibitor (eculizumab or ravulizumab) is the standard of care for treatment of atypical hemolytic uremic syndrome (aHUS) and leads to rapid resolution of thrombotic microangiopathy and improvement in renal function. The ideal duration of complement inhibition in aHUS is not established. Indefinite therapy is standard, though recent studies suggest that many patients with aHUS may safely discontinue therapy. Here, we present the outcomes of a physician-directed eculizumab discontinuation and monitoring protocol in a prospective cohort of 32 patients with aHUS. Methods: Consecutive patients with aHUS enrolled in the Hopkins Complement Associated Disease Registry between January 2014 and December 2019 who initiated eculizumab therapy during an acute episode of aHUS were included in the study. Patients starting eculizumab in the setting of renal transplant were excluded from the analysis. Physician directed discontinuation and monitoring was done according to the protocol outlined in Figure 1. We also evaluated relapse rate and renal outcomes and examined clinical and genetic risk factors for relapse. Results: Thirty-two consecutive patients who initiated eculizumab therapy for acute aHUS. Median age at initial diagnosis of aHUS was 44 (IQR 25, 53.5) years, 78.1% were female, and complement gene variants were present in 59.0% (13 of 22 patients with sequencing data available). Of these 32 patients, 25 (78%) discontinued eculizumab therapy after a median duration on therapy of 2.37 (IQR 1.06, 9.70) months. Six (18%) patients continued receiving it and 1 patient died during the first episode of aHUS. Of the 25 patients that discontinued eculizumab, 18 (72%) discontinued under physician direction (17 per protocol due to TMA remission including two with no renal recovery and end stage renal disease, and 1 due to non-response and a metabolic TMA thought more likely). Seven (28%) patients interrupted or discontinued therapy due to non-adherence. Overall relapse rate after eculizumab discontinuation was 20.0% (5 of 25); however, the relapse rate was higher in the case of non-adherence versus a physician directed cessation protocol (42.8% versus 11.1%, P=0.074) (Figure 2). Of the five patients who relapsed, four were re-treated and achieved remission without a decline in renal function with eculizumab; one patient died due to recurrent TMA and hypertensive emergency in the setting of non-adherence. On univariate analysis, non-adherence with therapy [OR 8.25 (95% CI 1.02 - 66.19) P=0.047] was associated with relapse while underlying complement gene variant [OR 1.39 (95% CI 0.39-4.87), P=0.598] and presence/absence of a trigger for aHUS [OR 0.66 (95% CI 0.09-4.79), P=0.687] were not significantly associated with relapse. We examined relapse rates in patients with CFH or MCP variants (40%, 2 of 5), other variants (33.3%, 2 of 6), no variants (0%, 0 of 6), and sequencing not completed (11.1%, 1 of 9) (P=0.217). These analyses are limited by the small sample size and limited number of events (5 relapses), which precluded multivariable regression analysis. Among patients that discontinued eculizumab, there was no significant decline in mean estimated glomerular filtration rate (eGFR) from the date of stopping eculizumab (47.09 + 28.28 ml/min/1.73 m2) until the most recent follow-up (56.95 + 28.02 ml/min/1.73 m2, one sided t-test P = 0.987). As seen in figure 3, improvement in eGFR (changed to a less severe eGFR category between stopping eculizumab and end of follow up) was seen in 9 of 25 patients (36%) and stable eGFR (no change in eGFR category) was seen in 15 of 25 patients (60%). Conclusion: Eculizumab discontinuation with close monitoring is safe in the majority of patients with aHUS (with native kidneys), with low rates of TMA recurrence and nearly complete salvage with eculizumab retreatment in the event of a recurrence. CFH and MCP variants may be associated with higher risk of relapse, which needs to be evaluated in larger, multicenter studies. Disclosures Moliterno: Pharmessentia: Consultancy; MPNRF: Research Funding. Chaturvedi:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Proenkephalin Predicts Organ Failure, Renal Replacement Therapy, and Mortality in Patients With Sepsis.

