Effect of Adopting the New Race-Free 2021 Chronic Kidney Disease Epidemiology Collaboration Estimated Glomerular Filtration Rate Creatinine Equation on Racial Differences in Kidney Disease Progression among People with Human Immunodeficiency Virus: An Observational Study

Background: The impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown. Methods: We defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models. Results: With the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI],. 73-.82), an equal risk of progressing from stage 2 to 3 (1.00;. 92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants. Conclusions: The original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD

Kidney function and markers of inflammation in elderly persons without chronic kidney disease: The health, aging, and body composition study

Inflammatory markers are elevated in persons with estimated glomerular filtration rates less than 60ml/min/1.73m2. As cystatin C may detect small changes in kidney function not detected by estimated glomerular filtration rate, we evaluated the association between cystatin C and serum markers of inflammation in older adults with estimated glomerular filtration rate ≥60. This is an analysis using measures from the Health, Aging, and Body Composition Study, a cohort of well-functioning adults aged 70–79 years. Cystatin C correlated with all five inflammatory biomarkers: C-reactive protein (r=0.08), interleukin-6 (r=0.19), tumor necrosis factor α (TNF-α) (r=0.41), soluble TNF receptor 1 (STNF-R1) (r=0.61), and soluble TNF receptor 2 (STNF-R2) (r=0.54); P<0.0005 for all. In adjusted analyses, cystatin C concentrations appeared to have stronger associations with each biomarker compared with estimated glomerular filtration rate or serum creatinine. Participants with a cystatin C≥1.0mg/l had significantly higher levels of all five biomarkers compared to those with a cystatin C<1.0 (mean differences ranging 16–29%, all P<0.05). Cystatin C has a linear association with inflammatory biomarkers in an ambulatory elderly cohort with estimated glomerular filtration rates ≥60; associations are particularly strong with TNF-α and the STNF-R

Marijuana Use and Estimated Glomerular Filtration Rate in Young Adults.

Marijuana use has become more widely accepted in the United States and has been legalized in many areas. Although it is biologically plausible that marijuana could affect kidney function, epidemiologic data are lacking. We conducted a cohort study among young adults with preserved eGFR ( &lt;i&gt;i.e.&lt;/i&gt; , eGFR≥60 ml/min per 1.73 m &lt;sup&gt;2&lt;/sup&gt; ) using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. At scheduled examinations occurring every 5 years and starting at study year 10 (calendar years, 1995-1996), cystatin C was collected over a 10-year period, and urine albumin-to-creatinine ratio was collected over a 15-year period. We investigated the cross-sectional association between current and cumulative marijuana use (in marijuana-years; one marijuana-year equals 365 days of marijuana use) and eGFR by cystatin C (eGFR &lt;sub&gt;cys&lt;/sub&gt; ) at year 10. In longitudinal analyses, we investigated the association between cumulative marijuana use and eGFR &lt;sub&gt;cys&lt;/sub&gt; change and rapid (≥3%/year) eGFR &lt;sub&gt;cys&lt;/sub&gt; decline over two 5-year intervals and prevalent albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) over a 15-year period. Past or current marijuana use was reported by 83% (3131 of 3765) of the cohort, and the mean eGFR &lt;sub&gt;cys&lt;/sub&gt; was 111 ml/min per 1.73 m &lt;sup&gt;2&lt;/sup&gt; at year 10. Over the following 10 years, 504 had rapid eGFR &lt;sub&gt;cys&lt;/sub&gt; decline, and over the following 15 years, 426 had prevalent albuminuria. Compared with no use, daily current use and ≥5 marijuana-years of cumulative use were associated with lower eGFR &lt;sub&gt;cys&lt;/sub&gt; at year 10: -4.5% (95% confidence interval, -8.1 to -0.7%; &lt;i&gt;P&lt;/i&gt; =0.02) and -3.0% (95% confidence interval, -5.6 to -0.4%; &lt;i&gt;P&lt;/i&gt; =0.03), respectively. Marijuana use was not significantly associated with eGFR &lt;sub&gt;cys&lt;/sub&gt; change, rapid eGFR &lt;sub&gt;cys&lt;/sub&gt; decline, or prevalent albuminuria. Although we identified a modest cross-sectional association between higher marijuana exposure and lower eGFR &lt;sub&gt;cys&lt;/sub&gt; among young adults with preserved eGFR, our findings were largely null and did not demonstrate a longitudinal association between marijuana use and eGFR &lt;sub&gt;cys&lt;/sub&gt; change, rapid eGFR &lt;sub&gt;cys&lt;/sub&gt; decline, or prevalent albuminuria. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_24_CJASNPodcast_17_10.mp3

