Methods Of Glomerular Filtration Rate Estimation Research Articles

Recommendations for the assessment of glomerular filtration rate in patients with cancer: A position statement and systematic review on behalf of the American Society of Onco-Nephrology (ASON).

e24143 Background: Accurate assessment of glomerular filtration rate (GFR) is crucial to guiding drug eligibility, dose-adjusting systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. To date, there has been a lack of guidance to standardize approaches to GFR estimation in the cancer population based on the available evidence. We aim to present data on the first systematic review (SR) of GFR estimating equations in patients with cancer. Methods: We conducted a SR on behalf of the American Society of Onco-Nephrology (ASON) on the accuracy of equations to estimate GFR in adult patients with cancer, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We required that studies use a reference methodology as comparator involving measured GFR via urinary or plasma clearance of an exogenous filtration marker or carboplatin. Two search strategies focusing on studies using serum creatinine (Cr) and cystatin C (Cys) were developed. Risk of bias and quality assessment was performed for all studies. Results: A total of 39 studies (21,949 patients in total, 19,025 with solid cancers) were included. Studies assessing populations in Europe were most frequent (50%), followed by Asia (27%) and the remaining from Australia/New Zealand and North and South America. Risk of bias and quality assessment allocated 15 studies (38%) as low or very low quality, and 24 (62%) as low-moderate or moderate quality. The most commonly assessed GFR estimating equations included Cockroft-Gault (32 studies), Modification of Diet Renal Disease (MDRD) (24 studies), Chronic Kidney Disese Epidemiology Collaboration Study (CKD-EPI)Cr (22 studies), Wright (13 studies), CKD-EPICys (8 studies), CKD-EPICr-Cys (8 studies), and Jeliffe (8 studies). Given the importance of accurate and timely eGFR assessment and the evidence supporting the performance (i.e., accuracy) of the CKD-EPI incorporating both Cr and Cys, we suggest the use of this equation in patients with cancer (grade 2C). Where Cys is unavailable, CKD-EPICr is the next preferred equation given the supporting data for its performance and widespread availability. Since included studies were moderate quality or lower, the ASON rated the certainty of evidence as low. Also, additional data on clinical outcomes related to the selection of eGFR equations is needed. We suggest measurement of GFR via an exogenous filtration marker in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials (ungraded). Conclusions: Based on the results of this SR, we suggest use of contemporary methods for estimation of GFR (CKD-EPICr-Cys and CKD-EPICr-Cr) and avoidance of older and less accurate formulae such as Cockcroft-Gault.

Refining GFR estimation: a quest for the unobservable truth?

Assessing glomerular filtration rate (GFR), which is central to evaluating kidney health, remains challenging. Measured GFR is not widely available and lacks standardization. Estimated GFR can be highly inaccurate for some patients and has limited applicability to many patient populations, such as those who are acutely ill. Recent metabolomic advances show promise for identifying new filtration markers that might enhance GFR estimation. Improving GFR assessment will require refinement in both GFR measurement and estimation methods.

Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers

BackgroundCarboplatin remains integral for treatment of gynaecological malignancies and dosing is based on glomerular filtration rate (GFR). Measurement via radiotracer decay [nuclear medicine GFR (nmGFR)] is ideal. However, this may be unavailable. Therefore GFR is often estimated using formulae that have not been validated in patients with cancer and/or specifically for gynaecological malignancies, leading to debate over optimal estimation. Suboptimal GFR estimation may affect efficacy or toxicity.MethodsWe surveyed several UK National Health Service Trusts to assess carboplatin dosing practise. We then explored single-centre accuracy, bias and precision of various formulae for GFR estimation, relative to nmGFR, before validating our findings in an external cohort.ResultsAcross 18 Trusts, there was considerable heterogeneity in GFR estimation, including the formulae used [Cockcroft–Gault (CG) versus Wright], weight adjustment and area under the curve (AUC; 5 versus 6). We analysed 274 and 192 patients in two centres. Overall, CamGFR v2 (a novel formula for GFR estimation developed at Cambridge University Hospitals NHS Foundation Trust) excelled, showing the highest accuracy and precision. This translated into accuracy of hypothetical carboplatin dosing; nmGFR-derived carboplatin dose fell within 20% of the Cam GFR v2-derived dose in 86.5% and 87% of patients across the cohorts. Among the CG formula and its derivatives, using adjusted body weight in those with body mass index ≥25 kg/m2 [CG-adjusted body weight (CG-AdBW)] was optimal. The Wright and unadjusted CG estimators performed most poorly.ConclusionsWhen compared with nmGFR assessment, accuracy, bias and precision varied widely between GFR estimators, with the newly developed Cam GFR v2 and CG-AdBW performing best. In general, weight (or body surface area)-adjusted formulae excelled, while the unadjusted CG and Wright formulae or the use of AUC6 (versus nmGFR AUC5) produced risk of significant overdose. Thus, individual centres should validate their GFR estimation methods. In the absence of validation, CG-AdBW or CamGFR v2 is likely to perform well while unadjusted CG/Wright formulae or AUC6 dosing should be avoided.

