Most adults with chronic kidney disease (CKD) in the United States are cared for by primary care providers (PCPs). We evaluated the feasibility and preliminary effectiveness of an electronic clinical ...decision support system (eCDSS) within the electronic health record with or without pharmacist follow-up to improve the management of CKD in primary care.
Pragmatic cluster-randomized trial.
524 adults with confirmed creatinine-based estimated glomerular filtration rates of 30 to 59mL/min/1.73m2 cared for by 80 PCPs at the University of California San Francisco. Electronic health record data were used for patient identification, intervention deployment, and outcomes ascertainment.
Each PCP’s eligible patients were randomly assigned as a group into 1 of 3 treatment arms: (1) usual care; (2) eCDSS: testing of creatinine, cystatin C, and urinary albumin-creatinine ratio with individually tailored guidance for PCPs on blood pressure, potassium, and proteinuria management, cardiovascular risk reduction, and patient education; or (3) eCDSS plus pharmacist counseling (eCDSS-PLUS).
The primary clinical outcome was change in blood pressure over 12 months. Secondary outcomes were PCP awareness of CKD and use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and statin therapy.
All 80 eligible PCPs participated. Mean patient age was 70 years, 47% were nonwhite, and mean estimated glomerular filtration rate was 56±0.6mL/min/1.73m2. Among patients receiving eCDSS with or without pharmacist counseling (n=336), 178 (53%) completed laboratory measurements and 138 (41%) had laboratory measurements followed by a PCP visit with eCDSS deployment. eCDSS was opened by the PCP for 102 (74%) patients, with at least 1 suggested order signed for 83 of these 102 (81%). Changes in systolic blood pressure were−2.1±1.5mm Hg with usual care, −2.8±1.8mm Hg with eCDSS, and −1.1±1.1 with eCDSS-PLUS (P=0.7). PCP awareness of CKD was 16% with usual care, 26% with eCDSS, and 32% for eCDSS-PLUS (P=0.09). In as-treated analyses, PCP awareness of CKD was significantly greater with eCDSS and eCDSS-PLUS (73% and 69%) versus usual care (47%; P=0.002).
Recruitment of smaller than intended sample size and limited uptake of the testing component of the intervention.
Although we were unable to demonstrate the effectiveness of eCDSS to lower blood pressure and uptake of the eCDSS was limited by low testing rates, eCDSS use was high when laboratory measurements were available and was associated with higher PCP awareness of CKD.
Grants from government (National Institutes of Health) and not-for-profit (American Heart Association) entities.
Registered at ClinicalTrials.gov with study number NCT02925962.
Whether inclusion of the coronary artery calcium score improves cardiovascular risk prediction in individuals with CKD, a population with unique calcium-phosphate homeostasis, is unknown. Among 6553 ...participants ages 45-84 years without prior cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium score was assessed for cardiovascular risk prediction beyond the Framingham predictors in those with (n=1284) and without CKD and contrasted with carotid intima-media thickness and ankle-brachial index (two other measures of subclinical atherosclerosis). During a median follow-up of 8.4 years, 650 cardiovascular events (coronary heart disease, stroke, heart failure, and peripheral artery disease) occurred (236 events in subjects with CKD). In Cox proportional hazards models adjusted for Framingham predictors, each subclinical measure was independently associated with cardiovascular outcomes, with larger adjusted hazard ratios (HRs; per 1 SD) for coronary artery calcium score than carotid intima-media thickness or ankle-brachial index in subjects without and with CKD (HR, 1.69; 95% confidence interval 95% CI, 1.45 to 1.97 versus HR, 1.12; 95% CI, 1.00 to 1.25 and HR, 1.20; 95% CI, 1.08 to 1.32, respectively). Compared with inclusion of carotid intima-media thickness or ankle-brachial index, inclusion of the coronary artery calcium score led to greater increases in C statistic for predicting cardiovascular disease and net reclassification improvement. Coronary artery calcium score performed best for the prediction of coronary heart disease and heart failure, regardless of CKD status. In conclusion, each measure improved cardiovascular risk prediction in subjects with CKD, with the greatest improvement observed with coronary artery calcium score.
