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1.  Racial and Ethnic Differences in Albuminuria in Individuals With Estimated GFR Greater Than 60 mL/min/1.73 m2: Results From the Kidney Early Evaluation Program (KEEP) 
Albuminuria is an important marker for chronic kidney disease and progression to end-stage renal disease in the general population; understanding racial and ethnic differences can help inform efforts to reduce health disparities. We sought to estimate independent associations of race/ethnicity with albuminuria to determine whether observed differences were attributable to known kidney disease risk factors.
This cross-sectional study included 64,161 Kidney Early Evaluation Program (KEEP) participants, 2000–2008, with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2, not on regular dialysis, and without previous kidney transplant. Albuminuria (urine albumin-creatinine ratio [ACR] ≥ 30 mg/g) was examined by self-reported race and ethnicity. Covariates were age, sex, educational level, body mass index, diabetes status or glucose level, hypertension status or blood pressure measurement, smoking status, health insurance status, and geographic region.
Albuminuria prevalence was 8% (n = 2303) in whites, 11% (n = 2310) in African Americans, 9% (n = 730) in Hispanics, 10% (n = 381) in Asians, and 15% (n = 344) in American Indians/Alaska Natives. Compared with whites, odds of albuminuria were higher for all groups after multivariate adjustment. Odds were highest for American Indians/Alaska Natives (adjusted odds ratio 1.93, 95% confidence interval 1.70–2.20), then Asians (1.42, 1.26–1.61), African Americans (1.38, 1.29–1.47), and Hispanics (1.19, 1.08–1.31).
In the KEEP study population, albuminuria prevalence was higher among African Americans, Hispanics, Asians, and American Indians/Alaska Natives than among non-Hispanic whites, suggesting a need for screening for early detection of kidney damage, especially among people at increased risk, in the community primary care setting.
PMCID: PMC3507474  PMID: 20172444
2.  Risk Factors for Chronic Kidney Disease among American Indians and Alaska Natives – Findings from the Kidney Early Evaluation Program 
American Journal of Nephrology  2008;29(5):440-446.
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.
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.
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.
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.
PMCID: PMC2821946  PMID: 19011277
Chronic kidney disease; Risk factors; American Indians; Alaska Natives
3.  Comparison of CKD Awareness in a Screening Population Using the Modification of Diet in Renal Disease (MDRD) Study and CKD Epidemiology Collaboration (CKD-EPI) Equations 
Low awareness of chronic kidney disease (CKD) may reflect uncertainty about the accuracy or significance of a CKD diagnosis in individuals otherwise perceived to be low-risk. Whether reclassification of CKD severity using the CKD Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) modifies estimates of CKD awareness is unknown.
In this cross-sectional study, we used data collected from 2000 to 2009 for 26,213 participants in the Kidney Early Evaluation Program (KEEP), a community-based screening program, with CKD based on GFR estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and measurement of albuminuria. We assessed CKD awareness after CKD stage was reclassified using the CKD-EPI equation.
Of 26,213 participants with CKD based on eGFRMDRD, 23,572 (90%) were also classified with CKD based on eGFRCKD-EPI. Based on eGFRMDRD, 9.5% of participants overall were aware of CKD, as were 4.9%, 6.3%, 9.2%, 41.9%, and 59.2% with Stages 1-5, respectively. Based on eGFRCKD-EPI, 10.0% of participants overall were aware of CKD, as were 5.1%, 6.6%, 10.0%, 39.3%, and 59.4% with Stages 1-5, respectively. Reclassification to a less advanced CKD stage with eGFRCKD-EPI was associated with lower odds for awareness (OR, 0.58; 95% CI, 0.50-0.67); reclassification to a more advanced stage was associated with higher odds for awareness (OR, 1.50; 95% CI, 1.05-2.13) after adjustment for confounding factors. Of participants unaware of CKD, 10.6% were reclassified as not having CKD using eGFRCKD-EPI.
Using eGFRCKD-EPI led to a modest increase in overall awareness rates, primarily due to reclassification of low-risk unaware participants.
PMCID: PMC3075598  PMID: 21338846
awareness; chronic kidney disease; CKD-EPI; estimated glomerular filtration rate
4.  Distribution of cardiovascular disease and retinopathy in patients with type 2 diabetes according to different classification systems for chronic kidney disease: a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study 
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF’s KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF’s KDOQI classification.
This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events.
Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF’s KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF’s KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF’s KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped into AKDN and KDIGO risk category 1 and moderate, respectively, and to a lesser extent into higher risk categories.
Though the new systems perform better than the NKF’s KDOQI in grading complications and identifying diabetic subjects without complications, they might underestimate CVD burden in patients assigned to lower risk categories and should be tested in large prospective studies.
Trial registration; NCT00715481
PMCID: PMC4008155  PMID: 24624891
Chronic kidney disease; Classification; eGFR; Albuminuria; Cardiovascular disease; Diabetic retinopathy
5.  Cardiovascular Disease in Chronic Kidney Disease: Data from the Kidney Early Evaluation Program (KEEP) 
Current diabetes reports  2011;11(1):47-55.