BackgroundKidney failure occurs frequently and is associated with high mortality during sepsis. Proenkephalin (PENK) is an emerging biomarker of kidney function. We explored whether PENK levels could predict severity, organ failure, and mortality in septic patients.MethodsWe measured the PENK level in the plasma of 215 septic patients using the sphingotest penKid assay (Sphingotec GmbH, Hennigsdorf, Germany). This was analyzed in terms of sepsis severity, vasopressor use, 30-day mortality, sequential organ failure assessment (SOFA) renal subscore, the Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (CKD-EPI eGFR) categories, and renal replacement therapy (RRT) requirement.ResultsThe PENK levels were significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (P=0.02, P=0.007, P<0.001, respectively). The PENK levels were significantly associated with SOFA renal subscore and CKD-EPI eGFR categories (both P<0.001). The distribution of lower eGFR (<60 mL/min/1.73 m2), RRT requirement, SOFA renal subscore, and the number of organ failures differed significantly according to the PENK quartile (P for trend<0.001 or 0.017). The 30-day mortality rate also differed significantly according to the PENK quartile (P for trend<0.001).ConclusionsPENK could be an objective and reliable marker to predict severity, organ failure, and 30-day mortality in septic patients.

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF.

Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure). We also examined the effect of dapagliflozin on kidney function after randomization. Patients who have HFrEF with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL·min-1·1.73 m-2 were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) according to eGFR category at baseline (<60 and ≥60 mL·min-1·1.73 m-2) and used eGFR at baseline as a continuous measure, as well. Secondary cardiovascular outcomes and a prespecified composite renal outcome (≥50% sustained decline eGFR, end-stage renal disease, or renal death) were also examined, along with a decline in eGFR over time. Of 4742 patients with a baseline eGFR, 1926 (41%) had eGFR <60 mL·min-1·1.73 m-2. The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% CI) for the primary end point in patients with chronic kidney disease was 0.71 (0.59-0.86) versus 0.77 (0.64-0.93) in those with an eGFR ≥60 mL·min-1·1.73 m-2 (interaction P=0.54). The composite renal outcome was not reduced by dapagliflozin (hazard ratio=0.71 [95% CI, 0.44-1.16]; P=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.40 to -0.77) versus placebo -2.85 (-3.17 to -2.53) mL·min-1·1.73 m-2 per year (P<0.001). This was observed in those with and without type 2 diabetes (P for interaction=0.92). Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF, and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Estimated GFR and Incidence of Major Surgery: A Population-Based Cohort Study

Kidney disease is associated with an increased risk for postoperative morbidity and mortality. However, the incidence of major surgery on a population level is unknown. We aimed to determine the incidence of major surgery by level of kidney function. Retrospective cohort study with entry from January 1, 2008, through December 31, 2009, and outcome surveillance from January 1, 2010, through December 31,2016. Population-based study using administrative health data from Alberta, Canada; adults with an outpatient serum creatinine measurement or receiving maintenance dialysis formed the study cohort. Participants were categorized into 6 estimated glomerular filtration rate (eGFR) categories:≥60 (G1-G2), 45 to 59 (G3a), 30 to 44 (G3b), 15 to 29 (G4), and<15mL/min/1.73m2 with (G5D) and without (G5) dialysis. eGFR was examined as a time-varying exposure based on means of measurements within 3-month ascertainment periods throughout the study period. Major surgery defined as surgery requiring admission to the hospital for at least 24 hours. Incidence rates (IRs) for overall major surgery were estimated using quasi-Poisson regression and adjusted for age, sex, income, location of residence, albuminuria, and Charlson comorbid conditions. Age- and sex-stratified IRs of 13 surgery subtypes were also estimated. 1,455,512 cohort participants were followed up for a median of 7.0 (IQR, 5.3) years, during which time 241,989 (16.6%) underwent a major surgery. Age and sex modified the relationship between eGFR and incidence of surgery. Men younger than 65 years receiving maintenance dialysis experienced the highest rates of major surgery, with an adjusted IR of 243.8 (95% CI, 179.8-330.6) per 1,000 person-years. There was aconsistent trend of increasing surgery rates at lower eGFRs for most subtypes of surgery. Outpatient preoperative serum creatinine measurement was necessary for inclusion and outpatient surgical procedures were not included. People with reduced eGFR have a significantly higher incidence of major surgery compared with those with normal eGFR, and age and sex modify this increased risk. This study informs our understanding of how surgical burden changes with differing levels of kidney function.

