Chronic Kidney Disease Epidemiology Collaboration Creatinine-cystatin Research Articles

β-Trace Protein and β2-Microglobulin do not Improve Estimation of Glomerular Filtration Rate in Kidney Transplant Recipients Compared With Creatinine and Cystatin C

Reliable estimates of glomerular filtration rate (eGFR) are important for detecting changes in graft function in kidney transplant recipients. Current eGFR equations are based on plasma creatinine and/or cystatin C; however, these are associated with significant bias. This study investigated if equations based on β-trace protein (BTP) and β2-microglobulin (B2M) performed better than the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on creatinine and cystatin C among kidney transplant recipients. We included samples and data from the clinical trial CONTEXT. Glomerular filtration rate (GFR) was measured by plasma clearance of an exogenous marker. The eGFR was calculated using the CKD-EPI equations for estimating GFR from BTP and/or B2M and the 2021 CKD-EPI creatinine and creatinine-cystatin C equations. The GFR estimates were evaluated 3 (n=82) and 12 (n=64) months after transplant using mean bias, precision, and accuracy. Furthermore, we analyzed the ability of the equations to correctly classify the direction of changes in measured GFR from 3 to 12 months. Among the BTP- and B2M-based equations, the combined eGFR-BTP-B2M performed best with respect to precision (SD=7.64 mL/min/1.73 m2) and accuracy (±10% from measured GFR=36%). The eGFR-BTP-B2M and the eGFR-creatinine-cystatin C (2021) performed similarly when comparing precision, accuracy, and residuals (P=.481). The BTP- and/or B2M-based equations did not perform better than the eGFR-creatinine-cystatin C (2021) in correctly classifying the direction of changes in measured GFR from 3 to 12 months. β-trace protein and/or B2M do not improve the estimation of GFR when compared with creatinine- and cystatin C-based 2021 CKD-EPI equations.

A-071 Comparison of eGFR Calculated by the MDRD, the 2021 CKD-EPI Creatinine and the 2021 CKD-EPI Creatinine-cystatin C Equations in Taiwanese

Abstract Background The new race-free 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine and the 2021 CKD-EPI Creatinine-cystatin C equations are endorsed by the National Kidney Foundation. This study aimed to evaluate the difference between the different equations in the results of eGFR <60 and ≥60 mL/min/1.73 m2 in different genders and ages in Taiwan. Methods We retrospectively collected 1403 laboratory data from adults with both serum creatinine and cystatin C tested results from January 2022 to October 2022, including 870 males and 533 females. We calculated the eGFR by MDRD, 2021 CKD-EPI Creatinine, and 2021 CKD-EPI Creatinine-cystatin C equations and divided the results into two groups according to eGFRMDRD <60 or ≥60 mL/min/1.73 m2, and then analyzed the bias and concordance between different equations according to age (18–29, 30–49, 50–69, ≥70) and gender, and used pair T-test or Wilcoxon sign rank test, P values less than 0.05 were considered statistically significant. Results (1) Compared with the eGFRMDRD, the results of eGFR2021 CKD-EPI Creatinine and eGFR2021 CKD-EPI Creatinine-cystatin C showed a positive bias of 2.2 (P < 0.001) and 1.8 (P < 0.001) mL/min/1.73 m2 in the eGFRMDRD < 60 group, 5.4 (P < 0.001) and 2.4 (P = 0.010) mL/min/1.73 m2 in the eGFRMDRD ≥60 group. (2) In addition, in the eGFRMDRD <60 group, there were 7.0% (42/601) male and 8.1% (28/345) female would be reclassified to the ≥60 group by the 2021 CKD-EPI Creatinine, and including 8.8% (53/601) male and 4.9% (17/345) female would be reclassified to the ≥60 group by the 2021 CKD-EPI Creatinine-cystatin C. (3) In eGFRMDRD ≥60 group, there was no patient would be reclassified to the <60 groups by the 2021 CKD-EPI Creatinine, and including 3.0% (8/269) male and 3.2% (6/188) female would be reclassified to the <60 group by the 2021 CKD-EPI Creatinine-cystatin C. Conclusion Compared with MDRD, most of the 2021 CKD-EPI Creatinine and 2021 CKD-EPI Creatinine-cystatin C equations showed positive bias. It also reflected that about 5% of patients whose eGFRMDRD <60 mL/min/1.73 m2 would be reclassified to the ≥60 group by the 2021 CKD-EPI Creatinine and 2021 CKD-EPI Creatinine-cystatin C. Clinical laboratories should fully understand the differences between different equations to ensure the quality of clinical testing.