Diabetes mellitus (DM) and hypertension (HTN) are leading joint risk factors for both cardiovascular disease (CVD) and chronic kidney disease (CKD). In the nationwide KEEP (Kidney Early Evaluation Program) an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 or a urine albumin:creatinine ratio ≥30 mg/g (3.4 mg/mmol) defines CKD. Overall in KEEP, the rates of identified CKD and self-reported CVD are 25.7% and 22.1%, respectively. The presence of CKD has been associated with younger ages of self-reported myocardial infarction and stroke. The combination of CVD and CKD in KEEP has been associated with shorter survival time. Finally, the presence of CVD or a prior history of coronary revascularization has been associated with modestly better rates of CVD risk factor control; however, the majority of patients with CKD have suboptimally controlled blood pressure, glucose, or lipids. These data suggest that patients with CKD are not only at higher risk for CVD and subsequent mortality, but are also ideal for targeted community—and practice-based interventions to improve risk factor control and, hopefully, reduce rates of subsequent cardiovacular events.
PMCID: PMC3206095  PMID: 21076895
Cardiovascular disease; Chronic kidney disease; Atherosclerosis; Myocardial infarction; Percutaneous coronary intervention; Microalbuminuria; Bypass surgery; Risk factors
6.  The Association between Parathyroid Hormone Levels and Hemoglobin in Diabetic and Nondiabetic Participants in the National Kidney Foundation's Kidney Early Evaluation Program 
Cardiorenal Medicine  2013;3(2):120-127.
Both anemia and secondary hyperparathyroidism are reflections of hormonal failure in chronic kidney disease (CKD). While the association of elevated levels of parathyroid hormone (PTH) and anemia has been studied among those with advanced CKD, less is known about this association in mild-to-moderate CKD.
In a cross-sectional analysis, the relationship between PTH and hemoglobin levels was investigated in 10,750 participants in the National Kidney Foundation's Kidney Early Evaluation Program with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2.
In the unadjusted analysis, higher PTH levels were associated with lower hemoglobin levels. However, after multivariable adjustment for age, race, gender, smoking status, education, cardiovascular disease, diabetes, hypertension, cancer, albuminuria, BMI, baseline eGFR, calcium, and phosphorus, the direction of association changed. As compared to the first PTH quintile, hemoglobin levels were 0.09 g/dl (95% CI: 0.01-0.18), 0.15 g/dl (95% CI: 0.07-0.24), 0.18 g/dl (95% CI: 0.09-0.26), and 0.13 g/dl (95% CI: 0.07-0.25) higher for the second, third, fourth, and fifth quintiles, respectively. Similarly, each standard deviation increase in natural log transformed PTH was associated with a 0.06 g/dl (95% CI: 0.03-0.09, p = 0.0003) increase in hemoglobin. However, a significant effect modification was seen for diabetes (p = 0.0003). Each standard deviation increase in natural log transformed PTH was associated with a 0.10 g/dl (95% CI: 0.054-0.138, p < 0.0001) increase in hemoglobin, while no association was seen among those without diabetes mellitus.
After multivariable adjustment, there was a small positive association between PTH and hemoglobin among diabetics but not among nondiabetics.
PMCID: PMC3721130  PMID: 23922552
Chronic kidney disease; Anemia; Secondary hyperparathyroidism

7.  Assessment of Proteinuria in Patients with Chronic Kidney Disease Stage 3: Albuminuria and Non-Albumin Proteinuria 
PLoS ONE  2014;9(5):e98261.
Background and Objective
Proteinuria assessment is key in investigating chronic kidney disease (CKD) but uncertainty exists regarding optimal methods. Albuminuria, reflecting glomerular damage, is usually measured, but non-albumin proteinuria (NAP), reflecting tubular damage, may be important. This study investigated the prevalence and associations of albuminuria and NAP, and the optimum number of urine specimens required.
1,741 patients with CKD stage 3, recruited from primary care, underwent medical history, clinical assessment, blood sampling, and submitted three early morning urine samples for albumin to creatinine ratio (uACR) and protein to creatinine ratios (uPCR). Albuminuria was defined as uACR ≥3 mg/mmol in at least two of three samples. Isolated NAP was defined as uPCR ≥17 mg/mmol in two of three samples and uACR <3 mg/mmol in all three. Prevalence and associations of albuminuria and NAP, degree of agreement between single uACR and average of three uACRs, and urine albumin to protein ratio (uAPR = uACR/uPCR) were identified.
Albuminuria prevalence was 16% and NAP 6%. Using a <1 mg/mmol threshold for uACR reduced NAP prevalence to 3.6%. Independent associations of albuminuria were: males (OR 3.06 (95% CI, 2.23–4.19)), diabetes (OR 2.14 (1.53–3.00)), lower estimated glomerular filtration rate ((OR 2.06 (1.48–2.85) 30–44 vs 45–59), and high sensitivity CRP ((OR 1.70 (1.25–2.32)). NAP was independently associated with females (OR 6.79 (3.48–13.26)), age (OR 1.62 (1.02–2.56) 80 s vs 70–79) and high sensitivity CRP ((OR 1.74 (1.14–2.66)). Of those with uPCR≥17 mg/mmol, 62% had uAPR<0.4. Sensitivity of single uACR was 95%, specificity 98%, PPV 90%. Bland Altman plot one vs average of three uACRs showed: mean difference 0.0064 mg/mmol (SD 4.69, limits of agreement −9.19 to +9.20, absolute mean difference 0.837).
