Discordance Between Serum Creatinine-Based and Combined Serum Creatinine/Cystatin C-Based Estimations of Kidney Function in Acutely Ill, Hospitalized Patients.

An Endorsement of the Removal of Race From GFR Estimation Equations: A Position Statement From the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

Estimation of GFR: A Comparison of New and Established Equations

The use of serum creatinine (SCr) for drug dosing has significant limitations and is influenced by many non-kidney factors. Cystatin C (cysC) is an alternative or additional marker of kidney function that is less affected by non-kidney factors. Although cysC may be useful in hospitalized patients, the use of cysC to calculate drug dosing in critically ill patients has been incompletely investigated. The objective of this study was to determine the rate of discordance in estimated glomerular filtration rate (eGFR) between SCr-based calculations and SCr/cysC-based calculations that affect drug dosing in critically ill patients. This was a single-center, retrospective, observational cohort study at an academic medical center including critically ill adult patients admitted in 2023 with SCr and cysC ordered. Data were collected via chart review. Demographic data were analyzed via descriptive statistics. Discordance, defined as the percentage of times at which there is at least one discrepancy in kidney dosing for a medication using Cockcroft-Gault (CG) creatinine clearance versus Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR creatinine-cystatin C (eGFRcr-cys) equations, was analyzed via Wilcoxon matched pair signed ranked sum. eGFR calculations were normalized for patients' body surface area for comparison. The study population included 232 patients (53.02% female; mean age 58.7 +/- 14.9 years; with 62.5% in medical, 23.28% in surgical, and 8.62% in neurological intensive care) with a median SCr of 0.94 mg/dL IQR [0.57-1.58] and median cysC of 1.92 mg/L IQR [1.27-2.77]. The median clearance rates were 68.5 mL/min (45.3-111.5) for CG and 53.9 mL/min (30.9-80.7) for CKD-EPI eGFRcr-cys; p < 0.001. The discordance rate across all study drugs was 32.3% (75/232). The four most common study drugs demonstrating discordance were cefepime 40.6% (52/128), vancomycin 38.3% (46/120), levetiracetam 35.1% (13/37), and piperacillin/tazobactam 11.6% (5/43). Clinically significant discordance exists between SCr and SCr/cysC-based estimates of kidney function. This study established a discordance rate, as defined by drug dosing, of 32.3% in adult patients admitted to the ICU.

Overcoming Vestiges of Structural Racism in Kidney Care and Renal Nutrition and Revisiting Cockcroft-Gault Creatinine Clearance and Its Weight Index

Should Estimated Glomerular Filtration Rate Be Adjusted for Race?

Introduction: Adjusting drug dose levels based on equations that standardize the estimated glomerular filtration rate (eGFR) to a body surface area (BSA) of 1.73m2 can pose challenges, especially for patients with extremely high or low body mass index (BMI). The objective of the present study of patients with CKD and diabetes was to assess the impact of deindexing creatinine-based equations on estimates of kidney function and on the frequency of inappropriate prescriptions of oral antidiabetic drugs (OADs). Methods: The prospective CKD-REIN cohort is comprised of patients with eGFR <60mL/min/1.73m2. The inclusion criteria for this study were the use of OADs and the availability of data on weight, height and serum creatinine. We compared data for three BMI subgroups (group 1 <30kg/m2; group 2 30-34.9kg/m2; group 3 ≥35kg/m2). Inappropriate prescriptions (contraindicated or over-dosed drugs) were assessed with regard to the summary of product characteristics and the patient's kidney function estimated with the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the 2021 CKD-EPI equation, the Modification of Diet in Renal Disease (MDRD) equation, the European Kidney Function Consortium (EKFC) equation, their deindexed estimates, and the Cockcroft-Gault (CG) formula. The impact of deindexing the equations was evaluated by assessing 1) the difference between the indexed and deindexed eGFRs, and 2) the difference in the proportion of patients with at least one inappropriate OAD prescription between the indexed and deindexed estimates. Results: At baseline, 694 patients were receiving OADs. The median BMI was 30.7kg/m2, the mean BSA was 1.98m2, and 90% of patients had a BSA >1.73m2. Deindexing the kidney function estimates led to higher eGFRs, especially in BMI group 3. The proportion of patients with at least one inappropriate prescription differed greatly when comparing indexed and deindexed estimates. The magnitude of the difference increased with the BMI: when comparing BMI group 1 with BMI group 3, the difference was respectively -4% and -10% between deindexed 2021 CKD-EPI and indexed CKD-EPI. Metformin and sitagliptin were the most frequent inappropriately prescribed OADs. Conclusion: We highlight significant differences between the BSA-indexed and deindexed versions of equations used to estimate kidney function, emphasizing the importance of using deindexed estimates to adjust drug dose levels - especially in patients with an extreme BMI.