Abstract P374: Greater Burden Of Chronic Kidney Disease Is Associated With Hypertension Prevalence And Management In South Africa

Introduction: Complications e.g., chronic kidney disease (CKD) are frequent with longstanding hypertension, particularly if poorly managed. Hypothesis: We assessed the hypothesis that prevalence and associations of CKD differed by hypertension prevalence, awareness, treatment and control in South Africa using five CKD estimates. Methods: In this randomly selected cross-sectional study, glomerular filtration rate (GFR) was estimated by CKD Epidemiology Collaboration (CKD-EPI) equations [CKD-EPI creatinine (CKD-EPIcr), CKD-EPI cystatin C, CKD-EPI creatinine-cystatin C], Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formula (CGF). Blood pressures were measured, and history of hypertension management collected. Results: Among 1092 participants, mean age 43.5 years, 64% women, the prevalence of hypertension was 42% with similar rates in men (41%) and women (43%). In participants with hypertension (n=460), awareness, treatment and control were 61.5% (283/460), 47.2% (217/460) and 27.0% (124/460), with better rates in women compared with men (p<0.001). CKD prevalence (GFR<60 mL/min/1.73m 2 ) was 2.0-5.9% overall using 5 formulae, and significantly higher in participants with (3.9-10.2%) compared to without hypertension (0.6-2.7%) (p<0.001). In participants with hypertension, CKD was higher in those aware (5.7-13.8%) vs unaware (1.1-4.5%) of their diagnosis (p≤0.015), on treatment (6.9-14.3%) vs none (1.2-6.6%) (p≤0.016), and those with controlled (BP<140/90 mmHg) vs uncontrolled hypertension (6.5-15.1% vs. 3-8%, p≤0.096). In models adjusted for age, sex and obesity, higher hypertension prevalence and awareness were significantly (p<0.05) associated with CKD by CKD-EPIcr and MDRD equations; hypertension treatment was significantly associated with CKD by CKD-EPIcr, MDRD and CGF formulae, while hypertension control was not associated with CKD. Conclusions: This study highlights the higher prevalence and greater likelihood of CKD in participants with hypertension and those who were diagnosed and receiving treatment, likely due to the longer duration of their hypertension compared with their counterparts. Higher CKD in the diagnosed and treated reinforces the need for optimal control, which was low in this cohort.

Importance of cystatin C in estimating glomerular filtration rate: the PARADIGM-HF trial.

The 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation combining creatinine and cystatin C provides a better estimation of glomerular filtration rate (GFR) compared to the creatinine-only equation. CKD-EPI creatinine-cystatin C equation (creatinine-cystatin) was compared to creatinine-only (creatinine) equation in a subpopulation of Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF). Patients were categorized according to difference in eGFR using the two equations: Group 1 (<-10 mL/min/1.73 m2, i.e. creatinine-cystatin more than 10 mL/min lower than creatinine), Group 2 (>-10 and <10 mL/min/1.73 m2), and Group 3 (>10 mL/min/1.73 m2, i.e. creatinine-cystatin more than 10 mL/min higher than creatinine). Cystatin C and creatinine were available in 1966 patients at randomization. Median (interquartile range) eGFR difference was -0.7 (-6.4-4.8) mL/min/1.73 m2. Compared to creatinine, creatinine-cystatin led to a substantial reclassification of chronic kidney disease stages. Overall, 212 (11%) and 355 (18%) patients were reallocated to a better and worse eGFR category, respectively. Compared to patients in Group 2, those in Group 1 (lower eGFR with creatinine-cystatin) had higher mortality and those in Group 3 (higher eGFR with creatinine-cystatin) had lower mortality. Increasing difference in eGFR (due to lower eGFR with creatinine-cystatin compared to creatinine) was associated with increasing elevation of biomarkers (including N-terminal pro-B-type natriuretic peptide and troponin) and worsening Kansas City Cardiomyopathy Questionnaire clinical summary score. The reason why the equations diverged with increasing severity of heart failure was that creatinine did not rise as steeply as cystatin C. The CKD-EPI creatinine-only equation may overestimate GFR in sicker patients. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01035255.