In CKD stage 3, albuminuria has associations distinct from those of isolated NAP (except for inflammatory markers). Single uACR categorised albuminuria but average of three performed better for quantification.
PMCID: PMC4035283  PMID: 24867154
8.  Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study Equations: Prevalence of and Risk Factors for Diabetes Mellitus in CKD in the Kidney Early Evaluation Program (KEEP) 
Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of prevalent risk factors across stages is unknown.
This is a cross-sectional analysis of data from the Kidney Early Evaluation Program (KEEP), a community-based health screening program targeting individuals 18 years and older with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease. Of 109,055 participants, 68.2% were women and 31.8% were African American. Mean age was 55.3 ± 0.05 years. Clinical, demographic, and laboratory data were collected from August 2000 through December 2009. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations.
CKD was present in 25.6% and 23.5% of the study population using the MDRD Study and CKD-EPI equations, respectively. Diabetes was present in 42.4% and 43.8% of participants with CKD, respectively. Prevalent risk factors for diabetes included obesity (body mass index >30 kg/m2), 44.0%; hypertension, 80.5%; cardiovascular disease, 23.2%; family history of diabetes, 55.9%; and dyslipidemia, 43.0%. In a logistic regression model after adjusting for age and other risk factors, odds for diabetes increased significantly compared with no CKD with each CKD stage based on the CKD-EPI equation and similarly with stages based on the MDRD Study equation. Using a CKD-EPI–adjusted model, ORs were: stage 1, 2.08 (95% CI, 1.90–2.27); stage 2, 1.86 (95% CI, 1.72–2.02); stage 3, 1.23 (95% CI, 1.17–1.30); stage 4, 1.69 (95% CI, 1.42–2.03); and stage 5, 2.46 (95% CI, 1.46–4.14).
Using the CKD-EPI equation led to a lower prevalence of CKD but to similar diabetes prevalence rates associated with CKD across all stages compared with the MDRD Study equation. Diabetes and other CKD risk factor prevalence was increased compared with the non-CKD population.
PMCID: PMC3237700  PMID: 21338847
Chronic kidney disease; diabetes mellitus; estimated glomerular filtration rate
9.  Awareness of Kidney Disease and Relationship to End-Stage Renal Disease and Mortality 
The American Journal of Medicine  2012;125(7):661-669.
Patients with chronic kidney disease are often reported to be unaware. We prospectively evaluated the association between awareness of kidney disease to end-stage renal disease and mortality.
We utilized 2000–2009 data from the National Kidney Foundation-Kidney Early Evaluation Program (KEEP™). Mortality was determined by cross reference to the Social Security Administration Death Master File, and development of end-stage by cross reference with the United States Renal Data System.
Of 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or eGFR <60ml/min/1.73m2. Only 9% (n=2660) reported being aware of kidney disease. Compared to those who were not aware, participants aware of chronic kidney disease had lower eGFR (49 vs 62ml/min/1.73m2) and a higher prevalence of albuminuria (52 vs 46%), diabetes (47 vs 42%), cardiovascular disease (43 vs 28%) and cancer (23 vs 14%). Over 8.5 years of follow-up, aware participants compared to those unaware had a lower rate of survival for end-stage (83% and 96%) and mortality (78 vs 81%), p<0.001 respectively. After adjustment for demographics, socioeconomic factors, comorbidity, and severity of kidney disease, aware participants continued to demonstrate an increased risk for end-stage renal disease [hazard ratio (95% CI) 1.37(1.07–1.75); p<0.0123] and mortality [1.27(1.07–1.52); p<0.0077] relative to unaware participants with chronic kidney disease.
Among persons identified as having chronic kidney disease at a health screening, only a small proportion had been made aware of their diagnosis previously by clinicians. This subgroup was at a disproportionately high risk for mortality and end-stage renal disease.
PMCID: PMC3383388  PMID: 22626510
KEEP; CKD; awareness; ESRD; mortality
10.  Gestational Diabetes Mellitus Alone in the Absence of Subsequent Diabetes Is Associated With Microalbuminuria 
Diabetes Care  2010;33(12):2586-2591.
Women with gestational diabetes mellitus (GDM) maintain a higher risk for recurrent GDM and overt diabetes. Overt diabetes is a risk factor for development of chronic kidney disease (CKD), but GDM alone, without subsequent development of overt diabetes, may also pose a risk for CKD.
This cross-sectional analysis included Kidney Early Evaluation Program (KEEP) participants from 2000 to 2009. Patient characteristics and kidney function among three categories (GDM alone, overt diabetes, and no history of diabetes) were compared. The prevalence of microalbuminuria, macroalbuminuria, and CKD stages 1–2 and 3–5 was assessed using logistic regression.
