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      Agreement and Precision Analyses of Various Estimated Glomerular Filtration Rate Formulae in Cancer Patients

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          Abstract

          The accuracy of the estimated glomerular filtration rate (eGFR) in cancer patients is very important for dose adjustments of anti-malignancy drugs to reduce toxicities and enhance therapeutic outcomes. Therefore, the performance of eGFR equations, including their bias, precision, and accuracy, was explored in patients with varying stages of chronic kidney disease (CKD) who needed anti-cancer drugs. The reference glomerular filtration rate (GFR) was assessed by the 99mTc-diethylene triamine penta-acetic acid ( 99mTc-DTPA) plasma clearance method in 320 patients and compared with the GFRs estimated by i) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, ii) the unadjusted for body surface area (BSA) CKD-EPI equation, iii) the re-expressed Modification of Diet in Renal Disease (MDRD) study equation with the Thai racial factor, iv) the Thai eGFR equation, developed in CKD patients, v) the 2012 CKD-EPI creatinine-cystatin C, vi) the Cockcroft-Gault formula, and vii) the Janowitz and Williams equations for cancer patients. The mean reference GFR was 60.5 ± 33.4 mL/min/1.73 m 2. The bias (mean error) values for the estimated GFR from the CKD-EPI equation, BSA-unadjusted CKD-EPI equation, re-expressed MDRD study equation with the Thai racial factor, and Thai eGFR, 2012 CKD-EPI creatinine-cystatin-C, Cockcroft-Gault, and Janowitz and Williams equations were −2.68, 1.06, −7.70, −8.73, 13.37, 1.43, and 2.03 mL/min, respectively, the precision (standard deviation of bias) values were 6.89, 6.07, 14.02, 11.54, 20.85, 10.58, and 8.74 mL/min, respectively, and the accuracy (root-mean square error) values were 7.38, 6.15, 15.97, 14.16, 24.74, 10.66, and 8.96 mL/min, respectively. In conclusion, the estimated GFR from the BSA-unadjusted CKD-EPI equation demonstrated the least bias along with the highest precision and accuracy. Further studies on the outcomes of anti-cancer drug dose adjustments using this equation versus the current standard equation will be valuable.

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          Most cited references 26

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          Asians are different from Caucasians and from each other in their body mass index/body fat per cent relationship.

          The objective was to study the relationship between body mass index (BMI) and body fat per cent (BF%) in different population groups of Asians. The study design was a literature overview with special attention to recent Asian data. Specific information is provided on Indonesians (Malays and Chinese ancestry), Singaporean Chinese, Malays and Indians, and Hong Kong Chinese. The BMI was calculated from weight and height and the BF% was determined by deuterium oxide dilution, a chemical-for-compartment model, or dual-energy X-ray absorptiometry. All Asian populations studied had a higher BF% at a lower BMI compared to Caucasians. Generally, for the same BMI their BF% was 3-5% points higher compared to Caucasians. For the same BF% their BMI was 3-4 units lower compared to Caucasians. The high BF% at low BMI can be partly explained by differences in body build, i.e. differences in trunk-to-leg-length ratio and differences in slenderness. Differences in muscularity may also contribute to the different BF%/BMI relationship. Hence, the relationship between BF% and BMI is ethnic-specific. For comparisons of obesity prevalence between ethnic groups, universal BMI cut-off points are not appropriate.
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            Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD.