Altered kidney function induced by SARS-CoV-2 infection and acute kidney damage markers predict survival outcomes of COVID-19 patients: a prospective pilot study

Background Literature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage markers and their predictive value for survival among hospitalized subjects with COVID-19. Methods Forty-seven participants was included and grouped as: ‘COVID-19 patients before treatment’, ‘COVID-19 patients after treatment’, ‘COVID-19 patients under treatment in intensive care unit (ICU)’, and ‘controls’. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan–Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well. Results Serum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine–cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups ‘COVID-19 patients before treatment’ and ‘COVID-19 patients under treatment in ICU’. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22–30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00–2.52; p = 0.09). Conclusions Our findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.

Comparison of cystatin C-based and creatinine-based glomerular filtration rate in the prediction of postoperative residual hypertension in aldosterone-producing adenoma patients after adrenalectomy

Renal function is associated with postoperative residual hypertension in aldosterone-producing adenoma(APA) patients. Cystatin C-based glomerular filtration rate (GFR) can more accurately estimate renal function than creatinine-based methods. However, which renal function estimation method can more accurately predict postoperative hypertension in APA patients is still unknown.We recruited 180 APA patients who underwent adrenalectomy. Preoperative creatinine and cystatin C-based GFRs were calculated. Residual hypertension was defined as persistent hypertension > 140/90 mmHg or requiring anti-hypertensive medications 1 year after surgery.Sixty-five(36.1%) of the 180 APA patients had residual hypertension. Multivariate logistic regression and receiver operating characteristic (ROC) curve analysis showed a combination of creatinine and cystatin method CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin GFR was significantly associated with residual postoperative hypertension and had the largest area under the ROC curve, which was statistically larger than that of Cockcroft-Gault creatinine-based GFR. In both net reclassification index and integrated discrimination index models, CKD-EPI creatinine-cystatin GFR significantly improved the discriminatory power of CG-GFR.Among these renal function estimations used in the presented study, creatinine-cystatin combined GFR was a precise method to predict residual postoperative hypertension in APA patients received adrenalectomy. These finding may help identify those patients with higher risk of residual hypertension after operation.

Urinary excretion of epidermal growth factor and rapid loss of kidney function.

Lower urinary excretion of the kidney tubule-specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population. Subjects without CKD or diabetes were recruited from the general population in Tromso, Norway [Renal Iohexol Clearance Survey (RENIS); N = 1249] and Groningen, the Netherlands [Prevention of REnal and Vascular END-stage disease (PREVEND); N = 4534], with a median follow-up of 5.6 and 7.4 years, respectively. GFR was measured by iohexol clearance in the RENIS and estimated using the CKD Epidemiology Collaboration creatinine-cystatin C equation in the PREVEND study. Rapid GFR decline was defined as an annual GFR loss >3.0 mL/min/1.73 m2 and in sensitivity analyses as subjects with the 10% steepest GFR slope within each cohort. Lower baseline uEGF excretion was associated with rapid GFR loss in both cohorts {RENIS, odds ratio [OR] per 1 μg/mmol lower uEGF 1.42 [95% confidence interval (CI) 1.06-1.91], P = 0.02; PREVEND, OR 1.29 [95% CI 1.10-1.53], P < 0.01}, adjusted for baseline GFR, albumin:creatinine ratio and conventional CKD risk factors. Similar results were obtained using the outcome of the 10% steepest GFR slope in each cohort. Lower uEGF levels were associated with incident CKD in the combined analysis of both cohorts. Lower uEGF levels are associated with increased risk of rapid GFR loss and incident CKD in the general population. This finding, together with previous findings in CKD and high-risk populations, supports that uEGF may serve as a broadly applicable biomarker representing the tubular component of the current glomerulus-centric clinical risk assessment system.