IntroductionEstimation of kidney function in critically ill patients with acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but challenging due to fluctuations in kidney function, creatinine metabolism and fluid balance. Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, the Cockcroft Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison to GFR measured by the infusion clearance of chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), in critically ill patients with early AKI after complicated cardiac surgery.MethodsThirty patients with early AKI were studied in the intensive care unit, 2 to 12 days after complicated cardiac surgery. The infusion clearance for 51Cr-EDTA obtained as a measure of GFR (GFR51Cr-EDTA) was calculated from the formula: GFR (mL/min/1.73m2) = (51Cr-EDTA infusion rate × 1.73)/(arterial 51Cr-EDTA × body surface area) and compared with the urinary CrCl and the estimated GFR (eGFR) from the three estimating equations. Urine was collected in two 30-minute periods to measure urine flow and urine creatinine. Urinary CrCl was calculated from the formula: CrCl (mL/min/1.73m2) = (urine volume × urine creatinine × 1.73)/(serum creatinine × 30 min × body surface area).ResultsThe within-group error was lower for GFR51Cr-EDTA than the urinary CrCl method, 7.2% versus 55.0%. The between-method bias was 2.6, 11.6, 11.1 and 7.39 ml/min for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. The error was 103%, 68.7%, 67.7% and 68.0% for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA.ConclusionsThe study demonstrated poor precision of the commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI, suggesting that this should not be used as a reference method when validating new methods for assessing kidney function in this patient population. The commonly used estimating equations perform poorly when estimating GFR, with high biases and unacceptably high errors.

Background: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are used to estimate kidney function. However, utility has been questioned in the obese population. Objective: To evaluate differences in estimates of kidney function in obese patients and implications for drug dosing. Methods: This was a retrospective study of adult inpatients with a body mass index ≥30 kg/m2 and stable kidney function. Patients were categorized based on creatinine clearance (CrCl): group 1—CrCl ≥ 60 mL/min and group 2—CrCl 15 to 59 mL/min. Mean estimates of kidney function and recommended doses of 8 renally eliminated medications were compared. Results: For the 166 patients included, mean estimates using CG, MDRD, and CKD-EPI for group 1 were 87 (23) mL/min, 91 (21) mL/min, and 96 (23) mL/min, respectively. Group 2 estimates were 42 (13) mL/min, 51 (15) mL/min, and 51 (16) mL/min, respectively. MDRD and CKD-EPI estimates were significantly higher than CG in 125 (75%) and 140 (84%) patients, respectively. Dose discrepancies were most often due to higher dose recommendations using MDRD or CKD-EPI compared to CG. Conclusion: Careful consideration of the method used to estimate kidney function, the method used for developing dosing recommendations, and the risk–benefit profile is warranted when designing drug regimens in obese individuals.

The elderly are at risk for adverse drug events because of inappropriate dosing of renally eliminated medications. The purpose of this study was to evaluate differences in estimates of kidney function and recommended doses of select medications in the elderly using the Modification of Diet in Renal Disease (MDRD) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations compared with the Cockcroft-Gault (CG) equation. Patients 65 years of age and older were included in this retrospective, observational analysis. Kidney function was estimated by CG, MDRD and CKD-EPI equations for all patients and by age category (65-69, 70-79, 80-89 and 90-100 years). Differences in estimates and dosing of allopurinol, enoxaparin, gabapentin, piperacillin/tazobactam and sulfamethoxazole/trimethoprim using the MDRD and CKD-EPI compared with the CG were assessed. In the 4160 patients (98% male, mean age 74 ± 7 years), the MDRD and CKD-EPI estimates were significantly higher than CG estimates for all patients and by age category (p < 0.001). Dosing discordance was predominantly because of a higher dose recommended by MDRD and CKD-EPI estimates compared with CG. Discordance was highest with gabapentin (27%), the medication with the greatest number of dosing stratifications by estimated kidney function, and increased by 66% from the youngest to the oldest age category. Until newer equations are used uniformly to develop dosing nomograms, it is prudent to adopt a process for drug dosing in the elderly that is more conservative than eGFR based dosing, but that considers the potential for underestimating kidney function with the CG equation.

