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Existing creatinine-based equations overestimate glomerular filtration rate in Indians.

ABSTRACT: Accurate 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.GFR 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.A 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?

SUBMITTER: Kumar V

PROVIDER: S-EPMC5796440 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Existing creatinine-based equations overestimate glomerular filtration rate in Indians.

Kumar Vivek V Yadav Ashok Kumar AK Yasuda Yoshinari Y Horio Masaru M Kumar Vinod V Sahni Nancy N Gupta Krishan L KL Matsuo Seiichi S Kohli Harbir Singh HS Jha Vivekanand V

BMC nephrology 20180201 1

<h4>Background</h4>Accurate 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 ...[more]

PMID: 29390980

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Project description:OBJECTIVES:To evaluate the performance of kidney function estimation equations and to determine the frequency of drug dose discordance in an older population. DESIGN:Cross-sectional analysis of data from community-dwelling volunteers randomly selected from the Baltimore Longitudinal Study of Aging from January 1, 2005, to December 31, 2010. SUBJECTS:A total of 269 men and women with a mean ± SD age of 81 ± 6 years, mean serum creatinine concentration (Scr ) of 1.1 ± 0.4 mg/dl, and mean 24-hour measured creatinine clearance (mClcr ) of 53 ± 13 ml/minute. MEASUREMENTS AND MAIN RESULTS:Kidney function was estimated by using the following equations: Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The performance of each equation was assessed by measuring bias and precision relative to mClcr . Dose calculation errors (discordance) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared with the dosages approved by the Food and Drug Administration. The CG equation was the least biased estimate of mClcr . The MDRD and CKD-EPI equations were significantly positively biased compared with CG (mean ± SD 34 ± 20% and 22 ± 15%, respectively, p<0.001) and mClcr (29 ± 47% and 18 ± 40%, respectively, p<0.001). Rounding low Scr values (less than 1.0 mg/dl) up to an arbitrary value of 1.0 mg/dl resulted in CG values (44 ± 10 ml/minute) that were significantly lower than mClcr (56 ± 12 ml/minute, p<0.001) and CG (56 ± 15 ml/minute, p<0.001). The MDRD and CKD-EPI equations had median dose discordance rates of 28.6% and 22.9%, respectively. CONCLUSION:The MDRD and CKD-EPI equations significantly overestimated creatinine clearance (mClcr and CG) in elderly individuals. This leads to dose calculation errors for many drugs, particularly in individuals with severe renal impairment. Thus equations estimating glomerular filtration rate should not be substituted in place of the CG equation in older adults for the purpose of renal dosage adjustments. In addition, the common practice of rounding or replacing low Scr values with an arbitrary value of 1.0 mg/dl for use in the CG equation should be avoided. Additional studies that evaluate alternative eGFR equations in the older populations that incorporate pharmacokinetic and pharmacodynamic outcomes measures are needed.

Project description:BACKGROUND:The 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. METHODS:We 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). RESULTS:eGFRCr-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). CONCLUSIONS:The 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:ImportanceEstimating glomerular filtration rate (GFR) is useful in many clinical conditions. However, very few studies have evaluated the performance of GFR-estimating equations in older adults at various degrees of kidney impairment.ObjectiveTo determine the performance of plasma-creatinine-based equations Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI), Lund-Malmö Revised, (LMR), full age spectrum (FAS), and Berlin Initiative Study (BIS) 1 in older adults across a broad spectrum of GFRs.Design, setting, and participantsSingle-center cross-sectional study performed in France including 2247 participants aged 65 to 90 years who underwent inulin GFR measurements from July 1, 2003, to July 30, 2017, for suspected or established renal dysfunction, for renal risk, before kidney donation, or after kidney transplant.Main outcomes and measuresThe main outcome measure was GRF measured by inulin clearance. Equation performance criteria considered bias (difference between estimated and measured GFR), precision (interquartile range of the median difference), and accuracy P30 (percentage of estimated GFRs lying between [measured GFR - 30% of measured GFR] and [measured GFR + 30% of measured GFR]).ResultsThe mean (SD) age of the 2247 participants was 71.5 (5) years and 1192 (53.0%) were male. The difference in median (95% CI) bias was significant between CKD-EPI vs LMR (-4.0 [-4.0 to -3.5 mL/min/1.73 m2; P?<?.001]) and CKD-EPI vs FAS (-2.0 [-3.5 to -2.5] mL/min/1.73 m2, P?<?.001) but not significant between CKD-EPI vs BIS 1 (0.0 [-1.5 to 0.5], P?=?.07, Mood test). In patients aged 65 to 74 years with measured GFR<45 mL/min/1.73 m2, the difference in median P30 (95% CI) was not significant between CKD-EPI vs LMR (P?=?.08) and CKD-EPI vs FAS (P?=?.48) but significant vs BIS 1 (P?=?.004, McNemar test). In subjects 75 years and older, with measured GFR less than 45 mL/min/1.73 m2, LMR and BIS 1 were more accurate than CKD-EPI and FAS (P30?=?74.5 [70.0-79.5] and 73.0 [68.0-78.0] vs 69.0 [64.5-74.0] and 69.0 [65.5-72.0]). In all patients, despite small statistical differences, the performance of CKD-EPI equation was not clinically different from that of LMR, FAS, or BIS 1.Conclusions and relevanceIn a referral group of patients 65 years and older who had GFR estimated using CDK-EPI, LMR, BIS 1, and FAS equations, a comparison with renal inulin clearance found that none of the equations had a superior diagnostic performance. Each had limitations regarding accuracy.

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: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.

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Existing creatinine-based equations overestimate glomerular filtration rate in Indians.

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Existing creatinine-based equations overestimate glomerular filtration rate in Indians.

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