Sympathetic nerve traffic overactivity in chronic kidney disease: a systematic review and meta-analysis.

Studies based on microneurographic sympathetic nerve activity (MSNA) recordings have shown that the sympathetic system is overactivated in chronic kidney disease (CKD) patients but the relationship between MSNA and renal function and other risk factors has not been systematically reviewed in this population. This meta-analysis compares MSNA in cardiovascular complications-free CKD patients (n = 638) and healthy individuals (n = 372) and assesses the relationship of MSNA with the eGFR, age, BMI and hemodynamic variables. In a global analysis, MSNA was higher in CKD patients than in healthy control individuals (P < 0.001). The difference in MSNA between patients and healthy individuals was more marked in end-stage kidney diseases patients than in stage 3A 3B CKD patients (P < 0.001). In an analysis combining patients and healthy individuals, MSNA rose gradually across progressively lower eGFR categories (P < 0.01). In separate meta-regression analyses in CKD patients and in healthy individuals, MSNA associated directly with age (CKD: r = 0.57, P = 0.022; healthy individuals: r = 0.71, P = 0.031) and with the BMI (r = 0.75, P = 0.001 and r = 0.93, P = 0.003). In both groups, MSNA correlated with heart rate (r = 0.77, P = 0.02 and r = 0.66, P = 0.01) but was unrelated to plasma norepinephrine. Independently of comorbidities, MSNA is markedly increased in CKD patients as compared with healthy individuals and it is related to renal function, age, the BMI and heart rate. Sympathetic activation intensifies as CKD progresses toward kidney failure and such an intensification is paralleled by a progressive rise in heart rate but it is not reflected by plasma norepinephrine.

ASIAN PACIFIC SOCIETY OF NEPHROLOGY CLINICAL PRACTICE GUIDELINE ON DIABETIC KIDNEY DISEASE.

ASIAN PACIFIC SOCIETY OF NEPHROLOGY CLINICAL PRACTICE GUIDELINE ON DIABETIC KIDNEY DISEASE.

Associations Between Prelude eGFR Category and Trajectories of Uric Acid and eGFR Prior to Dialysis Transition Among US Veterans

Associations Between Prelude eGFR Category and Trajectories of Uric Acid and eGFR Prior to Dialysis Transition Among US Veterans

Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study

Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown. Population-based retrospective cohort study. Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB. New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication. 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality. New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored. Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively. Observational design, BP measurement data unavailable. AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.

2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC.

Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read mginstead of mg (use with caution in 'supranormal' renal function).In the above-indicated cell, a footnote has also been added to state: Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk.Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazoleinstead of Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone.

Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial.

