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1.  Association Between Lack of Health Insurance and Risk of Death and ESRD: Results From the Kidney Early Evaluation Program (KEEP) 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1053/j.ajkd.2012.12.015
PMCID: PMC3739048  PMID: 23507267
Chronic kidney disease; end-stage renal disease; health insurance; mortality; public health
2.  Awareness of Kidney Disease and Relationship to End-Stage Renal Disease and Mortality 
The American Journal of Medicine  2012;125(7):661-669.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.amjmed.2011.11.026
PMCID: PMC3383388  PMID: 22626510
KEEP; CKD; awareness; ESRD; mortality
3.  Access to Health Care Among Adults Evaluated for CKD: Findings From the Kidney Early Evaluation Program (KEEP) 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1053/j.ajkd.2011.10.043
PMCID: PMC3694584  PMID: 22339901
Chronic kidney disease; health care access; health insurance; medication payment; socioeconomic status; educational status
4.  A Hypertension Risk Score for Middle-Aged and Older Adults 
Determining which demographic and medical variables predict the development of hypertension could help clinicians stratify risk in both prehypertensive and nonhypertensive persons. Subject-level data from 2 community-based biracial cohorts were combined to ascertain the relationship between baseline characteristics and incident hypertension. Hypertension, defined as diastolic blood pressure ≥90 mm Hg, systolic blood pressure ≥140 mm Hg, or reported use of medication known to treat hypertension, was assessed prospectively at 3, 6, and 9 years. Internal validation was performed by the split-sample method with a 2:1 ratio for training and testing samples, respectively. A scoring algorithm was developed by converting the multivariable regression coefficients to integer values. Age, level of systolic or diastolic blood pressure, smoking, family history of hypertension, diabetes mellitus, high body mass index, female sex, and lack of exercise were associated with the development of hypertension in the training sample. Regression models showed moderate to high capabilities of discrimination between hypertension vs nonhypertension (area under the receiver operating characteristic curve 0.75–0.78) in the testing sample at 3, 6, and 9 years of follow-up. This risk calculator may aide health care providers in guiding discussions with patients about the risk for progression to hypertension.
doi:10.1111/j.1751-7176.2010.00343.x
PMCID: PMC3683833  PMID: 21029343
5.  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.
Background
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.
Methods
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.
Results
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.
Conclusion
After multivariable adjustment, there was a small positive association between PTH and hemoglobin among diabetics but not among nondiabetics.
doi:10.1159/000351229
PMCID: PMC3721130  PMID: 23922552
Chronic kidney disease; Anemia; Secondary hyperparathyroidism

6.  Physician Utilization, Risk-Factor Control, and CKD Progression Among Participants in the Kidney Early Evaluation Program (KEEP) 
Background
Chronic kidney disease (CKD) is a well-known risk factor for cardiovascular mortality, but little is known about the association between physician utilization and cardiovascular disease risk-factor control in patients with CKD. We used 2005–2010 data from the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP) to examine this association at first and subsequent screenings.
Methods
Control of risk factors was defined as control of blood pressure, glycemia, and cholesterol levels. We used multinomial logistic regression to examine the association between participant characteristics and seeing a nephrologist after adjusting for kidney function and paired t tests or McNemar tests to compare characteristics at first and second screenings.
Results
Of 90,009 participants, 61.3% had a primary care physician only, 2.9% had seen a nephrologist, and 15.3% had seen another specialist. The presence of 3 risk factors (hypertension, diabetes, and hypercholesterolemia) increased from 26.8% in participants with CKD stages 1–2 to 31.9% in those with stages 4–5. Target levels of all risk factors were achieved in 7.2% of participants without a physician, 8.3% of those with a primary care physician only, 9.9% of those with a nephrologist, and 10.3% of those with another specialist. Of up to 7,025 participants who met at least one criterion for nephrology consultation at first screening, only 12.3% reported seeing a nephrologist. Insurance coverage was associated strongly with seeing a nephrologist. Of participants who met criteria for nephrology consultation, 406 (5.8%) returned for a second screening, of whom 19.7% saw a nephrologist. The percentage of participants with all risk factors controlled was higher at the second screening (20.9% vs 13.3%).