Glomerular Filtration Rate Estimation With Commonly Used Methods Among Healthy Live Kidney Donors of South Punjab, Pakistan.

BackgroundAccurate estimation of the donor’s glomerular filtration rate (GFR) is crucial for not only ensuring the medical appropriateness of the donor but also for the prediction of future allograft performance. The aim of this study was to compare the GFR estimation formulas and 24-hour urine creatinine clearance with diethylene triamine pentaacetic acid (DTPA) renal scan GFR.MethodsThis cross-sectional study was done at the Department of Nephro Urology Dialysis & Renal Transplantation, Bahawal Victoria Hospital, Quaid e Azam Medical College, Bahawalpur, Pakistan from September 2018 to September 2021. A total of 92 potential healthy live-related kidney donors of both genders, aged 18 to 60 years having body mass index below 35 kg/m2 were included. GFR was calculated with modification of diet in renal disease (MDRD), Cockcroft-Gault (CG), chronic kidney disease epidemiology (CKD-EPI) equations as well as by 24-hour urine creatinine clearance. DTPA renal scan was done to record GFR findings. GFR was compared using analysis of variance (ANOVA) among different methods.ResultsOut of a total of 92 individuals, 49 (53.3%) were male and 43 (46.7%) female. Mean age and BMI were noted to be 34.62±10.57 years and 24.40±2.71 kg/m2, respectively. Statistically significant differences existed between various methods of GFR estimation (p<0.001). Mean GFR as per DTPA renal scan findings was noted to be 97.32±9.39 ml/min/1.73 m2. Difference of 31.48±20.81, 27.37±21.1, 23.38±6.38, 15.52±37.52 was noted in estimated GFR (ml/min/1.73 m2) with CG formula, MDRD formula, EPI-CKD formula and 24-hour urine creatinine clearance respectively when compared with DTPA renal scan findings. The highest proportion of patients was seen with normal GFR with DTPA renal scan findings as 83 (90.2%) individuals while 24-hour urine creatinine clearance observed these to be 59 (64.1%), CG EPI-CKD formula 44 (47.8%), MDRD formula 39 (42.4%) and 40 (43.5%) with CG formula.ConclusionNone of the GFR estimation methods resulted in similar findings. With reference to the DTPA renal scan, 24-hour urine creatinine clearance was the closest GFR estimation followed by CKD-EPI and MDRD equations.

Posuzování funkce ledvin u pacientů s jaterním onemocněním

Accurate measurement of renal function in serious liver disease is very important not only for the estimation of renal damage (chronic kidney disease – CKD), safe drug management, prediction of illness follow-up, intensive methods including hemodialysis, hemodiafiltration or hemoperfusion, but also for the indication of liver transplantation. All methods of renal function measurement using serum creatinine for the estimation of glomerular filtration rate (GFR) are not accurate: they overestimate the value of GFR; the worse the liver damage is, the higher the level of overestimation; predominantly due to decreased endogenous creatinine production (creatinine generation rate – CGR). Using of cystatin C for GFR in liver disease is mainly promising in acute kidney injury (AKI), but obtained results have not been defi nitive yet and need more relevant data from diff erent methods of GFR estimation.

