Toward Equitable Kidney Function Estimation in Critical Care Practice: Guidance From the Society of Critical Care Medicine's Diversity, Equity, and Inclusion in Renal Clinical Practice Task Force.

OBJECTIVES: Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. DATA SOURCES: Literature review and expert consensus. STUDY SELECTION: English language publications evaluating GFR assessment and racial disparities. DATA EXTRACTION: We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. DATA SYNTHESIS: Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. CONCLUSIONS: The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.

Redressing the Harms of Race-Based Kidney Function Estimation.

This Viewpoint emphasizes the urgency of abolishing race-based medical practices and explains how they have unjustly contributed to racial inequities in clinical care and health outcomes.

Assessment of renal function in living kidney donors before and after nephrectomy: A Japanese prospective, observational cohort study.

OBJECTIVE: To investigate the utility of estimated glomerular filtration rate for assessing kidney function in living kidney donors before and after nephrectomy. METHODS: A total of 101 donors underwent inulin clearance measurements before and 1 year after nephrectomy. The mean of three inulin clearance values was used as the measured glomerular filtration rate. Estimated glomerular filtration rate based on serum creatinine and cystatin C levels was calculated using the Japanese estimated glomerular filtration rate equation, Chronic Kidney Disease Epidemiology Collaboration formula and new full age spectrum equation. Age-adjusted chronic kidney disease was defined as glomerular filtration rate <75 mL/min/1.73m2 for donors aged <40 years, <60 mL/min/1.73m2 for donors aged 40-65 years and <45 mL/min/1.73m2 for donors aged >65 years. RESULTS: The postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rate were 36.0% and 27.0%, respectively. In younger donors (aged <50 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rates were 5.3% and 26.3%, respectively. In older donors (aged >70 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rates were 75.0% and 33.3%, respectively. Donor age and measured glomerular filtration rate were significant predictors of postoperative measured glomerular filtration rate. The Japanese estimated glomerular filtration rate equation based on creatinine and cystatin C showed the strongest correlation with measured glomerular filtration rate. However, the Japanese estimated glomerular filtration rate equation based on creatinine overestimated the prevalence of measured glomerular filtration rate <60 mL/min/1.73m2 , whereas the Japanese estimated glomerular filtration rate based on cystatin C underestimated it. CONCLUSIONS: Aged donors might have an increased risk of lower glomerular filtration rate after donor nephrectomy; post-surgery, long-term monitoring of renal function is recommended. Measurement of glomerular filtration rate should be carried out for donors, especially pre-surgery. A more precise glomerular filtration rate equation is required in the future.

Cystatin C- and creatinine-based equations in the assessment of renal function in HIV-positive patients prior to commencing Highly Active Antiretroviral Therapy.

BACKGROUND: We evaluated the accuracy and precision of creatinine- and cystatin C-based prediction equations for estimating glomerular filtration rate compared to measured glomerular filtration rate in an antiretroviral-naive human immunodeficiency virus population. METHODS: The study population consisted of 100 treatment-naive HIV patients. Glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, as well as cystatin C-based equations (CKD-EPIcystatin C, cystatin Cvan Deventer and CKD-EPIcombined)) compared to (51)Cr-EDTA plasma clearance-measured glomerular filtration rate. We calculated percentage bias, standard deviation of the differences, accuracy within 15 and 30% of measured glomerular filtration rate and sensitivity and specificity for predicting measured glomerular filtration rate <60 mL/min/1.73 m(2). RESULTS: Bias for all estimating glomerular filtration rate equations ranged from -9.4% to 38.4%. The CKD-EPIcombined without ethnicity correction factor equation had the least bias, 2.9% (-2.9 to 8.8). Bias was higher for the Modification of Diet in Renal Disease and CKD-EPI equation with the African-American ethnicity factor (38.4 and 33.7%) than without (14.2 and 15.3%). Standard deviation of the differences ranged from 29.2% (CKD-EPIcombined without ethnicity factor) to 54.0% (Modification of Diet in Renal Disease with ethnicity factor). Accuracy within 30% of measured glomerular filtration rate ranged from 78% for CKD-EPIcombined without ethnicity factor to 56.7% for the Cockcroft-Gault equation. Sensitivity for creatinine-based equations was less than 50% and for the CKD-EPIcystatin C equation was 75%. CONCLUSION: Sensitivity of creatinine-based equations for predicting glomerular filtration rate was poor in this group of patients. The CKD-EPIcombined equation performed better than creatinine-based equations.

