Associations of Performance-Based Functional Assessments and Adverse Outcomes in Chronic Kidney Disease

Background: The comparative utility of performance-based functional assessments in predicting adverse outcomes in Chronic Kidney Disease (CKD) is unknown. We examined three performance-based functional assessments in an observational cohort of CKD patients to determine their relative utility. Methods: 350 participants with Stage II-V, pre-dialysis CKD were recruited. Participants were administered three performance-based functional assessments: Short Physical Performance Battery (SPPB), Modified Mini Mental Status Exam (M3SE), and Lawton Instrumental Activities of Daily Living (IADL). Scores were dichotomized based on the median and combined into a summary score. Outcomes included 50% glomerular filtration rate (GFR) reduction, end-stage kidney disease (ESKD), and death. Cox proportional hazards assessed the association of performance-based functional assessments with outcomes. Results: Compared to high performers, low SPPB performers had the highest adjusted rate of death, ESKD, or 50% reduction in GFR (HR: 1.96, 95% CI: 1.28, 2.99). Low SPPB had the strongest association with death when adjusted for multiple covariates (HR: 2.43, 95% CI: 1.36, 4.34). M3SE performance was not associated with any adverse outcome. None of the performance-based functional assessments were associated with ESKD, but a low IADL score was associated with a lower hazard ratio for ESKD or 50% decline GFR (HR: 0.49, 95% CI: 0.24, 1.00). Conclusions: Low SPPB score was the strongest predictor of death and all adverse outcomes as a composite. Future trials should determine if outcomes for CKD patients with poor physical performance and low SPPB scores are improved by targeted interventions.

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Chronic kidney disease and risk of atrial fibrillation and heart failure in general population-based cohorts – the BiomarCaRE project

European Heart Journal ◽

10.1093/eurheartj/ehab724.0449 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

M Rehm ◽

D Rothenbacher ◽

L Iacoviello ◽

S Costanzo ◽

H Tunstall-Pedoe ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

General Population ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Cox Proportional Hazards Models

Abstract Background Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. Purpose The aim of the study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. Methods This study was conducted as part of the BiomarCaRE project using harmonised data from 12 population-based cohorts (n=40,212) from Europe. Cox proportional hazards models were used to determine hazard ratios (HRs) for the incidence of AF and HF in CKD and with competing mortality risk after adjusting for covariates. Results Mean age at baseline was 51.1 (standard deviation 11.9) years, and 49.3% were men. Overall, 3.5% had CKD at baseline. The rate for incident AF was 3.9 per 1000 person-years during follow-up. The HR for AF for those with CKD compared with those without was 1.23 (95% CI 1.00–1.52, p=0.0465) after adjustment for covariates. The rate for incident HF was 3.9 per 1000 person-years and the associated risk in the presence of CKD was HR 1.67 (95% CI 1.39–2.01). In subjects with CKD, N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed an association with AF, while NT-proBNP and C-reactive protein (CRP) showed an association with HF. Conclusion CKD is an independent risk factor for subsequent AF and even more so for HF. In patients with CKD, NT-proBNP was clearly associated with subsequent risk of AF. In addition to this marker, hs-CRP was also associated with risk of subsequent HF. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 7th framework programme collaborative project, grant agreement no. HEALTH-F2-2011_278913. Atrial Fibrillation and HF in CKD

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Abstract MP012: Plasma Galectin-3 Levels and Subsequent Risk of Incident Chronic Kidney Disease

Circulation ◽

10.1161/circ.135.suppl_1.mp012 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Casey M Rebholz ◽

Elizabeth Selvin ◽

Menglu Liang ◽

Christie M Ballantyne ◽

Ron C Hoogeveen ◽

...