AimsStatins reduce cardiovascular risk in patients with acute coronary syndrome (ACS) and normal-to-moderately impaired renal function. It is not known whether proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide similar benefit across a range of renal function. We determined whether effects of the PCSK9 inhibitor alirocumab to reduce cardiovascular events and death after ACS are influenced by renal function.Methods and resultsODYSSEY OUTCOMES compared alirocumab with placebo in patients with recent ACS and dyslipidaemia despite intensive statin treatment. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 was exclusionary. In 18 918 patients, baseline eGFR was 82.8 ± 17.6 mL/min/1.73 m2, and low-density lipoprotein cholesterol (LDL-C) was 92 ± 31 mg/dL. At 36 months, alirocumab decreased LDL-C by 48.5% vs. placebo but did not affect eGFR (P = 0.65). Overall, alirocumab reduced risk of the primary outcome (coronary heart disease death, non-fatal myocardial infarction, ischaemic stroke, or unstable angina requiring hospitalization) with fewer deaths. There was no interaction between continuous eGFR and treatment on the primary outcome or death (P = 0.14 and 0.59, respectively). Alirocumab reduced primary outcomes in patients with eGFR ≥90 mL/min/1.73 m2 (n = 7470; hazard ratio 0.784, 95% confidence interval 0.670–0.919; P = 0.003) and 60 to <90 (n = 9326; 0.833, 0.731–0.949; P = 0.006), but not in those with eGFR < 60 (n = 2122; 0.974, 0.805–1.178; P = 0.784). Adverse events other than local injection-site reactions were similar in both groups across all categories of eGFR.ConclusionsIn patients with recent ACS, alirocumab was associated with fewer cardiovascular events and deaths across the range of renal function studied, with larger relative risk reductions in those with eGFR > 60 mL/min/1.73 m2.

Renal profile of chronic hepatitis C patients with sofosbuvir-based therapy.

The impact of SOF-based therapy on renal functions is quite controversial in clinical practice. Therefore, we aimed to evaluate the serial changes of renal indices during SOF-based therapy in CHC patients with normal kidney function or mild renal impairment. We retrospectively reviewed all CHC patients who received different SOF-based regimens from January 2015 until December 2017, and presented with a baseline eGFR ≥ 30ml/min/1.73m2. Patients who didn't achieve SVR, with missing creatinine or eGFR data, and patients with eGFR less than 30ml/min/1.73m2 at baseline were excluded. eGFR was calculated for each time of evaluation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. A total of 1004 patients were finally included. The mean serum creatinine and eGFR levels varied between 0.84mg/dl and 106.53ml/min/1.73m2 for baseline and 0.87mg/dl and 104.24ml/min/1.73m2 for SVR12, respectively. The maximum increase of creatinine was 3.69mg/dl and the maximum decrease of eGFR level was 83.30ml/min/1.73m2 during treatment. Moreover, 74.4% of treated patients stayed in the same eGFR category, 14.3% progressed to a higher eGFR category, and 11.3% had an improvement eGFR category at EOT and continued to SVR12. Age > 65years, baseline eGFR, and ribavirin-containing regimens were independent risk factors of eGFR decline during and after SOF-based treatment. SOF-based therapies seem to be safe in CHC patients with baseline normal or slightly impaired renal function.

Vascular peroxidase 1 is independently associated with worse kidney function in patients with peripheral artery disease

BackgroundOxidative stress is involved in cardiovascular disease such as peripheral artery disease (PAD). Vascular Peroxidase 1 (VPO1), a novel heme-containing peroxidase mainly expressed in the cardiovascular system, aggravates oxidative stress. Evidence in humans is limited. Current work aims to measure VPO1 in patients suffering from PAD, and to evaluate the association of VPO1 with conventional markers of cardiovascular risk factors (CVRF), including the estimated glomerular filtration rate (eGFR) and albuminuria categories.MethodsThis study is part of a longitudinal observational study. At baseline, 236 PAD-patients were included. VPO1 plasma levels (ng/mL) were measured by commercially available ELISA kits. A two-sided p level of < 0.05 was considered statistically significant.ResultsIn the cross-sectional analysis (n = 236), VPO1 associated with ageing (p = 0.035) as well as with eGFR and albuminuria category, the markers of chronic kidney disease (CKD)-progression (p = 0.042). The longitudinal 18-months follow-up analysis (n = 152) demonstrated that baseline VPO1 predicts rapid kidney function decline (RKFD) (n = 49), defined as more than − 3 mL/min/1.73m2 eGFR loss per year, (OR per one SD VPO1 1.60 (1.11–2.30); p = 0.009). This association between VPO1 and kidney function withstood the multivariable adjustment for traditional CVRF including baseline eGFR and urine albumin-to-creatinine ratio (UACR), (adjOR per one SD VPO1 1.73 (1.14–2.61); p = 0.046).ConclusionThis study is first to reveal that VPO1 is independently associated with declining kidney function in patients with PAD. VPO1 shows a tighter association to kidney function than to other CVRF. This finding points to VPO1 as a potential target protein to assess CKD-progression.