Agreement and Precision Analyses of Various Estimated Glomerular Filtration Rate Formulae in Cancer Patients

The accuracy of the estimated glomerular filtration rate (eGFR) in cancer patients is very important for dose adjustments of anti-malignancy drugs to reduce toxicities and enhance therapeutic outcomes. Therefore, the performance of eGFR equations, including their bias, precision, and accuracy, was explored in patients with varying stages of chronic kidney disease (CKD) who needed anti-cancer drugs. The reference glomerular filtration rate (GFR) was assessed by the 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA) plasma clearance method in 320 patients and compared with the GFRs estimated by i) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, ii) the unadjusted for body surface area (BSA) CKD-EPI equation, iii) the re-expressed Modification of Diet in Renal Disease (MDRD) study equation with the Thai racial factor, iv) the Thai eGFR equation, developed in CKD patients, v) the 2012 CKD-EPI creatinine-cystatin C, vi) the Cockcroft-Gault formula, and vii) the Janowitz and Williams equations for cancer patients. The mean reference GFR was 60.5 ± 33.4 mL/min/1.73 m2. The bias (mean error) values for the estimated GFR from the CKD-EPI equation, BSA-unadjusted CKD-EPI equation, re-expressed MDRD study equation with the Thai racial factor, and Thai eGFR, 2012 CKD-EPI creatinine-cystatin-C, Cockcroft-Gault, and Janowitz and Williams equations were −2.68, 1.06, −7.70, −8.73, 13.37, 1.43, and 2.03 mL/min, respectively, the precision (standard deviation of bias) values were 6.89, 6.07, 14.02, 11.54, 20.85, 10.58, and 8.74 mL/min, respectively, and the accuracy (root-mean square error) values were 7.38, 6.15, 15.97, 14.16, 24.74, 10.66, and 8.96 mL/min, respectively. In conclusion, the estimated GFR from the BSA-unadjusted CKD-EPI equation demonstrated the least bias along with the highest precision and accuracy. Further studies on the outcomes of anti-cancer drug dose adjustments using this equation versus the current standard equation will be valuable.

Relations of liver fat with prevalent and incident chronic kidney disease in the Framingham Heart Study: A secondary analysis.

Prior studies demonstrated an association between non-alcoholic fatty liver disease and chronic kidney disease (CKD), though data are conflicting. We examined the association between liver fat and prevalent and incident CKD in the Framingham Heart Study (FHS). We included FHS participants who underwent computed tomography (CT) from 2002 to 2005 (n=1315). After excluding heavy alcohol use (n=211) and missing covariates (n=117), the final sample included 987 participants. For the incident CKD analysis, we excluded 73 participants with prevalent CKD. Liver fat was measured by the average liver attenuation on CT. Estimated glomerular filtration rate (eGFR) was obtained using the CKD Epidemiology Collaboration Creatinine-Cystatin C equation, and CKD was defined as eGFR<60ml/min/1.73m2 . Microalbuminuria was defined by sex-specific urinary albumin-creatinine ratio cut-offs. Multivariable-adjusted regression models were performed to determine the association between liver fat and CKD. The prevalence of hepatic steatosis and CKD were 19% and 14% respectively (55.9% women, mean age 60±9years). After adjusting for covariates, we observed no significant associations between liver fat and CKD, microalbuminuria or eGFR in cross-sectional analyses. We observed positive associations between liver fat, incident microalbuminuria and reduced eGFR in age- and sex-adjusted models; these relationships were not significant in multivariable-adjusted models. In this community-based cohort study, we did not observe significant associations between liver fat and prevalent or incident CKD with a median follow-up time of 12.5years. The association between NAFLD and CKD may be accounted for by shared risk factors; confirmatory studies are needed.

Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT

Random assignment to the intensive systolic blood pressure (SBP) arm (<120mmHg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in more rapid declines in estimated glomerular filtration rates (eGFRs) than in the standard arm (SBP<140mmHg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown. Longitudinal subgroup analysis of clinical trial participants. Random sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined as eGFR<60mL/min/1.73m2 by the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation at baseline. Urine biomarkers of tubule function (β2-microglobulin [B2M], α1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach. 978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72±9 years and eGFR was 46.1±9.4mL/min/1.73m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1 and year 4. None of the8 tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two tubule function markers (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year 1 in the intensive versus standard arm, respectively. Exclusion of persons with diabetes, and few participants had advanced CKD. Among participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells.