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Disease Risk ◽

Positive Association ◽

Cox Proportional Hazards ◽

Diabetes Status ◽

Incident Chronic Kidney Disease ◽

Galectin 3

Introduction: Galectin-3 is a 35 kDa β-galactoside-binding lectin which has been proposed as a novel biomarker of heart failure primarily due to its involvement in myocardial fibrosis. Elevated levels of galectin-3 may be associated with fibrosis of other organs, such as the kidney, and increase the risk of developing kidney disease. Methods: Using Cox proportional hazards regression, we prospectively analyzed Atherosclerosis Risk in Communities (ARIC) study participants with measurements of plasma galectin-3 levels at baseline (visit 4, 1996-98) and without prevalent kidney disease or heart failure (N=9,647). Incident chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 accompanied by 25% eGFR decline, chronic kidney disease-related hospitalization or death, or end-stage renal disease between baseline and December 31, 2013. Results: 2,105 participants (22%) developed incident chronic kidney disease over a median follow-up of 16 years. The mean (standard deviation) plasma level of galectin-3 was 14.7 (4.4) ng/mL. At baseline, galectin-3 was cross-sectionally associated with eGFR (r = -0.31) and urine albumin-to-creatinine ratio (UACR) (r = 0.19). After adjusting for demographics and kidney disease risk factors, there was a significant, graded, and positive association between galectin-3 and incident chronic kidney disease (quartile 4 vs. 1 HR: 1.84, 95% CI: 1.62, 2.09, p for trend <0.001). The association between galectin-3 and incident chronic kidney disease was attenuated but remained significant after accounting for eGFR and UACR (quartile 4 vs. 1 HR: 1.58, 95% CI: 1.39, 1.80, p for trend <0.001). The association was similar by diabetes status (p for interaction = 0.33) and stronger among those with hypertension (p for interaction = 0.004). Conclusion: In this community-based population, higher plasma galectin-3 levels were associated with elevated risk of developing incident chronic kidney disease, particularly among those with hypertension.

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Abstract P147: Association Of Rosuvastatin Use With Risk Of Rhabdomyolysis Across Chronic Kidney Disease Status

Circulation ◽

10.1161/circ.143.suppl_1.p147 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Jung-Im Shin ◽

Yao Qiao ◽

Aditya Surapaneni ◽

Lesley Inker ◽

Derek Fine ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Disease Status ◽

Cox Proportional Hazards ◽

Lower Egfr ◽

Threatening Condition ◽

Life Threatening ◽

End Stage

Introduction: Statin-induced rhabdomyolysis is a rare, but potentially life-threatening condition. It is unknown whether specific statins carry a greater risk of rhabdomyolysis and whether the risk differs between patients with and without chronic kidney disease (CKD). The objective of this study was to investigate the association of rosuvastatin use vs. atorvastatin use with the risk of rhabdomyolysis across CKD status. Hypothesis: Rosuvastatin use is associated with a higher risk of rhabdomyolysis as compared to atorvastatin use and the risk is greater among those with CKD than those without CKD. Methods: We identified adult patients who initiated rosuvastatin or atorvastatin between January 1, 2004 and December 31, 2018 and were free of end-stage kidney disease at the time of prescription in the Geisinger Health System. The association between rosuvastatin use and rhabdomyolysis was assessed using Cox proportional hazards regression models with an interaction between rosuvastatin use and CKD (i.e., estimated glomerular filtration rate <60 ml/min/1.73 m 2 ) in an inverse probability of treatment weighted (IPTW) sample. Results: Of 8,748 rosuvastatin users (mean [SD] age, 59.7 [12.6] years; 49.8% female; 11.8% CKD) and 31,770 atorvastatin users (mean [SD] age, 59.1 [12.6] years; 48.2% female; 11.9% CKD), 0.7% and 0.4% patients developed rhabdomyolysis, respectively, during a median follow-up of 5.1 years. Rosuvastatin use was associated with a higher risk of rhabdomyolysis in patients with CKD (hazard ratio [HR], 3.29; 95% CI, 1.53-7.09), but not in those without CKD (HR, 1.29; 95% CI, 0.82-2.03; p-interaction=0.04). A higher risk of rhabdomyolysis associated with rosuvastatin use in lower eGFR was also observed in the analysis with continuous eGFR ( Figure ). Conclusions: The findings suggest that rosuvastatin use in patients with CKD may be associated with excess risk of rhabdomyolysis as compared to atorvastatin.