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Predicts Chronic Renal Disease in Patients without Diabetes Mellitus (STELLA Study).

Background: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been included in the potential indices for atherosclerosis in chronic kidney disease (CKD). In this study, we addressed the role of the TG/HDL-C ratio on CKD prediction defined by both classified estimated glomerular filtration rate (eGFR) and classified urinary albumin-to-creatinine ratio (UACR) in non-diabetic participants. Methods: One hundred and eighty-three subjects with a mean age 67.3 ± 15.6 years old were included. Our participants were classified in both eGFR and UACR categories according to the Kidney Disease Improving Global Outcomes 2012 criteria. Estimated pulse wave velocity (ePWV) was calculated using an equation from age and mean blood pressure. The TG/HDL-C ratio was calculated. X2 tests and adjusted models were applied using confounders. Results: The TG/HDL-C ratio was inversely associated with eGFR and positively with both UACR and ePWV. We divided our patients in two groups according to the found ROC curve of the TG/HDL-C ratio cut-off point, either with an eGFR of less or more than 60 mL/min/1.73 m2. X2 tests showed significant association between the high TG/HDL-C ratio and classified eGFR, and classified UACR and hypertension (x2 = 24.5, p = 0.001, x2 = 12.5, p = 0.002 and x2 = 12.6, p = 0.001, respectively). The adjusted model showed the high TG/HDL-C ratio to be an independent predictor for both a low eGFR and UACR (OR = 1.5, 1.2–1.9 and OR = 1.22, 1.02–1.47, respectively) in combination with old age and hypertension. Conclusion: The TG/HDL-C ratio was revealed to be a potential predictor for both a low eGFR and micro/macroalbuminuria in non-diabetic patients. The arterial stiffening was included in the main underlying pathophysiological mechanisms.

Chronic Kidney Disease and Its Impact on a Prothrombotic State in Patients with Atrial Fibrillation.

It is unclear whether chronic kidney disease (CKD) increases thromboembolism in atrial fibrillation (AF). We conducted a retrospective cross-sectional analysis of 502 non-anticoagulated AF patients (median age, 66 (60–73) years, median CHA2DS2-VASc score, 3.0 (2.0–4.0)) with an estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2. Endogenous thrombin potential (ETP), clot permeability (Ks), and clot lysis time (CLT), among others, were determined. Patients with stage 4 CKD (n = 87; 17.3%) had higher ETP and prolonged CLT compared with those with stage 3 CKD. In patients with stages 3 to 4 CKD (n = 180; 35.9%) N-terminal pro-B-type natriuretic peptide predicted low Ks (the lowest quartile, odds ratio [OR] per 100 pg/mL: 1.03, 95% confidence interval [CI]: 1.01–1.06) and prolonged CLT (the top quartile, OR per 100 pg/mL: 1.05, 95% CI: 1.02–1.08), but not high ETP. In the whole cohort, after adjustment for CHA2DS2-VASc score, stage 4 CKD, but not stage 3 CKD, predicted high ETP (OR: 9.06; 95% CI: 4.44−18.46) and prolonged CLT (OR: 3.58; 95% CI: 1.76–7.28), but not low Ks. compared to the reference eGFR category. This study is the first to demonstrate the prothrombotic and antifibrinolytic alterations in AF patients with stage 4 CKD, but not stage 3 CKD irrespective of clinical stroke risk factors.