Combined creatinine-cystatin C CKD-EPI equation significantly underestimates measured glomerular filtration rate in people with type 2 diabetes mellitus

AimTo evaluate the accuracy of creatinine and cystatin C (cysC) equations to estimate glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM) patients and healthy adults. MethodsCase-control study including 84 patients with type 2 DM and 100 healthy adults with measured GFR (mGFR)≥60mL/min/1.73m2. GFR was measured by 51Cr-EDTA and estimated (eGFR) by the following equations using creatinine, cysC or both markers: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Caucasian Asian Pediatrics and Adults (CAPA), CKD-EPI creatinine-cystatin C (CKDEPI-CC), and CKD-EPI cystatin C (CKDEPIcysC). Agreement was evaluated by Bland & Altman analysis. ResultsHealthy individuals were 66% females, aged 38±14years; they presented mGFR 112±19mL/min/1.73m2 and eGFR by CKD-EPI, CKDEPI-CC, CKDEPIcysC and CAPA equations, respectively, 108±17, 102±15, 97±16 and 93±16mL/min/1.73m2. DM group were 50% females, aged 59±19years and presented mGFR 104±27 and eGFR 87±19, 80±18, 74±20 and 73±18mL/min/1.73m2, respectively. All equations significantly underestimated mGFR, excepting creatinine-based CKD-EPI in the healthy group. The performance was considerably worse for GFRs above 120mL/min/1.73m2. ConclusionIn both healthy and type 2 DM patients, cystatin C-based equations, including the combined CKD-EPI creatinine-cystatin equation, failed to improve the accuracy of GFR estimation, especially for normal and high normal GFR values.

CKD-EPI creatinine-cystatin C glomerular filtration rate estimation equation seems more suitable for Chinese patients with chronic kidney disease than other equations

BackgroundThe aim of this study was to identify the optimal equation that accurately estimates the glomerular filtration rate (GFR) and the chronic kidney disease (CKD) stage in the Chinese population.MethodsA total of 1296 Chinese patients aged 18–65 years old were enrolled in this study. The estimated GFRs (eGFRs) calculated separately by three Diet in Renal Disease (MDRD) equations and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations were compared with the reference GFR (rGFR) measured by the 99Tcm-DTPA renal dynamic imaging method.ResultsBy Bland-Altman analysis, eGFRcys and eGFRscr_cys performed similarly, showing the tightest limits of agreement among the six equations. They also achieved the first and second highest 30% and 50% accuracies. Using a combination of the serum creatinine and cystatin C levels (eGFRscr_cys) could improve the bias (−0.3 for eGFRscr_cys) of the equation and achieve the highest diagnostic accuracy for renal insufficiency (AUC60, 0.953; P < 0.05, except for eGFR_MDRD). All equations predicted stage 3 CKD with moderate accuracy (49.7–51.4%) and stage 5 CKD with good accuracy (90.2–96.4%). For stage 1 CKD, eGFRcys showed a higher percentage of misclassification than the other equations. All equations seemed to perform poorly at predicting stage 2 and 4 CKD, as compared to the other CKD stages. eGFRscr_cys was the best-performing equation in terms of accurate classification of the CKD stage based on the overall performance (kappa value, 0.423).ConclusionFor a Chinese population, the CKD-EPIscr_cys equation seems more suitable for estimating the GFR than the other equations. Each equation had its own advantages in predicting different CKD stages.

Predictive performance of different kidney function estimation equations in lung transplant patients

