Stacey E. Jolly

Blood Pressure Components and End-stage Renal Disease in Persons With Chronic Kidney Disease: The Kidney Early Evaluation Program (KEEP)

BACKGROUNDnTreatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known.nnnMETHODSnWe studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16,129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m(2) using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP ≥ 150 or DBP ≥ 90 mm Hg).nnnRESULTSnThe mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74-1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21-2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51-4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88-1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02-1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33-2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00-2.07] for PP ≥ 80 mm Hg compared with PP < 50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP ≥ 150 mm Hg or DBP ≥ 90 mm Hg), mostly due to isolated systolic hypertension (54%).nnnCONCLUSIONSnIn this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD.

Higher Cardiovascular Disease Prevalence and Mortality among Younger Blacks Compared to Whites

BACKGROUNDnBlacks have higher rates of cardiovascular disease than whites. The age at which these differential rates emerge has not been fully examined.nnnOBJECTIVEnWe examined cardiovascular disease prevalence and mortality among black and white adults across the adult age spectrum and explored potential mediators of these differential disease prevalence rates.nnnMETHODSnWe conducted a cross-sectional analysis of National Health and Nutrition Examination Survey data from 1999-2006. We estimated age-adjusted and age-specific prevalence ratios (PR) for cardiovascular disease (heart failure, stroke, or myocardial infarction) for blacks versus whites in adults aged 35 years and older and examined potential explanatory factors. From the National Compressed Mortality File 5-year aggregate file of 1999-2003, we determined age-specific cardiovascular disease mortality rates.nnnRESULTSnIn young adulthood, cardiovascular disease prevalence was higher in blacks than whites (35-44 years PR 1.9; 95% confidence interval [CI], 1.1-3.4). The black-white PR decreased with each decade of advancing age (P for trend=.04), leading to a narrowing of the racial gap at older ages (65-74 years PR 1.2; 95% CI, 0.8-1.6; > or =75 years PR 1.0; 95% CI, 0.7-1.4). Clinical and socioeconomic factors mediated some, but not all, of the excess cardiovascular disease prevalence among young to middle-aged blacks. Over a quarter (28%) of all cardiovascular disease deaths among blacks occurred in those aged <65 years, compared with 13% among whites.nnnCONCLUSIONSnReducing black/white disparities in cardiovascular disease will require a focus on young and middle-aged blacks.

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

BACKGROUND AND OBJECTIVESnThe incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnWe examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan-Meier survival curves, and time-dependent analysis.nnnRESULTSnOut of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality.nnnCONCLUSIONSnLow serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients.

Development and Validation of an Electronic Health Record–Based Chronic Kidney Disease Registry

BACKGROUND AND OBJECTIVESnChronic kidney disease (CKD) is increasing, and outcomes-related research from diverse health care settings is needed to target appropriate efforts and interventions. We developed an electronic health record (EHR)-based CKD registry at the Cleveland Clinic and validated comorbid conditions.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnPatients who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider and (1) had two estimated GFR values <60 ml/min per 1.73 m(2) >90 days apart as of January 1, 2005 and/or (2) were patients with International Classification of Diseases-9 (ICD-9) diagnosis codes for kidney disease were included.nnnRESULTSnOur registry includes 57,276 patients (53,399 patients met estimated GFR criteria and 3877 patients met ICD-9 diagnosis code criteria) as of March 2010. Mean age was 69.5 ± 13.4 years, with 55% women and 12% African Americans. Medicare is the primary insurer for more than one half of the study cohort. The κ statistics to assess the extent of agreement between the administrative dataset extracted from the EHR and actual EHR chart review showed substantial agreement (>0.80) for all conditions except for coronary artery disease and hypertension, which had moderate agreement (<0.60).nnnCONCLUSIONSnDevelopment of an EHR-based CKD registry is feasible in a large health system, and the comorbid conditions included in the registry are reliable. In addition to conducting research studies, such a registry could help to improve the quality of care delivered to CKD patients and complement the ongoing nationwide efforts to develop a CKD surveillance project.