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Abstract MP07: Soluble Urokinase-type Plasminogen Activator Receptor is associated with progression of hypertension-attributed chronic kidney disease in African Americans

Circulation ◽

10.1161/circ.137.suppl_1.mp07 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Shengyuan Luo ◽

Josef Coresh ◽

Adrienne Tin ◽

Casey M Rebholz ◽

Teresa K Chen ◽

...

Keyword(s):

Chronic Kidney Disease ◽

African Americans ◽

Kidney Disease ◽

Plasminogen Activator ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Ckd Progression ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Plasminogen Activator Receptor

Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, has been linked to incident and progressive chronic kidney disease (CKD) in select patient populations, often with few African Americans. Hypothesis: We assessed the hypothesis that higher circulating levels of suPAR are associated with risk for progression of hypertension-attributed CKD in African Americans. Methods: We quantified baseline plasma levels of suPAR in participants of the African-American Study of Kidney Disease and Hypertension (AASK), a clinical trial of African Americans with hypertension-attributed CKD, and regular assessment of measured glomerular filtration rate (mGFR), and proteinuria. We used Cox proportional hazards regression to assess the associations of suPAR with CKD progression (defined as doubling of serum creatinine or end-stage renal disease [ESRD]), ESRD, worsening proteinuria (pre-ESRD doubling of 24-hour urine protein to creatinine ratio [UPCR] to ≥220 mg/g), and all-cause death. Results: Among 955 AASK participants, the median baseline suPAR was 4462 pg/mL (25 th to 75 th percentile: 3425-5923 pg/mL), mean mGFR was 46 mL/min per 1.73 m 2 , and median 24-hour UPCR was 79.6 mg/g. After controlling for baseline demographics, AASK trial arm, mGFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.42-times higher risk for CKD progression per two-fold higher baseline suPAR (HR 1.42, 95% CI: 1.17-1.71, p <0.001). Higher suPAR was also independently associated with ESRD (HR 1.59, 95% CI: 1.26-2.00, p <0.001) and death (HR 1.40, 95% CI: 1.12-1.75, p =0.003). Only in patients with two APOL1 risk alleles was suPAR associated with worsening proteinuria (HR 1.77, 95% CI 1.11-2.82, p =0.016; p interaction =0.008). Conclusion: Our study provides evidence of associations between higher suPAR levels and risk for various adverse outcomes in African Americans with hypertension-attributed CKD, independent of proteinuria and GFR.

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Hyperlipidemia and Statins Use for the Risk of New Diagnosed Sarcopenia in Patients with Chronic Kidney: A Population-Based Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17051494 ◽

2020 ◽

Vol 17 (5) ◽

pp. 1494 ◽

Cited By ~ 2

Author(s):

Min-Hua Lin ◽

She-Yu Chiu ◽

Pei-Hsuan Chang ◽

Yu-Liang Lai ◽

Pau-Chung Chen ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Research Database ◽

Newly Diagnosed ◽

Hazards Model

Background: Previous research found that statins, in addition to its efficiency in treating hyperlipidemia, may also incur adverse drug reactions, which mainly include myopathies and abnormalities in liver function. Aim: This study aims to assess the risk for newly onset sarcopenia among patients with chronic kidney disease using statins. Material and Method: In a nationwide retrospective population-based cohort study, 75,637 clinically confirmed cases of chronic kidney disease between 1997 and 2011were selected from the National Health Insurance Research Database of Taiwan. The selection of the chronic kidney disease cohort included a discharge diagnosis with chronic kidney disease or more than 3 outpatient visits with the diagnosis of chronic kidney disease found within 1 year. After consideration of patient exclusions, we finally got a total number of 67,001 cases of chronic kidney disease in the study. The Cox proportional hazards model was used to perform preliminary analysis on the effect of statins usage on the occurrence of newly diagnosed sarcopenia; the Cox proportional hazards model with time-dependent covariates was conducted to take into consideration the individual temporal differences in medication usage, and calculated the hazard ratio (HR) and 95% confidence interval after controlling for gender, age, income, and urbanization. Results: Our main findings indicated that patients with chronic kidney disease who use statins seem to effectively prevent patients from occurrences of sarcopenia, high dosage of statins seem to show more significant protective effects, and the results are similar over long-term follow-up. In addition, the risk for newly diagnosed sarcopenia among patients with lipophilic statins treatment was lower than that among patients with hydrophilic statins treatment. Conclusion: It seems that patients with chronic kidney disease could receive statin treatment to reduce the occurrence of newly diagnosed sarcopenia. Additionally, a higher dosage of statins could reduce the incidence of newly diagnosed sarcopenia in patients with chronic kidney disease.