A Risk Assessment of the Jaffe vs Enzymatic Method for Creatinine Measurement in an Outpatient Population.

BACKGROUND: The Jaffe and enzymatic methods are the two most common methods for measuring serum creatinine. The Jaffe method is less expensive than the enzymatic method but is also more susceptible to interferences. Interferences can lead to misdiagnosis but interferences may vary by patient population. The overall risk associated with the Jaffe method depends on the probability of misclassification and the consequences of misclassification. This study assessed the risk associated with the Jaffe method in an outpatient population. We analyzed the discordance rate in the estimated glomerular filtration rate based on serum creatinine measurements obtained by the Jaffe and enzymatic method. METHODS: Method comparison and risk analysis. Five hundred twenty-nine eGFRs obtained by the Jaffe and enzymatic method were compared at four clinical decision limits. We determined the probability of discordance and the consequence of misclassification at each decision limit to evaluate the overall risk. RESULTS: We obtained 529 paired observations. Of these, 29 (5.5%) were discordant with respect to one of the decision limits (i.e. 15, 30, 45 or 60 ml/min/1.73m2). The magnitude of the differences (Jaffe result minus enzymatic result) were significant relative to analytical variation in 21 of the 29 (72%) of the discordant results. The magnitude of the differences were not significant relative to biological variation. The risk associated with misclassification was greatest at the 60 ml/min/1.73m2 decision limit because the probability of misclassification and the potential for adverse outcomes were greatest at that decision limit. CONCLUSION: The Jaffe method is subject to bias due to interfering substances (loss of analytical specificity). The risk of misclassification is greatest at the 60 ml/min/1.73m2 decision limit; however, the risk of misclassification due to bias is much less than the risk of misclassification due to biological variation. The Jaffe method may pose low risk in selected populations if eGFR results near the 60 ml/min/1.73m2 decision limit are interpreted with caution.

Methods Used in Economic Evaluations of Chronic Kidney Disease Testing - A Systematic Review.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression. AIMS: This systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur. METHODS: Articles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies. RESULTS: The initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model. CONCLUSION: Future economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis.

Differential scaling of glomerular filtration rate and ingested metabolic burden: implications for gender differences in chronic kidney disease outcomes.

BACKGROUND: Men commence dialysis with a higher estimated glomerular filtration rate (eGFR) than women and are more likely to transition from chronic kidney disease (CKD) to end-stage renal disease. We hypothesized that for a given estimated body surface area (BSA) men have a greater metabolic burden, and that consequently, the practice of indexing GFR to BSA results in gender differences in the degree of biochemical uraemia. METHODS: Metabolic burden was assessed as estimated dietary protein, calorie, phosphorus, sodium and potassium intakes and urinary urea nitrogen excretion in the Chronic Renal Insufficiency Cohort, Modification of Diet in Renal Disease study, and National Health and Nutrition Examinations Surveys (NHANES) 1999-2010. Uraemia was characterized by serum biochemistry. RESULTS: Per m(2) BSA, men had greater urea nitrogen excretion and intakes of all dietary parameters (P < 0.001 for all). For a given BSA-indexed iothalamate GFR or eGFR, male gender was associated with a 10-15% greater serum urea nitrogen (P < 0.001), giving men with a BSA-indexed GFR of 70-75 mL/min/1.73 m(2) the same serum urea nitrogen concentration as women with a GFR of 60 mL/min/1.73 m(2). However, indexing metabolic burden and GFR to alternative body size measures (estimated total body water, lean body mass or resting energy expenditure) abolished/reversed the gender associations. In NHANES, BSA-indexed eGFR distribution was very similar for men and women, so that adjusting for eGFR had little effect on the gender difference in serum urea. CONCLUSIONS: Indexing GFR to BSA across genders may approximate nature's indexing approach, but gives men a greater ingested burden of protein, calories, sodium, phosphorus and potassium per mL/min GFR. This has implications for gender differences in CKD outcomes.