Assessment of calculated glomerular filtration rate using percutaneous nephrostomy creatinine clearance

Background: Radionuclide scintigraphy is considered the most widely used method for estimation of glomerular filtration rate (GFR) in clinical use. The present study was conducted to assess calculated glomerular filtration rate (cGFR) using percutaneous nephrostomy creatinine clearance and comparing it with measured glomerular filtration rate (mGFR) calculated by radionuclide scintigraphy. Materials & Methods: 40 cases of kidney disease of both genders were included. The mGFR and cGFR estimation was done after complete stabilization of the patient and resolution of the indication for which PCN was inserted and after stabilization of PCN output. The DTPA/EC scan was performed by Gates method. Results: Out of 40 patients, males were 22 and females were 18. mGFR (mean) was 11.4 ml/min, cGFR (mean) was 7.42 ml/min, highest calculated GFR was 8.74 ml/min, mGFR 30 was seen in 5 and mGFR could not calculated in 1 patient. A strong overall correlation was found between the two methods of GFR estimation. Conclusion: GFR calculated by PCN creatinine clearance can be used to estimate kidney function when radionuclide scan is not available. However, further studies are required due to small sample size of our study.

Is DtPa the Gold Standard for Glomerular Filtration Rate Estimation in Voluntary Kidney Donors before and after Donor Nephrectomy?

Introduction: Precise assessment of renal function of voluntary kidney donors has important implications for both donor and recipient health outcome. The ideal test for assessment of overall renal function is measurement of Glomerular Filtration Rate (GFR). Various centres use various creatinine based formulae to calculate the GFR, however when compared to GFR measurements by 99mTc-diethylenetriaminepentaacetic acid (DTPA) isotope clearance, their performance remain inconclusive. Aim: To assess the efficacy of creatinine-based GFR estimating equations in comparison to DTPA scan in voluntary kidney donors before and after donor nephrectomy. Materials and Methods: This study was conducted on 50 voluntary kidney donors who underwent donor nephrectomy at Army Hospital (R&amp;R), New delhi. This study was conducted from November 2016 to March 2018 as a single centre, prospective, longitudinal cohort study on living related kidney donors with follow up at 1 and 3 months after kidney donation. The predictive capabilities of GFR estimation by Cockroft Gault (CG) equation, CG equation corrected for GFR and 24-hour urine Creatinine Clearance (CrCl) corrected for Body Surface Area (BSA), for both pre- and postdonor nephrectomy at 90 days, were assessed and further compared with DTPA-GFR as reference GFR. Individual quantitative parameters were compared using Student t test. For the normally distributed GFR data, Pearson’s correlation coefficient was also calculated. Statistical Package for the Social Sciences (SPSS), version 24.0, software and MS Excel were used for analysis. Results: Out of 50 subjects studied, 38 (76%) were females and 12 (24%) were males. Majority of donors were spouses. The mean GFR measured by 99mTc-DTPA scan was 99.47±14.4 ml/min/1.73m2 and 62.1±11.5 ml/min/1.73 m2 pre and postdonation respectively. All the equations being evaluated in this study underestimated the GFR as measured by 99mTc DTPA renal scan prior to kidney donation whereas GFR estimation postdonor nephrectomy by CG CrCl and CG GFR overestimated the GFR values while Urine CrCl underestimated it. Conclusion: All the equations performed unsatisfactorily. Even the best performing equation urine-CrCl was also found to be suboptimal for donor evaluation. More accurate methods of GFR estimation, should, thus be used keeping the potential risks of living kidney donation in perspective.