Of 37,716 KEEP female participants, 571 (1.5%) had GDM alone and 12,100 (32.1%) had overt diabetes. Women with GDM had a higher rate of microalbuminuria but not macroalbuminuria than their nondiabetic peers (10.0 vs. 7.7%) that was substantially lower than the 13.6% prevalence in diabetic women. In multivariate analysis, women with GDM alone, compared with nondiabetic women, demonstrated increased odds of CKD stages 1–2 (multivariate odds ratio 1.54 [95% CI 1.16–2.05]) similar to the odds for women with overt diabetes (1.68 [1.55–1.82]). In stratified analyses, age, race, BMI, and hypertension modified the odds for CKD stages 1 –2 but not CKD stages 3–5 among women with GDM.
Women with GDM alone have a higher prevalence of microalbuminuria than women without any history of diabetes, translating to higher rates of CKD stages 1–2. These results suggest that GDM, even in the absence of subsequent overt diabetes, may increase the risk for future cardiovascular and kidney disease.
PMCID: PMC2992195  PMID: 20807871
11.  Body mass index and metabolic factors predict glomerular filtration rate and albuminuria over 20 years in a high-risk population 
BMC Nephrology  2013;14:177.
The number of individuals suffering from chronic kidney disease (CKD) is increasing. Therefore, early identification of modifiable predictors of CKD is highly desirable. Previous studies suggest an association between body mass index (BMI), metabolic factors and CKD.
Data of 241 high risk patients with information on renal function and albuminuria from the Renal Disease in Vorarlberg (RENVOR) study (2010–2011) were linked with long-term measurements of metabolic factors in the same patients from the population-based Vorarlberg Health Monitoring & Prevention Program (VHM&PP) cohort study (1988–2005). Actual estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (ACR) were determined. BMI, blood pressure, fasting glucose, total cholesterol, triglycerides and Gamma-glutamyltransferase (GGT) were available from previous health examinations performed up to 25 years ago. Linear regression models were applied to identify predictors of current renal function.
At all-time points BMI was significantly inversely associated with actual eGFR and positively with actual albuminuria in men, but not in women. Serum GGT and triglycerides were significantly positively associated with albuminuria in men at all-time points. Fasting glucose levels more than 20 years earlier were associated with increased albuminuria in women and reduced eGFR in men, whereas at later time points it was associated with albuminuria in men.
BMI, serum GGT, and triglycerides are long-term predictors of renal function in men. In women however, anthropometric and metabolic parameters seem to be less predictive of eGFR and albuminuria.
PMCID: PMC3765663  PMID: 23962027
Body mass index; Glomerular filtration rate; Albuminuria; Obesity; Gamma glutamyltransferase; Epidemiology
12.  Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes 
Diabetes & Metabolism Journal  2012;36(6):433-442.
To determine the frequency of chronic kidney disease (CKD) and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.
Patients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.
We recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years). The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval) being 1.93 (1.28 to 2.93), 1.70 (1.09 to 2.64), and 1.03 (1.00 to 1.06), respectively.
In conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.
PMCID: PMC3530714  PMID: 23275937
Albuminuria; Chronic kidney disease; Diabetes mellitus, type 2; Risk factors
13.  Access to Health Care Among Adults Evaluated for CKD: Findings From the Kidney Early Evaluation Program (KEEP) 
Data are scant regarding access to health care in patients with chronic kidney disease (CKD). We performed descriptive analyses using data from the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP), a nationwide health screening program for adults at high risk of CKD.
From 2000–2010, a total of 122,502 adults without end-stage renal disease completed KEEP screenings; 27,927 (22.8%) met criteria for CKD (10,082, stages 1–2; 16,684, stage 3; and 1,161, stages 4–5). CKD awareness, self-rated health status, frequency of physician visits, difficulty obtaining medical care, types of caregivers, insurance status, and medication coverage and estimated costs were assessed.
Participants with CKD were more likely to report fair/poor health status than those without CKD. Health care utilization increased at later CKD stages; ~95% of participants at stages 3–5 had visited a physician during the preceding year compared with 83.7% of participants without CKD. More Hispanic and African American than white participants at all CKD stages reported not having a physician. Approximately 40% of participants younger than 65 years reported fair/poor health status at stages 4–5 compared with ~30% who were 65 years and older. Younger participants at all stages were more likely to report extreme or somewhat/moderate difficulty obtaining medical care. Comorbid conditions (diabetes, hypertension, and prior cardiovascular events) were associated with increased utilization of care. Utilization of nephrology care was poor at all CKD stages; <6% of participants at stage 3 and <30% at stages 4–5 reported ever seeing a nephrologist.
Lack of health insurance and perceived difficulty obtaining medical care with lower health care utilization, both of which are consistent with inadequate access to health care, are more likely for KEEP participants who are younger than 65 years, nonwhite, and without previously diagnosed comorbid conditions. Nephrology care is infrequent in elderly participants with advanced CKD who are nonwhite, have comorbid disease, and have high-risk states for cardiovascular disease.
PMCID: PMC3694584  PMID: 22339901
Chronic kidney disease; health care access; health insurance; medication payment; socioeconomic status; educational status
14.  Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey 
Diabetes & Metabolism Journal  2014;38(2):109-119.