Conclusion
Control of cardiovascular risk factors is poor in the KEEP population. The percentage of participants seeing a nephrologist is low, although better after the first screening. Identifying communication barriers between nephrologists and primary care physicians may be a new focus for KEEP.
doi:10.1053/j.ajkd.2011.11.019
PMCID: PMC3654535  PMID: 22339899
Cardiovascular disease risk factors; chronic kidney disease; nephrologist care; primary care
7.  A patient self-assessment diabetes screening score: 
Annals of internal medicine  2009;151(11):775-783.
Background
National guidelines disagree on who should be screened for undiagnosed diabetes. No existing diabetes risk score is highly generalizable or widely followed.
Objectives
To develop a new diabetes screening score and compare it to other available screening instruments (Centers for Disease Control and Prevention, American Diabetes Association (ADA) and U.S. Preventive Services Task Force guidelines; two ADA risk questionnaires; and Rotterdam model)
Design
Cross-sectional data.
Setting
National Health and Nutrition Examination Survey (NHANES) 1999–2004 for model development, and NHANES 2005–2006 plus a combined cohort of two community studies, Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS), for validation.
Participants
U.S. adults ≥20 years old.
Measurements
A risk scoring algorithm for undiagnosed diabetes, defined as fasting plasma glucose ≥7.0 mmol/L(126 mg/dL) without known diabetes, was developed in the development dataset. Logistic regression was used to determine participant characteristics that were independently associated with undiagnosed diabetes. The new algorithm and other methods were evaluated by standard diagnostic and feasibility measures.
Results
Age, sex, family history of diabetes, history of hypertension, obesity, and physical activity were associated with undiagnosed diabetes. In NHANES (in ARIC/CHS), the cutpoint of ≥5 selected 30(40)% of persons for diabetes screening and yielded sensitivity of 79(72)%, specificity of 67(62)%, positive predictive value of 10(10)% and likelihood ratio-positive of 2.39(1.89). In contrast, the comparison scores yielded sensitivity of 44–100%, specificity of 10–73%, positive predictive value of 5–8%, and likelihood ratio-positive of 1.11–1.98.
Limitations
Data during pregnancy were not available.
Conclusions
This new diabetes screening score, simple and easily implemented, seems to demonstrate improvements upon the existing methods. Future studies are needed to evaluate it in diverse populations in real world settings.
Primary Funding Source
Clinical and Translational Science Center at Cornell Medical College.
doi:10.1059/0003-4819-151-11-200912010-00005
PMCID: PMC3633111  PMID: 19949143
8.  Dysglycemia but not lipids is associated with abnormal urinary albumin excretion in diabetic kidney disease: a report from the Kidney Early Evaluation Program (KEEP) 
BMC Nephrology  2012;13:104.
Background
The relationship between glycemic control and lipid abnormalities with urinary albumin-creatinine ratio (ACR) in chronic kidney disease (CKD) patients with diabetes mellitus (DM) is unknown. We sought to investigate the association of dyslipidemia and glycemic control with levels of albuminuria in the National Kidney Foundation (NKF) Kidney Early Evaluation Program (KEEP) participants with DM and CKD stage 3 or higher.
Methods
We performed a cross-sectional study of 6639 eligible KEEP patients with DM and CKD Stage 3 to 5 from June 2008 to December 2009. Multivariate logistic regression was used to evaluate the association of lipid parameters (per 10 mg/dl change in serum level) and glycosylated hemoglobin (HbA1c) values with three degrees of albuminuria normo (<30 mg⁄g), micro (30 to 300 mg⁄g) and macro (>300 mg⁄g).
Results
2141 KEEP participants were included. HbA1c levels were strongly associated with micro-albuminuria (compared to normo-albuminuria) and macro-albuminuria (compared to normo-albuminuria and micro-albuminuria). Each 1.0% increase in HbA1c increased the odds of micro-albuminuria by 32% (OR 1.32, 95% CI 1.23-1.42) and the odds of macro-albuminuria (vs. microalbuminuria) by 16% (OR 1.16, 95% CI 1.05-1.28). Only increases in serum HDL were associated with decreased odds of micro-albuminuria; otherwise, the association between other components of the serum lipid profile with urinary ACR did not reach statistical significance.
Conclusion
In this cross-sectional study of 2141 KEEP participants with DM and CKD stages 3–5, overall glycemic control but not lipids were associated with abnormal urinary albumin excretion, a marker of increased risk for progressive disease.
doi:10.1186/1471-2369-13-104
PMCID: PMC3480932  PMID: 22958709
Chronic Kidney Disease; Diabetes Mellitus; Proteinuria; Dyslipidemia; Glycosylated hemoglobin
9.  Sugar-sweetened soda consumption, hyperuricemia, and kidney disease 
Kidney International  2009;77(7):609-616.
