Dataset Information

Effect of Two Cystatin C Reagents and Four Equations on Glomerular Filtration Rate Estimations After Standardization.

ABSTRACT:

Background

Serum cystatin C (cysC), which is less affected by sex, race, and muscle mass than creatinine, is a useful biomarker of the estimated glomerular filtration rate (eGFR). The standardization of cysC measurements remains controversial, although a certified reference material (ERM-DA471/IFCC) is available. Moreover, the effect of combinations of cysC reagents and equations for eGFR is unclear.

Methods

We conducted a simulation analysis of cysC measured using two reagents standardized against ERM-DA471/IFCC-Gentian cystatin C immunoassay (Gentian_cys; GentianAS, Moss, Norway) and Roche Tina-quant Cystatin C Gen.2 (Roche_cys; Roche, Mannheim, Germany)-on a Cobas c702 system (Roche) and eGFR generated by eight combinations of four equations: 2012 cystatin C-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI_cys); the Caucasian, Asian, pediatric, and adult equation (CAPA_eq); full age spectrum equation (FAS_eq); and 2023 cystatin C-based European Kidney Function Consortium equation (EKFC_cys).

Results

A total of 148 participants (mean age, 60.5±14.5 years; 43% female) were enrolled. The mean cysC was 1.72±1.44 mg/L for Gentian_cys and 1.71±1.35 mg/L for Roche_cys. Regression analysis showed concordance between the reagents within 0.85-4.40 mg/L when using ±7.61% total allowable error. Lin's concordance correlation coefficient of eGFR, by combining the measuring system and equation, varied from 0.73 to 1.00.

Conclusions

The equivalence of cysC values at low concentrations (<0.85 mg/L) between the two reagents was unsatisfactory. Results obtained with different measurement systems could lead to larger differences in eGFR varying with the combination.

SUBMITTER: Lee HS

PROVIDER: S-EPMC10345172 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Effect of Two Cystatin C Reagents and Four Equations on Glomerular Filtration Rate Estimations After Standardization.

Lee Hyun-Seung HS Bae Go-Eun GE Lee Jung Eun JE Park Hyung-Doo HD

Annals of laboratory medicine 20230630 6

<h4>Background</h4>Serum cystatin C (cysC), which is less affected by sex, race, and muscle mass than creatinine, is a useful biomarker of the estimated glomerular filtration rate (eGFR). The standardization of cysC measurements remains controversial, although a certified reference material (ERM-DA471/IFCC) is available. Moreover, the effect of combinations of cysC reagents and equations for eGFR is unclear.<h4>Methods</h4>We conducted a simulation analysis of cysC measured using two reagents st ...[more]

PMID: 37387489

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Project description:BackgroundThe Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends use of a cystatin C-based estimated glomerular filtration rate (eGFR) to confirm creatinine-based eGFR between 45 and 59 mL · min(-1) · (1.73 m(2))(-1). Prior studies have demonstrated that comorbidities such as solid-organ transplant strongly influence the relationship between measured GFR, creatinine, and cystatin C. Our objective was to evaluate the performance of cystatin C-based eGFR equations compared with creatinine-based eGFR and measured GFR across different clinical presentations.MethodsWe compared the performance of the CKD-EPI 2009 creatinine-based estimated GFR equation (eGFRCr) and the newer CKD-EPI 2012 cystatin C-based equations (eGFRCys and eGFRCr-Cys) with measured GFR (iothalamate renal clearance) across defined patient populations. Patients (n = 1652) were categorized as transplant recipients (n = 568 kidney; n = 319 other organ), known chronic kidney disease (CKD) patients (n = 618), or potential kidney donors (n = 147).ResultseGFRCr-Cys showed the most consistent performance across different clinical populations. Among potential kidney donors without CKD [stage 2 or higher; eGFR >60 mL · min(-1) · (1.73 m(2))(-1)], eGFRCys and eGFRCr-Cys demonstrated significantly less bias than eGFRCr; however, all 3 equations substantially underestimated GFR when eGFR was <60 mL · min(-1) · (1.73 m(2))(-1). Among transplant recipients with CKD stage 3B or greater [eGFR <45 mL · min(-1) · (1.73 m(2))(-1)], eGFRCys was significantly more biased than eGFRCr. No clear differences in eGFR bias between equations were observed among known CKD patients regardless of eGFR range or in any patient group with a GFR between 45 and 59 mL · min(-1) · (1.73 m(2))(-1).ConclusionsThe performance of eGFR equations depends on patient characteristics that are readily apparent on presentation. Among the 3 CKD-EPI equations, eGFRCr-Cys performed most consistently across the studied patient populations.

