Cockcroft-Gault eGFR Research Articles

The influence of pharmaceutically induced weight changes on estimates of renal function: A patient-level pooled analysis of seven randomised controlled trials of glucose lowering medication

BackgroundEstimation of kidney function (eGFR) is essential in monitoring of patients with kidney disease. Estimates of kidney function based on serum creatinine are derived from cross-sectional studies. If body weight (BW) changes, this might affect creatinine and eGFR. The Cockcroft–Gault (CG) equation includes creatinine and BW, whereas the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations only include creatinine. MethodsData were pooled from the six LEAD (Liraglutide Effect and Action in Diabetes) trials and the LIRA-DPP4 trial. The trials were conducted in patients with type 2 diabetes and of 26weeks duration.We investigated changes in eGFR for patients treated with liraglutide, and for patients treated with glucose-lowering medications with less weight-reducing effects (insulin glargine, glimepiride, exenatide and rosiglitazone). ResultsWe included 5100 patients (liraglutide n=3173, comparator n=1927). Mean (SD) CKD-EPI eGFR was 81.2 (20.6) ml/min/1.73m2 for liraglutide and 81.6 (20.3) ml/min/1.73m2 for comparator.For liraglutide, BW changed −1.9 (95% CI (−2.0; −1.8)) kg, for comparator BW changed 0.2 (95% CI (0.03; 0.3)) kg. Using regression modelling, a 10% BW decrease yielded no change in creatinine, MDRD eGFR or CKD-EPI eGFR for both liraglutide and comparator, but was associated with a 10.2% (−11.3%; −9.1%) decrease in CG eGFR for liraglutide, and a 10.6% (−12.0%; −9.1%) decrease for comparator. ConclusionsA liraglutide-induced weight reduction of 1.9kg was not associated with change in creatinine. Accordingly, there was no change in weight-independent estimates of GFR, whereas weight-dependent estimates were changed. The MDRD and CKD-EPI equations can be used in patients experiencing pharmaceutically induced weight reductions.

ESTIMATING GLOMERULAR FILTRATION RATE IN PALLIATIVE CARE PATIENTS: COMPARISON OF THE COCKROFT- GAULT AND ABBREVIATED MODIFICATION OF DIET IN RENAL DISEASE FORMULAS-IS IT RELEVANT TO CLINICAL PRACTICE?

BackgroundThe National Kidney Foundation, Kidney Disease Outcomes Quality Initiative recommends the Cockcroft Gault (CG) or abbreviated modified diet in renal disease (aMDRD) formulas for estimating Glomerular Filtration Rate (GFR). Clinical...

Development of a new equation to estimate GFR in cancer patients.

e13503 Background: Renal function affects chemotherapy pharmacokinetics. Carboplatin dosing by Calvert’s formula is more pharmacologically rational, but requires an accurate glomerular filtration rate (GFR). Calvert argues that this requires measuring GFR (mGFR) instead of an estimated GFR (eGFR). Considering skeletal muscle is the major source for creatinine, this study looks to develop a new eGFR equation in cancer patients using lean body mass (LBM). Methods: We prospectively followed 22 stage IV cancer patients (10 female, 12 male; median age 69) who received carboplatin. mGFR by 24 hr creatinine clearance was compared to eGFR by Wright, Cockcroft-Gault (CG), CKD-EPI, MDRD and CT-determined LBM (eGFR = [Muscle Surface Area X 42]/CR). Simulated carboplatin dosing with each eGFR was then compared retrospectively in 100 Non-Small Cell Lung Cancer (NSCLC) patients for accuracy. Results: MDRD, CG, and Wright equations correlated variably with mGFR (R2 0.47, 0.57, and 0.69 respectively). Conversely, mGFR strongly correlated with LBM eGFR (R2 0.84). The Table compares eGFR calculations with mean residual error. In simulated carboplatin dosing of 100 stage IV NSCLC patients using LBM and CG eGFR, the mean residual error of the CG-determined carboplatin dose was 10% (0.5% min, max 39.7%, median 9.3%), assuming the LBM eGFR was better at estimating eGFR. This means that in approximately half of patients, carboplatin dose may be incorrect by CG if the new LBM eGFR method is truly more accurate. Conclusions: We propose a new formula for eGFR in cancer patients that appears superior to current formulas and may have implications for chemotherapy efficacy and toxicity. Studies to validate this formula are under way. [Table: see text]

Comparison of cystatin C- and creatinine-based estimation of glomerular filtration rate according to glycaemic status in Type 2 diabetes