Renal function and attributable risk of death and cardiovascular hospitalization in participants with diabetes from a registry-based cohort

AimsTo estimate the attributable risk of renal function on all-cause mortality and cardiovascular hospitalization in patients with diabetes. MethodsA prospective cohort study in 19,469 adults with diabetes, free of cardiovascular disease, attending primary care in Spain (2008–2011). The estimated glomerular filtration rate (eGFR) and other variables were collected and patients were followed to the first hospitalization for coronary or stroke event, or death, until the end of 2012. The cumulative incidence of the study endpoints by eGFR categories was graphically displayed and adjusted population attributable risks (PARs) for low eGFR was calculated. ResultsMean follow-up was 3.2 years and 506 deaths and 1720 hospitalizations were recorded. The cumulative risk for the individual events increased as eGFR levels decreased. The PAR associated with having an eGFR of 60mL/min/1.73m2 or less was 11.4% (95% CI 4.8–18.3) for all-cause mortality, 9.2% (95% CI 5.3–13.4) for coronary heart disease, and 2.6% (95% CI −1.8 to 7.4) for stroke. ConclusionsReduced eGFR levels were associated with a larger proportion of avoidable deaths and cardiovascular hospitalizations in people with diabetes compared to previously reported results in people with other cardiovascular risk factors.

Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart Failure.

CKD is associated with higher health care costs that increase with disease progression. However, research is lacking on the type of health care costs associated with CKD across all stages in a general population with a substantial comorbidity burden. Using electronic medical records of an integrated delivery system, we evaluated health care costs by expenditure type in general and in patients with CKD by eGFR and presence of comorbidities. We categorized 146,132 patients with eGFR data in 2016 or 2017 and examined nonmutually exclusive groups according to presence of diabetes mellitus, cardiovascular disease, or heart failure. We used 1 year of follow-up data to calculate outpatient, inpatient, emergency, pharmaceutical, dialysis, and total health care costs by eGFR (Kidney Disease Improving Global Outcomes-defined eGFR categories), adjusted for age, sex, and nonwhite race. Mean total health care costs among patients with CKD without comorbidities were 31% higher than among patients without CKD ($7374 versus $5631, respectively). Hospitalizations accounted for 35% of total costs among those with CKD and no comorbidities but up to 55% among patients with CKD and heart failure. The proportion of costs attributable to hospitalizations accelerated with declining kidney function, reaching as high as 66%. Poorer kidney function and the presence of diabetes mellitus, cardiovascular disease, or heart failure drive substantial health care costs and increase the proportion of costs attributable to inpatient care. The large contribution of inpatient costs begins in earlier stages of CKD and escalates as kidney function declines. Additional therapies to reduce CKD incidence, slow CKD progression, and lower hospitalization risk are needed to benefit patients and reduce CKD's economic burden.

OP0297 EFFICACY AND SAFETY OF ROMOSOZUMAB AMONG POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS AND MILD-TO-MODERATE CHRONIC KIDNEY DISEASE