BackgroundThe most commonly used glomerular filtration rate estimating equations for drug dosing are Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. However there is still a concern about whether to use MDRD and CKD-EPI interchangeably with CG for drug dosage adjustment.MethodsThe study was initiated to determine the concordance between MDRD, CKD-EPI and CG equations and associated factors in patients with chronic kidney disease at Saint Paul’s Hospital Millennium Medical College (SPHMMC). This was a cross sectional study which involved patient chart review and physicians self-administered questionnaire. Serum creatinine level ≥ 1.2 mg/dL was used as a cutoff point in pre-selection of patients. The correctness of the drug dose prescribed for the level of renal function were compared to the drug database (Lexi-Comp) available through Up-to-date version 21.2.ResultsAmong the total of 422 patients, 249 (59%) were males. Mean age of patients was 46.09 years. The use of MDRD equation for drug dose adjustment by physicians working in the renal clinic of SPHMMC was six out of nine physicians. The Pearson correlation coefficient between the CG with MDRD and CKD-EPI equations was r = 0.94, P < 0.001 and r = 0.95, P < 0.001, respectively. The concordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories was 73.7%, Kappa = 0.644 and 74.9%, Kappa = 0.659, respectively. Concordance between the CG with MDRD and CKD-EPI equations for the drug dosing recommendation was 89.6%, kappa = 0.782 and 92%, kappa = 0.834, respectively. Age > 70 years was associated with discordance between CG and MDRD equations for drug dosing recommendation whereas serum creatinine 1.2–3.5 mg/dL, weight < 61 Kg and age > 70 years were associated with discordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories. However, none of the factors associated with discordance between CG and CKD-EPI for drug dosing.ConclusionMDRD equation can be used interchangeably with CG equation for drug dosing recommended in all adult patients between the age of 18 and 70 years. CKD-EPI can be used interchangeably with CG in all adult Ethiopian patients with CKD.

We evaluated the performance of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations against creatinine clearance (CrCl) to estimate glomerular filtration rate (GFR) in 51 patients with Type 2 diabetes. The CrCl value was obtained from the average of two consecutive 24-h urine samples. Results were adjusted for body surface area using the Dubois formula. Serum creatinine was measured using the kinetic Jaffe method and was calibrated to standardized levels. Bland-Altman analysis and kappa statistic were used to examine agreement between measured and estimated GFR. Estimates of GFR from the CrCl, MDRD, CKD-EPI and CG equations were similar (overall P = 0.298), and MDRD (r = 0.58; 95% CI: 0.36-0.74), CKD-EPI (r = 0.55; 95% CI: 0.33-0.72) and CG (r = 0.61; 95% CI: 0.39-0.75) showed modest correlation with CrCl (all P < 0.001). Bias was -0.3 for MDRD, 1.7 for CKD-EPI and -5.4 for CG. All three equations showed fair-to-moderate agreement with CrCl (kappa: 0.38-0.51). The c-statistic for all three equations ranged between 0.75 and 0.77 with no significant difference (P = 0.639 for c-statistic comparison). The MDRD equation seems to have a modest advantage over CKD-EPI and CG in estimating GFR and detecting impaired renal function in sub-Saharan African patients with Type 2 diabetes. The overall relatively modest correlation with CrCl, however, suggests the need for context-specific estimators of GFR or context adaptation of existing estimators.

ObjectivesThe aim of this study was to determine whether the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)- or Cockcroft−Gault (CG)-based estimated glomerular filtration rates (eGFRs) performs better in the cohort setting for predicting moderate/advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD).MethodsA total of 9521 persons in the EuroSIDA study contributed 133 873 eGFRs. Poisson regression was used to model the incidence of moderate and advanced CKD (confirmed eGFR < 60 and < 30 mL/min/1.73 m2, respectively) or ESRD (fatal/nonfatal) using CG and CKD-EPI eGFRs.ResultsOf 133 873 eGFR values, the ratio of CG to CKD-EPI was ≥ 1.1 in 22 092 (16.5%) and the difference between them (CG minus CKD-EPI) was ≥ 10 mL/min/1.73 m2 in 20 867 (15.6%). Differences between CKD-EPI and CG were much greater when CG was not standardized for body surface area (BSA). A total of 403 persons developed moderate CKD using CG [incidence 8.9/1000 person-years of follow-up (PYFU); 95% confidence interval (CI) 8.0–9.8] and 364 using CKD-EPI (incidence 7.3/1000 PYFU; 95% CI 6.5–8.0). CG-derived eGFRs were equal to CKD-EPI-derived eGFRs at predicting ESRD (n = 36) and death (n = 565), as measured by the Akaike information criterion. CG-based moderate and advanced CKDs were associated with ESRD [adjusted incidence rate ratio (aIRR) 7.17; 95% CI 2.65–19.36 and aIRR 23.46; 95% CI 8.54–64.48, respectively], as were CKD-EPI-based moderate and advanced CKDs (aIRR 12.41; 95% CI 4.74–32.51 and aIRR 12.44; 95% CI 4.83–32.03, respectively).ConclusionsDifferences between eGFRs using CG adjusted for BSA or CKD-EPI were modest. In the absence of a gold standard, the two formulae predicted clinical outcomes with equal precision and can be used to estimate GFR in HIV-positive persons.