Diabetic nephropathy is a leading cause of end stage renal disease and is associated with an increased risk of cardiovascular mortality. It manifests as albuminuria or impaired glomerular filtration rate (GFR), and the prevalence of diabetic nephropathy varies with ethnicity. The prevalence of diabetic nephropathy and its determinants in Korean adults have not previously been studied at the national level. This cross-sectional study was undertaken to ascertain the prevalence and determinants of albuminuria and chronic kidney disease (CKD) in Korean patients with diabetes.
The Korea National Health and Nutrition Examination Survey (KNHANES) V, conducted in 2011, was used to define albuminuria (n=4,652), and the dataset of KNHANES IV-V (2008-2011) was used to define CKD (n=21,521). Selected samples were weighted to represent the entire civilian population in Korea. Albuminuria was defined as a spot urine albumin/creatinine ratio >30 mg/g. CKD was defined as a GFR <60 mL/min/1.73 m2.
Among subjects with diabetes, 26.7% had albuminuria, and 8.6% had CKD. Diabetes was associated with an approximate 2.5-fold increased risk of albuminuria, with virtually no difference between new-onset and previously diagnosed diabetes. Only systolic blood pressure was significantly associated with albuminuria, and old age, high serum triglyceride levels, and previous cardiovascular disease (CVD) were related with CKD in subjects with diabetes.
Korean subjects with diabetes had a higher prevalence of albuminuria and CKD than those without diabetes. Blood pressure was associated with albuminuria, and age, triglyceride level, and previous CVD were independent determinants of CKD in subjects with diabetes.
PMCID: PMC4021298  PMID: 24851205
Albuminuria; Chronic renal disease; Diabetes mellitus; Diabetic nephropathy; Korea
15.  Prevalence of chronic kidney disease among people living with HIV/AIDS in Burundi: a cross-sectional study 
BMC Nephrology  2011;12:40.
Since little is known about chronic kidney disease (CKD) among people living with HIV/AIDS (PLWHA) in Sub-Saharan Africa, the prevalence and nature of CKD were assessed in Burundi through a multicenter cross-sectional study.
Patients underwent assessments at baseline and 3 months later. Glomerular Filtration Rate (GFR) was estimated using abbreviated 4-variable Modification of Diet in Renal Diseases (MDRD) and Cockroft-Gault estimation methods. Patients were classified at month 3 into various CKD stages using the National Kidney Foundation (NKF) definition, which combines GFR and urinary abnormalities. Risk factors for presence of proteinuria (PRO) and aseptic leukocyturia (LEU) were further analyzed using multiple logistic regression.
Median age of the patients in the study (N = 300) was 40 years, 70.3% were female and 71.7% were on highly active antiretroviral therapy. Using the MDRD method, CKD prevalence in patients was 45.7%, 30.2% of whom being classified as stage 1 according to the NKF classification, 13.5% as stage 2 and 2% as stage 3. No patient was classified as stage 4 or 5. Among CKD patients with urinary abnormality, PRO accounted for 6.1% and LEU for 18.4%. Significant associations were found between LEU and non-steroidal anti-inflammatory drug (NSAID) use, previous history of tuberculosis, low body mass index and female gender and between PRO and high viral load.
Our study, using a very sensitive definition for CKD evaluation, suggests a potentially high prevalence of CKD among PLWHA in Burundi. Patients should be regularly monitored and preventative measures implemented, such as monitoring NSAID use and adjustment of drug dosages according to body weight. Urine dipsticks could be used as a screening tool to detect patients at risk of renal impairment.
PMCID: PMC3175155  PMID: 21864389
chronic kidney disease; kidney damage; aseptic leukocyturia; proteinuria; risk factors; prevalence
16.  Association of Educational Attainment With Chronic Disease and Mortality: The Kidney Early Evaluation Program (KEEP) 
Recent reports have suggested a close relationship between education and health, including mortality, in the United States.
Study Design
Observational cohort
Setting and Participants
We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP).
Self-reported educational attainment
Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality
We evaluated the cross-sectional associations between self-reported educational attainment with the chronic diseases listed above using logistic regression models adjusted for demographics, access to care, behaviors, and co-morbidities. The association of educational attainment with survival was determined by multivariable Cox proportional hazards regression.
Higher educational attainment was associated with lower prevalence of each of the chronic conditions listed above. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of reduced kidney function to 37% lower odds of cardiovascular disease. Over a mean follow-up time of 3.9 years (median, 3.7 years), 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had a 24% lower mortality, compared to participants who had completed at least some high school.
A lack of income data does not allow us to disentangle the independent effects of education from income.
In this diverse, contemporary cohort, higher educational attainment was independently associated with lower prevalence of chronic diseases and short-term mortality among all age and race/ethnicity groups.
PMCID: PMC3144262  PMID: 21601328
education; mortality; chronic kidney disease
17.  Association Between Lack of Health Insurance and Risk of Death and ESRD: Results From the Kidney Early Evaluation Program (KEEP) 
Uninsured adults in the United States have poor access to health care services and worse health outcomes than insured adults. Little is known about the association between lack of insurance and chronic kidney disease (CKD) progression to end-stage renal disease (ESRD) or death in patients at high risk of kidney disease. We used 2000–2011 data from the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP) to examine this association.