Formulas Estimating Glomerular Filtration Rate in the Evaluation of Living Kidney Donor Candidates: Comparison of Different Formulas With Scintigraphy-Measured Glomerular Filtration Rate

IntroductionEstimation of kidney function is crucial in the evaluation of living kidney donor candidates. Despite the multitude of glomerular filtration rate (GFR) formulas, no equation is universal, and none were validated in the population of kidney donors. Novel biomarkers, including beta trace protein (BTP) and cystatin C, are studied to help estimate GFR and improve the safe qualification of living kidney donors. AimThis study compares the accuracy of different formulas that estimate GFR with reference scintigraphy-measured GFR in the population of living kidney donor candidates. Material and MethodsThis study enrolled 30 healthy living kidney donor candidates. GFR was measured using the following 11 different formulas. For reference, GFR was assessed using 99m-Technetium-diethylenetriaminepentaacetic acid. ResultsThe accuracy of estimation was generally low in all formulas. The strongest correlation between measured GFR (mGFR) and estimated GFR (eGFR) was achieved by the Nankivell formula (R = 0.47, P = .009); however, in the group of patients with a body mass index of >25 kg/m2, only the equations based on BTP had a statistically significant correlation with mGFR: White (R = 0.59; P = .016) and Poge (R = 0.53; P = .035). Bland-Altman plots revealed wide limits of agreement between eGFRs and mGFR in all groups of patients. ConclusionIn living kidney donor candidates, GFR estimation formulas should be chosen individually. White formula, which is based on BTP, may be a promising tool in estimating GFR in overweight potential living kidney donor candidates. More than 1 formula and personalized choice of GFR estimation method regarding the given patient should be performed in qualification of kidney donors.

Assessment of the glomerular filtration rate (GFR) in kidney transplant recipients using Bayesian estimation of the iohexol clearance.

Background Plasma iohexol clearance (CLiohexol) is a reference technique for glomerular filtration rate (GFR) determination. In routine practice, CLiohexol is calculated using one of several formulas, which have never been evaluated in kidney transplant recipients. We aimed to model iohexol pharmacokinetics in this population, evaluate the predictive performance of three simplified formulas and evaluate whether a Bayesian algorithm improves CLiohexol estimation. Methods After administration of iohexol, six blood samples were drawn from 151 patients at various time points. The dataset was split into two groups, one to develop the population pharmacokinetic (POPPK) model (n = 103) and the other (n = 48) to estimate the predictive performances of the various GFR estimation methods. GFR reference values (GFRref) in the validation dataset were obtained by non-compartmental pharmacokinetic (PK) analysis. Predictive performances of each method were evaluated in terms of bias (ME), imprecision (root mean square error [RMSE]) and number of predictions out of the ±10% or 15% error interval around the GFRref. Results A two-compartment model best fitted the data. The Bayesian estimator with samples drawn at 30, 120 and 270 min allowed accurate prediction of GFRref (ME = 0.47%, RMSE = 3.42%), as did the Brøchner-Mortensen (BM) formula (ME = - 0.0425%, RMSE = 3.40%). With both methods, none of the CL estimates were outside the ±15% interval and only 2.4% were outside the ±10% for the BM formula (and none for the Bayesian estimator). In patients with GFR ≤30 mL/min/1.73 m2, the BM formula performed very well, while the Bayesian method could not be evaluated in depth due to too small a number of patients with adequate sampling times. Conclusions GFR can be estimated with acceptable accuracy in kidney transplant patients using the BM formula, but also using a Bayesian algorithm.

Glomerular Filtration Rate Estimation Formulas for Pediatric and Neonatal Use.

Renal function assessment is of the utmost importance in predicting drug clearance and in ensuring safe and effective drug therapy in neonates. The challenges to making this prediction relate not only to the extreme vulnerability and rapid maturation of this pediatric subgroup but also to the choice of renal biomarker, covariates, and glomerular filtration rate (GFR) estimating formula. In order to avoid burdensome administration of exogenous markers and/or urine collection in vulnerable pediatric patients, estimation of GFR utilizing endogenous markers has become a useful tool in clinical practice. Several estimation methods have been developed over recent decades, exploiting various endogenous biomarkers (serum creatinine, cystatin C, blood urea nitrogen) and anthropometric measures (body length/height, weight, muscle mass). This article reviews pediatric GFR estimation methods with a focus on their suitability for use in the neonatal population.

