Impact of using different renal function estimation equations on vancomycin dosing.

The Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formulae are often used to estimate glomerular filtration rate (GFR). The objective was to determine the best method for estimating GFR in older adults. A cross-sectional study was conducted at the geriatric wards of two hospitals in The Netherlands. Patients aged 70 years or above with an estimated (e)GFR below 60 ml min⁻¹ 1.73 m⁻² were included. The CG, CG calculated with ideal bodyweight (IBW), MDRD and CKD-EPI formulae were compared with a criterion standard, sinistrin clearance. Renal function was classified into five stages according to the National Kidney Foundation Disease Outcomes Quality Initiative chronic kidney disease classification, as follows (in ml min⁻¹ 1.73 m)⁻²: stage 1, eGFR ≥ 90; stage 2, eGFR of 60-89; stage 3, eGFR of 30-59; stage 4, eGFR of 15-29; and stage 5, eGFR < 15. Sixteen patients, 50% male, with a mean age of 82 years (range 71-87 years) and mean body mass index 26 kg m⁻² (range 18-36 kg m⁻²), were included. On average, all formulae slightly overestimated GFR, as follows (in ml min⁻¹ 1.73 m⁻²: CG +0.05 [95% confidence interval (CI) -28 to +28]; CG with IBW +0.03 (95% CI -20 to +20); MDRD +9 (95% CI -16 to +34); and CKD-EPI +5 (95% CI -20 to +29). They classified kidney disease correctly in 68.8% (CG), 75% (CG with IBW), 43.8% (MDRD) and 68.8% (CKD-EPI) of the participants, respectively. The CG, CG with IBW, MDRD and CKD-EPI formulae estimate the mean GFR of a population rather well. In individual cases, all formulae may misclassify kidney disease by one stage.

Background: The glomerular filtration rate (GFR) is considered the gold standard for assessing renal function. According to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, GFR estimation is often carried out using predictive equations that incorporate serum creatinine levels, along with demographic factors such as age, gender, race, and body size. However, these equations exhibit varying levels of accuracy across different populations, necessitating the evaluation of their performance and clinical relevance in diverse patient groups.Objectives: This study aimed to evaluate the performance of three commonly used GFR estimation equations, the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, along with their race-modified versions, by comparing them with measured 24-hour creatinine clearance (CrCl) in adult patients with chronic kidney disease (CKD).Methods: A cross-sectional descriptive study was conducted at Jos University Teaching Hospital (JUTH) between November 2019 and July 2020, involving 111 consecutively recruited CKD patients. Data collection included medical history, physical examination, laboratory investigations, calculation of CrCl, estimated glomerular filtration rate (eGFR) using different equations, and albumin-creatinine ratio (ACR). Statistical analysis was performed using SPSS version 20 (IBM Inc., Armonk, New York), with p-values <0.05 considered statistically significant.Results: The mean age of participants was 51.1±15.5 years. Diabetes mellitus was the most common cause of CKD, affecting 38% of the cohort. Among participants, 31% and 22% were classified as having stage 5 and stage 4 CKD, respectively. The median CrCl was 26 (9-56) mL/min. The median eGFR values across the equations were as follows: CG, 26 (11-60) mL/min/1.73m²; MDRD, 26 (11-60) mL/min/1.73m²; MDRD1, 22 (9-50) mL/min/1.73m²; CKD-EPI, 26 (10-62) mL/min/1.73m²; and CKD-EPI1, 22 (9-53) mL/min/1.73m². Strong positive correlations were observed between measured CrCl and the estimated GFR from each equation: CG (r=0.948, p=0.001), MDRD (r=0.940, p=0.001), MDRD1 (r=0.939, p=0.001), CKD-EPI (r=0.943, p=0.001), and CKD-EPI1 (r=0.942, p=0.001). Furthermore, significant correlations were found between the different GFR equations themselves, with the highest correlation observed between MDRD and CKD-EPI (r=0.999, p=0.001). The median ACR was 395.5 (45.3-2887.0) mg/g, and albuminuria was present in 82% of participants. All three GFR equations closely approximated the measured CrCl of 26 mL/min/1.73m². The equations performed optimally in patients with GFR values below 45 mL/min, with the CG equation exhibiting the least bias and the highest precision. Regression analysis revealed a significant association between albuminuria and all GFR equations and a notable association between age and CrCl, CG, and CKD-EPI estimates.Conclusion: The CG, MDRD, and CKD-EPI equations demonstrated comparable accuracy to measured 24-hour CrCl in estimating GFR in Nigerian patients with CKD. These findings support the clinical use of these predictive equations for renal function assessment in CKD, though local validation in diverse populations is recommended for optimal clinical application.

