Relevance of correction for drift and day-to-day variation in cystatin C measurement: a post-hoc analysis of the PREVEND cohort, with independent replication in the ESTHER cohort

2015 ◽  
Vol 53 (9) ◽  
Author(s):  
Priya Vart ◽  
Stephan J. L. Bakker ◽  
Ben Schöttker ◽  
Dick de Zeeuw ◽  
Dietrich Rothenbacher ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cystatin C ◽  
Cardiovascular Events ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Standard Laboratory ◽  
Post Hoc Analysis ◽  
Independent Replication ◽  
Post Hoc ◽  
Dutch Cohort

AbstractDespite standard laboratory quality control, drift and day-to-day variability in cystatin C measurements can be observed. We investigated whether correction for drift and day-to-day variation in cystatin C measurements improves the association of estimated glomerular filtration rate (eGFR) with chronic kidney disease (CKD) risk factors and prognosis.Plasma samples of the PREVEND study (Dutch cohort study, n=8592) were used to measure cystatin C (Gentian assay) on 243 random days. A correction factor was calculated for each measurement day. GFR was estimated with CKD-EPI equation using routinely measured cystatin C (eGFRCompared to non-reclassified participants, participants re-classified upward had significantly lower age, body mass index, blood pressure, cholesterol, glucose and albuminuria, whereas the opposite was true for participants reclassified downward. CKD risk factors explained more variance in eGFRCorrection for drift and day-to-day variation in cystatin C measurement improves eGFR using cystatin C for its association with CKD risk factors and incident cardiovascular events.

scholarly journals Effect of once‐weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: A post hoc analysis of the EXSCEL trial

2020 ◽  
Vol 22 (12) ◽  
pp. 2493-2498
Author(s):  
Annemarie B. van der Aart‐van der Beek ◽  
Lindsay E. Clegg ◽  
Robert C. Penland ◽  
David W. Boulton ◽  
C. David Sjöström ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals Different glomerular filtration rate estimating formula for prescribing DOACs in oldest patients: appropriate dosage and bleeding risk. Post hoc analysis of a prospective cohort

2021 ◽  
Author(s):  
Valeria Calsolaro ◽  
Chukwuma Okoye ◽  
Sara Rogani ◽  
Alessia Maria Calabrese ◽  
Umberto Dell’Agnello ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Cystatin C ◽  
Prospective Cohort ◽  
Filtration Rate ◽  
Statistical Significance ◽  
Bleeding Risk ◽  
Post Hoc Analysis ◽  
Ckd Stage ◽  
Post Hoc

Abstract Background Direct oral anticoagulants (DOACs) pharmacokinetics depends on estimated glomerular filtration rate (eGFR), whose estimation is crucial for optimal risk/benefit balance. Aims To assess the concordance among different eGFR formulas and the potential impact on DOACs prescription appropriateness and bleeding risk in oldest hospitalized patients. Methods Post hoc analysis of a single-centre prospective cohort study. eGFR was calculated by creatinine-based (MDRD, CKD-EPICr, BIS1) and creatinine–cystatin-C-based (CKD-EPIComb and BIS2) formulas. Patients were stratified according to eGFR [severely depressed (SD) 15–29; moderately depressed (MD) 30–49; preserved/mildly depressed (PMD): ≥ 50 ml/min/1.73 m2]. Concordance between the different equations was assessed by Cohen’s kappa coefficient. Results Among AF patients, 841 (59.2% women, mean age 85.9 ± 6.5 years) received DOACs. By CKD-EPICr equation, 135 patients were allocated in the SD, 255 in the MD and 451 in the PMD group. The concordance was excellent only between BIS 2 and CKD-EPIComb and MDRD and CKD-EPICr, while was worse (from good to poor) between the other formulas. Indeed, by adding cystatin-C almost over 1/3 of the patients were reallocated to a worse eGFR class. Bleeding prevalence increased by 2–3% in patients with discordant eGFR between formulas, reallocated to a worse chronic kidney disease (CKD) stage, although without reaching statistical significance. CKD-EPIComb resulted the best predictor of bleeding events (AUROC 0.71, p = 0.03). Discussion This study highlights the variability in CKD staging according to different eGFR formulas, potentially determining inappropriate DOACs dosing. Although the cystatin-C derived CKDEPIComb equation is the most accurate for stratifying patients, BIS1 may represent a reliable alternative.

scholarly journals Cardio/Kidney Composite End Points: A Post Hoc Analysis of the EMPA‐REG OUTCOME Trial

2021 ◽  
Author(s):  
João Pedro Ferreira ◽  
Bettina Johanna Kraus ◽  
Isabella Zwiener ◽  
Sabine Lauer ◽  
Bernard Zinman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Kidney Failure ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Cox Regression ◽  
Event Analysis ◽  
End Points ◽  
Post Hoc Analysis ◽  
Post Hoc

