Performance of Serum β2-Microglobulin- and β-Trace Protein-Based Panel Markers and 2021 Creatinine- and Cystatin-Based GFR Estimating Equations in Pakistan.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC8988004 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
Publications
Performance of Serum β2-Microglobulin- and β-Trace Protein-Based Panel Markers and 2021 Creatinine- and Cystatin-Based GFR Estimating Equations in Pakistan.
Wang Yeli Y Levey Andrew S AS Inker Lesley A LA Jessani Saleem S Bux Rasool R Samad Zainab Z Yaqub Sonia S Karger Amy B AB Allen John C JC Jafar Tazeen H TH
Kidney medicine 20220308 4
Similar Datasets
Project description:BackgroundCurrent 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.MethodsWe 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.ResultsIn 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 m2 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 m2; 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 m2; 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 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 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.ConclusionsNew 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.).
| S-EPMC8822996 | biostudies-literature
Project description:Background and objectiveseGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equations on the basis of creatinine, cystatin C, and both (eGFR creatinine-cystatin C) compared with measured GFR by iothalamate clearance and evaluated their non-GFR determinants and associations across 15 cardiovascular risk factors.Design, setting, participants, & measurementsA cross-sectional cohort of 1139 kidney transplant recipients >1 year after transplant was analyzed. eGFR bias, precision, and accuracy (percentage of estimates within 30% of measured GFR) were assessed. Interaction of each cardiovascular risk factor with eGFR relative to measured GFR was determined.ResultsMedian measured GFR was 55.0 ml/min per 1.73 m(2). eGFR creatinine overestimated measured GFR by 3.1% (percentage of estimates within 30% of measured GFR of 80.4%), and eGFR Modification of Diet in Renal Disease underestimated measured GFR by 2.2% (percentage of estimates within 30% of measured GFR of 80.4%). eGFR cystatin C underestimated measured GFR by -13.7% (percentage of estimates within 30% of measured GFR of 77.1%), and eGFR creatinine-cystatin C underestimated measured GFR by -8.1% (percentage of estimates within 30% of measured GFR of 86.5%). Lower measured GFR associated with older age, women, obesity, longer time after transplant, lower HDL, lower hemoglobin, lower albumin, higher triglycerides, higher proteinuria, and an elevated cardiac troponin T level but did not associate with diabetes, smoking, cardiovascular events, pretransplant dialysis, or hemoglobin A1c. These risk factor associations differed for five risk factors with eGFR creatinine, six risk factors for eGFR Modification of Diet in Renal Disease, ten risk factors for eGFR cystatin C, and four risk factors for eGFR creatinine-cystatin C.ConclusionsThus, eGFR creatinine and eGFR creatinine-cystatin C are preferred over eGFR cystatin C in kidney transplant recipients because they are less biased, more accurate, and more consistently reflect the same risk factor associations seen with measured GFR.
| S-EPMC5012488 | biostudies-literature
Project description:Backgroundβ-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 designStudy of diagnostic test accuracy.Setting & participantsPooled 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).Index testsGFR estimated using creatinine, cystatin C, BTP, or B2M level.Reference testGFR measured as the urinary clearance of iothalamate.ResultsFor 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.LimitationsNo external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race.ConclusionsBTP 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.
| S-EPMC4695294 | biostudies-literature
Project description:Current guidelines recommend reporting eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations unless other equations are more accurate, and recommend the combination of creatinine and cystatin C (eGFRcr-cys) as more accurate than either eGFRcr or eGFRcys alone. However, preferred equations and filtration markers in elderly individuals are debated. In 805 adults enrolled in the community-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we measured GFR (mGFR) using plasma clearance of iohexol, standardized creatinine and cystatin C, and eGFR using the CKD-EPI, Japanese, Berlin Initiative Study (BIS), and Caucasian and Asian pediatric and adult subjects (CAPA) equations. We evaluated equation performance using bias, precision, and two measures of accuracy. We first compared the Japanese, BIS, and CAPA equations with the CKD-EPI equations to determine the preferred equations, and then compared eGFRcr and eGFRcys with eGFRcr-cys using the preferred equations. Mean (SD) age was 80.3 (4.0) years. Median (25th, 75th) mGFR was 64 (52, 73) ml/min per 1.73 m(2), and the prevalence of decreased GFR was 39% (95% confidence interval, 35.8 to 42.5). Among 24 comparisons with the other equations, CKD-EPI equations performed better in 9, similar in 13, and worse in 2. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr in four metrics, better than eGFRcys in two metrics, and similar to eGFRcys in two metrics. In conclusion, neither the Japanese, BIS, nor CAPA equations were superior to the CKD-EPI equations in this cohort of community-dwelling elderly individuals. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr or eGFRcys.