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Bypass Grafting vs Endovascular Therapy in Patients With Non-Dialysis-Dependent Chronic Kidney Disease and Chronic Limb-Threatening Ischemia (CRITISCH Registry)

Journal of Endovascular Therapy ◽

10.1177/1526602820938465 ◽

2020 ◽

Vol 27 (4) ◽

pp. 599-607

Author(s):

Konstantinos Stavroulakis ◽

Asimakis Gkremoutis ◽

Matthias Borowski ◽

Giovanni Torsello ◽

Dittmar Böckler ◽

...

Keyword(s):

Myocardial Infarction ◽

Chronic Kidney Disease ◽

Overall Survival ◽

Kidney Disease ◽

Endovascular Therapy ◽

Proportional Hazards ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Bypass Grafting ◽

Cox Regression Analysis

Purpose: To report the outcomes of bypass grafting (BG) vs endovascular therapy (EVT) in patients with non-dialysis-dependent chronic kidney disease (CKD) and chronic limb-threatening ischemia (CLTI). Materials and Methods: The CRITISCH Registry is a prospective, national, interdisciplinary, multicenter registry evaluating the current practice of all available treatment options in 1200 consecutive CLTI patients. For the purposes of this analysis, only the 337 patients with non-dialysis-dependent CKD treated by either BG (n=86; median 78 years, 48 men) or EVT (n=251; median age 80 years, 135 men) were analyzed. The primary composite outcome was amputation-free survival (AFS); secondary outcomes were overall survival (OS) and amputation-free time (AFT). All outcomes were evaluated in Cox proportional hazards models; the results are reported as the hazard ratio (HR) and 95% confidence interval (CI). Results: The Cox regression analysis revealed a significantly greater hazard of amputation or death after BG (HR 1.78, 95% CI 1.05 to 3.03, p=0.028). The models for AFT and overall survival also suggested a higher hazard for BG, but the differences were not significant (AFT: HR 1.66, 95% CI 0.78 to 3.53, p=0.188; OS: HR 1.41, 95% CI 0.80 to 2.47, p=0.348). The absence of runoff vessels (HR 1.73, 95% CI 1.15 to 2.60, p=0.008) was associated with a decreased AFS. The likelihood of amputation was higher in male patients (HR 2.21, 95% CI 1.10 to 4.45, p=0.027) and was associated with a lack of runoff vessels (HR 1.95, 95% CI 0.96 to 3.95, p=0.065) and myocardial infarction (HR 3.74, 95% CI 1.23 to 11.35, p=0.020). Death was more likely in patients without runoff vessels (HR 1.76, 95% CI 1.11 to 2.80, p=0.016) and those with a higher risk score (HR 1.73, 95% CI 1.03 to 2.91, p=0.038). Conclusion: This analysis suggested that BG was associated with poorer AFS than EVT in patients with non-dialysis-dependent CKD and CLTI. Male sex, previous myocardial infarction, and the absence of runoff vessels were additionally identified as predictors of poorer outcomes.