The metabolism of high-fructose corn syrup used to sweeten soda drinks may lead to elevations in uric acid levels. Here we determined whether soda drinking is associated with hyperuricemia and, as a potential consequence, reduced kidney function. At baseline, 15,745 patients in the Atherosclerosis Risk in Communities Study completed a dietary questionnaire and had measurements of their serum creatinine and uric acid. After 3 and 9 years of follow-up, multivariate odds ratios from logistic regressions for binary outcome of hyperuricemia and chronic kidney disease (eGFR less than 60 ml/min per 1.73 m2) were evaluated. Compared to participants who drank less, consumption of over one soda per day was associated with increased odds of prevalent hyperuricemia and chronic kidney disease. The odds ratio for chronic kidney disease significantly increased to 2.59 among participants who drank more than one soda per day and had a serum uric acid level over 9.0 mg/dl. In longitudinal analyses, however, drinking more than one soda per day was not associated with hyperuricemia or chronic kidney disease. Neither preexistent hyperuricemia nor development of hyperuricemia modified the lack of association between soda drinking and incident chronic kidney disease. Thus our study shows that high consumption of sugar-sweetened soda was associated with prevalent but not incident hyperuricemia and chronic kidney disease.
doi:10.1038/ki.2009.500
PMCID: PMC3299001  PMID: 20032963
chronic kidney disease; epidemiology; fructose; soda; uric acid
10.  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) 
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1053/j.ajkd.2010.11.009
PMCID: PMC3237700  PMID: 21338847
Chronic kidney disease; diabetes mellitus; estimated glomerular filtration rate
11.  Gestational Diabetes Mellitus Alone in the Absence of Subsequent Diabetes Is Associated With Microalbuminuria 
Diabetes Care  2010;33(12):2586-2591.
OBJECTIVE
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.
RESEARCH DESIGN AND METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
doi:10.2337/dc10-1095
PMCID: PMC2992195  PMID: 20807871
12.  Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel 
Purpose:
A synthetic adrenocorticotropin (ACTH) analog has shown efficacy in Europe as primary and secondary therapy for nephrotic syndrome, but there is no published experience using the natural, highly purified ACTH gel formulation, available in the United States, for nephrotic syndrome. We therefore investigated the use of ACTH gel for nephrotic syndrome in the United States.
Patients and methods:
Twenty-one patients with nephrotic syndrome treated with ACTH gel outside of research settings in the United States, with initiation of therapy by December 31, 2009, allowing a minimum 6 months follow-up. We defined complete remission as stable renal function with proteinuria falling to <500 mg/day, and partial remission as stable renal function with >50% reduction in proteinuria from 500 to 3500 mg/day.
Results:
Twenty-one patients with nephrotic syndrome were treated: 11 with idiopathic membranous nephropathy (iMN), 4 with membranoproliferative glomerulonephritis (MPGN), 1 with focal segmental glomerulosclerosis (FSGS), 1 with minimal change disease (MCD), 1 with immunoglobulin A (IgA) nephropathy, 1 with class V systemic lupus erythematosus (SLE) glomerulonephritis, 1 with monoclonal diffuse proliferative glomerulonephritis, and 1 with unbiopsied nephrotic syndrome. ACTH was used as primary therapy for 3 patients; the remaining patients had previously failed a mean 2.3 immunosuppressive regimens. Eleven patients achieved a complete or partial remission, with 4 (19%) in complete remission. Of the 11 patients who achieved remission, 9 had iMN, 1 had FSGS, and 1 had IgA nephropathy. Of the 11 patients with iMN, 3 (27%) achieved complete remission and 6 (55%) achieved partial remission despite having previously failed a mean 2.4 therapies. Five patients reported steroid-like adverse effects, but there were no severe infections. The limitations were retrospective data analysis with short-term follow-up.
Conclusion:
ACTH gel may be a viable treatment option for resistant nephrotic syndrome due to membranous nephropathy. Short-term data suggest that remission rates may approach 80%.
doi:10.2147/DDDT.S17521
PMCID: PMC3063118  PMID: 21448451
nephrotic syndrome; membranous nephropathy; chronic kidney disease
13.  Diabetic Cardiovascular Disease Predicts Chronic Kidney Disease Awareness in the Kidney Early Evaluation Program 
Cardiorenal Medicine  2011;1(1):45-52.