Background Numerous equations have been developed to estimate kidney function. Recently, Chronic Kidney Disease‐Epidemiology Collaboration (CKD‐EPI) estimated glomerular filtration rate (eGFR) equations reformulated without race have been recommended by the National Kidney Foundation (NKF)–American Society of Nephrology Taskforce and by the NKF Workgroup for Implementation of Race‐Free eGFR‐Based Medication‐Related Decisions. The objective of this survey was to examine current pharmacy practices on the implementation of these recommendations. Methods A survey was distributed primarily to specific American College of Clinical Pharmacy Practice and Research Network listservs between February and March 2024. Results There were 275 survey respondents who answered at least one question. Of pharmacists who completed the demographics section, the majority were from the United States and were female, with the most common practice sites being academic health centers and community hospitals. Regarding kidney estimation and dosing, 199 (72.4%) indicated that their institution has a kidney dose adjustment policy, with the majority (162/199, 81.4%) utilizing the Cockcroft‐Gault (C‐G) estimated creatinine clearance (eCrCL) equation within their policy and C‐G being the only equation within some policies. Additionally, 88/275 (32%) reported rounding up serum creatinine values for elderly patients when using the C‐G equation, with 47 of those 88 (53.4%) rounding it to 1 mg/dL. There was also notable variability regarding the choice of patient weight for C‐G eCrCL calculations: actual body weight was used by 137/275 (49.8%), adjusted body weight by 146/275 (53%), and ideal body weight by 113/275 (41.1%). If utilizing an eGFR equation for medication dosing, 36/275 (13.1%) reported adjusting eGFR for body surface area (BSA) in all patients, and 44/275 (16%) reported adjusting for BSA in those with extreme body weights. Conclusions There is considerable variability in kidney function assessment for drug dosing by pharmacists, highlighting the need for education and adoption of non–race‐based CKD‐EPI equations to standardize care and improve outcomes.

Background Pivotal randomized trials of non-vitamin K antagonist oral anticoagulants (NOACs) adopted Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of NOACs. However, Modified Diet in Renal Disease (MDRD]) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae are commonly used in clinical practice. In the present study, we investigated the agreements/disagreements of eGFRs calculated using different equations in Asian AF patients. Second, we studied the impacts of using different equations on the dosages of NOACs used, and finally, clinical outcomes compared to warfarin were assessed. Methods This retrospective study used medical data from a multicenter healthcare provider in Taiwan which included 39,239 AF patients whose data about body weight (BWs) and serum Creatinine (sCr) were available. Among these patients, there were 11,185 and 2,323 AF patients treated with NOACs and warfarin, respectively. Results At the cutoff values of eGFR of &amp;lt;15 mL/min, 15–50 mL/min and &amp;gt;50 mL/min, the agreements were 78% between MDRD and CG, and 81% between CKD-EPI and CG. The disagreements between different equations were largely due to over-estimations (21% for MDRD and 17% for CKD-EPI), especially for patients aged &amp;gt;75 years and BWs &amp;lt;50kg (58.8% for MDRD and 50.9% for CKD-EPI). For patients treated with NOACs, around 7.6% (MDRD) and 6.5% (CKD-EPI) had dosages of NOACs that were discordant compared to using the CG equation, with the highest percentages for rivaroxaban (11–13%) and lowest for edoxaban (1%). Among patients receiving NOACs whose dosages were defined as “on-label” based on MDRD or CKD-EPI, only those whose dosages were “truly on-label” based on CG were associated with a lower risk of ischemic stroke/systemic embolism (IS/SE) (adjusted hazard ratio [aHR] 0.78, 95% CI 0.61–1.00), major bleeding (aHR 0.34, 95% CI 0.26–0.45) and IS/SE or major bleeding (aHR 0.55, 95% CI 0.46–0.66) compared to warfarin (Figure). The risk of IS/SE (aHR 0.82, 95% CI 0.39–1.72), major bleeding (aHR 0.57, 95% CI 0.25–1.32) and IS/SE or major bleeding (aHR 0.69, 95% CI 0.40–1.19) were similar between warfarin and patients treated with NOACs whose dosages were disconcordant between eGFRs calculated using MDRD and CG (Figure). Conclusions The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of NOACs (mainly overdosing) which would attenuate the advantages of NOACs compared to warfarin. Therefore, the CG equation should be used as the “gold standard” for the calculations of eGFRs to guide the NOAC dosages. Funding Acknowledgement Type of funding source: None

The difficulties of classifying renal disease in HIV-infected patients*