The study population included KEEP participants younger than 65 years. Outcomes were time to ESRD (chronic kidney failure treated by renal replacement therapy) and time to death. Incident ESRD was ascertained by linkage to the US Renal Data System, and vital status, by linkage to the Social Security Administration Death Master File. We used Cox proportional hazard regression to examine the association between insurance and risk of death or ESRD after adjusting for demographic variables.
Of 86,588 participants, 27.8% had no form of insurance, 10.3% had public insurance, and 61.9% had private insurance; 15.0% had CKD (defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or urine albumin-creatinine ratio ≥30 mg/g), 63.3% had hypertension, and 27.7% had diabetes. Of participants with CKD, 29.3% had no health insurance. Participants without insurance were younger, more likely to be Hispanic and to have 12 or fewer years of education, and less likely to have seen a physician in the past year. After adjustment for demographic characteristics, uninsured KEEP participants were 82% more likely than privately insured participants to die (HR, 1.82; 95% CI, 1.56–2.12; P < 0.001) and 72% more likely to develop ESRD (HR, 1.72; 95% CI, 1.33–2.22; P < 0.001). The association between insurance and outcomes varied by CKD stage.
Lack of insurance is an independent risk factor for early death and ESRD in this population at high risk of kidney disease. Considering the high morbidity and mortality and increasing cost associated with ESRD, access to appropriate health insurance coverage is warranted.
PMCID: PMC3739048  PMID: 23507267
Chronic kidney disease; end-stage renal disease; health insurance; mortality; public health
18.  Association of HbA1c and cardiovascular and renal disease in an adult Mediterranean population 
BMC Nephrology  2013;14:151.
Increasing evidence suggests a mechanistic link between the glycemic environment and renal and cardiovascular events, even below the threshold for diabetes. We aimed to assess the association between HbA1c and chronic kidney disease (CKD) and cardiovascular disease (CVD).
A cross-sectional study involving a random representative sample of 2270 adults from southern Spain (Malaga) was undertaken. We measured HbA1c, serum creatinine and albuminuria in fasting blood and urine samples.
Individuals without diabetes in the upper HbA1c tertile had an unfavorable cardiovascular and renal profile and shared certain clinical characteristics with the patients with diabetes. Overall, a higher HbA1c concentration was strongly associated with CKD or CVD after adjustment for traditional risk factors. The patients with known diabetes had a 2-fold higher odds of CKD or CVD. However, when both parameters were introduced in the same model, the HbA1c concentration was only significantly associated with clinical endpoints (OR: 1.4, 95% CI, 1.1-1.6, P = 0.002). An increase in HbA1c of one percentage point was associated with a 30% to 40% increase in the rate of CKD or CVD. This relationship was apparent in persons with and without known diabetes. ROC curves illustrated that a HbA1c of 37 mmol/mol (5.5%) was the optimal value in terms of sensitivity and specificity for predicting endpoints in this population.
HbA1c levels were associated with a higher prevalence of CKD and CVD cross-sectionally, regardless of diabetes status. These data support the value of HbA1c as a marker of cardiovascular and renal disease in the general population.
PMCID: PMC3720537  PMID: 23865389
Glycated hemoglobin; Chronic kidney disease; Cardiovascular disease
19.  Association of Chronic Kidney Disease with Atrial Fibrillation Among Adults in the United States: Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study 
Atrial fibrillation (AF) is common among patients with end-stage renal disease, but few data are available on its prevalence among adults with chronic kidney disease (CKD) of lesser severity.
Methods and Results
We evaluated the association of CKD with electrocardiogram-detected AF among 26,917 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a population-based cohort of African-American and white US adults ≥45 years of age. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation and albuminuria was defined as a urinary albumin to creatinine ratio ≥30 mg/g. Participants were categorized by renal function: no CKD (eGFR ≥60 ml/min/1.73m2 without albuminuria, n=21,081), stage 1–2 CKD (eGFR ≥60 ml/min/1.73m2 with albuminuria n=2,938), stage 3 CKD (eGFR 30 to 59 ml/min/1.73m2, n=2,683) and stage 4–5 CKD (eGFR <30 ml/min/1.73m2, n=215). The prevalence of AF among participants without CKD, and with stage 1–2, stage 3, and stage 4–5 CKD was 1.0%, 2.8%, 2.7% and 4.2%, respectively. Compared to participants without CKD, the age, race, sex adjusted odds ratios for prevalent AF were 2.67 (95% CI 2.04 – 3.48), 1.68 (95% CI 1.26 – 2.24) and 3.52 (95% CI 1.73–7.15) among those with stage 1–2, stage 3 and stage 4–5 CKD. The association between CKD and prevalent AF remained statistically significant after further multivariable adjustment and was consistent across numerous subgroups.
- Regardless of severity, CKD is associated with an increased prevalence of AF among US adults.
PMCID: PMC3049935  PMID: 21076159
chronic kidney disease; atrial fibrillation; electrocardiography
20.  The Association between Parathyroid Hormone Levels and the Cardiorenal Metabolic Syndrome in Non-Diabetic Chronic Kidney Disease 
Cardiorenal Medicine  2011;1(2):123-130.