Background Cardio/kidney composite end points are clinically relevant but rarely analyzed in cardiovascular trials. This post hoc analysis of the EMPA‐REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial evaluated cardio/kidney composite end points by 2 statistical approaches. Methods and Results A total of 7020 patients with type 2 diabetes mellitus and established cardiovascular disease were treated with empagliflozin 10 or 25 mg (n=4687) or placebo (n=2333) on top of standard care. Cardio/kidney composite end points studied were: (1) cardiac or kidney death, kidney failure, hospitalization for heart failure, sustained decline in estimated glomerular filtration rate ≥40% from baseline, or sustained progression to macroalbuminuria; (2) cardiac or kidney death, kidney failure, hospitalization for heart failure, or sustained estimated glomerular filtration rate decline ≥40% from baseline; and (3) cardiac or kidney death, kidney failure, hospitalization for heart failure, or sustained doubling in serum creatinine from baseline. Cox regression using time‐to‐first‐event analysis and win ratio (WR) using hierarchical order of events were applied. Empagliflozin reduced the risk of all cardio/kidney composites. The results varied only slightly between Cox and WR (eg, composite 1: hazard ratio, 0.56 [95% CI, 0.49–0.64]; WR, 1.76 [95% CI, 1.53–2.02]. WR prioritizes events by clinical importance; in particular, all fatal events are evaluated, whereas Cox regression ignores deaths when preceded by nonfatal events. Of the 285 cardio/kidney deaths in the analysis, 44 to 56 (15%–20%), depending on the composite, occurred after a nonfatal event and were not evaluated in Cox regression but evaluated by the WR. Conclusions By considering the clinical relevance of different event types, the WR represents an appropriate method to complement the traditional time‐to‐first‐event analysis in cardio/kidney outcomes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01131676.

80-OR: Treatment with Once-Weekly Semaglutide 2.4 mg Improves Cardiometabolic Risk Factors in Adults with Overweight/Obesity and Type 2 Diabetes: STEP 2 Post-hoc Analysis

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 80-OR
Author(s):  
ROBERT F. KUSHNER ◽  
MELANIE J. DAVIES ◽  
JOHN DEANFIELD ◽  
W. TIMOTHY GARVEY ◽  
OLE JEPPESEN ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiometabolic Risk ◽  
Cardiometabolic Risk Factors ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract 6277: Predictive Value of Estimated Glomerular Filtration Rate for Cardiovascular Events: The Treating to New Targets Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
James Shepherd ◽  
Chuan-Chuan Wun ◽  
Daniel J Wilson ◽  
Andrea L Zuckerman
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Cardiovascular Events ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Lipid Lowering ◽  
Final Visit ◽  
The Relationship ◽  
Dose Dependent

We previously demonstrated a dose-dependent improvement in renal function and reduction in cardiovascular risk in TNT with intensive lipid lowering with atorvastatin (ATV) 80 mg vs 10 mg. This post hoc analysis examines the relationship between the observed improvement in estimated glomerular filtration rate (eGFR) and reduction of major cardiovascular events (MCVE). After 8 weeks open-label therapy with ATV 10 mg, 10,001 patients with CHD were randomized to double-blind therapy with either ATV 10 or 80 mg. Patients were followed for a median of 4.9 years for the occurrence of MCVEs (CHD death, nonfatal MI, and stroke). The relationship between change from baseline eGFR (using the MDRD equation) at the final visit prior to a MCVE and the risk of MCVE was assessed using a Cox proportional hazards model adjusting for baseline eGFR and other baseline characteristics. Of 9656 patients with complete renal data, 156 had a MCVE before follow-up eGFR assessment and were excluded. In the remaining 9500 patients, mean baseline eGFR was 65.3 mL/min/1.73 m 2 and mean change from baseline was 4.3 mL/min/1.73 m 2 . This represented a reduction in the risk of MCVE of 2.7% per mL increase in eGFR (HR 0.973, 95% CI 0.967– 0.980, P <0.0001). This association remained significant in patients with eGFR <60 and those with eGFR ≥60 mL/min/1.73 m 2 at baseline, with no significant interaction between eGFR change and baseline renal status ( P =0.98). A 5 mL/min on-treatment improvement in eGFR was associated with a 12.6% reduction in MCVE, while a 5 mL/min reduction was associated with a 14.4% increase in MCVE. Mean change from baseline eGFR was 3.5 mL/min/1.73 m 2 with ATV 10 mg and 5.2 mL/min/1.73 m 2 with ATV 80 mg, representing significant 9.3% and 12.4% reductions in risk, respectively. Analysis of interaction between treatment and eGFR change for prediction of MCVE demonstrated a stronger association between eGFR change and MCVE in the ATV 80 mg treatment group ( P =0.011). Improvement in eGFR was highly associated with a reduction in MCVE, irrespective of baseline renal function. This relationship was dose dependent. Improvement in eGFR may be a biomarker for the response to atorvastatin, and for the stabilization of atherosclerotic cardiovascular disease.

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