Assessment of bladder and kidney functioning in adult spina bifida patients by Dutch urologists: a survey.

AIMS: To investigate how urologists generally perform the follow-up of adult spina bifida (SB) patients and to see to which extent recommendations from guidelines on neurogenic lower urinary tract dysfunction are followed. METHODS: A self-designed electronic multiple choice questionnaire was sent to all 365 urologists in the Netherlands. RESULTS: Overall 100 urologists (27.4%) responded, of which 96 (26.3%) responses were usable. Of 95 urologists, 18 (18.9%) saw no adult SB patients, 47 (49.5%) saw 1-5 patients/year, 15 (15.8%) saw 6-10, and 15 urologists (15.8%) saw >10 adult SB patients/year. Of 96 urologists, a specialized clinic for adult SB patients was present in only 11 (11.5%) cases. Ultrasonography was performed regularly (at least once every 1-5 years) by 68/74 (91.9%) urologists. Glomerular filtration rate (GFR) was determined at least every 5 years by 66/74 (89.1%) urologists. For determination of GFR, serum creatinine was most often used (94.5%). Renography and video-urodynamic investigations (UDS) were performed on a regular basis by 8.1% and 24.3%, respectively. CONCLUSIONS: In adult SB patients, the responding Dutch urologists regularly evaluate bladder and kidney function using GFR and ultrasonography, although less frequently than recommended by the guidelines. UDS is performed on indication only, which is not in accordance with the guidelines. Regular UDS might be valuable to detect risk factors for insidious renal damage. The role of renography, as well as the desirability of multidisciplinary teams, has yet to be determined.

Simplified methods for assessment of renal function as the ratio of glomerular filtration rate to extracellular fluid volume.

BACKGROUND: Instead of scaling glomerular filtration rate (GFR) to a body surface area of 1.73 m(2), it has been suggested to scale GFR to extracellular fluid volume (ECV). The ratio GFR/ECV has physiological meaning in that it indicates how often 'that which is to be regulated' (i.e. ECV) comes into contact with the 'regulator' (i.e. the kidneys). AIM: The aim of the present study was as follows: to analyse two published calculation methods for determining ECV and GFR/ECV; to develop a new simple and accurate formula for determining ECV; and to compare and evaluate these methods. MATERIALS AND METHODS: GFR was determined as (51)Cr-EDTA clearance. The study comprised 128 individuals (35 women, 66 men and 27 children) with a full (51)Cr-EDTA plasma concentration curve, determined from injection until 4-5 h p.i. Reference values for GFR and ECV were calculated from the full curve. One-pool approximations C/(1) and V(1) were calculated using only the final-slope curve. Four calculation methods were compared: simple one-pool values; GFR/ECV according to Peters and colleagues; ECV according to Brøchner-Mortensen (BM); and ECV according to a new method (JBM): y=2x-1, where x=Cl(1)/Cl and y=V(1)/ECV. RESULTS: The new JBM method is accurate and can be explained theoretically. BM has a slight bias for high renal function. The Peters method had bias in our data. GFR/ECV had better precision than ECV alone, especially for BM and JBM, which were within -4% to +7% of the reference values (95% limits of agreement in adults). CONCLUSION: GFR/ECV can be precisely determined, especially with the BM and JBM methods. Expressing GFR/ECV in unit %/h gives a simple interpretation. Normal ranges for GFR/ECV need to be established.

Combining multiple continuous tests for the diagnosis of kidney impairment in the absence of a gold standard.

Receiver operating characteristic (ROC) curves are commonly used to summarize the classification accuracy of diagnostic tests. It is not uncommon in medical practice that multiple diagnostic tests are routinely performed or multiple disease markers are available for the same individuals. When the true disease status is verified by a gold standard (GS) test, a variety of methods have been proposed to combine such potential correlated tests to increase the accuracy of disease diagnosis. In this article, we propose a method of combining multiple diagnostic tests in the absence of a GS. We assume that the test values and their classification accuracies are dependent on covariates. Simulation studies are performed to examine the performance of the combination method. The proposed method is applied to data from a population-based aging study to compare the accuracy of three screening tests for kidney function and to estimate the prevalence of moderate kidney impairment.