The relationship between parathyroid hormone (PTH) and the cardiorenal metabolic syndrome was examined among non-diabetic persons with chronic kidney disease (CKD).
In a cross-sectional analysis, the relationship between PTH levels and the cardiorenal metabolic syndrome was investigated in 3,215 non-diabetic participants in the National Kidney Foundation-Kidney Early Evaluation Program (KEEP 2.0) found to have CKD (eGFR <60 ml/min/1.73 m2).
In unadjusted analyses, the prevalence of the cardiorenal metabolic syndrome increased along increasing PTH quartiles (31.7, 33.8, 37.3, and 48.7%, respectively, p for trend <0.0001). After multivariate adjustment, as compared to the first PTH quartile, odds of the cardiorenal metabolic syndrome were 16% (p = 0.18), 35% (p = 0.006), and 80% (p < 0.0001) higher for the second, third, and fourth quartiles, respectively. When taken as a continuous predictor, each standard deviation increase of natural log transformed PTH was associated with 26% (p < 0.0001) higher odds of the cardiorenal metabolic syndrome. The association of PTH with the cardiorenal metabolic syndrome was not modified by age or gender (p for interaction was not significant for both modifiers).
Among an outpatient non-diabetic population with CKD, higher PTH levels were associated with a higher prevalence of the cardiorenal metabolic syndrome.
PMCID: PMC3101512  PMID: 22258399
Chronic kidney disease; Hyperparathyroidism; KEEP; Metabolic syndrome
21.  Angiopoietin-2 Is Associated with Albuminuria and Microinflammation in Chronic Kidney Disease 
PLoS ONE  2013;8(3):e54668.
Although cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic kidney disease (CKD), the pathophysiology is not thoroughly understood. Given that elevated albuminuria or circulating angiopoietin-2 associates with CVD and mortality in CKD patients, we were intrigued by the relationship between albuminuria and angiopoietin-2. A total of 416 patients with CKD stages 3 to 5 were stratified by urine albumin-creatinine ratio as normoalbuminuria (<30 mg/g), microalbuminuria (30–300 mg/g), or macroalbuminuria (>300 mg/g). The levels of plasma angiopoietin-2 and vascular endothelial growth factor (VEGF) increased, and soluble Tie-2 decreased in the subgroups of albuminuria; whereas angiopoietin-1 did not change. Linear regression showed a positive correlation between urine albumin-creatinine ratio (ACR) and plasma angiopoietin-2 (correlation coefficient r = 0.301, 95% confidence interval 0.211–0.386, P<0.0001), but not between ACR and VEGF or soluble Tie-2. Multivariate linear regression analysis showed that plasma angiopoietin-2 was independently associated with ACR (P = 0.025). Furthermore, plasma angiopoietin-2 was positively correlated with high sensitive C-reactive protein (r = 0.114, 95% confidence interval 0.018–0.208, P = 0.020). In conclusion, plasma angiopoietin-2 was associated with albuminuria and markers of systemic microinflammation in CKD patients. Although previous evidence has shown that angiopoietin-2 destabilizes vasculature and induces inflammation in different scenarios, further study will be required to delineate the role of angiopoietin-2 in albuminuria and microinflammation in CKD patients.
PMCID: PMC3585725  PMID: 23469160
22.  Diabetic Cardiovascular Disease Predicts Chronic Kidney Disease Awareness in the Kidney Early Evaluation Program 
Cardiorenal Medicine  2011;1(1):45-52.
Lack of chronic kidney disease (CKD) awareness is common. Recent data suggest that the presence of concurrent diabetes may heighten CKD awareness, but current data have not supported the hypothesis that healthcare delivery or insurance status improves awareness in the diabetic population. Diabetes is associated with high cardiovascular disease (CVD) morbidity, especially in patients with CKD. We hypothesized that a highly prevalent co-morbid condition such as CVD in patients with diabetes would predict CKD awareness.
We utilized data from the National Kidney Foundation-Kidney Early Evaluation Program (KEEPTM), a large screening program designed to identify high-risk individuals for CKD and promote awareness.
Among 77,077 participants, CKD was identified in 20,200 and diabetes in 23,082. Prevalence of CVD was higher in participants with than without diabetes (39.5 vs. 22.0%) and in stage 3–5 compared to stage 1–2 CKD (43.3 vs. 34.4%). Patients with diabetes and CVD had a higher level of awareness than those without diabetes (8.2 vs. 2.2%). Among patients with diabetes and CVD, the presence of congestive heart failure was a better predictor of awareness [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.40–2.43] than endpoints such as myocardial infarction or stroke [OR 1.35 (95% CI 1.04–1.73) and OR 1.34 (95% CI 1.04–1.72), respectively].
While prevalence of CKD awareness remained low, our data suggest that in patients with diabetes the presence of CVD was associated with increased awareness in a targeted screening program for CKD awareness.