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Low lung function and the risk of incident chronic kidney disease in the Malmö Preventive Project cohort

BMC Nephrology ◽

10.1186/s12882-020-01758-0 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Suneela Zaigham ◽

Anders Christensson ◽

Per Wollmer ◽

Gunnar Engström

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Lung Function ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Main Diagnosis ◽

Men And Women ◽

Increased Risk ◽

Incident Chronic Kidney Disease ◽

Future Risk

Abstract Background Although the prevalence of kidney disease is higher in those with reduced lung function, the longitudinal relationship between low lung function and future risk of chronic kidney disease (CKD) has not been widely explored. Methods Baseline lung function was assessed in 20,700 men and 7325 women from 1974 to 1992. Mean age was 43.4 (±6.6) and 47.5 (±7.9) for men and women respectively. Sex-specific quartiles of FEV1 and FVC (L) were created (Q4: highest, reference) and the cohort was also divided by the FEV1/FVC ratio (≥ or < 0.70). Cox proportional hazards regression was used to determine the risk of incident CKD events (inpatient or outpatient hospital diagnosis of CKD) in relation to baseline lung function after adjustment for various confounding factors. Results Over 41 years of follow-up there were 710 and 165 incident CKD events (main diagnosis) in men and women respectively. Low FEV1 was strongly associated with future risk of CKD in men (Q1 vs Q4 adjusted HR: 1.46 (CI:1.14–1.89), p-trend 0.002). Similar findings were observed for FVC in men (1.51 (CI:1.16–1.95), p-trend 0.001). The adjusted risks were not found to be significant in women, for either FEV1 or FVC. FEV1/FVC < 0.70 was not associated with increased incidence of CKD in men or women. Conclusion Low FEV1 and FVC levels at baseline are a risk factor for the development of future incident CKD in men. Monitoring kidney function in those with reduced vital capacity in early life could help with identifying those at increased risk of future CKD.

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Use of Phosphorus Binders among Non-Dialysis Chronic Kidney Disease Patients and Mortality Outcomes

American Journal of Nephrology ◽

10.1159/000474959 ◽

2017 ◽

Vol 45 (5) ◽

pp. 431-441 ◽

Cited By ~ 3

Author(s):

Simran K. Bhandari ◽

In-Lu A. Liu ◽

Dean A. Kujubu ◽

Trung Huynh ◽

Hind Behayaa ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Mortality Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Clinical Environment ◽

Inverse Probability ◽

Immortal Time Bias ◽

Stage Renal Disease

Background: Whether the benefits of phosphorus binders extend to those without end stage renal disease is uncertain. Among a large diverse non-dialysis chronic kidney disease (CKD) population with hyperphosphatemia, we sought to evaluate phosphorus binder use and compare mortality risk between patients prescribed and not prescribed binders. Methods: A retrospective cohort study within an integrated health system (January 1, 1998 - December 31, 2012) among CKD patients (age ≥18) was performed. Non-dialysis CKD patients with 2 separate estimated glomerular filtrate rate (eGFR) <30 mL/min/1.73 m2 and serum phosphorus ≥5.0 mg/dL within 180 days of eGFR were included. Multivariable cox proportional hazards and inverse probability of treatment-weighted models were used to estimate mortality hazard ratios (HRs) for patients who received phosphorus binders compared to no binders. Results: Among 10,165 study patients, 2,733 subjects (27%) received phosphorus binders. Compared to the no-phosphorus-binder group, the binder group had mortality HRs (95% CI) of 0.86 (0.79-0.94) and 0.86 (0.80-0.93) using traditional multivariable and inverse probability of treatment-weighted models respectively. Sensitivity analyses removing patients who were prescribed binders >180 days after index date revealed no difference in mortality between those with binders and with no binders. Conclusion: Our findings from a real-world clinical environment revealed that 27% of hyperphosphatemic non-dialysis CKD patients were prescribed binders. They also had lower risk of mortality compared to those not prescribed phosphorus binders. However, the lower mortality risk was not observed when we accounted for immortal time bias. Whether phosphorus binder use in CKD improves survival remains to be determined.