Symmetrical dimethylarginine outperforms CKD-EPI and MDRD-derived eGFR for the assessment of renal function in patients with adult congenital heart disease.

BACKGROUND/AIMS: Adults with congenital heart disease exhibit a 3-fold higher mortality in the presence of chronic kidney disease, hence assessment of renal function is crucial in this patient population. Formulas for the estimation of glomerular filtration rate (GFR) have not been evaluated in this patient population. Therefore, this study compares different markers and equations for the estimation of renal function in adults with congenital heart disease. METHODS: Renal function was assessed in 102 patients using the Modification of Diet in Renal Disease (MDRD) equation, the simplified MDRD equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the Cockcroft-Gault formula. Additionally, symmetrical dimethylarginine (SDMA) was measured. Those parameters were compared to cystatin C-derived GFR using the Larsson equation. RESULTS: GFR estimates using the original MDRD (r = 0.465, p < 0.001) and the CKD-EPI equation (r = 0.462, p < 0.001) showed a similar strong correlation with the cystatin C-based eGFR equation, while eGFR using the simplified MDRD equation showed a slightly weaker correlation (r = 0.439, p < 0.001). The Cockcroft-Gault formula showed no correlation at all to the cystatin C-based eGFR (r = 0.144, p = 0.17). The strongest correlation was observed for SDMA and cystatin C-based eGFR (r = -0.552, p < 0.001). CONCLUSION: GFR in adults with congenital heart disease should be estimated using the original MDRD or the CKD-EPI formula. SDMA seems to be a promising marker of renal function for this patient group.

The morbidity and mortality associated with kidney disease in an HIV-infected cohort in Puerto Rico.

INTRODUCTION: Nephropathy in HIV-infected patients has been associated with progression to AIDS and death. The virus, several comorbid conditions and certain medications may contribute to the development and progression of kidney disease. METHODS: This study analyzed data collected from HIV-infected persons enrolled in a HIV registry in Puerto Rico during January 1998 through September 2006. Demographic factors, clinical manifestations, laboratory findings at enrollment, and antiretroviral therapy (ART) prescriptions were compared between patients with and without kidney disease. Death status and cause of death by December 2006 were also evaluated and compared. RESULTS: The study included 1,283 subjects, 69.0% male, 39.7% injecting drug users, 19.5% hepatitis C infected, 6.5% with diabetes mellitus (DM-2), 11.6% had hypertension (HTN) and 9.0% had kidney disease. Patients with kidney disease had significantly higher (P < .05) HIV viral load mean (273,499 vs. 202,858 copies/mL), CD4 T-cell count < 200 (57.0% vs. 44.4%), underweight (22.9% vs. 10.9%), DM-2 (13.9% vs. 5.8%), HTN (27.8% vs 10.0%) and mortality (15.9 vs 5.7 deaths per 100 years of follow-up) than those without it. Cox proportional hazard analysis showed that patients with kidney disease had a higher mortality risk (2.1) after controlling for age, sex, HIV risk factor, ART prescription in the last year and HIV disease duration. CONCLUSIONS: This study demonstrated a substantial disparity in mortality for Puerto Rican HIV-infected patients with nephropathy. Kidney disease preventive strategies that include aggressive control of HIV-infection and chronic medical conditions, such as hypertension and diabetes, are recommend as an approach to reduce this health disparity.

Evaluation of aminoglycoside clearance using the modification of diet in renal disease equation versus the Cockcroft-Gault equation as a marker of glomerular filtration rate.