Project description:IntroductionGlomerular filtration rate (GFR) is typically estimated with equations that use biomarkers such as serum creatinine and/or cystatin-C. The impact of these different biomarkers on GFR estimates in glomerular disease patients is unclear. In this study, we compared the different GFR estimating equations in the Cure Glomerulonephropathy (CureGN) cohort of children and adults with glomerular disease.MethodsAll available cystatin-C measurements from CureGN study participants were matched to same-day serum creatinine measurements to estimate GFR. To explore the strength of agreement between eGFR values obtained from the "Under 25" (U25) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations, we used intraclass correlation coefficients. Multivariable linear mixed effects models were used to determine which factors were independently associated with differences in eGFR values.ResultsA total of 928 cystatin-C measurements were matched to same-day serum creatinine measurements from N = 332 CureGN study participants (58% male, 69% White/Caucasian, 20% Black/African American). Among 628 measurements collected while study participants were under 25 years old, there was moderate agreement (0.731) in serum creatinine versus cystatin-C U25 equations. Models showed that higher eGFR values were associated with larger differences between the two equations (p < 0.001). Among 253 measurements collected while study participants were at least 18 years old, there was excellent agreement (0.891-0.978) among CKD-Epi equations using serum creatinine alone, cystatin-C alone, or the combination of both. Younger age was associated with larger differences between CKD-Epi equations (p = 0.06 to p = 0.016).ConclusionExcellent agreement between CKD-Epi equations indicates continued use of serum creatinine alone for GFR estimation could be appropriate for adults. In contrast, only moderate agreement between U25 equations indicates a need for more frequent measurement of cystatin-C among children and young adults, especially as eGFR increases.

Project description:BackgroundEstimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR.MethodsUsing cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials.ResultsMean measured GFRs were 68 and 70 ml per minute per 1.73 m(2) of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine-cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m(2) with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m(2) with the creatinine equation and the cystatin C equation (P=0.07 and P=0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m(2), respectively [P=0.001 and P<0.001]), and the results were more accurate (percentage of estimates that were >30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m(2), the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m(2) or greater than or equal to 60 ml per minute per 1.73 m(2) (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m(2) as having a GFR of 60 ml or higher per minute per 1.73 m(2).ConclusionsThe combined creatinine-cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Project description:BackgroundAccurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians.MethodsGFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations.ResultsA total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPICys was not significantly different from mGFR (p = 0.38). The CKD-EPICys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m2 (95% CI: -0.608 to -0.98)] and highest accuracy (P30: 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m2.ConclusionExisting creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

Project description:BackgroundSerum creatinine (S-Cr)-based prediction equations are commonly used for estimating glomerular filtration rate (GFR). However, S-Cr concentration is also affected by other factors such as tubular secretion, muscle mass, diet, gender and age. Serum cystatin C (S-Cys C)-based prediction equations have been proposed as an improved potential alternative as S-Cys C levels are not influenced by many of the factors that affect creatinine concentration other than GFR. This may be of great benefit to patients with low muscle mass such as those infected with human immunodeficiency virus who are at increased risk for the development of renal impairment. The aim of this study was to develop and evaluate a S-Cys C-based prediction equation for different stages of renal disease in black South Africans.MethodsOne hundred patients with varying degrees of renal function were enrolled in the study. The plasma clearance of (51)Cr-EDTA, a gold standard method, was used to measure GFR (mGFR). In addition, serum was analysed for S-Cr and S-Cys C on each participant. This dataset was split into a development dataset (n = 50) and a test dataset (n = 50). The development dataset was used to formulate a S-Cys C- and S-Cr-based prediction equation using multiple linear regression analysis. These equations together with the four-variable MDRD and CKD-EPI equation were then tested on the test dataset.ResultsIn the test dataset, accuracy within 15% of measured GFR was 68% for the S-Cys C equation and 48% for the S-Cr equation. Root mean square error for S-Cr eGFR was 10.7 mL/min/1.73 m(2) for those patients with mGFR < 60 mL/min/1.73 m(2) and 25.5 mL/min/1.73 m(2) for those patients with mGFR > 60 mL/min/1.73 m(2). Root mean square error for S-Cys C eGFR was 10.2 mL/min/1.73 m(2) for those patients with mGFR < 60 mL/min/1.73 m(2) and 11.9 mL/min/1.73 m(2) for those patients with mGFR > 60 mL/min/1.73 m(2).ConclusionsIn this study, S-Cys C-based prediction equations appear to be more precise than those of S-Cr for those patients with mGFR > 60 mL/min/1.73 m(2) and may therefore be of benefit in the earlier detection of renal impairment.

Dataset Information

Effect of Two Cystatin C Reagents and Four Equations on Glomerular Filtration Rate Estimations After Standardization.

Background

Methods

Results

Conclusions

Publications

Effect of Two Cystatin C Reagents and Four Equations on Glomerular Filtration Rate Estimations After Standardization.

Similar Datasets

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