In Reply to ‘Estimated GFR for Drug Dosing: A Bedside Formula’, ‘Drug Dose Adjustments in Patients With Renal Impairment’, ‘Use of the MDRD Study Equation for Drug Dosing’, and ‘Estimated GFR vs Creatinine Clearance for Drug Dosing’

BackgroundLenalidomide is an immunomodulatory drug used to treat multiple myeloma that requires renal dosing adjustment based on Cockcroft-Gault (CG). Various equations to estimate kidney function exist and pose a potential issue with lenalidomide dosing.ObjectiveThe objective of this analysis was to evaluate the impact of estimating kidney function in newly diagnosed multiple myeloma patients with CG, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and their potential impact on lenalidomide dosing.MethodsData from 1121 multiple myeloma patients at the time of diagnosis acquired from the Mayo Clinic were used to calculate creatinine clearance (CrCl) using Cockcroft-Gault with actual body weight (CGABW), ideal body weight (CGIBW), or adjusted body weight (CGAdjBW); MDRD; and CKD-EPI for each subject. Discordances in dosing were then analyzed, and lenalidomide exposure was calculated for each subject to assess impact on pharmacokinetics of lenalidomide for patients who received discordant doses.ResultsOverall, approximately 16% of patients received a discordant dose when using MDRD or CKD-EPI instead of CGABW. The most common dose discordance was the decrease of a full dose of lenalidomide 25 mg when using CGABW down to 10 mg and when using MDRD or CKD-EPI with 53.8% to 55.6% of all discordances in this category. When assessing different body weights, the most common discordance was a decrease from 25 to 10 mg when using CGIBW instead of CGABW; the same trend was observed when using CGAdjBW instead as well. Patients were also at risk of over- or underexposure based on area under the concentration versus time curve (AUC) for discordant dosing.Conclusion and RelevanceA significant proportion of patients are at risk of under- or overdose of lenalidomide if CKD-EPI or MDRD are used instead of CGABW. Physicians should use CGABW when estimating renal function to dose lenalidomide.

Clinical trials used Cockcroft-Gault (CG) formula to calculate the estimated glomerular filtration rate (eGFR) in order to dose rivaroxaban for patients with atrial fibrillation (AF). The aim of this study is to evaluate rivaroxaban dosing appropriateness in patients with AF with or without renal impairment based on the CG formula and other formulae, including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the isotope dilution mass spectrometry (IDMS) traceable Modification of Diet in Renal Disease (MDRD) Study equation and the associated clinical outcomes. A retrospective cohort study conducted at Sultan Qaboos University Hospital (SQUH) from 1st January 2016 to 31st December 2020, included all adult patients (≥ 18 years) treated with rivaroxaban for AF and followed up for one year after starting the treatment. Based on the CG formula, the rivaroxaban dose was inappropriately prescribed in 27% of the patients (21% overdosed and 6% underdosed). Higher baseline creatinine (P=0.0014) and concurrent use of antiplatelet therapy (P<0.001) were associated with the tendency to rivaroxaban overdosing. Higher Body Mass Index (BMI) (P=0.002), female sex (P=0.032), and CKD (P=0.003) were associated with rivaroxaban underdosing. The degree of agreement between the renal function tests when comparing MDRD vs CG and CKD-EPI vs CG in terms of estimated glomerular filtration rate/creatine clearance (eGFR/CrCl) calculation was moderate (κ=0.46) and poor (κ=0.00), respectively, while, in terms of rivaroxaban dose appropriateness was almost perfect (κ=0.82) and substantial (κ=0.77). Clinical outcomes measured by stroke and bleeding events were not significantly different according to the appropriateness of the rivaroxaban dose. This study has shown a relatively high consistency with the gold standard in dosing rivaroxaban in AF patients using CG formula. Treatment efficiency and safety were not affected by the proportion of dose inappropriateness found in this cohort.

