Proportion of Patients with CKD Detected by CKD Stage Prior to Study Visit Compared to Proportion of Patient-reported CKD Awareness.

<p>Proportion of Patients with CKD Detected by CKD Stage Prior to Study Visit Compared to Proportion of Patient-reported CKD Awareness.</p

Prevalence of Chronic Kidney Disease by Stage based on Estimated Glomerular Filtration Rate and Relevant Laboratory Tests at Study Visit (Patients Who Could be Assessed for Chronic Kidney Disease).

<p>Abbreviations: ACR  =  albumin/creatinine ratio; CKD  =  chronic kidney disease; eGFR  =  estimated glomerular filtration rate; N  =  number of patients; N/A  =  not applicable.</p><p>True Positive: Patients who reported as diagnosed with CKD (on CKD History eCRF page) and with actual presence of CKD based on laboratory results from the Study Visit;</p><p>True Negative: Patients who reported as not diagnosed with CKD (on CKD History eCRF page) and without actual presence of CKD based on laboratory results from the Study Visit;</p><p>False Positive: Patients who reported as diagnosed with CKD (on CKD History eCRF page) and without actual presence of CKD based on laboratory results from the Study Visit;</p><p>False Negative: Patients who reported as not diagnosed with CKD (on CKD History eCRF page) and with actual presence of CKD based on laboratory results from the Study Visit.</p><p>a: A total of 9339 patients enrolled in the study, but only 9307 patients had the laboratory test results and medical history records to assess as True Positive, True Negative, False Positive, or False Negative for CKD.</p><p>b: If eGFR, urine dipstick, and urine ACR data were all available:</p><p>•No CKD: Normal eGFR (≥60 mL/min/1.73 m²) with neither positive protein in urine nor urine ACR ≥30 mg/g.</p><p>•Stage 1: Normal eGFR (≥90 mL/min/1.73 m²) with either positive protein in urine or urine ACR ≥30 mg/g.</p><p>•Stage 2: eGFR 60 to 89 mL/min/1.73 m² with either positive protein in urine or urine ACR ≥30 mg/g.</p><p>•Stage 3: eGFR  = 30 to 59 mL/min/1.73 m²;</p><p>•Stage 4: eGFR  = 15to 29 mL/min/1.73 m²; and</p><p>•Stage 5: eGFR <15 mL/min/1.73 m² (Stages 3, 4, 5 were based on eGFR value alone).</p><p>If eGFR, urine dipstick, and urine ACR data were not all available: classify with the worst CKD stage based on the available data from eGFR, urine dipstick, and/or urine ACR.</p><p>Prevalence of Chronic Kidney Disease by Stage based on Estimated Glomerular Filtration Rate and Relevant Laboratory Tests at Study Visit (Patients Who Could be Assessed for Chronic Kidney Disease).</p

Recruitment Flow Diagram.

<p>Recruitment Flow Diagram.</p

Genetics of Plasma Soluble Receptor for Advanced Glycation End-Products and Cardiovascular Outcomes in a Community-based Population: Results from the Atherosclerosis Risk in Communities Study

<div><p>Plasma soluble Receptor for Advanced Glycation End-products (sRAGE) is a strong marker of vascular outcomes although evidence on the direction of association is mixed. Compared to whites, blacks have lower levels of sRAGE. We hypothesized that genetic determinants of sRAGE would help clarify the causal role of sRAGE and the black-white difference in sRAGE levels. We conducted a genome-wide analysis of sRAGE in whites and blacks from the Atherosclerosis Risk in Communities Study. Median plasma sRAGE levels were lower in blacks than whites (728 vs. 1067 pg/ml; P<0.0001). The T (vs. C) allele of rs2070600, a missense variant in <i>AGER</i>, the gene encoding RAGE, was associated with approximately 50% lower sRAGE levels in both whites (N = 1,737; P = 7.26x10^-16; minor allele frequency (MAF) = 0.04) and blacks (N = 581; P = 0.02; MAF = 0.01). In blacks, the T (vs. C) allele of rs2071288, intronic to <i>AGER</i>, was associated with 43% lower sRAGE levels (P = 2.22x10^-8; MAF = 0.10) and was nearly absent in whites. These <i>AGER</i> SNPs explained 21.5% and 26% of the variation in sRAGE in blacks and whites, respectively, but did not explain the black-white difference in sRAGE. These SNPs were not significantly associated with incident death, coronary heart disease, diabetes, heart failure, or chronic kidney disease in whites (N = 8,130–9,017) or blacks (N = 2,293–2,871) (median follow up ~20 years). We identified strong genetic determinants of sRAGE that did not explain the large black-white difference in sRAGE levels or clearly influence risk of clinical outcomes, suggesting that sRAGE may not be a causal factor in development of these outcomes.</p></div