Utilizing harmonization and common surveillance methods to consolidate 4 cohorts: the Western Alaska Tribal Collaborative for Health (WATCH) study

Background According to health status reports, chronic disease prevalence appears to be rising in western Alaska Native (AN) people, and accurate population-based data are needed. Four cohort studies of western AN people were conducted in the Norton Sound and Yukon-Kuskokwim regions, but none have been large enough to allow reliable estimates of rates of chronic diseases and evaluate their risk factors. Objective In this article, the methods used to combine 4 major cohort studies of rural western AN people are described and the benefits and challenges encountered in combining data and standardizing surveillance methods for these studies are discussed. Design Tribal permission was obtained for each cohort study and the consolidated study. Data from baseline exams were directly combined or harmonized into new variables. Common surveillance methods were developed and implemented to identify incidence and risk factors for cardiovascular disease (CVD) events and type 2 diabetes. Results A cohort of 4,569 western AN participants (2,116 men and 2,453 women), aged 18–95 years, was established to study CVD and diabetes prevalence. Prospective surveillance data over an average 6.7-year follow-up can now be used to study CVD and diabetes incidence and associated risk factors in a subset of 2,754 western AN participants (1,218 men and 1,536 women) who consented to initial surveillance. Conclusions The combined cohort provides statistical power to examine incidence rates and risk factors for CVD and diabetes and allows for analyses by geographic region. The data can be used to develop intervention programmes in these populations and others.

Low 25-Hydroxyvitamin D Levels and Mortality in Non–Dialysis-Dependent CKD

BACKGROUNDnLow 25-hydroxyvitamin D (25[OH]D) levels are common in patients with non-dialysis-dependent chronic kidney disease (CKD). The associations between low 25(OH)D levels and mortality in non-dialysis-dependent patients with CKD are unclear.nnnSTUDY DESIGNnRetrospective cohort study.nnnSETTING & PARTICIPANTSnPatients with stages 3-4 CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2); n = 12,673) who had 25(OH)D levels measured after the diagnosis of CKD in the Cleveland Clinic Health System.nnnPREDICTORn25(OH)D levels categorized into 3 groups: <15, 15-29, and ≥30 ng/mL.nnnOUTCOMESnWe examined factors associated with low 25(OH)D levels and associations between low 25(OH)D levels and all-cause mortality (ascertained using the Social Security Death Index and our electronic medical record) using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves.nnnMEASUREMENTSn25(OH)D was measured using chemiluminescence immunoassay.nnnRESULTSnOf 12,763 patients with CKD, 15% (n = 1,970) had 25(OH)D levels <15 ng/mL, whereas 45% (n = 5,749) had 25(OH)D levels of 15-29 ng/mL. Male sex, African American race, diabetes, coronary artery disease, and lower estimated glomerular filtration rate were associated significantly with 25(OH)D level <30 ng/mL. A graded increase in risk of 25(OH)D level <30 ng/mL was evident across increasing body mass index levels. Patients who had 25(OH)D levels measured in fall through spring had higher odds for 25(OH)D levels <30 ng/mL. After covariate adjustment, patients with CKD with 25(OH)D levels <15 ng/mL had a 33% increased risk of mortality (95% CI, 1.07-1.65). The group with 25(OH)D levels of 15-29 ng/mL did not show a significantly increased risk of mortality (HR, 1.03; 95% CI, 0.86-1.22) compared with patients with 25(OH)D levels ≥30 ng/mL.nnnLIMITATIONSnSingle-center observational study, lack of data for albuminuria and other markers of bone and mineral disorders, and attrition bias.nnnCONCLUSIONSn25(OH)D level <15 ng/mL was associated independently with all-cause mortality in non-dialysis-dependent patients with CKD.

Serum Potassium, End-Stage Renal Disease and Mortality in Chronic Kidney Disease

Background/Aims: Hypokalemia and hyperkalemia are often noted in chronic kidney disease (CKD) patients, but their impact on mortality and end-stage renal disease (ESRD) is less well understood. We aimed at studying the associations between potassium disorders, and mortality and progression to ESRD in a CKD population. Methods: Using our electronic health record-based CKD registry, 36,359 patients with eGFR <60 ml/min/1.73 m2 and potassium levels measured from January 1, 2005 to September 15, 2009 were identified. We examined factors associated with hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) using logistic regression models and associations between serum potassium levels (both as continuous and categorical variables) and all-cause mortality or ESRD using Cox-proportional hazards models. Results: Serum potassium <3.5 mmol/l was noted among 3% and >5.0 mmol/l among 11% of the study population. In the multivariable logistic regression analysis, lower eGFR, diabetes and use of ACE inhibitors or Angiotensin-Receptor Blockers were associated with higher odds of having hyperkalemia. Heart failure and African American race were factors associated with higher odds of hypokalemia. After adjustment for covariates including kidney function, serum potassium <4.0 and >5.0 mmol/l were significantly associated with increased mortality risk, but there was no increased risk for progression to ESRD. Time-dependent repeated measures analysis confirmed these findings. When potassium was examined as a continuous variable, there was a U-shaped association between serum potassium levels and mortality. Conclusion: In patients with stage 3-4 CKD, serum potassium levels <4.0 and >5.0 mmol/l are associated with higher mortality but not with ESRD.

