The global burden of chronic kidney disease: estimates, variability and pitfalls.

Chronic kidney disease (CKD) is currently defined by abnormalities of kidney structure or function assessed using a matrix of variables - including glomerular filtration rate (GFR), thresholds of albuminuria and duration of injury - and is considered by many to be a common disorder globally. However, estimates of CKD prevalence vary widely, both within and between countries. The reasons for these variations are manifold, and include true regional differences in CKD prevalence, vagaries of using estimated GFR (eGFR) for identifying CKD, issues relating to the use of set GFR thresholds to define CKD in elderly populations, and concerns regarding the use of one-off testing for assessment of eGFR or albuminuria to define the prevalence of CKD in large-scale epidemiological studies. Although CKD is common, the suggestion that its prevalence is increasing in many countries might not be correct. Here, we discuss the possible origins of differences in estimates of CKD prevalence, and present possible solutions for tackling the factors responsible for the reported variations in GFR measurements. The strategies we discuss include approaches to improve testing methodologies for more accurate assessment of GFR, to improve awareness of factors that can alter GFR readouts, and to more accurately stage CKD in certain populations, including the elderly.

The pressing need for real-time risk assessment of hospital-acquired acute kidney injury.

Acute Kidney Injury (AKI) is associated with short- and long-term outcomes that reflect the severity of the injury. Recent studies have suggested that 'early' initiation of renal replacement therapy may alter the course of AKI and improve short-term outcomes like inpatient mortality. The current Kidney Disease Improving Global Outcomes (KDIGO) consensus definition of AKI has been criticized for misclassification bias, lack of sensitivity and the static manner in which AKI stages are defined. This editorial reviews various approaches to improving the specificity and sensitivity of the KDIGO AKI criteria, and also concludes that a staging system based on creatinine trajectories would be better suited for developing a prognostic index for real-time, dynamic risk assessment that the current KDIGO staging criteria.

Association of Reduced eGFR and Albuminuria with Serious Fall Injuries among Older Adults.

BACKGROUND AND OBJECTIVES: Falls are common and associated with adverse outcomes in patients on dialysis. Limited data are available in earlier stages of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed data from 8744 Reasons for Geographic and Racial Differences in Stroke Study participants ≥65 years old with Medicare fee for service coverage. Serious fall injuries were defined as a fall-related fracture, brain injury, or joint dislocation using Medicare claims. Hazard ratios (HRs) for serious fall injuries were calculated by eGFR and albumin-to-creatinine ratio (ACR). Among 2590 participants with CKD (eGFR<60 ml/min per 1.73 m(2) or ACR≥30 mg/g), cumulative mortality after a serious fall injury compared with age-matched controls without a fall injury was calculated. RESULTS: Overall, 1103 (12.6%) participants had a serious fall injury over 9.9 years of follow-up. The incidence rates per 1000 person-years of serious fall injuries were 21.7 (95% confidence interval [95% CI], 20.3 to 23.2), 26.6 (95% CI, 22.6 to 31.3), and 38.3 (95% CI, 31.2 to 47.0) at eGFR levels ≥60, 45-59, and <45 ml/min per 1.73 m(2), respectively, and 21.3 (95% CI, 20.0 to 22.8), 31.7 (95% CI, 27.5 to 36.5), and 42.2 (95% CI, 31.3 to 56.9) at ACR levels <30, 30-299, and ≥300 mg/g, respectively. Multivariable adjusted HRs for serious fall injuries were 0.91 (95% CI, 0.76 to 1.09) and 1.09 (95% CI, 0.86 to 1.37) for eGFR=45-59 and <45 ml/min per 1.73 m(2), respectively, versus eGFR≥60 ml/min per 1.73 m(2) and 1.31 (95% CI, 1.11 to 1.54) and 1.81 (95% CI, 1.30 to 2.50) for ACR=30-299 and ≥300 mg/g, respectively, versus ACR<30 mg/g. Among participants with CKD, cumulative 1-year mortality rates among patients with a serious fall and age-matched controls were 21.0% and 5.5%, respectively. CONCLUSIONS: Elevated ACR but not lower eGFR was associated with serious fall injuries. Evaluation for fall risk factors and fall prevention strategies should be considered for older adults with elevated ACR.