Background:Osteoporosis and renal insufficiency are coexisting disease states in a substantial proportion of postmenopausal women. Since bisphosphonates are generally contraindicated in patients with estimated glomerular filtration rate (eGFR) &lt;35 mL/min, it is important to evaluate other osteoporosis treatments in this setting.Objectives:To determine if baseline renal function affects the efficacy and safety of romosozumab.Methods:We performed post hoc analyses of two clinical trials of romosozumab in postmenopausal women with osteoporosis. In ARCH (NCT01631214), 4,093 patients were randomised 1:1 to romosozumab 210 mg monthly or alendronate 70 mg weekly for 12 months (mean age: 74.3 years; 96.1% with prevalent vertebral fractures [VFx]). In FRAME (NCT01575834), 7,180 patients were randomised 1:1 to romosozumab 210 mg or placebo monthly for 12 months (mean age: 70.9 years; 18.3% with prevalent VFx). For these analyses, patients were categorised by baseline eGFR (mL/min/1.73m2): normal renal function (eGFR ≥90), mild renal insufficiency (eGFR 60–89), or moderate renal insufficiency (eGFR 30–59). Least squares mean (LSM) percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck; incidence of new VFx and adverse events (AEs); and changes in renal function were assessed for each eGFR category at Month 12 of the double-blind treatment period.Results:At baseline, most patients had mild/moderate renal insufficiency: 84% in ARCH, 88% in FRAME. In both studies, change from baseline in BMD was significantly higher in the romosozumab group across baseline eGFR categories (Figure). There was an interaction between BMD increase and renal function, and although BMD increase was not as large in women with impaired renal function, differences between romosozumab and control groups remained significant (Figure). In ARCH, among patients with eGFR ≥90, 60–89, and 30–59, the incidence of new VFx (romosozumab vs alendronate) at Month 12 was 3.3% vs 7.3%, 3.2% vs 3.9%, and 3.4% vs 6.2% in ARCH. In FRAME, the incidence of new VFx (romosozumab vs placebo) at Month 12 was 0.5% vs 3.0%, 0.4% vs 1.5%, and 0.6% vs 2.1%.In both studies, the incidences of AEs and serious AEs were similar in both treatment groups within and across eGFR categories. AEs of mild-to-moderate hypocalcaemia (investigator reported) occurred in two patients in ARCH (one romosozumab [eGFR 60–89] and one alendronate [eGFR ≥90]), and one patient in FRAME (romosozumab [eGFR 60–89]). Five patients in ARCH (all in the alendronate group) and 19 patients in FRAME (14 romosozumab, 5 placebo) had decreases in serum Ca levels (albumin adjusted); in the romosozumab group all were mild (&lt;LLN–8.0 mg/dL) or moderate (&lt;8.0–7.0 mg/dL). A similar percentage of patients in each group had changes in renal function over 12 months of treatment.Conclusion:The efficacy and safety of romosozumab vs alendronate or placebo was similar among postmenopausal women with osteoporosis and different levels of renal function.Acknowledgments:This study was funded by Amgen, Astellas and UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Paul Miller Grant/research support from: Amgen, Radius Health, Ultragenyx, Consultant of: Amgen, Radius Health, Jonathan Adachi Consultant of: Amgen, Speakers bureau: Amgen, Ben-Hur Albergaria Consultant of: Amgen Inc., Eli Lilly, Speakers bureau: Amgen Inc., Eli Lilly, Angela M Cheung Consultant of: Amgen, Eli Lilly, Arkadi Chines Shareholder of: Amgen Inc., Employee of: Amgen Inc., Evelien Gielen Consultant of: Amgen Inc., Takeda, Sandoz and UCB Pharma, Speakers bureau: Amgen Inc., Takeda, Sandoz and UCB Pharma, Bente Langdahl Grant/research support from: Amgen, NovoNordisk, Consultant of: Amgen Inc., Eli Lilly, UCB Pharma, Akimitsu Miyauchi Consultant of: Amgen Inc., Astellas BioPharma K.K., Teijin Pharma, Mary Oates Shareholder of: Amgen Inc., Employee of: Amgen Inc., Ian Reid Consultant of: Amgen Inc., Eli Lilly, Speakers bureau: Amgen Inc., Eli Lilly, Norma Ruiz Santiago Shareholder of: Amgen Inc., Employee of: Amgen Inc., Mark Vanderkelen Employee of: UCB Pharma, Wenjing Yang Shareholder of: Amgen Inc., Employee of: Amgen Inc., Zhigang Yu Shareholder of: Amgen Inc., Employee of: Amgen Inc.