BACKGROUND: Accurate estimation of kidney function is essential for safe administration of renally cleared drugs. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft-Gault (CG) equation as an estimation of glomerular filtration rate. Few data exist regarding the utility of the Modification of Diet in Renal Disease (MDRD) equation in drug dosing. OBJECTIVE: To evaluate glomerular filtration rate based on creatinine clearance (CrCl) derived from the MDRD or the CG equation compared with patient-specific CrCl calculated from aminoglycoside peak and trough concentrations. METHODS: Medical records of patients who received aminoglycoside antibiotics were reviewed over 1 year. Patients who received aminoglycosides via conventional dosing with peak and trough concentrations at steady state were included. Calculations based on standard pharmacokinetic equations were used to estimate CrCl from aminoglycoside serum concentrations. Patient-specific CrCl estimated from aminoglycoside concentrations was compared with estimated CrCl from the CG or MDRD equation. RESULTS: Fifty-five patients were included in the final analysis. The primary outcome showed concordance between estimated and actual aminoglycoside clearance was 0.53 (95% CI 0.18 to 0.88) for the CG equation and 0.41 (95% CI 0.04 to 0.78) for the MDRD equation. Subgroup analysis also favored CG as a better predictor of CrCl. This signified a stronger correlation between the CG equation and aminoglycoside clearance. CONCLUSIONS: Compared with the MDRD equation, the CG equation provided better correlation of estimated glomerular filtration rate for aminoglycoside antibiotics. Institutions should continue to use the CG equation as the standard of practice to safely adjust aminoglycoside doses in patients with renal dysfunction.

Study Protocol--accurate assessment of kidney function in Indigenous Australians: aims and methods of the eGFR study.

BACKGROUND: There is an overwhelming burden of cardiovascular disease, type 2 diabetes and chronic kidney disease among Indigenous Australians. In this high risk population, it is vital that we are able to measure accurately kidney function. Glomerular filtration rate is the best overall marker of kidney function. However, differences in body build and body composition between Indigenous and non-Indigenous Australians suggest that creatinine-based estimates of glomerular filtration rate derived for European populations may not be appropriate for Indigenous Australians. The burden of kidney disease is borne disproportionately by Indigenous Australians in central and northern Australia, and there is significant heterogeneity in body build and composition within and amongst these groups. This heterogeneity might differentially affect the accuracy of estimation of glomerular filtration rate between different Indigenous groups. By assessing kidney function in Indigenous Australians from Northern Queensland, Northern Territory and Western Australia, we aim to determine a validated and practical measure of glomerular filtration rate suitable for use in all Indigenous Australians. METHODS/DESIGN: A cross-sectional study of Indigenous Australian adults (target n = 600, 50% male) across 4 sites: Top End, Northern Territory; Central Australia; Far North Queensland and Western Australia. The reference measure of glomerular filtration rate was the plasma disappearance rate of iohexol over 4 hours. We will compare the accuracy of the following glomerular filtration rate measures with the reference measure: Modification of Diet in Renal Disease 4-variable formula, Chronic Kidney Disease Epidemiology Collaboration equation, Cockcroft-Gault formula and cystatin C- derived estimates. Detailed assessment of body build and composition was performed using anthropometric measurements, skinfold thicknesses, bioelectrical impedance and a sub-study used dual-energy X-ray absorptiometry. A questionnaire was performed for socio-economic status and medical history. DISCUSSION: We have successfully managed several operational challenges within this multi-centre complex clinical research project performed across remote North, Western and Central Australia. It seems unlikely that a single correction factor (similar to that for African-Americans) to the equation for estimated glomerular filtration rate will prove appropriate or practical for Indigenous Australians. However, it may be that a modification of the equation in Indigenous Australians would be to include a measure of fat-free mass.

A comparison of measured creatinine clearance versus calculated glomerular filtration rate for assessment of renal function before autologous and allogeneic BMT.

Common blood and marrow transplantation (BMT) eligibility criteria include a minimum glomerular filtration rate (GFR) that may vary by regimen intensity. GFR is often estimated by measurement of creatinine clearance in a 24-hour urine collection (24-hr CrCl), an inconvenient and error-prone method that overestimates GFR. The study objectives were to determine which of 6 GFR calculations: Cockroft-Gault (CG), modified CG (mCG), Modification of Diet in Renal Disease 1 (MDRD1), MDRD2, Jelliffe, and Wright, consistently underestimated measured 24-hr CrCl pre-BMT. We retrospectively analyzed 98 consecutive allogeneic (n = 48) or autologous (n = 50) adult BMT patients from January 2006 to April 2007. All 6 formulas were significantly (P < .001) correlated with 24-hr CrCl with R = 0.64 (Wright), 0.63 (CG), 0.61 (mCG), 0.61 (Jelliffe), 0.54 (MDRD2), and 0.50 (MDRD1). When compared to the measured 24-hr CrCl, MDRD2 consistently underestimated it in the highest proportion of patients (66%, P < .001), compared with MDRD1 (65%, P < .001), Jelliffe (61%, P = NS), mCG (55%, P = NS), Wright (34%, P < .001), and CG (34%, P = .001). Measured 24-hr CrCl, pre-BMT serum Cr, and all 6 equations were not predictive of renal regimen-related toxicity (RRT) post-BMT. The Wright and CG formulas are closest to, but overestimate 24-hr CrCl in 66% of patients. In comparison, MDRD2 consistently underestimates 24-hr CrCl in 66%. Although MDRD2 is the most conservative formula, all 6 formulas gave reasonable estimates of GFR and any of the 6 equations can replace the measured 24-hr CrCl. Larger analyses and transplantation of patients with GFR <50 mL/min may better define subgroups at risk for renal RRT.