The influence of hyperglycaemia on the performance of glomerular filtration rate (GFR) estimating equations remains to be determined. We compared the performance of creatinine-based GFR with cystatin C-based GFR in patients with Type 2 diabetes according to glycaemic status. In a cross-sectional study of 210 patients with Type 2 diabetes, we staged glycaemic status by HbA(1c) tertiles [HbA(1c) ≤ 75 mmol/mol (9.0%) (n = 70), HbA(1c) 76-95 mmol/mol (9.1-10.8%) (n = 70), HbA(1c) >95 mmol/mol (10.8%) (n = 70)] and measured GFR. Isotopic GFR was measured using renal dynamic imaging with (99m) Tc-diethylene-triamine-penta-acetic acid. Estimated GFR (eGFR) was measured using creatinine-based formulae (Cockcroft-Gault-eGFR, the Modification of Diet in Renal Disease equation-eGFR and the Chronic Kidney Disease Epidemiology Collaboration formula-eGFR) and a cystatin C-based formula (cystatin C-eGFR). The isotopic GFR of all patients was 93.1 ± 34.1 ml min(-1) 1.73 m(-2). All methods for estimating GFR underestimated isotopic GFR [Cockcroft-Gault-eGFR (68.8 ± 38.6 ml min(-1) 1.73 m(-2) ) (P < 0.05), Modification of Diet in Renal Disease-eGFR (74.8 ± 31.3 ml min(-1) 1.73 m(-2) ) (P < 0.05), Chronic Kidney Disease Epidemiology Collaboration-eGFR (72.9 ± 26.6 ml min(-1) 1.73 m(-2)) (P < 0.05) and cystatin C-eGFR (83.5 ± 33.2 ml min(-1) 1.73 m(-2)) (P < 0.05)]. In all patient groups, cystatin C-eGFR was less biased and more accurate than the creatinine-based formulae, especially in the group with HbA(1c) > 95 mmol/mol (10.8%) where there was no difference between cystatin C-eGFR and isotopic GFR. Performance of cystatin C-eGFR was superior to creatinine-based GFR in patients with Type 2 diabetes with HbA(1c) >95 mmol/mol (10.8%).

Clinical Assessment of Follow-Up Cystatin C-Based eGFR in Live Kidney Donors

PurposeWe aimed to compare the cystatin C-based estimated glomerular filtration rate (eGFR) and the serum creatinine-based eGFR and to investigate the clinical roles of the cystatin C-based eGFR in assessing the follow-up renal function of kidney donors.Materials and MethodsWe enrolled 121 healthy kidney donors who underwent live donor nephrectomy between October 2009 and December 2010 in a prospective manner. Serum creatinine and cystatin C were measured preoperatively and were followed after the surgery (1st, 4th, and 7th postoperative day and 1st, 3rd, 6th, and 12th postoperative month). We also compared the sensitivity and specificity of each eGFR method for predicting the development of chronic kidney disease (CKD) after donor nephrectomy.ResultsFor those who had a Modification of Diet in Renal Disease postoperative day 4 eGFR of less than 60 ml/min/1.73 m2, the probability of developing CKD was 89.0% (Chronic Kidney Disease Epidemiology Collaboration eGFR, 66.0%; Cockcroft-Gault eGFR, 74.0%; cystatin C eGFR, 57.1%). A cystatin C eGFR of below 60 ml/min/1.73 m2 at postoperative day 4 predicted CKD at 6 months with a specificity of 90.3%, which was the highest among the estimation methods used. Cystatin C eGFRs were generally higher than the creatinine-based eGFRs.ConclusionsWe conclude that cystatin C-based estimations of the GFR are helpful for predicting the recovery of renal function in kidney donors and could be added to the follow-up protocol of kidney donors who may develop CKD, especially patients whose immediate postoperative renal function is marginal.

Limitations of Cockcroft-Gault and MDRD formulas in estimating GFR among top-level rugby players

We measured serum creatinine concentrations in 17 male athletes of the Italian national rugby team. Blood was obtained before the start of training and during the competitive season. Serum creatinine level was measured by Jaffé reaction at 4 time points during the season, with a formal measure of creatinine clearance in midseason. The values of estimated glomerular filtration rate (eGFR) calculated with the Cockcroft-Gault (CG) equation were higher than those calculated with the Modification of Diet in Renal Disease (MDRD) Study formula (p<0.001). This difference was significantly decreased but still present when the MDRD formula was corrected for body surface area (BSA). When compared with measured creatinine clearance (CrCl), the MDRD underestimates the CrCl by 51 ml/min (95% confidence interval [95% CI], 36-67 ml/min, p<0.0001). When corrected for BSA, this difference falls to 27 ml/min (95% CI, 13-44 ml/min, p=0.001). The CG eGFR gave a better estimate of CrCl, differing by 1 ml/min (95% CI, -16 to +17 ml/min, p=NS). The MDRD formula underestimates the CrCl in rugby players, even when corrected for BSA. Conversely, the CG formula more closely approximates the actual CrCl measurement. The equations to estimate GFR should be used with caution in subjects having atypical anthropometric characteristics.