Background. In clinical practice, the glomerular filtration rate (GFR) is often estimated by the Modification of Diet in Renal Disease (MDRD) or Cockcroft-Gault (CG) formulae. No data are available, however, on the performance of these formulae in Arab individuals. Methods. Plasma creatinine samples were obtained from 90 consecutive normal Arab kidney donors for the estimation of GFR (eGFR) using the simplified MDRD and CG formulae. The GFR was measured in these donors with chromium labelled EDTA {[51Cr] EDTA). Bias was assessed by calculating the difference between the measured GFR and the calculated GFR using each of the two formulae; precision was calculated using the r value of the regression analysis. Results. The group studied consisted of 90 donors, of whom 64 were males (71%). The mean age was 30.8 years (± 9.8) and mean BMI was 25.7 (± 5.7). The measured GFR (mean 112.4 ± 17.5) correlated better with the calculated GFR by CG formula (mean 107.7 ± 29.7) and showed poor correlation with the GFR estimated by the MDRD (mean 89.2 ± 13.8); bias = 4.8 and 23.3, respectively (p = 0.1 and < 0.0001, respectively). The correlation with CG formula was better in males (bias = 2, p = 0.5) and those under 30 years of age (bias = 1.0, p = 0.9). Based on our data, we calculated a correction factor to the CG formula to improve the correlation with the measured GFR in Arab individuals. By multiplying the CG formula by 1.0446, the bias was reduced from 4.8 (p = 0.1) to 0.0 (p = 0.5) with an increase in precision from 0.2 (p = 0.05) to 0.43 (p = 0.0001). Using CG formula, the frequency for values within 30% of the mean of the measured value was 75%, which improved to 80% using the revised formula. Conclusions. CG formula was found to be the most appropriate for calculation of GFR in Arab individuals. It is possible to reduce the bias and improve precision in Arab individuals with normal renal function by multiplying the result obtained by CG formula by 1.0446.

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.

Background: This paper aims to evaluate the concordance between the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and alternative equations and to assess their predictive power for all-cause mortality in unselected patients discharged alive from a cardiology ward. Methods: We retrospectively included patients admitted to our Cardiology Division independently of their diagnosis. The total population was classified according to Kidney Disease: Improving Global Outcomes (KDIGO) categories, as follows: G1 (estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2); G2 (eGFR 89–60 mL/min/1.73 m2); G3a (eGFR 59–45 mL/min/1.73 m2); G3b (eGFR 44–30 mL/min/1.73 m2); G4 (eGFR 29–15 mL/min/1.73 m2); G5 (eGFR <15 mL/min/1.73 m2). Cockcroft-Gault (CG), CG adjusted for body surface area (CG-BSA), Modification of Diet in Renal Disease (MDRD), Berlin Initiative Study (BIS-1), and Full Age Spectrum (FAS) equations were also assessed. Results: A total of 806 patients were included. Good agreement was found between the CKD-EPI formula and CG-BSA, MDRD, BIS-1, and FAS equations. In subjects younger than 65 years or aged ≥85 years, CKD-EPI and MDRD showed the highest agreement (Cohen’s kappa (K) 0.881 and 0.588, respectively) while CG showed the lowest. After a median follow-up of 407 days, overall mortality was 8.2%. The risk of death was higher in lower eGFR classes (G3b HR4.35; 95%CI 1.05–17.80; G4 HR7.13; 95%CI 1.63–31.23; G5 HR25.91; 95%CI 6.63–101.21). The discriminant capability of death prediction tested with ROC curves showed the best results for BIS-1 and FAS equations. Conclusion: In our cohort, the concordance between CKD-EPI and other equations decreased with age, with the MDRD formula showing the best agreement in both younger and older patients. Overall, mortality rates increased with the renal function decreasing. In patients aged ≥75 years, the best discriminant capability for death prediction was found for BIS-1 and FAS equations.

BackgroundAlthough the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has been recommended for accurate estimates of glomerular filtration rate (eGFR), there is little information regarding differences in GFR estimates obtained using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations in East Asian cancer patients. We investigated discrepancies in GFR and toxicities in patients treated with cisplatin-based chemotherapy using three equations equations.MethodsA total of 229 patients were retrospectively recruited. We calculated eGFR using the three equations and separated patients into three categories based on GFR < 10 (group A), 10–50 (group B), and > 50 (group C) mL/min/1.73m2. We analyzed chemotherapy toxicities.ResultsThe mean eGFR calculated using the CG was the lowest of the values derived using the three equations. Estimates using the MDRD and CKD-EPI equations resulted in reclassifying 32 (71.1%) and 33 (73.3%) of 45 patients, originally placed in group B using the CG into group C. However, only 1 (7.7%) of 13 patients placed in group B using the MDRD were reclassified into group C using the CKD-EPI. Twenty-eight of 45 patients classified into group B using the CG equation were treated with reduced doses of cisplatin. However, these patients did not show significant differences in toxicities compared with other patients taking full doses of cisplatin.ConclusionThe CG equations underestimated GFR compared to the MDRD and CKD-EPI equations. Therefore, when GFR is estimated using CG equations, East Asian cancer patients may receive insufficient doses of chemotherapeutic agents, including cisplatin.