BackgroundThere has been limited examination of the performance of glomerular filtration rate estimation (eGFR) equations in lung transplant populations. This study aimed to compare the performance of serum creatinine and cystatin C based eGFR equations with Tc-99m diethylenetriaminepentaacetic acid (DTPA) GFR measurements in individuals with end-stage lung disease, either prior to, or following, lung transplantation. MethodsIn this prospective observational study, participants underwent GFR measurements with Tc-99m Pentetate. Measured results were compared with GFR estimates derived from estimation equations [4-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C and creatinine-cystatin C combined equations]. ResultsNinety-seven individuals were studied (77 post- and 20 wait-listed for transplantation). Median (range) radionucleotide GFR was 56.7ml/min/1.73m2 (22.8–109.2ml/min/1.73m2). In the study cohort as a whole, the CKD-EPI creatinine-cystatin C combined equation showed the highest performance, but was only slightly superior to the CKD-EPI creatinine equation. However, in individuals with cystic fibrosis, low arm muscle mass and/or low body mass index, all of the creatinine-based equations showed unacceptable performance. In these subgroups, improved GFR estimation was seen with the CKD-EPI cystatin C equation, and predictions were better still using the CKD-EPI creatinine-cystatin C combined equation. ConclusionsThis study shows adequate predictive ability of CKD-EPI creatinine in the cohort as a whole, but unacceptable performance in patients with cystic fibrosis, low arm muscle mass and/or low body mass index. Our findings demonstrate that cystatin C may be a preferable filtration marker in these subgroups.

Estimated GFR, Albuminuria, and Cognitive Performance: The Maastricht Study

Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population. Cross-sectional analyses of a prospective population-based cohort study. 2,987 individuals aged 40 to 75 years from the general population (The Maastricht Study). eGFR and urinary albumin excretion (UAE). Memory function, information processing speed, and executive function. Analyses were adjusted for demographic variables (age, sex, and educational level), lifestyle factors (smoking behavior and alcohol consumption), depression, and cardiovascular disease risk factors (glucose metabolism status, waist circumference, total to high-density lipoprotein cholesterol ratio, triglyceride level, use of lipid-modifying medication, systolic blood pressure, use of antihypertensive medication, and prevalent cardiovascular disease). UAE was<15mg/24 h in 2,439 (81.7%) participants, 15 to<30 mg/24 h in 309 (10.3%), and≥30mg/24 h in 239 (8.0%). In the entire study population, UAE≥30mg/24 h was associated with lower information processing speed as compared to UAE<15mg/24 h (β [SD difference]=-0.148; 95% CI,-0.263 to-0.033) after full adjustment, whereas continuous albuminuria was not. However, significant interaction terms (P for interaction< 0.05) suggested that albuminuria was most strongly and extensively associated with cognitive performance in older individuals. Mean (±SD) eGFR, estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin C equation (eGFRcr-cys), was 88.4±14.6 mL/min/1.73m2. eGFRcr-cys was not associated with any of the domains of cognitive performance after full adjustment. However, significant interaction terms (P for interaction< 0.05) suggested that eGFRcr-cys was associated with cognitive performance in older individuals. Cross-sectional design, which limited causal inferences. In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFRcr-cys was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals.

GFR Estimation Using β-Trace Protein and β2-Microglobulin in CKD

β-Trace protein (BTP) and β2-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers. Study of diagnostic test accuracy. Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N=3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study). GFR estimated using creatinine, cystatin C, BTP, or B2M level. GFR measured as the urinary clearance of iothalamate. For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation. No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race. BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use.

Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA)

Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear. Retrospective cohort study. 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60mL/min/1.73 m(2) using the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation. Serum bicarbonate concentrations. Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60mL/min/1.73 m(2) with minimum rate of eGFR loss of 1 mL/min/1.73 m(2) per year). Average bicarbonate concentration was 23.2 ± 1.8mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. Cause of metabolic acidosis cannot be determined in this study. Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m(2). If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m(2).

Uric Acid Levels, Kidney Function, and Cardiovascular Mortality in US Adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002