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Association of Arterial Stiffness With Kidney Function Among Adults Without Chronic Kidney Disease

American Journal of Hypertension ◽

10.1093/ajh/hpaa097 ◽

2020 ◽

Vol 33 (11) ◽

pp. 1003-1010

Author(s):

Seiji Itano ◽

Yuichiro Yano ◽

Hajime Nagasu ◽

Hirofumi Tomiyama ◽

Hiroshi Kanegae ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Arterial Stiffness ◽

Kidney Function ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Kidney Dysfunction ◽

Cox Proportional Hazards Models ◽

Egfr Decline

Abstract BACKGROUND Our aims were to assess whether arterial stiffness is associated with a higher risk for kidney dysfunction among persons without chronic kidney disease (CKD). METHODS We analyzed data from the national health checkup system in Japan; for our analyses, we selected records of individuals who completed assessments of cardio-ankle vascular index (CAVI) and kidney function from 2005 to 2016. We excluded participants who had CKD at baseline, defined as the presence of proteinuria or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. We compared 2 groups of CAVI measurements—the highest quartile (≧8.1) and the combined lower 3 quartiles (<8.1). We used Cox proportional hazards models to assess associations between these 2 groups and subsequent CKD events, proteinuria, eGFR <60 ml/min/1.73 m2, and rapid eGFR decline (greater than or equal to −3 ml/min/1.73 m2 per year). RESULTS The mean age of the 24,297 included participants was 46.2 years, and 60% were female. Over a mean follow-up of 3.1 years, 1,435 CKD events occurred. In a multivariable analysis, the hazard ratios with 95% confidence intervals (CIs) for the highest vs. combined lower quartiles of CAVI measurements were 1.3 (1.1, 1.5) for CKD events, 1.3 (0.96, 1.62) for proteinuria, 1.4 (1.1, 1.7) for eGFR <60 ml/min/1.73 m2, and the odds ratio with 95% CI was 1.3 (1.1, 1.4) for rapid eGFR decline. CONCLUSIONS Persons with CAVI measurements ≧8.1 had a higher risk for CKD events compared with their counterparts with CAVI measurements <8.1. Greater arterial stiffness among adults without CKD may be associated with kidney dysfunction.

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Abstract P037: Progression Of Coronary Artery Calcification And Risk Of Clinical Events In Chronic Kidney Disease

Circulation ◽

10.1161/circ.143.suppl_1.p037 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Joshua D Bundy ◽

Ling Tian ◽

Matthew J Budoff ◽

Julia J Scialla ◽

Rupal Mehta ◽

...

Keyword(s):

Myocardial Infarction ◽

Chronic Kidney Disease ◽

Coronary Artery ◽

Kidney Disease ◽

Coronary Artery Calcification ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Clinical Events ◽

Prospective Longitudinal

Introduction: Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease (CVD) events. Coronary artery calcification (CAC) and progression of CAC are associated with higher risk of clinical events in the general population, but this has not been quantified among patients with CKD. Hypothesis: Progression of CAC is independently associated with CVD events and mortality among patients with CKD stages 2-4. Methods: We pooled individual-level data from 2 prospective longitudinal cohort studies (the Chronic Renal Insufficiency Cohort [CRIC] Study and the Multi-Ethnic Study of Atherosclerosis [MESA]). We included participants with CKD, defined as an estimated glomerular filtration rate <60 mL/min/1.73m 2 or urinary albumin-to-creatine ratio ≥30 mg/g. In both cohorts, CAC was measured at baseline and a follow-up visit using electron beam or multidetector computed tomography. Multivariable-adjusted Cox proportional hazards regression models were used to assess the associations of CAC progression between visits with risks of adjudicated atherosclerotic CVD events (myocardial infarction, stroke) and all-cause mortality. Analyses were stratified by presence or absence of CAC at baseline. Results: 2111 participants with CKD were included (1314 with and 797 without CAC at baseline). Over an average of 3 years between CAC scans, 192 (24%) participants without baseline CAC developed CAC while 222 participants (17%) with baseline CAC increased ≥100 Agatston units per year. Over an average 9.4-year follow-up after the second CAC scan, we observed 272 atherosclerotic CVD events (178 myocardial infarction, 94 stroke) and 570 deaths. After multivariable adjustment, CAC progression was significantly associated with higher risk of atherosclerotic CVD and mortality, particularly among those with CAC at baseline (Table). Conclusions: Among adults with CKD stages 2-4, progression of CAC over approximately 3 years is significantly associated with atherosclerotic CVD and mortality.

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