            Serum cystatin C was proposed as a potential replacement for serum creatinine in glomerular filtration rate (GFR) estimation. We report the development and evaluation of GFR-estimating equations using serum cystatin C alone and serum cystatin C, serum creatinine, or both with demographic variables. Test of diagnostic accuracy. Participants screened for 3 chronic kidney disease (CKD) studies in the United States (n = 2,980) and a clinical population in Paris, France (n = 438). Measured GFR (mGFR). Estimated GFR using the 4 new equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both with age, sex, and race. New equations were developed by using linear regression with log GFR as the outcome in two thirds of data from US studies. Internal validation was performed in the remaining one third of data from US CKD studies; external validation was performed in the Paris study. GFR was measured by using urinary clearance of iodine-125-iothalamate in the US studies and chromium-51-EDTA in the Paris study. Serum cystatin C was measured by using Dade-Behring assay, standardized serum creatinine values were used. Mean mGFR, serum creatinine, and serum cystatin C values were 48 mL/min/1.73 m(2) (5th to 95th percentile, 15 to 95), 2.1 mg/dL, and 1.8 mg/L, respectively. For the new equations, coefficients for age, sex, and race were significant in the equation with serum cystatin C, but 2- to 4-fold smaller than in the equation with serum creatinine. Measures of performance in new equations were consistent across the development and internal and external validation data sets. Percentages of estimated GFR within 30% of mGFR for equations based on serum cystatin C alone, serum cystatin C, serum creatinine, or both levels with age, sex, and race were 81%, 83%, 85%, and 89%, respectively. The equation using serum cystatin C level alone yields estimates with small biases in age, sex, and race subgroups, which are improved in equations including these variables. Study population composed mainly of patients with CKD. Serum cystatin C level alone provides GFR estimates that are nearly as accurate as serum creatinine level adjusted for age, sex, and race, thus providing an alternative GFR estimate that is not linked to muscle mass. An equation including serum cystatin C level in combination with serum creatinine level, age, sex, and race provides the most accurate estimates.
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              Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study.

              The Renal Insufficiency and Cancer Medications (IRMA) study is a French national observational study. The results from this study of nearly 5,000 patients demonstrated the high prevalence of renal impairment in a population of patients with solid tumors. Every cancer patient who presented at oncology departments that participated in the study over at least 1 of 2 predefined periods during 2004 were included. Renal function was calculated using Cockcroft-Gault and abbreviated Modification of Diet in Renal Disease (aMDRD) formulae to estimate the prevalence of renal insufficiency (RI) according to the Kidney Disease Outcomes Quality Initiative-Kidney Disease Improving Global Outcomes definition and stratification. Anticancer drugs were studied with regard to their potential renal toxicity and dosage adjustment. Of the 4,684 patients from the 15 centers, 7.2% had serum creatinine levels >110 micromol/L. However, when they were assessed using Cockcroft-Gault and aMDRD formulae, 57.4% and 52.9% of patients had abnormal renal function or RI, respectively. Of the 7,181 anticancer drug prescriptions, 53.4% required dose adjustments for RI. Of the patients treated, 79.9% received at least 1 such drug. And 80.1% received potentially nephrotoxic drugs. RI was common in patients with cancer, and drug dosage adjustments often were necessary. Renal function should be evaluated in all cancer patients using either the Cockcroft-Gault formula or the aMDRD formula, including patients with normal serum creatinine levels. In patients who are at high risk for drug toxicity, the dosage should be adapted to renal function, and the use of nephrotoxic therapies should be avoided whenever possible. (c) 2007 American Cancer Society.
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                Author and article information

                Contributors
                wiwat.cha@mahidol.ac.th
                a_leelahavanit@yahoo.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                18 December 2019
                18 December 2019
                2019
                : 9
                Affiliations
                [1 ]ISNI 0000 0004 1937 0490, GRID grid.10223.32, Nephrology Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, , Mahidol University, ; Bangkok, Thailand
                [2 ]ISNI 0000 0001 0244 7875, GRID grid.7922.e, Immunology Unit, Department of Microbiology, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
                [3 ]ISNI 0000 0001 0244 7875, GRID grid.7922.e, Division of Nephrology, Department of Medicine, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
                [4 ]ISNI 0000 0001 0244 7875, GRID grid.7922.e, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, , Chulalongkorn University, ; Bangkok, Thailand
                [5 ]ISNI 0000 0001 0244 7875, GRID grid.7922.e, Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
                Article
                55833
                10.1038/s41598-019-55833-0
                6920413
                31852941
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                chronic kidney disease, oncology, kidney

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