Chronic kidney disease (CKD) and hyperuricemia often coexist, and both conditions are increasing in prevalence in the United States. However, their shared role in cardiovascular risk remains highly debated. Cross-sectional and longitudinal. Participants in the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2002 (n = 10,956); data were linked to mortality data from the National Death Index through December 31, 2006. Serum uric acid concentration, categorized as the sex-specific lowest (< 25th), middle (25th- < 75th), and highest (≥ 75th) percentiles; and kidney function assessed by estimated glomerular filtration rate (eGFR) based on the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation and urinary albumin-creatinine ratio (ACR). Cardiovascular death and all-cause mortality. Uric acid levels were correlated with eGFR(cr-cys) (r = -0.29; P < 0.001) and were correlated only slightly with ACR (r = 0.04; P < 0.001). There were 2,203 deaths up until December 31, 2006, of which 981 were due to cardiovascular causes. Overall, there was a U-shaped association between uric acid levels and cardiovascular mortality in both women and men, although the lowest risk of cardiovascular mortality occurred at a lower level of uric acid for women compared with men. There was an association between the highest quartile of uric acid level and cardiovascular mortality even after adjustment for potential confounders (HR, 1.48; 95% CI, 1.13-1.96), although this association was attenuated after adjustment for ACR and eGFR(cr-cys) (HR, 1.25; 95% CI, 0.89-1.75). The pattern of association between uric acid levels and all-cause mortality was similar. GFR not measured; mediating events were not observed. High uric acid level is associated with cardiovascular and all-cause mortality, although this relationship was no longer statistically significant after accounting for kidney function.

Is the Chronic Kidney Disease Epidemiology Collaboration creatinine&amp;ndash;cystatin C equation useful for glomerular filtration rate estimation in the elderly?

BackgroundWe aimed to evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine–cystatin C equation in a cohort of elderly Chinese participants.Materials and methodsGlomerular filtration rate (GFR) was measured in 431 elderly Chinese participants by the technetium-99m diethylene-triamine-penta-acetic acid (99mTc-DTPA) renal dynamic imaging method, and was calibrated equally to the dual plasma sample 99mTc-DTPA-GFR. Performance of the CKD-EPI creatinine–cystatin C equation was compared with the Cockcroft–Gault equation, the re-expressed 4-variable Modification of Diet in Renal Disease (MDRD) equation, and the CKD-EPI creatinine equation.ResultsAlthough the bias of the CKD-EPI creatinine–cystatin C equation was greater than with the other equations (median difference, 5.7 mL/minute/1.73 m2 versus a range from 0.4–2.5 mL/minute/1.73 m2; P<0.001 for all), the precision was improved with the CKD-EPI creatinine–cystatin C equation (interquartile range for the difference, 19.5 mL/minute/1.73 m2 versus a range from 23.0–23.6 mL/minute/1.73 m2; P<0.001 for all comparisons), leading to slight improvement in accuracy (median absolute difference, 10.5 mL/minute/1.73 m2 versus 12.2 and 11.4 mL/minute/1.73 m2 for the Cockcroft–Gault equation and the re-expressed 4-variable MDRD equation, P=0.04 for both; 11.6 mL/minute/1.73 m2 for the CKD-EPI creatinine equation, P=0.11), as the optimal scores of performance (6.0 versus a range from 1.0–2.0 for the other equations). Higher GFR category and diabetes were independent factors that negatively correlated with the accuracy of the CKD-EPI creatinine–cystatin C equation (β=−0.184 and −0.113, P<0.001 and P=0.02, respectively).ConclusionCompared with the creatinine-based equations, the CKD-EPI creatinine–cystatin C equation is more suitable for the elderly Chinese population. However, the cost-effectiveness of the CKD-EPI creatinine–cystatin C equation for clinical use should be considered.

Performance of Creatinine and Cystatin C GFR Estimating Equations in an HIV-Positive Population on Antiretrovirals

To evaluate the performance of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C, and creatinine-cystatin C estimating equations in HIV-positive patients. We evaluated the performance of the Modification of Diet in Renal Disease (MDRD) Study and CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012, and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate (GFR) estimating equations compared with GFR measured using plasma clearance of iohexol in 200 HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were standardized to certified reference materials. Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an undetectable HIV viral load. Mean (SD) measured GFR (mGFR) was 87 (26) mL/min per 1.73 m. All CKD-EPI equations performed better than the MDRD Study equation. All 3 CKD-EPI equations had similar bias and precision. The cystatin C equation was not more accurate than the creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the cystatin C equation, and there was a trend toward greater accuracy than the creatinine equation. Accuracy was equal or better in most subgroups with the combined equation compared to either alone. The CKD-EPI cystatin C equation does not seem to be more accurate than the CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-EPI creatinine equation for routine clinical care for use in North American populations with HIV. The use of both filtration markers together as a confirmatory test for decreased estimated GFR based on creatinine in individuals who are HIV-positive requires further study.