Impact of standardization of creatinine methodology on the assessment of glomerular filtration rate in children.

There is a global effort to standardize clinical laboratory serum creatinine measurements to the reference method of isotope-dilution mass spectrometry (IDMS). Creatinine values in serum and urine are frequently used in children to calculate creatinine clearance (mCrCl) or estimate glomerular filtration rate (GFR) by Schwartz's equation (eGFR). The original normative data of mCrCl and eGFR were developed using Jaffe method. To investigate what impact the differences in methodologies of creatinine analysis will have on mCrCl and eGFR, we measured creatinine in random serum and urine samples by three commercially available assays: Jaffe (J), enzymatic (E) and enzymatic method traceable to IDMS (E-IDMS). There was a significant bias in the two enzymatic methods when compared with J method. The theoretical predicted errors in overestimating mCrCl ranged from 1.10 to 1.34 by E and 1.20 to 1.54 by E-IDMS; and in calculating eGFR 1.07-1.16 by E and 1.30-1.46 by E-IDMS, which was further confirmed in children who had formal GFR evaluation. Thus, as the clinical laboratories calibrate their creatinine assays to the gold standard IDMS method, it is important for the pediatric nephrology community to develop new equations for estimation of GFR based on the new creatinine assay.

Standardization of serum creatinine and estimated GFR in the Kidney Early Evaluation Program (KEEP).

BACKGROUND: Creatinine calibration by clinical laboratories is important because variability among assays adversely affects the accuracy of glomerular filtration rate (GFR) estimation. We describe the calibration of creatinine assays used in the National Kidney Foundation Kidney Early Evaluation Program (KEEP). METHODS: Creatinine values were requested for 200 samples at each of the 2 KEEP laboratories, Satellite Laboratory Services, LLC (2000 to 2005) and Clinical Laboratory Services (CLS; 2005 to present), for comparison with samples at the Cleveland Clinic Research Laboratory (CCRL). Linear regression and Deming regression were used to obtain slopes adjusted for measurement error and regression to the mean. RESULTS: After exclusion of outliers, mean creatinine level in 184 samples was 0.94 mg/dL at Satellite compared with 0.89 mg/dL at CCRL. Deming regression showed a slope of 1.003 (95% confidence interval (CI), 0.99 to 1.02; P < 0.001) and intercept of -0.04 (95% CI, -0.59 to -0.02; P = 0.003) with R(2) = 0.9853. Final calibration consists of intercept alone because of a small slope. After exclusion of outliers, mean creatinine level in 199 samples was 1.06 mg/dL at CLS compared with 0.96 mg/dL at CCRL. Deming regression showed a slope of 1.08 (95% CI, 1.07 to 1.09; P < 0.001) and intercept of -0.18 (95% CI, -0.19 to -0.17; P < 0.001) with R(2) = 0.9939. GFR estimates were minimally affected by the Satellite calibration. At a serum creatinine value of 1 mg/dL, the change in estimated GFR was 1 mL/min/1.73 m(2) after calibration. Conversely, higher range GFR estimates were affected by calibration of the CLS creatinine assay. At a serum creatinine value of 1 mg/dL, the GFR estimate was 6 mL/min/1.73 m(2) higher after calibration. CONCLUSION: Calibration of KEEP creatinine measurements had a greater impact on the current laboratory than on the laboratory previously used. The calibration process has worked to decrease overestimation of eGFR at the high range and decrease misclassification bias.