Cisplatin Induced Renal Insufficiency Measured by Glomerular Filtration Rate with 99mTc-DTPA and by using Serum Creatinine based Formulae: A Prospective Study.

Cisplatin also known as Cis-Diammine-Dichloroplatinum (CDDP) is a chemotherapeutic alkylating nephrotoxic agent. Thus, it is necessary to know if renal function is normal before starting chemotherapy. Glomerular Filtration Rate (GFR) can be assessed directly by using a radiopharmaceutical (dGFR). Estimated GFR (eGFR) method use, Serum Creatinine (SCR) levels in mathematical formulae such as Cockroft-Gault (CG) and abbreviated. Modified Diet in Renal Disease (aMDRD). The serum creatinine level is a function of GFR but is relatively insensitive for detecting early renal insufficiency. We aimed to correlate the incidence of Renal Insufficiency (RI) before and one month after completion of chemotherapy treatment by various methods. In this prospective study, we examined 64 patients with locally advanced head neck and uterine cervix cancers, before and one month after chemotherapy treatment with CDDP. Single agent CDDP was used with dose range between 35mg/m2 as concurrent weekly chemotherapy. Baseline RI was seen in 9.3% of patients by SCR levels, in 21.8% by the dGFR method, in 43.75% by the GFR-CG method and in 25% by the GFR-aMDRD formula. We considered GFR of <60 ml/min and SCR >1.5mg% as RI. After completion of treatment, the median RI was seen in 12.5% by SCR levels, 34.38% by dGFR method, 53.13% by GFR-CG method and 40.63% by GFR-aMDRD formula. None of the methods of GFR estimation showed statistically significant increase in RI one month after CDDP infusion. Only a weak correlation was seen between dGFR and eGFR based on SCR value (p=0.006). Baseline RI was detected in 12% more cases when measured by dGFR as compared with SCR level. However, mathematical formulae overestimated baseline RI as compared to dGFR. One month after completion of treatment with CDDP chemotherapy, RI increased in 10%-15% cases as detected by all the four evaluated methods. There is weak correlation between SCR and dGFR thus implicating the importance of dGFR in assessing RI. Thus, despite normal SCR levels, GFR by radioisotope method should also be done as pre-treatment workup for cisplatin based chemotherapy.

Estimation of glomerular filtration rate with and without height: effect of age and renal function level.

The current glomerular filtration rate (GFR) equation (CKiD) may be less accurate in adolescents and children with higher GFR. This was a retrospective study (n = 161, 247 (99)mTc DTPA-GFRs). Six equations were evaluated for bias, accuracy, and low GFR diagnosis: (1) CKiD; (2) historic center; (3) Hoste(age); (4) Hoste(height); (5) modified Pottel; (6) Gao. Children with ≥ vs. <90 ml/min/1.73 m(2)) and < vs. ≥16 years were compared. Two adult equations were evaluated in children ≥16 years. Most equations underestimated GFR by 1-14 % in the higher GFR group, least so for Hoste(age). In the low GFR group, Hoste(age) and historic center overestimated GFR significantly more than CKiD (p < 0.05). Accuracy (within 30 % GFR) was similar across equations and GFR subgroups (66-86 %). In the ≥16 years group, CKiD underestimated GFR by ∼10 %, vs. ∼3 % for Hoste(height). Accuracy was 5-10 % lower in the older group and most equations were more sensitive than specific for detecting low GFR; this discrepancy was less for the Hoste equations. Adult equations were highly inaccurate. GFR estimation in older children and with higher GFR is suboptimal. The Hoste(height) may be an alternative GFR estimation method; Hoste(age) may allow for height-independent GFR estimation in patients with normal GFR.