Primary Care Provider Self-Reported Clinical Practice Patterns of Screening Frequency and Factors that Influence Their Likelihood to Screen Patients for Chronic Kidney Disease (Selected Parameters of Interest).

<p>Abbreviations: ACR  =  albumin/creatinine ratio; CKD  =  chronic kidney disease; CVD  =  cardiovascular disease; eGFR  =  estimated glomerular filtration rate; N  =  number of patients; T2DM  =  type 2 diabetes mellitus.</p>a<p>. Only sites with at least 10 enrolled patients were included for this analysis. Sensitivity for each investigator site was defined as (No. of True Positive)/(No. of True Positive + No. of False Negative) x 100%.</p>b<p>. Provider could check more than one category.</p><p>Primary Care Provider Self-Reported Clinical Practice Patterns of Screening Frequency and Factors that Influence Their Likelihood to Screen Patients for Chronic Kidney Disease (Selected Parameters of Interest).</p

Manhattan plot for genome-wide association for ln(sRAGE) in whites (N = 1,737).

<p>Manhattan plot for genome-wide association for ln(sRAGE) in whites (N = 1,737).</p

<i>AGER</i> SNPs and risk of death, incident coronary heart disease, heart failure, diabetes, and chronic kidney disease by race.

<p>Abbreviations: CHD, coronary heart disease; CKD, chronic kidney disease. Hazard ratio for T vs. C allele adjusted for age, sex, and center. Median follow up in years displayed.</p

Manhattan plot for genome-wide association for ln(sRAGE) in blacks (N = 581).

<p>Manhattan plot for genome-wide association for ln(sRAGE) in blacks (N = 581).</p

Characteristics of black and white participants with sRAGE levels (N = 2,329).^a^,^b^,^c^,^d

<p>^a Continuous variables reported as means (SD) and categorical variables as n (%). Median (p25, p75) provided for sRAGE.</p><p>^b Education, n = 1739 for whites and 588 for blacks; prevalent CHD, n = 1707 for whites and n = 577 for blacks; eGFR, n = 568 for blacks; fasting glucose, n = 1726 for whites and n = 586 for blacks</p><p>^c P<0.05 for differences between race groups for all characteristics</p><p>^d Abbreviations: sRAGE, soluble receptor for advanced glycation end-products; BMI, body mass index; CHD, coronary heart disease; eGFR, estimated glomerular filtration rate</p><p>Characteristics of black and white participants with sRAGE levels (N = 2,329).<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128452#t001fn001" target="_blank">^a</a>^,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128452#t001fn002" target="_blank">^b</a>^,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128452#t001fn003" target="_blank">^c</a>^,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128452#t001fn004" target="_blank">^d</a></p

Genetic variants and the black-white difference in ln(sRAGE).

<p>Model 1: age + race + gender + center</p><p>Model 2: Model 1 + rs2070600 + rs2071288</p><p>Model 3: Model 2 + education</p><p>Model 4: Model 3 + BMI, eGFR, fasting glucose, prevalent CHD</p><p>^aBeta for difference in ln(sRAGE) for T vs. C allele</p><p>Genetic variants and the black-white difference in ln(sRAGE).</p