CONTEXT A triple-marker approach for chronic kidney disease (CKD) evaluation has not been well studied. OBJECTIVE To evaluate whether combining creatinine, cystatin C, and urine albumin-to-creatinine ...ratio (ACR) would improve identification of risks associated with CKD compared with creatinine alone. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study involving 26 643 US adults enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from January 2003 to June 2010. Participants were categorized into 8 groups defined by estimated glomerular filtration rate (GFR) determined by creatinine and by cystatin C of either <60 or ≥60 mL/min/1.73 m2 and ACR of either <30 or ≥30 mg/g. MAIN OUTCOME MEASURES All-cause mortality and incident end-stage renal disease with median follow-up of 4.6 years. RESULTS Participants had a mean age of 65 years, 40% were black, and 54% were women. Of 26 643 participants, 1940 died and 177 developed end-stage renal disease. Among participants without CKD defined by creatinine, 24% did not have CKD by either ACR or cystatin C. Compared with those with CKD defined by creatinine alone, the hazard ratio for death in multivariable-adjusted models was 3.3 (95% confidence interval CI, 2.0-5.6) for participants with CKD defined by creatinine and ACR; 3.2 (95% CI, 2.2-4.7) for those with CKD defined by creatinine and cystatin C, and 5.6 (95% CI, 3.9-8.2) for those with CKD defined by all biomarkers. Among participants without CKD defined by creatinine, 3863 (16%) had CKD detected by ACR or cystatin C. Compared with participants who did not have CKD by any measure, the HRs for mortality were 1.7 (95% CI, 1.4-1.9) for participants with CKD defined by ACR alone, 2.2 (95% CI, 1.9-2.7) for participants with CKD defined by cystatin C alone, and 3.0 (95% CI, 2.4-3.7) for participants with CKD defined by both measures. Risk of incident end-stage renal disease was higher among those with CKD defined by all markers (34.1 per 1000 person-years; 95% CI, 28.7-40.5 vs 0.33 per 1000 person-years; 95% CI, 0.05-2.3) for those with CKD defined by creatinine alone. The second highest end-stage renal disease rate was among persons missed by the creatinine measure but detected by both ACR and cystatin C (rate per 1000 person-years, 6.4; 95% CI, 3.6-11.3). Net reclassification improvement for death was 13.3% (P < .001) and for end-stage renal disease was 6.4% (P < .001) after adding estimated GFR cystatin C in fully adjusted models with estimated GFR creatinine and ACR. CONCLUSION Adding cystatin C to the combination of creatinine and ACR measures improved the predictive accuracy for all-cause mortality and end-stage renal disease.
Background Kidney disease has been associated with venous thromboembolism (VTE) risk, but results conflict and there is little information regarding blacks. Study Design Prospective cohort study. ...Setting & Participants 30,239 black and white adults 45 years or older enrolled in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study 2003 to 2007. Predictors Estimated glomerular filtration rate (eGFR) using the combined creatinine–cystatin C (eGFRcr-cys ) equation and urinary albumin-creatinine ratio (ACR). Outcomes The primary outcome was adjudicated VTE, and secondary outcomes were provoked and unprovoked VTE, separately. Mortality was a competing-risk event. Results During 4.6 years of follow-up, 239 incident VTE events occurred over 124,624 person-years. Cause-specific HRs of VTE were calculated using proportional hazards regression adjusted for age, sex, race, region of residence, and body mass index. Adjusted VTE HRs for eGFRcr-cys of 60 to <90, 45 to <60, and <45 versus ≥90 mL/min/1.73 m2 were 1.28 (95% CI, 0.94-1.76), 1.30 (95% CI, 0.77-2.18), and 2.13 (95% CI, 1.21-3.76). Adjusted VTE HRs for ACR of 10 to <30, 30 to <300, and ≥300 versus <10 mg/g were 1.14 (95% CI, 0.84-1.56), 1.15 (95% CI, 0.79-1.69), and 0.64 (95% CI, 0.25-1.62). Associations were similar for provoked and unprovoked VTE. Limitations Single measurement of eGFR and ACR may have led to misclassification. Smaller numbers of events may have limited power. Conclusions There was an independent association of low eGFR (<45 vs ≥90 mL/min/1.73 m2 ) with VTE risk, but no association of ACR and VTE.