Epidemiology of Posttransplantation Chronic Kidney Disease Can Be Altered by Choice of Formula Estimating Glomerular Filtration Rate

BackgroundEpidemiology of posttransplantation chronic kidney disease (CKDPT) has different characteristics than in the general population. Precise determination of glomerular filtration rate (GFR) is essential in the clinical decision making process as well as in management of a population that is based on epidemiological data. The aim of our study was to analyze the impact of an applied GFR estimation method on the epidemiology of CKDPT during the first year after transplantation. MethodsWe estimated GFR (eGFR) using the 4-variable Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula in 215 renal transplant recipients. We also measured and estimated creatinine clearance using the Cockroft-Gault (C-G) formula. Based on these data, we analyzed the influence of these formulas on the epidemiology of CKDPT. ResultsThe largest fraction of patients is in stage 3 of CKDPT (40% to 62%). Application of the CKD-EPI formula instead of MDRD results in a decrease of prevalence of stage 3 by 3.9% at the early period (weeks 2 to 8) and by 13.8% at the late period (weeks 9 to 52) after transplantation. This is coexistent with reclassification from stage 3B to 3A and 3A to stage 2. Use of a measured or C-G–based creatinine clearance instead of the MDRD formula results in decrease of prevalace of stage 3 by 16.5% and 13%, respectively, in the early period and by 32.5% or 27%, respectively, in the late period. ConclusionsEpidemiology of CKDPT depends on the method of calculation of eGFR. Application of creatinine clearance or the C-G formula results in an increase of prevalence of patients with better graft function.

Glomerular Filtration Rate Estimation in Prospective Living Kidney Donors: Preliminary Study

IntroductionKidney transplantation prolongs life expectancy in end-stage renal disease patients at a lesser cost than dialysis. Estimation of kidney function is crucial in the evaluation of prospective living kidney donors. Although unsurpassed in their precision methods of glomerular filtration rate (GFR) measurement with exogenous substances are invasive, expensive, and carry a risk for anaphylactic reactions. Alternatively, kidney function can also be assessed by GFR estimation formulas based on serum creatinine or novel markers such as cystatin C or β-trace protein (BTP). The aim of this study was to compare the performance of GFR estimation methods with reference scintigraphy-measured GFR in population of living kidney donor candidates. MethodsWe included 25 prospective kidney donors (aged 28–64 years) and measured GFR with the following equations: Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Mayo Clinic, Nankivell, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; including cystatin C), and BTP based. GFR were assessed by 99mTc-DTPA for reference. All estimation methods were compared with a reference by general linear models. ResultsThe precision of GFR estimation by all methods is unsatisfactory (30% margin of reference held in <50% of cases). Direction of regression coefficients is negative for some of the methods even when adjusted for body mass index (BMI). Of the study subjects, 64% were overweight/obese. BMI value is significantly correlated with measured GFR (P < .01). CKD-EPI estimation equations are the most precise methods of GFR estimation in this analysis; in addition, CKD-EPI cystatin C and combined creatinine/cystatin C estimators are robust to overweight/obesity. ConclusionsThe precision of GFR estimation is unsatisfactory, in part because of overweight, which adversely influences measured GFR, but also renders estimation methods unusable, except for CKD-EPI cystatin C and combined creatinine/cystatin C formulae. GFR measurement with exogenous substances remains the method of choice in the assessment of kidney function in prospective kidney donors. In addition, it provides useful information on differential (split) renal function.

Looking for a Better Creatinine

Our kidneys maintain a constant internal environment and circulatory volume through a combination of filtration, selective reabsorption and secretion, and production of several key hormones. Young, healthy individuals filter >100 L of blood each day; however, their kidneys then reabsorb most of this for a mean urine output of only 1.5 L/day. This filtration process is necessary to eliminate byproducts of ongoing metabolism (so-called uremic toxins). Indeed, a minimum amount of kidney function is essential for life, and one can demonstrate increased morbidity and mortality when the glomerular filtration rate (GFR)3 chronically dips low enough. Thus, GFR is widely considered the single most important and useful indicator of overall kidney function. It is possible to directly measure GFR by administration of small molecules that are freely filtered by the kidneys and neither metabolized, secreted, nor reabsorbed. Examples include inulin, iothalamate, and iohexol, for which the renal clearance of these molecules equals GFR. However, protocols that use these exogenous agents to measure GFR require some combination of intravenous or subcutaneous administration of the marker, multiple blood draws, and carefully timed urine collections. Thus, direct measurement of GFR is not practical for most routine situations. For these reasons, several methods of GFR estimation have been developed on the basis of endogenous molecules. The best example is creatinine, a byproduct of muscle metabolism that is freely filtered, produced in a relatively consistent manner, and not reabsorbed. Although some creatinine is secreted, this amount is usually small enough that creatinine remains a useful marker of GFR. A bigger problem, however, is that muscle mass (and consequently serum creatinine) varies widely between individuals. Thus, although serum creatinine goes up as GFR goes down, the GFR for a given serum creatinine can vary widely between individuals. For example, a “normal” serum creatinine of 1.0 mg/dL …