Racial and Ethnic Differences in Mortality among Individuals with Chronic Kidney Disease: Results from the Kidney Early Evaluation Program (KEEP)

BACKGROUND AND OBJECTIVESnChronic kidney disease (CKD) is prevalent in minority populations and racial/ethnic differences in survival are incompletely understood.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnSecondary analysis of Kidney Early Evaluation Program participants from 2000 through 2008 with CKD, not on dialysis, and without previous kidney transplant was performed. Self-reported race/ethnicity was categorized into five groups: non-Hispanic white, African American, Asian, American Indian/Alaska Native, and Hispanic. CKD was defined as a urinary albumin to creatinine ratio of ≥30 mg/g among participants with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) or an eGFR of <60 ml/min per 1.73 m(2). The outcome was all-cause mortality. Covariates used were age, sex, obesity, diabetes, hypertension, albuminuria, baseline eGFR, heart attack, stroke, smoking, family history, education, health insurance, geographic region, and year screened.nnnRESULTSn19,205 participants had prevalent CKD; 55% (n = 10,560) were White, 27% (n = 5237) were African American, 9% (n = 1638) were Hispanic, 5% (n = 951) were Asian, and 4% (n = 813) were American Indian/Alaska Native. There were 1043 deaths (5.4%). African Americans had a similar risk of death compared with Whites (adjusted Hazard Ratio (AHR) 1.07, 95% CI 0.90 to 1.27). Hispanics (AHR 0.66, 95% CI 0.50 to 0.94) and Asians (AHR 0.63, 95% CI 0.41 to 0.97) had a lower mortality risk compared with Whites. In contrast, American Indians/Alaska Natives had a higher risk of death compared with Whites (AHR 1.41, 95% CI 1.08 to 1.84).nnnCONCLUSIONSnSignificant differences in mortality among some minority groups were found among persons with CKD detected by community-based screening.

Implications of the CKD-EPI GFR estimation equation in clinical practice.

BACKGROUND AND OBJECTIVESnChronic kidney disease (CKD) is a significant public health problem whose diagnosis and staging relies upon GFR-estimating equations, including the new CKD-EPI equation. CKD-EPI demonstrated superior performance compared with the existing MDRD equation but has not been applied to a healthcare system.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnWe identified 53,759 patients with stages 3 to 5 CKD on the basis of either MDRD or CKD-EPI equations using two eGFR values <60 ml/min per 1.73 m² > 90 days apart from an outpatient setting. We compared patient characteristics, presence of related diagnosis codes, and time CKD classification between equations.nnnRESULTSnThe number of patients identified with CKD decreased 10% applying CKD-EPI versus MDRD. Changes varied substantially by patient characteristics including a 35% decrease among patients < 60 years and a 10% increase among patients > 90 years. Women, non-African Americans, nondiabetics, and obese patients were less likely to be classified on the basis of CKD-EPI. Time to CKD classification was significantly longer with CKD-EPI among younger patients. 14% of patients identified with CKD on the basis of either estimating equation also had a related ICD-9 diagnosis, ranging from 19% among patients < 60 years to 7% among patients > 90 years.nnnCONCLUSIONSnConsistent with findings in the general population, CKD-EPI resulted in substantial declines in equation-based CKD diagnoses in a large healthcare system. Further research is needed to determine whether widespread use of CKD-EPI with current guidelines could lead to delayed needed care among younger patients or excessive referrals among older patients.

Risk factors for chronic kidney disease among American Indians and Alaska Natives - Findings from the kidney early evaluation program

Background: American Indians and Alaska Natives (AIAN) have a high incidence of end-stage renal disease. Less is known about chronic kidney disease (CKD) among AIAN and whether risk factors differ for low estimated glomerular filtration rate (eGFR) versus albuminuria with a normal eGFR. Methods: Cross-sectional study examining the associations of age, sex, smoking, obesity, diabetes, hypertension, family history, and geographic region with CKD among a screened population of AIAN participants in the Kidney Early Evaluation Program from 2000 to 2006. CKD was defined by the presence of either a low eGFR, <60 ml/min/1.73 m2, or albuminuria, a urine albumin/creatinine ratio ≥30 mg/g. Results: The prevalence of any CKD was 29%, of low eGFR was 17%, and of albuminuria with a normal eGFR was 12%. Older age was the strongest predictor of low eGFR (61+ years OR 8.42, 95% CI 5.92–11.98), followed by hypertension (OR 2.38, 95% CI 1.74–3.26). In contrast, diabetes (OR 2.04, 95% CI 1.57–2.64) and hypertension (OR 2.63, 95% CI 1.93–3.59) were the only predictors of albuminuria among persons with a normal eGFR. Conclusion: The burden of CKD was high among this screened population of AIAN, and different risk factor patterns were associated with low eGFR and albuminuria. Innovative programs and longitudinal research are needed to address CKD among AIAN.