| S-EPMC4520174 | biostudies-literature
Project description:IntroductionThe creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation was calibrated for the general Pakistan population (eGFRcr-PK) to eliminate bias and improve accuracy. Cystatin C-based CKD-EPI equations (eGFRcys and eGFRcr-cys) have not been assessed in this population, and non-GFR determinants of cystatin C are unknown.MethodsWe assessed eGFRcys, eGFRcr-cys, and non-GFR determinants of cystatin C in a cross-sectional study of 557 participants (≥40 years of age) from Pakistan. We compared bias (median difference in measured GFR [mGFR] and eGFR), precision (interquartile range [IQR] of differences), accuracy (percentage of eGFR within 30% of mGFR), root mean square error (RMSE), and classification of mGFR <60 ml/min/1.73 m2 (area under the receiver operating characteristic curve [AUC] and net reclassification index [NRI]) among eGFR equations.ResultsWe found that eGFRcys underestimated mGFR (bias, 12.7 ml/min/1.73 m2 [95% confidence interval {CI} 10.7-15.2]). eGFRcr-cys did not improve performance over eGFRcr-PK in precision (P = 0.52), accuracy (P = 0.58), or RMSE (P = 0.49). Results were consistent among subgroups by age, sex, smoking, body mass index (BMI), and eGFR. NRI was 7.31% (95% CI 1.52%-13.1%; P < 0.001) for eGFRcr-cys versus eGFRcr-PK, but AUC was not improved (0.92 [95% CI 0.87-0.96] vs. 0.90 [95% CI 0.86-0.95]; P = 0.056). Non-GFR determinants of higher cystatin C included male sex, smoking, higher BMI and total body fat, and lower lean body mass.ConclusioneGFRcys underestimated mGFR in South Asians and eGFRcr-cys did not offer substantial advantage compared with eGFRcr-PK. Future studies are warranted to better understand the large bias in eGFRcys and non-GFR determinants of cystatin C in South Asians.
| S-EPMC8071622 | biostudies-literature
Project description:β2-Microglobulin and cystatin C may have advantages over creatinine in assessing risk associated with kidney function. We therefore investigated whether emerging filtration markers, β2-microglobulin and cystatin C, are prospectively associated with risk of the development of peripheral artery disease (PAD). We conducted nested case-control studies among women within the Nurses' Health Study (1990-2010) and among men within the Health Professionals Follow-up Study (1994-2008) with the use of archived blood samples collected before PAD diagnosis. During follow-up, symptomatic PAD was confirmed in 144 women and 143 men. Controls were matched 3:1 based on age, race, smoking status, fasting status, and date of blood sampling. Conditional logistic regression models were used to estimate relative risks (RRs) and were adjusted for plasma creatinine and cardiovascular risk factors. In women, the RRs (95% CI) per 1-SD) increment were 1.16 (0.85 to 1.58) for β2-microglobulin and 0.94 (0.69 to 1.28) for cystatin C. Corresponding RRs in men were 1.50 (1.08 to 2.09) for β2-microglobulin and 1.54 (1.07 to 2.22) for cystatin C. There was no association between creatinine and PAD risk in women, whereas the association in men (RR 1.41, 95% CI 1.10 to 1.81) disappeared after adjustment for either β2-microglobulin or cystatin C. In pooled analyses of men and women, only β2-microglobulin was associated with PAD risk (RR 1.31, 95% CI 1.04 to 1.64). In pooled analyses, β2-microglobulin was associated with an increased risk of symptomatic PAD; a similar association with cystatin C was observed only in men. The findings suggest that β2-microglobulin may capture the atherosclerosis-promoting or atherosclerosis-related elements of kidney dysfunction better than creatinine.
| S-EPMC4310365 | biostudies-literature
Project description:IntroductionGlomerular filtration rate (GFR) is routinely used for clinical assessment of kidney function. However, the accuracy of estimating equations in older adults is uncertain.MethodsIn 66 adults with ≥50 years type 1 diabetes (T1D) duration and 73 nondiabetic controls from age/sex-matched subgroups (65 ± 8 years old and 77[55%] were women) we evaluated the performance of estimated GFR (eGFR) by creatinine (Modification of Diet and Renal Disease [MDRD], Chronic Kidney Disease-Epidemiology [CKD-EPI]cr), cystatin C (CKD-EPIcys, CKD-EPIcr-cys), and β2-microglobulin (β2M) compared with measured GFR by inulin clearance (mGFR). Performance was evaluated using metrics of bias (mean difference), precision (SD), and accuracy (proportion of eGFR that differed by >20% of mGFR).ResultsMean mGFR was 104 ± 18 ml/min per 1.73 m2 (range: 70-154 ml/min per 1.73 m2) and was not different between T1D and controls (103 ± 17 vs. 105 ± 19 ml/min per 1.73 m2, P = 0.39). All equations significantly underestimated mGFR (bias: -15 to -30 ml/min per 1.73 m2, P < 0.001 for all comparisons) except for β2M, which had bias of 1.9 ml/min per 1.73 m2 (P = 0.61). Bias was greatest in cystatin C-based equations. Precision was lowest for β2M (SD: 43.5 ml/min per 1.73 m2, P < 0.001 for each comparison). Accuracy was lowest for CKD-EPIcysC (69.1%, P < 0.001 for each comparison). Cystatin C-based equations demonstrated greater bias and lower accuracy in older age subgroups (<60, 60-69, ≥70 years). All equations demonstrated greater bias across higher ranges of mGFR (60-89, 90-119, ≥120 ml/min per 1.73 m2). Results were similar between T1D and controls except that β2M had lower performance in T1D.ConclusionBetter estimates of GFR in older adults are needed for research and clinical practice, as this subgroup of the population has an amplified risk for the development of chronic kidney disease (CKD) that requires accurate GFR estimation methods.