Supplementary Material for: A Risk Score to Guide Cystatin C Testing to Detect Occult-Reduced Estimated Glomerular Filtration Rate

<strong><em>Background/Aims:</em></strong> Persons with occult-reduced estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m² detected by serum cystatin C but missed by creatinine) have high risk for complications. Among persons with preserved kidney function by creatinine-based eGFR (eGFRcreat >60 ml/min/1.73 m²), tools to guide cystatin C testing are needed. <b><i>Methods:</i></b> We developed a risk score to estimate an individual's probability of reduced eGFR by cystatin C (eGFRcys <60 ml/min/1.73 m²) in The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and externally validated in the Third National Health and Nutrition Examination Survey (NHANES III). We used logistic regression with Bayesian model averaging and variables available in practice. We assessed performance characteristics using calibration and discrimination measures. <b><i>Results:</i></b> Among 24,877 adults with preserved kidney function by creatinine, 13.5% had reduced eGFRcys. Older and Black participants, current smokers and those with higher body mass index, lower eGFRcreat, diabetes, hypertension and history of cardiovascular disease were more likely to have occult-reduced eGFR (p < 0.001). The final risk function had a c-statistic of 0.87 in REGARDS and 0.84 in NHANES. By risk score, 72% of occult-reduced eGFR cases were detected by screening only 22% of participants. <b><i>Conclusions:</i></b> A risk score using characteristics readily accessible in clinical practice can identify the majority of persons with reduced eGFRcys, which is missed by creatinine.<br

Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study

The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle-brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P = 0.44), but a higher prevalence of ABI 0.9-1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0.9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9-1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53-15.31) and men (3.49, 1.39-8.72). However, ABI 0.9-1.0 was significantly associated with incident clinical PAD (3.33, 1.44-7.70) and incident stroke (2.45, 1.38-4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD

Cystatin C versus Creatinine in Determining Risk Based on Kidney Function

<p>BACKGROUND</p><p>Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined.</p><p>METHODS</p><p>We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C.</p><p>RESULTS</p><p>In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR.</p><p>CONCLUSIONS</p><p>The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations.</p>

CKD-EPI and EKFC GFR Estimating Equations: Performance and Other Considerations for Selecting Equations for Implementation in Adults.

New eGFR equations from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) using creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice, leading to uncertainty in selecting equations for implementation. The authors evaluated performance of equations in an independent population of 4050 adults and evaluated other considerations important for implementation. They found that CKD-EPI and EKFC equations are approaching convergence, with better performance of eGFRcr-cys equations in the overall group and fewer differences among race, sex, and age subgroups than eGFRcr equations. Larger differences among eGFRcr equations reflect regional population differences in creatinine, forcing a trade-off between accuracy and uniformity in global implementation of eGFRcr equations. More widespread use of cystatin C could avoid this trade-off. New CKD-EPI and EKFC eGFR equations using eGFRcr, eGFRcys, and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice. A better understanding of the equations, including their performance in race, sex and age subgroups, is important for selection of eGFR equations for global implementation. We evaluated performance (bias and P 30 ) of equations and methods used for equation development in an independent study population comprising 4050 adults pooled from 12 studies. The mean (SD) measured GFR was 76.4 (29.6) ml/min per 1.73 m 2 and age 57.0 (17.4) years, with 1557 (38%) women and 579 (14%) Black participants. Coefficients for creatinine, cystatin C, age, and sex in the CKD-EPI and EKFC equations are similar. Performance of the eGFRcr-cys equations in the overall population (bias &lt;±5 ml/min per 1.73 m 2 and P 30 &gt;90%) was better than the eGFRcr or eGFRcys equations, with fewer differences among race, sex, and age subgroups. Differences in performance across subgroups reflected differences in diversity of source populations and use of variables for race and sex for equation development. Larger differences among eGFRcr equations reflected regional population differences in non-GFR determinants of creatinine. CKD-EPI and EKFC equations are approaching convergence. It is not possible to maximize both accuracy and uniformity in selecting one of the currently available eGFRcr equations for implementation across regions. Decisions should consider methods for equation development in addition to performance. Wider use of cystatin C with creatinine could maximize both accuracy and uniformity of GFR estimation using currently available equations

New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.

Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct. We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations. In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m &lt;sup&gt;2&lt;/sup&gt; of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m &lt;sup&gt;2&lt;/sup&gt; ; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m &lt;sup&gt;2&lt;/sup&gt; ; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m &lt;sup&gt;2&lt;/sup&gt; ; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m &lt;sup&gt;2&lt;/sup&gt; ; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks. New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)