World Health Organization (WHO) predicts Indonesia's population with Type 2 Diabetes Mellitus (T2DM) will rise from 8.4 million in 2000 to 21.3 million in 2030. The primary cause of disability and death in people with Diabetes Mellitus (DM) is nephropathy. The early stages of diabetic nephropathy are characterized by glomerular hyperfiltration and an increase in the estimated-Glomerular Filtration Rate (eGFR). Other markers of diabetic nephropathy in addition to eGFR are increased creatinine, albuminuria, and proteinuria. The currently developed formulas for eGFR assessment are the Cockcroft-Gault (CG) formula, the Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI). This study aimed to determine the relationship between eGFR using the CKD-EPI formula for serum creatinine and CG in T2DM patients. Fifty-three DM patients participated in a cross-sectional study of the population of patients diagnosed with T2DM by clinicians at Hasanuddin University Hospital between March and June 2022. Version 25 of the Statistical Package for Social Science (SPSS) software was used to analyze the data. Statistical tests for the Normality of data distribution used the Kolmogorov-Smirnov test to determine the normality of data, the ANOVA test was used for comparison, and the Spearman test was used as a correlation test. The relationship between CKD-EPI and CG was highly correlated (r=0.868, p&lt;0.001). Urine albumin levels and eGFR CKD EPI (r= -0.283, p=0.042) and CG (r= -0.282, p=0.043) showed a significant connection. There was a very strong relationship between CKD-EPI and CG.

Should Estimated Glomerular Filtration Rate Be Adjusted for Race?

SAT0129 Kidney Function, Endothelial Activation and Atherosclerosis in Black and White Africans with Rheumatoid Arthritis

CHARLOTTE, N.C. — The two predominant equations used to stage chronic kidney disease give significantly different results in elderly people, suggest data compiled on 1,535 hospitalized patients with an average age of 79 years. Thiruvinvamalai S. Dharmarajan, MD, of Montefiore Medical Center in New York City and his colleagues analyzed data from hospitalized older adults with chronic kidney disease using the Modification of Diet in Renal Disease (MDRD) equation and the Cockcroft-Gault (C-G) equation to determine each patient's stage of disease. Nearly half the patients had come to the hospital from nursing homes. The G-C approximates glomerular filtration rate by calculating creatinine clearance from age, sex, body weight, and serum creatinine. In contrast, the MDRD calculates glomerular filtration rate using age, sex, race, and serum creatinine. Neither equation has been well validated in patients older than 70 years, Dr. Dharmarajan noted. The researchers found that the equations placed many patients in different disease stages. For example, the C-G indicated that 10% of the patients had stage I disease, whereas the MDRD put that number at 23%. The proportions of patients in stages II through V were 25%, 44%, 16%, and 5%, respectively, using the G-C versus 38%, 28%, 6%, and 5%, respectively, using the MDRD. The study findings were presented in a poster at the Annual Symposium. The two equations also yielded different results in a subset of 562 patients whom primary care physicians had diagnosed as having “renal insufficiency.” In this subgroup, the C-G placed 19%, 52%, and 29% in stages II, III, and IV of disease, respectively, whereas the MDRD put 9%, 39%, and 52% in those respective categories. In this group, as in the overall population, the discrepancy between the two measures increased dramatically with age. About half the patients with decline in kidney function may be poorly staged, monitored, and evaluated depending on which formula is used, the researchers wrote. “Perhaps this is an indication for further modification of existing formulae or the need for new methodology,” the researchers said. A new formula based on the MDRD has been developed by the Chronic Kidney Disease Epidemiology Collaboration, but it has yet to be validated in older patients, they added. The team declared no conflict of interest related to this study.