Variants in the APOL1 gene are associated with kidney disease in blacks. We examined associations of APOL1 with incident albuminuria and kidney function decline among 3030 young adults with preserved ...GFR in the Coronary Artery Risk Development in Young Adults (CARDIA) study. eGFR by cystatin C (eGFRcys) and albumin-to-creatinine ratio were measured at scheduled examinations. Participants were white (n=1700), high-risk black (two APOL1 risk alleles, n=176), and low-risk black (zero/one risk allele, n=1154). Mean age was 35 years, mean eGFRcys was 107 ml/min per 1.73 m(2), and 13.2% of blacks had two APOL1 alleles. The incidence rate per 1000 person-years (95% confidence interval) for albuminuria over 15 years was 15.6 (10.6-22.1) for high-risk blacks, 7.8 (6.4-9.4) for low-risk blacks, and 3.9 (3.1-4.8) for whites. Compared with whites, the odds ratio (95% confidence interval) for incident albuminuria was 5.71 (3.64-8.94) for high-risk blacks and 2.32 (1.73-3.13) for low-risk blacks. Adjustment for risk factors attenuated the difference between low-risk blacks and whites (odds ratio 1.21, 95% confidence interval 0.86-1.71). After adjustment, high-risk blacks had a 0.45% faster yearly eGFRcys decline over 9.3 years compared with whites. Low-risk blacks also had a faster yearly eGFRcys decline compared with whites, but this difference was attenuated after adjustment for risk factors and socioeconomic position. In conclusion, blacks with two APOL1 risk alleles had the highest risk for albuminuria and eGFRcys decline in young adulthood, whereas disparities between low-risk blacks and whites were related to differences in traditional risk factors.
IMPORTANCE: Trials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the ...risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown. OBJECTIVES: To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to investigate if more intensive compared with less intensive BP control is associated with reduced mortality risk in persons with CKD stages 3 to 5. DATA SOURCES: Ovid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov electronic databases. STUDY SELECTION: All RCTs were included that compared 2 defined BP targets (either active BP treatment vs placebo or no treatment, or intensive vs less intensive BP control) and enrolled adults (≥18 years) with CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m2) exclusively or that included a CKD subgroup between January 1, 1950, and June 1, 2016. DATA EXTRACTION AND SYNTHESIS: Two of us independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, trial investigators were contacted to request data within the CKD subset of their original trials. MAIN OUTCOME AND MEASURE: All-cause mortality during the active treatment phase of each trial. RESULTS: This study identified 30 RCTs that potentially met the inclusion criteria. The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15 924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P = .01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups. CONCLUSIONS AND RELEVANCE: Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.
Objective
To examine whether grip strength, gait speed, and the combination of the two physical functioning measures modified the association of systolic BP (SBP) and diastolic BP (DBP) with ...mortality.
Design
Nationally representative cohort study.
Setting
Health and Retirement Study.
Participants
7,492 U.S. adults aged ≥65 years.
Measurements
Grip strength was measured by a hand dynamometer and classified as normal (≥16 kg for female; ≥26 kg for male) and weak. Gait speed was assessed over a 98.5‐inch walk and classified as non‐slow (≥0.60 m/s for female; ≥0.52 m/s for male) and slow.
Results
Over an average follow‐up time of 6.0 years, 1,870 (25.0%) participants died. After adjustment for socio‐demographic, behavioral, and clinical measures, elevated SBP (≥150 mmHg) and DBP (≥90 mmHg) was associated with a 24% (95% CI, 7–43%) and 25% (95% CI, 5–49%) higher mortality among participants with normal grip strength. In contrast, elevated SBP and DBP was associated with a 6% (95% CI, 31 to −27%) and a 16% (95% CI, 46 to −26%) lower mortality among those with weak grip strength (P‐values of interactions: both=.07). The inverse relations between BP with death were most pronounced among slow walkers with weak grip strength. The HRs of elevated SBP and DBP for death was 0.85 (95% CI, 0.56–1.29) and 0.53 (95% CI, 0.30–0.96), respectively, and was substantially different from non‐slow walkers with normal grip strength (HR = 1.24 and 1.15, respectively; P‐values of interactions: both <.001). Therefore, associations of BP with death varied modestly by gait speed.