PMCID: PMC3101520  PMID: 22258465
Cardiovascular disease; Chronic kidney disease; Diabetes mellitus; KEEP
23.  Albuminuria in Hematopoietic Cell Transplant Patients: Prevalence, Clinical Associations and Impact on Survival 
Chronic kidney disease is common after hematopoietic cell transplant. We prospectively measured urinary albumin to creatinine ratios (ACR) in 142 patients. Total (intact) monomeric albumin was determined by liquid chromatography of untreated urine samples collected weekly to day 100 after transplant. Albuminuria was defined as ACR (mg/g creatinine) >30 and proteinuria as ACR >300. Cox and logistic regressions analyses evaluated ACR as a risk factor for clinical events.
The prevalence of albuminuria at baseline, day 100 and 1 year was 37%, 64% and 50%, respectively. Proteinuria occurred in 4% of patients at baseline, 15% at day 100 and 4% at 1 year. Characteristics associated with albuminuria include age, gender, donor type, hypertension and sinusoidal obstruction syndrome. Albuminuria was associated with an increased risk of acute GVHD and bacteremia, but not acute kidney injury. Albuminuria at day 100 was associated with chronic kidney disease at 1 year (OR= 4.0; 95%CI 1.1–14.6). Non-relapse mortality risk was elevated (HR=6.8; 95%CI 1.1–41.5) among patients with overt proteinuria at day 100.
Albuminuria occurs frequently after HCT and correlates with acute GVHD, bacteremia, hypertension and progression of renal disease. Proteinuria at day 100 is associated with an 6-fold increased risk of non-relapse mortality by one year post transplant.
PMCID: PMC2801567  PMID: 19041058
24.  Americans’ Use of Dietary Supplements That Are Potentially Harmful in CKD 
The prevalence in the United States of dietary supplement use that may be harmful to those with chronic kidney disease (CKD) is unknown. We sought to characterize potentially harmful supplement use by individual CKD status.
Study Design
Cross-sectional national survey (National Health and Nutrition Examination Survey, 1999-2008)
Setting & Participants
Community-based survey of 21,169 non-pregnant, non-institutionalized U.S. civilian adults (≥20 years)
CKD status (no CKD, at risk for CKD [presence of diabetes, hypertension and/or cardiovascular disease], stage 1/2 [albuminuria only (albumin-creatinine ratio ≥30 mg/g)], or stage 3/4 [estimated glomerular filtration rate of 15-59 ml/min/1.73 m2]).
Self-reported use of dietary supplements containing any of 37 herbs the National Kidney Foundation identified as potentially harmful in the setting of CKD.
Albuminuria and estimated glomerular filtration rate assessed from urine and blood samples; demographics and comorbid conditions assessed by standardized questionnaire.
An estimated 8.0% of U.S. adults reported potentially harmful supplement use within the last 30 days. Lower crude estimated prevalence of potentially harmful supplement use was associated with higher CKD severity (no CKD, 8.5%; at risk, 8.0%; stage 1/2, 6.1%; and stage 3/4, 6.2%; p<0.001). However, after adjustment for confounders, those with or at risk for CKD were as likely to use a potentially harmful supplement as those without CKD: at-risk OR, 0.93 (95% CI, 0.79 -1.09); stage 1/2 OR, 0.83 (95% CI, 0.64 -1.08); stage 3/4 OR, 0.87 (95% CI, 0.63 -1.18); all vs. no CKD.
Herb content was not available and the list of potentially harmful supplements examined is unlikely to be exhaustive.
The use of dietary supplements potentially harmful to people with CKD is common, regardless of CKD status. Healthcare providers should discuss the use and potential risks of supplements with patients with and at risk for CKD.
PMCID: PMC3628413  PMID: 23415417
25.  Association of kidney disease with prevalent gout in the United States in 1988–1994 and 2007–2010☆ 
To determine the prevalence of gout associated with progressive degrees of kidney disease in the US population.
We performed a cross-sectional analysis among non-institutionalized adults (age 20 and older) of the National Health and Nutrition Examination Surveys in 1988–1994 and 2007–2010. Gout status was ascertained by self-report of physician-diagnosed gout. Chronic kidney disease (CKD) was defined in stages based on estimated glomerular filtration rate (GFR) and single albuminuria measurements (albumin-to-creatinine ratio). Prevalence ratios comparing successive categories of GFR, albuminuria, and CKD as well as temporal trends over a 22-year interval were determined via Poisson regression.
In the US, the crude prevalence of gout was 2–3% among participants without CKD, 4% among participants with CKD stage 1, 6–10% for stage 2, 11–13% for stage 3, and over 30% for stage 4. The adjusted prevalence ratio comparing the CKD stage 4 stratum to participants without CKD was 3.20 (95% CI: 1.96, 5.24) in 2007–2010 and remained significant even after adjustment for serum uric acid. Notably, there was a statistically significant, progressively greater adjusted prevalence ratio of gout associated with successively lower categories of GFR and higher categories of albuminuria.
Among US adults, there exists a strong dose–response association between impaired renal function and prevalent gout. Health providers should be aware of the elevated burden of gout among patients with CKD especially when evaluating new onset joint pain and swelling.
PMCID: PMC3754853  PMID: 23312548
Gout; Chronic kidney disease; Glomerular filtration rate; Albuminuria; NHANES

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