Validation of an Albuminuria Self-assessment Tool in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: We previously developed an 8-item self-assessment tool to identify individuals with a high probability of having albuminuria. This tool was developed and externally validated among non-Hispanic Whites and non-Hispanic Blacks. We sought to validate it in a multi-ethnic cohort that also included Hispanics and Chinese Americans. DESIGN: This is a cross-sectional study. SETTING: Data were collected using standardized questionnaires and spot urine samples at a baseline examination in 2000-2002. The 8 items in the self-assessment tool include age, race, gender, current cigarette smoking, history of diabetes, hypertension, or stroke, and self-rated health. PARTICIPANTS: Of 6,814 community-dwelling adults aged 45-84 years participating in the Multi-Ethnic Study of Atherosclerosis (MESA), 6,542 were included in the primary analysis. MAIN OUTCOME MEASURES: Albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g at baseline. RESULTS: Among non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Chinese Americans, the prevalence of albuminuria was 6.0%, 11.3%, 11.6%, and 10.8%, respectively. The c-statistic for discriminating participants with and without albuminuria was .731 (95% CI: .692, .771), .728 (95% CI: .687, .761), .747 (95% CI: .709, .784), and .761 (95% CI: .699, .814) for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Chinese Americans, respectively. The self-assessment tool over-estimated the probability of albuminuria for non-Hispanic Whites and Blacks, but was well-calibrated for Hispanics and Chinese Americans. CONCLUSIONS: The albuminuria self-assessment tool maintained good test characteristics in this large multi-ethnic cohort, suggesting it may be helpful for increasing awareness of albuminuria in an ethnically diverse population.

Validation study of medicare claims to identify older US adults with CKD using the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

BACKGROUND: Health care claims data may provide a cost-efficient approach for studying chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We compared characteristics and outcomes for individuals with CKD defined using laboratory measurements versus claims data from 6,982 REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study participants who had Medicare fee-for-service coverage. PREDICTORS: Presence of CKD as defined by both the REGARDS Study (CKDREGARDS) and Medicare data (CKDMedicare), presence of CKDREGARDS but not CKDMedicare, and presence of CKDMedicare but not CKDREGARDS, and absence of both CKDREGARDS and CKDMedicare. OUTCOMES: Mortality and incident end-stage renal disease (ESRD). MEASUREMENTS: The research study definition of CKD (CKDREGARDS) included estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m(2) or albumin-creatinine ratio > 30mg/g at the REGARDS Study visit. CKD in Medicare (CKDMedicare) was identified during the 2 years before each participant's REGARDS visit using a claims-based algorithm. RESULTS: Overall, 32% of participants had CKDREGARDS and 6% had CKDMedicare. Sensitivity, specificity, and positive and negative predictive values of CKDMedicare for identifying CKDREGARDS were 15.5% (95% CI, 14.0%-17.1%), 97.7% (95% CI, 97.2%-98.1%), 75.6% (95% CI, 71.4%-79.5%), and 71.5% (95% CI, 70.4%-72.6%), respectively. Mortality and ESRD incidence rates, expressed per 1,000 person-years, were higher for participants with versus without CKDMedicare (mortality: 72.5 [95% CI, 61.3-83.7] vs 33.3 [95% CI, 31.5-35.2]; ESRD: 16.4 [95% CI, 11.2-21.6] vs 1.3 [95% CI, 0.9-1.6]) and with versus without CKDREGARDS (mortality: 59.9 [95% CI, 55.4-64.4] vs 25.5 [95% CI, 23.6-27.4]; ESRD: 6.8 [95% CI, 5.4-8.3] vs 0.1 [95% CI, 0.0-0.3]). Among participants with CKDREGARDS, those with abdominal obesity, diabetes, anemia, lower eGFR, more outpatient visits, hospitalization, and a nephrologist visit in the 2 years before their REGARDS visit were more likely to have CKDMedicare. LIMITATIONS: CKDREGARDS relied on eGFR and albuminuria assessed at a single visit. CONCLUSIONS: CKD, whether defined in claims or through research study measurements, was associated with increased mortality and ESRD. However, individuals with CKD identified in claims may represent a select high-risk population.

Low income and albuminuria among REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants.