Aims
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.
Methods
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.
Results
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].
Conclusions
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.
doi:10.1159/000322862
PMCID: PMC3101520  PMID: 22258465
Cardiovascular disease; Chronic kidney disease; Diabetes mellitus; KEEP
14.  Screening for kidney disease in vascular patients: SCreening for Occult REnal Disease (SCORED) experience 
Nephrology Dialysis Transplantation  2009;24(8):2452-2457.
Background. SCreening for Occult REnal Disease (SCORED) is a novel screening guideline recently developed to identify individuals with a high likelihood of having prevalent chronic kidney disease (CKD). This simple scoring system, developed from general US representative samples and independently validated, was shown to outperform current clinical practice guidelines. Recently, CKD screening in individuals with cardiovascular disease (CVD) has been emphasized. We therefore evaluated the SCORED model in CVD patients in order to better understand the implications of CKD screening in this population.
Methods. Two clinical trials that enrolled patients with heart attack (N = 2481) or stroke (N = 3680) were combined to create our sample. The performance of the SCORED guideline was evaluated by standard diagnostic measures. Correlations among various risk scores and their predictive abilities for recurrent CVD were ascertained.
Results. For heart attack and stroke patients, respectively, the SCORED guideline yielded sensitivity of 94 and 97%, specificity of 27 and 11%, positive predictive value of 32 and 30%, negative predictive value of 93 and 89%, with AUC of 0.75 and 0.68. SCORED was strongly correlated with other risk scores and exhibited a similar performance in the prediction of recurrent CVD.
Conclusions. The higher risk of CKD in CVD patients with high SCORED values is demonstrated. This simple education and screening tool may help promote awareness of CKD in CVD patients, in addition to general populations, and assess the CKD risk and its relationship with recurrent CVD.
doi:10.1093/ndt/gfp124
PMCID: PMC2734171  PMID: 19324913
CKD; CVD; ENRICHD; VISP
15.  Interaction of Aldosterone and Extracellular Volume in the Pathogenesis of Obesity-Associated Kidney Disease: A Narrative Review 
American Journal of Nephrology  2009;30(2):140-146.
Obesity and obesity-associated kidney injuries have played an important role in the rising prevalence of chronic kidney disease (CKD). The link between obesity and kidney disease begins with obesity's well-known associations with diabetes and hypertension, the two leading etiologies of CKD. However, a growing body of evidence suggests that elevated aldosterone levels and expanded extracellular volume are key components of obesity-induced renal disease via aldosterone's non-epithelial effects on the kidney. Highlighting these blood pressure- and diabetes-independent mechanisms of kidney injury in obesity allows an exploration of whether mineralocorticoid receptor blockade, coupled with weight loss and salt restriction, is an optimal treatment for overweight CKD patients.
doi:10.1159/000209744
PMCID: PMC2909635  PMID: 19299892
Aldosterone; Extracellular volume; Obesity; Chronic kidney disease
16.  A Simple Algorithm to Predict Incident Kidney Disease 
Archives of internal medicine  2008;168(22):2466-2473.
Background
Despite the growing burden of chronic kidney disease (CKD), there are no algorithms (to our knowledge) to quantify the effect of concurrent risk factors on the development of incident disease.
Methods
A combined cohort (N = 14 155) of 2 community-based studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, was formed among men and women 45 years or older with an estimated glomerular filtration rate (GFR) exceeding 60 mL/min/1.73 m2 at baseline. The primary outcome was the development of a GFR less than 60 mL/min/1.73 m2 during a follow-up period of up to 9 years. Three prediction algorithms derived from the development data set were evaluated in the validation data set.
Results
The 3 prediction algorithms were continuous and categorical best-fitting models with 10 predictors and a simplified categorical model with 8 predictors. All showed discrimination with area under the receiver operating characteristic curve in a range of 0.69 to 0.70. In the simplified model, age, anemia, female sex, hypertension, diabetes mellitus, peripheral vascular disease, and history of congestive heart failure or cardiovascular disease were associated with the development of a GFR less than 60 mL/min/1.73 m2. A numeric score of at least 3 using the simplified algorithm captured approximately 70% of incident cases (sensitivity) and accurately predicted a 17% risk of developing CKD (positive predictive value).