Accuracy and variability of equations to estimate glomerular filtration rates in renal transplant patients receiving sirolimus and/or calcineurin inhibitor immunosuppression*

Measured glomerular filtration rates (mGFRs) were obtained by (99)mTc-DPTA, (125)I-iothalamate, iohexol, (51)Cr-EDTA, non-radiolabeled iothalamate, or inulin clearance from centers agreeing to perform mGFR in six completed and one ongoing Wyeth Research multicenter trials evaluating sirolimus (SRL) in regimens with or without a calcineurin inhibitor (CNI). Estimated GFRs (eGFRs) were calculated by the Cockcroft-Gault (eGFR(CG)), Nankivell (eGFR(NK)), and simplified Modification of Diet in Renal Disease (eGFR(MDRD)) equations. Bias, precision, and accuracy for each of these equations were estimated by tertiles and by regimen. For the Rapamune Maintenance Regimen (RMR) trial, eGFR outcomes were also compared between treatments {[SRL-cyclosporine (CsA) versus SRL]} using the three eGFR formulas. In the lowest mGFR tertile (6-40 ml/min), eGFR(MDRD) gave the best accuracy with the least bias whereas eGFR(NK) and eGFR(CG) performed better in the highest mGFR tertile (58-139 ml/min). At 24 months in the RMR study, mean differences in eGFR between treatments were 13.6, 14.2, and 13.5 ml/min/1.73 m(2) for eGFR(CG), eGFR(NK), and eGFR(MDRD), respectively, favoring CsA withdrawal (P-values for all <0.001). The accuracy of the three eGFR equations was affected by mGFR range but not by immunosuppressive regimens utilizing SRL, SRL-CNI or CNI-based therapy.

Performance of the Cockcroft-Gault and Modification of Diet in Renal Disease Equations in Estimating GFR in Ill Hospitalized Patients

Estimating glomerular filtration rate (GFR) in severely ill inpatients is clinically important for therapeutic interventions and prognosis, but notoriously difficult to do accurately. The Modification of Diet in Renal Disease (MDRD) equation and Cockcroft-Gault (CG) formula are widely used to estimate renal function in sick hospitalized patients; however, neither method has been validated in this setting. Iodine 125-iothalamate clearances (iGFR) performed in 107 sick inpatients with renal dysfunction were compared with estimated GFRs (eGFRs) from the 6- and 4-variable MDRD (MDRD eGFR) and CG (CG eGFR) equations. Mean serum creatinine (SCr) level was 3.5 +/- 2.0 mg/dL (309 +/- 177 micromol/L), and mean iGFR was 17.1 +/- 17.9 mL/min/1.73 m2 (0.29 +/- 0.30 mL/s/1.73 m2). Six-variable MDRD eGFR was 22.5 +/- 17.4 mL/min/1.73 m2 (0.38 +/- 0.29 mL/s/1.73 m2), 4-variable MDRD eGFR was 23.9 +/- 16.3 mL/min/1.73 m2 (0.40 +/- 0.27 mL/s/1.73 m2), and CG eGFR was 26.0 +/- 17.1 mL/min/1.73 m2 (0.43 +/- 0.29 mL/s/1.73 m2). Blood urea nitrogen (BUN)/SCr ratios greater than 20 were seen in 58% of patients. Overall, the CG and MDRD equations overestimated iGFR, with poor agreement. Overestimation of at least 25% of measured iGFR was seen in 63%, 67%, and 70% of all inpatients when using the 6-variable MDRD, 4-variable MDRD, and CG equations, respectively. Accuracy of eGFR within 50% of measured iGFR was 55% for the 6-variable MDRD equation, 49% for the 4-variable MDRD equation, and 40% for the CG formula. The performance of both methods deteriorated further in patients with a BUN/SCr ratio greater than 20. Estimation equations are performed poorly compared with iGFR and are not reliable measures of actual level of function in sick hospitalized patients, especially those with a high BUN/SCr ratio. Although use of the 6-variable MDRD equation provides a better estimation of GFR, it still is unsuitable for clinical application in this population.