Glomerular Filtration Rate Equations Do Not Accurately Predict Vancomycin Trough Concentrations in Pediatric Patients

The Bedside Chronic Kidney Disease in Children (CKiD) equation was developed using data from children with chronic kidney disease. Some institutions are using this equation in all pediatric patients, regardless of renal function, to adjust medications. No data have shown that the Bedside CKiD equation is equivalent or better than the Schwartz equation in estimating glomerular filtration rate (GFR) in pediatric patients with normal renal function. To compare GFR estimates using the Bedside CKiD and Schwartz equations and determine if either offers sufficient vancomycin dosing guidance in hospitalized pediatric patients. This retrospective review at a single-center, academic, pediatric hospital included patients 2 to 12 years old with a steady-state vancomycin trough collected between January 1, 2010 and December 31, 2011. Patients with acute kidney injury or lacking essential data (e.g., height and serum creatinine), were excluded. An estimated GFR (eGFR) was calculated using the Schwartz and Bedside CKiD equations. Pearson correlations and linear regressions compared the eGFR values and vancomycin troughs. A total of 50 vancomycin troughs were analyzed. There was a weak relationship between the eGFR and troughs for the Schwartz equation (r (2) = 0.028) and Bedside CKiD equation (r (2) = 0.028). A weak relationship between serum creatinine and troughs was observed (r (2) = 0.132). Limitations include small sample size and retrospective design. Neither equation correlates well with vancomycin troughs, suggesting that therapeutic monitoring remains important. Better GFR estimation methods are needed in pediatrics to aid appropriate dosing of renally eliminated medications.

Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma

BackgroundSingle cycle carboplatin, dosed by glomerular filtration rate (GFR), is standard adjuvant therapy for stage 1 seminoma. Accurate measurement of GFR is essential for correct dosing. Isotopic methods remain the gold standard for the determination of GFR. Formulae to estimate GFR have improved the assessment of renal function in non-oncological settings. We assessed the utility of these formulae for carboplatin dosing. MethodsWe studied consecutive subjects receiving adjuvant carboplatin for stage 1 seminoma at our institution between 2007 and 2012. Subjects underwent 51Cr-ethylene diamine tetra-acetic acid (EDTA) measurement of GFR with carboplatin dose calculated using the Calvert formula. Theoretical carboplatin doses were calculated from estimated GFR using Chronic Kidney Disease-Epidemiology (CKD-EPI), Management of Diet in Renal Disease (MDRD) and Cockcroft–Gault (CG) formulae with additional correction for actual body surface area (BSA). Carboplatin doses calculated by formulae were compared with dose calculated by isotopic GFR; a difference <10% was considered acceptable. Results115 patients were identified. Mean isotopic GFR was 96.9ml/min/1.73m2. CG and CKD-EPI tended to overestimate GFR whereas MDRD tended to underestimate GFR. The CKD-EPI formula had greatest accuracy. The CKD-EPI formula, corrected for actual BSA, performed best; 45.9% of patients received within 10% of correct carboplatin dose. Patients predicted as underdosed (13.5%) by CKD-EPI were more likely to be obese (p=0.013); there were no predictors of the 40.5% receiving an excess dose. ConclusionsOur data support further evaluation of the CKD-EPI formula in this patient population but clinically significant variances in carboplatin dosing occur using non-isotopic methods of GFR estimation. Isotopic determination of GFR should remain the recommended standard for carboplatin dosing when accuracy is essential.