Conclusions
An algorithm containing commonly understood variables helps to stratify middle-aged and older individuals at high risk for future CKD. The model can be used to guide population-level prevention efforts and to initiate discussions between practitioners and patients about risk for kidney disease.
doi:10.1001/archinte.168.22.2466
PMCID: PMC2849985  PMID: 19064831
17.  Association of C-Reactive Protein and Microalbuminuria (from the National Health and Nutrition Examination Surveys, 1999 to 2004) 
The American journal of cardiology  2007;101(3):401-406.
Chronic kidney disease and cardiovascular disease share many risk factors. Injury to the vascular endothelium, measured by elevated levels of serum C-reactive protein (CRP), may play a role in kidney and cardiovascular disease. We therefore examined the association of CRP with microalbuminuria, a marker of early kidney injury. We conducted a cross-sectional analysis of a nationally representative, population-based survey. Weighted multiple logistic regression was used to study the association between CRP and microalbuminuria, adjusting for well-known risk factors. CRP was analyzed by a continuous variable and two categorized variables using quartiles and clinically recommended cutpoints. CRP concentration was positively associated with microalbuminuria. In the multivariate model, a one unit (in milligrams per liter) increase in CRP concentration was associated with a 2% increased odds of microalbuminuria (odds ratio 1.02, 95% confidence interval [CI] 1.01 to 1.02, p = 0.0003). When CRP concentrations were stratified by clinically recommended cutpoints, compared with persons with CRP concentrations <1 mg/dl, persons with CRP concentrations between 1 and 3 mg/L and >3 mg/L were 1.15 times (95% CI 0.94 to 1.42) and 1.33 times (95% CI 1.08 to 1.65) more likely to have microalbuminuria, respectively. In subgroup analyses, the strength of association was comparable or stronger. In conclusion, elevated CRP levels were associated with microalbuminuria in a large, nationally representative data set. Vascular inflammation, as measured by CRP, may be a common contributor to early heart and kidney disease.
doi:10.1016/j.amjcard.2007.08.041
PMCID: PMC2848170  PMID: 18237609
18.  Disordered aldosterone-volume relationship in end-stage kidney disease 
Introduction
Sodium loading, and subsequent volume expansion, suppresses aldosterone levels in individuals with normal renal function. We hypothesised that loss of renal function impairs this volume-aldosterone relationship.
Materials and methods
With multifrequency bioimpedance spectroscopy, we measured total body water (TBW), extracellular volume (ECV), and intracellular volume in five haemodialysis patients at varied states of hydration and in five healthy volunteers during low-, normal-, and high-salt diets. Serum aldosterone, potassium, and C-reactive protein were measured simultaneously. Scatterplots and general estimating equations were used to examine the relationship among these variables.
Results
In healthy volunteers with salt loading, and in haemodialysis subjects with increased inter-dialytic weight gain, expansion of ECV led to reciprocal declines in serum aldosterone concentrations. The relationship was more profound in healthy volunteers (p<0.001) than in haemodialysis subjects (p=0.1). Notably, haemodialysis subjects posted consistently higher levels of ECV (median 49.6% TBW, IQR 43.9–51.8% compared to 41.1%, 39.9–42.8% in volunteers) and serum aldosterone (median 26.7 ng/dl, IQR 19.8–29.6 compared to 12.4 ng/dl, 8.8–16.0 in volunteers). Serum potassium did not appear to influence aldosterone concentration (p=0.9).
Conclusions
The shift of the volume-aldosterone curve in haemodialysis subjects suggests that end-stage kidney disease is a state of high volume and inappropriately high aldosterone. These data have important clinical implications, as dialysis patients may benefit from both volume reduction and mineralocorticoid receptor blockade.
doi:10.1177/1470320309352353
PMCID: PMC2848168  PMID: 19864488
aldosterone; chronic kidney disease; extracellular volume; haemodialysis; mineralocorticoid receptor blockers
20.  Colonic necrosis due to sodium polystyrene sulfate (Kayexalate) 
The American journal of emergency medicine  2009;27(6):753.e1-753.e2.
The rising prevalence of chronic and end-stage kidney disease is accompanied by a concomitant rising risk of hyperkalemia in these patients. Sodium polystyrene sulfonate (Kayexalate, sanofi-aventis, Bridgemater, NJ) is a commonly used treatment of hyperkalemia. We present a case of Kayexalate-induced colonic necrosis as a reminder of this rare, but potentially avoidable, toxicity of a commonly used medication.
doi:10.1016/j.ajem.2008.10.002
PMCID: PMC2843909  PMID: 19751641

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