| S-EPMC6551543 | biostudies-literature
Project description:ObjectiveTo evaluate the performance of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C, and creatinine-cystatin C estimating equations in HIV-positive patients.MethodsWe 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.ResultsOf 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.ConclusionsThe 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.
| S-EPMC3598619 | biostudies-literature
Project description:BackgroundWith the increasing prevalence of childhood obesity and related development of chronic kidney disease (CKD), there is a critical need to understand how best to assess kidney function in children with obesity. Since serum creatinine (SCr) is recommended as marker of first choice for GFR estimation, we evaluated and compared creatinine-based GFR equations in children with overweight and obesity.MethodsSix hundred children with overweight and obesity (53.5% female; mean age 12.20 ± 3.28 years; mean BMI z-score 3.31 ± 0.75) were included from the Centre for Overweight Adolescent and Children's Healthcare (COACH).ResultsSerum creatinine (SCr), normalized using Q-age polynomials obtained from reference values, results in median and mean SCr/Q value close to "1" for all age groups, and 96.5% of the children have a SCr/Q within the reference band [0.67-1.33], corresponding to the 2.5th and 97.5th percentile. eGFR CKiD (bedside Schwartz equation) and Schwartz-Lyon decreased with age, whereas eGFR EKFC and modified CKD-EPI40 showed no age-dependency, but the distribution of eGFR values was not symmetrical. eGFR CKiD under 25 (CKiDU25) demonstrated no age-dependency but major sex differences were observed. eGFR FAS age, FAS height, and adjusted-creatinine revised Lund-Malmö (LMR18) showed a relatively symmetrical distribution and no age-dependency.ConclusionsSerum creatinine (SCr) values of children with overweight and obesity are mostly within the reference range for children. Normalization of SCr using reference Q-age polynomials works very well in this cohort. After evaluation of the different equations, we suggest that FAS age, FAS height, and LMR18 are the preferred creatinine-based GFR-estimating equations in children with overweight and obesity.Clinical trial registrationClinicaltrialgov; Registration Number: NCT02091544. A higher resolution version of the Graphical abstract is available as Supplementary information.
| S-EPMC9395456 | biostudies-literature
Project description:Rationale & objectiveUse of cystatin C in addition to creatinine to estimate glomerular filtration rate (estimated glomerular filtration rate based on cystatin C [eGFRcys] and estimated glomerular filtration rate based on creatinine [eGFRcr], respectively) is increasing. When eGFRcr and eGFRcys are discordant, it is not known which is more accurate, leading to uncertainty in clinical decision making.Study designCross-sectional analysis.Setting & participantsFour thousand fifty participants with measured glomerular filtration rate (mGFR) from 12 studies in North America and Europe.ExposuresSerum creatinine and serum cystatin C.OutcomesPerformance of creatinine-based and cystatin C-based glomerular filtration rate estimating equations compared to mGFR.Analytical approachWe evaluated the accuracy of eGFRcr, eGFRcys, and the combination (eGFRcr-cys) compared to mGFR according to the magnitude of the difference between eGFRcr and eGFRcys (eGFRdiff). We used CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations to estimate glomerular filtration rate. eGFRdiff was defined as eGFRcys minus eGFRcr and categorized as less than -15, -15 to <15, and ≥15 mL/min/1.73 m2 (negative, concordant, and positive groups, respectively). We compared bias (median of mGFR minus eGFR) and the percentage of eGFR within 30% of mGFR.ResultsThirty percent of participants had discordant eGFRdiff (21.0% and 9.6% negative and positive eGFRdiffs, respectively). In the concordant eGFRdiff group, all equations displayed similar accuracy. In the negative eGFRdiff groups, eGFRcr had a large overestimation of mGFR (-13.4 [-14.5 to -12.2] mL/min/1.73 m2) and eGFRcys had a large underestimation (9.9 [9.1-11.2] mL/min/1.73m2), with opposite results in the positive eGFRdiff group. In both negative and positive eGFRdiff groups, eGFRcr-cys was more accurate than either eGFRcr or eGFRcys. These results were largely consistent across age, sex, race, and body mass index.LimitationsFew participants with major comorbid conditions.ConclusionsDiscordant eGFRcr and eGFRcys are common. eGFR using the combination of creatinine and cystatin C provides the most accurate estimates among persons with discordant eGFRcr or eGFRcys.
| S-EPMC10518599 | biostudies-literature