The Chronic Kidney Disease Epidemiology Collaboration equation outperforms the Modification of Diet in Renal Disease equation for estimating glomerular filtration rate in chronic systolic heart failure

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula estimates glomerular filtration rate (GFR) better than the simplified Modification of Diet in Renal Disease (sMDRD) formula in numerous populations. It has not previously been validated in heart failure patients. The GFR was measured in 120 patients with chronic systolic heart failure (CHF) using [(125)I]iothalamate clearance (GFR(IOTH)) and estimated using the sMDRD and CKD-EPI equations. Accuracy, bias, and prognostic performance were compared. Cockcroft-Gault, CKD-EPI serum cystatin C, and CKD-EPI creatinine-serum cystatin C equations were compared in secondary analyses. Mean age was 59 ± 12 years, 80% were male. Mean LVEF was 29 ± 10%. Mean GFR(IOTH) was 74 ± 27 mL/min/1.73 m(2), and mean estimated GFR was 66 ± 23 mL/min/1.73 m(2) (CKD-EPI) and 63 ± 21 mL/min/1.73m(2) (sMDRD). CKD-EPI showed less bias than sMDRD (-8 ± 15 vs. -11 ± 16 mL/min/1.73 m(2), P < 0.001). Both equations underestimate at higher and overestimate at lower GFR(IOTH). Eleven patients (9%) were accurately reclassified into lower CKD classes with CKD-EPI. Cockcroft-Gault showed lower bias (-3 ± 16 mL/min/1.73 m(2)) but worse precision and accuracy. Cystatin C-based estimation showed the lowest bias (-3 ± 14 mL/min/1.73 m(2)) and the best precision and accuracy. Prognostic value did not differ between all GFR estimates The CKD-EPI equation more accurately estimates measured GFR than the sMDRD equation in CHF patients, with less bias and greater accuracy and precision. The prognostic power of all GFR assessments was equivalent. Based on better performance and equal risk prediction, we believe the CKI-EPI equation should be the preferred creatinine-based GFR estimation method in heart failure patients, particularly those with preserved or moderately impaired renal function.

Understanding kidney function assessment: The basics and advances

Multiple kidney function assessment modalities are available, but their appropriateness is constantly questioned. This review provides practitioners with in-depth understanding of kidney function assessment methods, their clinical utility, and comparisons. PUBMED search was conducted by relevant subject headings. Glomerular filtration rate (GFR) is the best indicator of kidney function. Exogenous compounds like inulin help measure GFR, but endogenous substances (like creatinine) are more convenient, although exhibiting greater variability. Cystatin C is advocated as a functional marker; its clinical significance is under study. Proteinuria adds value to GFR estimation. There are commonly used equations estimating GFR like the creatinine-based Cockcroft-Gault and the modification of diet in renal disease. The new creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation demonstrates higher accuracy of patient classification in earlier stages of disease. Recently, the Chronic Renal Insufficiency Cohort (CRIC) study has devised an equation combining serum creatinine and cystatin C in longitudinal modeling of kidney function. Current GFR estimation methods have limitations, and are useful for populations they have been tested in. Practitioners should be well informed on emerging equations that provide greater accuracy in CKD diagnosis; this would help implement appropriate prevention and intervention strategies.

Estimating Renal Function in Morbidly Obese Patients

This paper aims to evaluate, in a clinical context, current creatinine-based formulas commonly used to calculate renal function in morbidly obese patients. A retrospective analysis was performed of the estimates of renal function of 63 obese or morbidly obese patients undergoing gastric bypass surgery. Each patient's glomerular filtration rate (GFR) was calculated using five methods, both before and after surgery, and these approximations were then compared. Prior to surgery, the values offered by the five formulas for the renal function of this population ranged widely, by over a factor of 2. After surgery, the three weight-based GFR estimation methods indicated that a significant change in GFR had occurred, but the two non-weight-based formulas showed no significant change in estimated GFR. At baseline and after significant weight loss, creatinine-based formulas differ twofold in their estimates of renal function of the morbidly obese. An accurate method for calculating these patients' renal function is required to improve patient safety with drug dosing as well as to ensure early detection of renal failure.