Background and Aims Glomerular filtration rate (GFR) is the most important and accurate parameter of kidney function in the course of chronic kidney disease (CKD). Renal or plasma inulin, diethylenetriaminepentaacetate (DTPA), ethylenediaminetetraacetate (EDTA), radiocontrast agents (iohexol, iothalamate) and some other substances clearances are the reference methods for determining GFR. However, these methods cannot be applied routinely because of the inconvenience. Several available methods have been developed to estimate GFR in a simpler manner and at low costs. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is widely used to evaluate the GFR in practice. However, this equation is not accurate for the full age spectrum. In 2016, the new equation, full age spectrum equation, based on the serum creatinine (FAScr), was developed and can be applicable to all ages. However, data on the benefits of using the FAScr-method in different populations are contradictory. In particular, it is unclear whether the FAScr provides any advantages over the CKD-EPI method in adults. In this regards, we attempted to compare data obtained FAScr method with results some non-reference and reference methods in adult Russian population. Method We examined 120 Caucasian patients (M:F - 52:68; age 18-76 year) with CKD 1 - 5 stages. Patients with nephrotic syndrome and congestive heart failure were excluded. GFR (reference method) measured by plasma clearance of 99mTc-DTPA (CDTPA). CDTPA determined by one- compartment model 2-4 h method using a Chantler-Barratt linear correction. Estimation GFRs (eGFR) were established by Cockcroft-Gault creatinine clearance (CG), CKD-EPI (creatinine), FAScr and Modification of Diet in Renal Disease (MDRD) methods. Also, renal creatinine clearance (Ccr; UV/P method) was measured. Only GFRs values corrected on 1.73 m2 body surface area had been use. Results The values of GFR (Mean(SEM)) are: CDTPA 67.0(2.46); FAS 69.7(2.50); CKD-EPI 64.3(2.54); MDRD 60.9(2.62); CG 77.6(3.31); Ccr 85.2(3.40), мл/мин/1.73 m2. MDRD was significantly lower (paired Student t-test with correction on multiply comparison by Benjamini-Hochberg method) than CDTPA (P=0.0024), CG (P=0.0001) or Ccr (P&amp;lt;0.0001) were significantly higher. The bias (CDTPA minus non reference GFR) were: FAS -2.67(1.71); CKD-EPI 2.72(1.58); MDRD 6.12(1.78); CG -10.57(2.51); Ccr -18.22(2.26), ml/min. All biases are significantly differ between themselves (P from 0.00064 to &amp;lt;0.000001). The percentage of P30 of the FAS 81.6(3.5) was not significant differ from P30 of CKD-EPI (78.3(3.8); P=0.524) or MDRD (71.7(4.1); P=0.071). However, P30 of CG (67.5(4.3),%; P=0.01) or Ccr (54.2(5.42),%; P&amp;lt;0,001) were significant lower, than P30 of FAS. There were significant comparable direct correlations between CDTPA and FAS (r=0.764), CKD-EPI (r=0.801), MDRD (r=0.756), CG (r=0.656), Ccr (r=0.749); P&amp;lt;0.00001 in all cases. Conclusion In adult Russian population FAScr-method of GFR estimation had not any advantage over CKD-EPIcr-method.

Renal function is often estimated using one of several glomerular filtration rate (GFR) estimating equations. However, there is no consensus which estimating equation performs best in patients with advanced renal failure. We compared the performance of five different estimated GFR (eGFR) equations [Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease (CKD) Epidemiology collaboration (CKD-EPI) and Mayo Clinic and Lund-Malmö] with measured GFR (plasma iohexol clearance) in 2098 referred CKD patients with mGFR <30 mL/min/1.73 m(2). There were 398 patients with an mGFR ≤ 10 mL/min/1.73 m(2), 1974 with a measured GFR (mGFR) 11-20 mL/min/1.73 m(2) and 749 patients with mGFR 21-30 mL/min/1.73 m(2). Across the entire range, the median bias of eGFR was lowest for the Lund-Malmö equation (0.7 mL/min/1.73 m(2)), followed by the CKD-EPI (1.2 mL/min/1.73 m(2)), the MDRD (1.6 mL/min/1.73 m(2)), Mayo Clinic equation (1.7 mL/min/1.73 m(2)) and Cockcroft-Gault equation (4.6 mL/min/1.73 m(2)). The best accuracy within 30% of mGFR was also for Lund-Malmö (76%), while it was similar for CKD-EPI, MDRD and Mayo (65-67%). The Cockcroft-Gault had the worst accuracy of only ∼54%.The median bias was stable across mGFR categories, while the accuracy within 30% of mGFR became worse with decreasing mGFR. All equations performed best among patients with hereditary kidney diseases and tubulointerstitial disease. Accuracy was generally worse for patients >65 years of age and for those with diabetic nephropathy. In patients with advanced renal failure, the GFR-estimating equations show reasonably good performance on the population level. On the individual patient level, they are inaccurate, especially in elderly patients and those with diabetic nephropathy.