Conclusion
Grip strength modified the association of BP with death. Combination of grip strength and gait speed has incremental value for modifying the association of BP with death.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although cystatin C is a stronger predictor of clinical outcomes associated with CKD than creatinine, the clinical role for cystatin C is unclear. We included 11,909 participants from the ...Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) and assessed risks for death, cardiovascular events, heart failure, and ESRD among persons categorized into mutually exclusive groups on the basis of the biomarkers that supported a diagnosis of CKD (eGFR <60 ml/min per 1.73 m(2)): creatinine only, cystatin C only, both, or neither. We used CKD-EPI equations to estimate GFR from these biomarkers. In MESA, 9% had CKD by the creatinine-based equation only, 2% had CKD by the cystatin C-based equation only, and 4% had CKD by both equations; in CHS, these percentages were 12, 4, and 13%, respectively. Compared with those without CKD, the adjusted hazard ratios (HR) for mortality in MESA were: 0.80 (95% CI 0.50 to 1.26) for CKD by creatinine only; 3.23 (95% CI 1.84 to 5.67) for CKD by cystatin C only; and 1.93 (95% CI 1.27 to 2.92) for CKD by both; in CHS, the adjusted HR were 1.09 (95% CI 0.98 to 1.21), 1.78 (95% CI 1.53 to 2.08), and 1.74 (95% CI 1.58 to 1.93), respectively. The pattern was similar for cardiovascular disease (CVD), heart failure, and kidney failure outcomes. In conclusion, among adults diagnosed with CKD using the creatinine-based CKD-EPI equation, the adverse prognosis is limited to the subset who also have CKD according to the cystatin C-based equation. Cystatin C may have a role in identifying persons with CKD who have the highest risk for complications.
Background Whether elevations in levels of urinary biomarkers of tubular injury (urine neutrophil gelatinase-associated lipocalin NGAL and kidney injury molecule 1 KIM-1) are associated with future ...risk of kidney disease has not been investigated. Study Design 1:1 nested case-control study. Setting & Participants 686 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Predictor NGAL and KIM-1 were measured at baseline, expressed as log-transformed continuous variables, and categorized into deciles. Outcomes Kidney function was estimated by cystatin C level using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Incident CKD stage 3 was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and an eGFR decrease >1 mL/min/1.73 m2 per year, and rapid kidney function decrease was defined as decrease ≥3 mL/min/1.73 m2 per year. Measurements Cases were defined as persons with eGFR >60 mL/min/1.73 m2 who subsequently developed incident CKD stage 3 and/or had rapid kidney function decrease by the MESA year-5 visit. Controls were matched for age, sex, race, diabetes, and baseline eGFR. We adjusted for age, hypertension, and presence of albuminuria (albumin-creatinine ratio ≥30 mg/g). Results Of 343 cases, 145 had incident CKD stage 3, 141 had rapid kidney function decrease, and 57 had both. Mean eGFR for controls was 81 ± 10 mL/min/1.73 m2 at baseline and 80 ± 10 mL/min/1.73 m2 at follow-up compared with 82 ± 13 and 58 ± 10 mL/min/1.73 m2 for cases. Each doubling of KIM-1 level (in picograms per milliliter) was associated with an OR of 1.15 (95% CI, 1.02-1.29) for incident CKD stage 3 and/or rapid kidney function decrease. Compared with the lowest 90%, the highest decile of KIM-1 level was associated with an OR of 2.02 (95% CI, 1.15-3.56) for the outcome; these associations were independent of albuminuria. NGAL levels (in nanograms per milliliter) were not associated with incident CKD stage 3 and/or rapid kidney function decrease (OR, 1.04; 95% CI, 0.99-1.10). Results were similar when KIM-1 and NGAL levels were standardized for urine creatinine. Limitations The case-control design limits the ability to account for persons who died or were not available for follow-up. Conclusions Urinary KIM-1 level is associated with future risk of kidney disease independent of albuminuria. Urinary biomarkers of tubular injury are a promising tool for identifying persons at risk of CKD.
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