BACKGROUND: Albuminuria is an important risk factor for progressive chronic kidney disease (CKD) and is more prevalent in black than white adults. We sought to determine the association between low income and albuminuria and whether this association differs for blacks and whites. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 9,144 black and 13,684 white US adults 45 years and older in the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. PREDICTORS: Self-reported annual household income category (≥$75,000, $35,000-$74,999, $20,000-$34,999, and <$20,000); black and white race. OUTCOMES & MEASUREMENTS: Albuminuria defined as high (30-300 mg/g) or very high (>300 mg/g) urinary albumin-creatinine ratio (ACR). Multinomial logistic regression used to examine the race-stratified association between categories of income and albuminuria (normal, high, or very high ACR). RESULTS: Overall, geometric mean ACR was 10.2 mg/g and was higher for blacks (11.8 mg/g) than whites (9.3 mg/g), P<0.001. Lower income was associated with a higher prevalence of albuminuria for both whites and blacks in unadjusted analyses. After adjustment for demographics, lifestyle factors, comorbid illnesses, and estimated glomerular filtration rate, there was a trend toward a stronger association between lower income levels and high ACR in blacks (ORs of 1.38 [95% CI, 1.07-1.77], 1.36 [95% CI, 1.05-1.75], and 1.58 [95% CI, 1.21-2.05] for income levels of $35,000-$74,999, $20,000-$34,999, and <$20,000, respectively; reference group is those with income≥$75,000) compared with whites (ORs of 0.95 [95% CI, 0.81-1.12], 0.95 [95% CI, 0.79-1.14], and 1.26 [95% CI, 1.02-1.55], respectively); P interaction=0.08 between race and income. Results were similar for very high ACR and subgroups of participants with diabetes or hypertension. LIMITATIONS: Cross-sectional design; not all REGARDS participants provided their annual income. CONCLUSIONS: Lower income may be associated more strongly with albuminuria in blacks than whites and may be a determinant of racial disparities in albuminuria.

Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate.

CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking. OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics. DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012. MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years). RESULTS: Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

Development and validation of a self-assessment tool for albuminuria: results from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

BACKGROUND: The prevalence of albuminuria in the general population is high, but awareness of it is low. Therefore, we sought to develop and validate a self-assessment tool that allows individuals to estimate their probability of having albuminuria. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: The population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study for model development and the National Health and Nutrition Examination Survey (NHANES) 1999-2004 for model validation. US adults 45 years or older in the REGARDS Study (n = 19,697) and NHANES 1999-2004 (n = 7,168). PREDICTOR: Candidate items for the self-assessment tool were collected using a combination of interviewer- and self-administered questionnaires. OUTCOME: Albuminuria was defined as a urinary albumin to urinary creatinine ratio ≥30 mg/g in spot samples. RESULTS: 8 items were included in the self-assessment tool (age, race, sex, current smoking, self-rated health, and self-reported history of diabetes, hypertension, and stroke). These items provided a C statistic of 0.709 (95% CI, 0.699-0.720) and good model fit (Hosmer-Lemeshow χ(2)P = 0.49). In the external validation data set, the C statistic for discriminating individuals with and without albuminuria using the self-assessment tool was 0.714. Using a threshold of ≥10% probability of albuminuria from the self-assessment tool, 36% of US adults 45 years or older in NHANES 1999-2004 would test positive and be recommended for screening. Sensitivity, specificity, and positive and negative predictive values for albuminuria associated with a probability ≥10% were 66%, 68%, 23%, and 93%, respectively. LIMITATIONS: Repeated urine samples were not available to assess the persistency of albuminuria. CONCLUSIONS: 8 self-report items provide good discrimination for the probability of having albuminuria. This tool may encourage individuals with a high probability to request albuminuria screening.

Poverty and racial disparities in kidney disease: the REGARDS study.

UNLABELLED: There are pronounced disparities among black compared to white Americans for risk of end-stage renal disease. This study examines whether similar relationships exist between poverty and racial disparities in chronic kidney disease (CKD) prevalence. METHODS: We studied 22,538 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study. We defined individual poverty as family income below USD 15,000 and a neighborhood as poor if 25% or more of the households were below the federal poverty level. RESULTS: As the estimated glomerular filtration rate (GFR) declined from 50-59 to 10-19 ml/min/ 1.73 m2, the black:white odds ratio (OR) for impaired kidney function increased from 0.74 (95% CI 0.66, 0.84) to 2.96 (95% CI 1.96, 5.57). Controlling for individual income below poverty, community poverty, demographic and comorbid characteristics attenuated the black:white prevalence to an OR of 0.65 (95% CI 0.57, 0.74) among individuals with a GFR of 59-50 ml/min/1.73 m2 and an OR of 2.21 (95% CI 1.25, 3.93) among individuals with a GFR between 10 and 19 ml/min/ 1.73 m2. CONCLUSION: Household, but not community poverty, was independently associated with CKD and attenuated but did not fully account for differences in CKD prevalence between whites and blacks.

Physical and psychological burden of chronic kidney disease among older adults.

INTRODUCTION: The purpose of the study is to determine if functional status and quality of life (QoL) vary with glomerular filtration rate (GFR) among older adults. METHODS: We studied adults aged 45 years and older participating in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study. Data included demographic and health information, serum creatinine and hemoglobin, the 4-item Center for Epidemiologic Studies Depression Scale (CES-D-4), the 4-item Cohen's Perceived Stress Scale (PSS-4), reported health status and inactivity and the Medical Outcomes Study Short Form-12 (SF-12) QoL scores. RESULTS: CKD (GFR <60 ml/min/1.73 m(2)) was present in 11.6% of the subjects. As GFR declined, the SF-12 physical component score, adjusted for other participant attributes, declined from 38.9 to 35.9 (p = 0.0001). After adjustment for other risk factors, poorer personal health scores (p < 0.0001) and decreased physical activity (p < 0.0001) were reported as GFR declined. In contrast, after adjusting for other participant characteristics, depression scores and stress scores and the mental component score of the SF-12 were not associated with kidney function. CONCLUSION: Older individuals with CKD in the US population experience an increased prevalence of impaired QoL that cannot be fully explained by other individual characteristics.

Chronic kidney disease: a public health problem that needs a public health action plan.

For a health problem or condition to be considered a public health issue, four criteria must be met: 1) the health condition must place a large burden on society, a burden that is getting larger despite existing control efforts; 2) the burden must be distributed unfairly (i.e., certain segments of the population are unequally affected); 3) there must be evidence that upstream preventive strategies could substantially reduce the burden of the condition; and 4) such preventive strategies are not yet in place. Chronic kidney disease meets these criteria for a public health issue. Therefore, as a complement to clinical approaches to controlling it, a broad and coordinated public health approach will be necessary to meet the burgeoning health, economic, and societal challenges of chronic kidney disease.

Survival advantage of black patients with kidney disease after acute myocardial infarction.

Black individuals have a disproportionate incidence of ESRD when compared with white individuals, and among patients with ESRD, black patients experience better survival. The aim of this analysis is to assess, in a nationally representative sample of patients with cardiovascular disease, ethnic differences in survival among predialysis patients with kidney disease. A retrospective cohort analysis was conducted of Cooperative Cardiovascular Project data of Medicare patients who were aged > 65 yr and admitted for incident acute myocardial infarction and had 3 yr of mortality follow-up. Cox regression models and Kaplan Meier estimates were performed to examine differences in survival between black and white patients stratified by severity of kidney disease. Of 57,942 patients, 7.3% were black. Black patients were younger and more likely to be female and were less likely to have decreased kidney function. A significant interaction between race and kidney function existed with respect to mortality among patients who survived to discharge. The adjusted hazard ratios for death, black compared with white patients, were 1.00 (95% confidence interval 0.90 to 1.11) among patients with a GFR > or = 60 ml/min per 1.73 m2 and decreased monotonically among patients with lower GFR to 0.79 (95% confidence interval 0.61 to 0.97) among patients with a GFR 15 to 29 ml/min per 1.73 m2. Among patients with incident acute myocardial infarction, black patients with more severe kidney disease, when compared with their white counterparts, experience better survival. Further investigation into the reasons for ethnic differences in survival and progression of kidney disease is warranted.

Delay in time to receipt of thrombolytic medication among Medicare patients with kidney disease.

BACKGROUND: Patients with kidney disease and acute myocardial infarction (AMI) receive standard therapy, including thrombolytic medication, less frequently than patients with normal kidney function. Our goal is to identify potential differences in thrombolytic medication delays and thrombolytic-associated bleeding events by severity of kidney disease. METHODS: This is a retrospective cohort analysis of Cooperative Cardiovascular Project data for all Medicare patients with AMI from 4,601 hospitals. Outcome measures included time to administration of thrombolytic medication censored at 6 hours and bleeding events. RESULTS: Of 109,169 patients (mean age, 77.4 years; 50.6% women), 13.9% received thrombolysis therapy. Average time to thrombolytic therapy was longer in patients with worse kidney function. Adjusted hazard ratios for minutes to thrombolytic therapy were 0.83 (95% confidence interval [CI], 0.79 to 0.87) for patients with a serum creatinine level of 1.6 to 2.0 mg/dL (141 to 177 micromol/L) and 0.58 (95% CI, 0.53 to 0.63) for patients with a creatinine level greater than 2.0 mg/dL (>177 micromol/L) or on dialysis therapy compared with those with normal kidney function. Odds ratios for bleeding events in patients administered thrombolytics versus those who were not decreased with worse kidney function: adjusted odds ratios, 2.28 (95% CI, 2.16 to 2.42) in patients with normal kidney function and 1.84 (95% CI, 1.09 to 3.10) in dialysis patients. CONCLUSION: Patients with worse kidney function experienced treatment delays, but were not at greater risk for thrombolysis-associated excess bleeding events. Physician concerns of thrombolytic-associated bleeding may not be sufficient reason to delay the administration of thrombolytic medication.