Age-adapted percentiles of measured glomerular filtration in healthy individuals: extrapolation to living kidney donors over 65 years

Abstract Objectives Most data on glomerular filtration rate (GFR) originate from subjects <65 years old, complicating decision-making in elderly living kidney donors. In this retrospective multi-center study, we calculated percentiles of measured GFR (mGFR) in donors <65 years old and extrapolated these to donors ≥65 years old. Methods mGFR percentiles were calculated from a development cohort of French/Belgian living kidney donors <65 years (n=1,983), using quantiles modeled as cubic splines (two linear parts joining at 40 years). Percentiles were extrapolated and validated in an internal cohort of donors ≥65 years (n=147, France) and external cohort of donors and healthy subjects ≥65 years (n=329, Germany, Sweden, Norway, France, The Netherlands) by calculating percentages within the extrapolated 5th–95th percentile (P5–P95). Results Individuals in the development cohort had a higher mGFR (99.9 ± 16.4 vs. 86.4 ± 14 and 82.7 ± 15.5 mL/min/1.73 m2) compared to the individuals in the validation cohorts. In the internal validation cohort, none (0%) had mGFR below the extrapolated P5, 12 (8.2%) above P95 and 135 (91.8%) between P5–P95. In the external validation cohort, five subjects had mGFR below the extrapolated P5 (1.5%), 25 above P95 (7.6%) and 299 (90.9%) between P5–P95. Conclusions We demonstrate that extrapolation of mGFR from younger donors is possible and might aid with decision-making in elderly donors.

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FC 055PERCENTILES OF NORMAL MEASURED GLOMERULAR FILTRATION RATE BASED ON DATA FROM LIVING KIDNEY DONORS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab130.003 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

François Gaillard ◽

Pierre Delanaye ◽

Jessica Van Der Weijden ◽

Geir Mjøen ◽

Ingela Fehrman-Ekholm ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

General Population ◽

Glomerular Filtration ◽

Filtration Rate ◽

Validation Cohort ◽

External Validation ◽

Kidney Donation ◽

Older Individuals ◽

Living Kidney Donation ◽

Internal Validation

Abstract Background and Aims Studies of healthy individuals or candidates for living kidney donation, in various geographical areas and ethnic groups, describe a decline of glomerular filtration rate (GFR) with age. Most data on GFR are obtained from subjects in the general population or from candidates for kidney donation who are younger than 65 years. It is currently unknown whether the definition of normal GFR in subjects older than 65 years is similar to the definition in those younger than 65 years. Because the age of candidates for living kidney donation is increasing worldwide, lack of GFR references for older donors complicates the selection process. Moreover, older individuals are most likely to have a mildly decreased GFR that may be misinterpreted as chronic kidney disease. In this study, we calculated percentiles of measured GFR (mGFR) from a large cohort of effective kidney donors (EKD) younger than 65 years, and extrapolated them to subjects older than 65 years. Additionnaly, we collected mGFR data from different centers within Europe from EKD and/or healthy people (HP) from the general population older than 65 years. We tested if the distribution of mGFR of these older subjects fitted with the extrapolated percentiles. Method In this retrospective, observational, multi-center study, percentiles of mGFR in EKD were calculated from a development cohort of French and Belgian EKD younger than 65 years (n=1983). From the French kidney donor study, 147 EKD older than 65 years were considered as the internal validation cohort. In an external validation cohort, data on mGFR of subjects older than 65 years, either EKD or HP from the general population (from Germany, Sweden (2), Norway, Netherlands and France, n=2459) were included. Data were fully anonymized and this retrospective study was approved by the respective ethics committees. Percentiles were derived for the development database, using quantiles modeled as cubic splines with two linear parts joining at one age-knot of 40 years. The median quantile had a constant first part (slope of zero) and a second part with a negative slope of -0.88235 mL/min/1.73m² per year. To maintain consistency, all quantiles were adjusted to show the same shape as the medium quantile. Above 65 years, the percentile values were extrapolated using the same mathematical model. We then calculated the percentage of results from the internal and external validation cohorts that were within the 5th extrapolated percentile (P5) and 95th percentile (P95). A sensitivity analysis including the EKD only was performed. Results Individuals in the development cohort were younger than in the internal or external validation cohort (47.3±10.5 years vs. 68.8±2.9 years and 71.4±6.4 years; respectively, both p<0.001). Individuals in the development cohort had a higher mGFR than in the internal or external validation cohort (99.9±16.4 mL/min/1.73m2 vs. 86.4±14 mL/min/1.73m2 and 82.7±15.5 mL/min/1.73m2; respectively, both p < 0.001). Among the 147 EKD from the internal validation cohort, none (0%) had mGFR below the extrapolated P5 and12 (8.1%) had mGFR higher than the extrapolated P95. Consequently, 135/147 (91.2%) of subjects were between P5-P95. (Figure 1). Considering the whole external validation cohort (n=329), 5 subjects had mGFR lower than extrapolated P5 (1.5%), 25 were above P95, leaving 299 (90.9%) with mGFR between P5 and the extrapolated P95. Conclusion We demonstrate that extrapolated percentiles of mGFR (calculated in individuals younger than 65) fits well with the distribution of mGFR in individuals older than 65. Extrapolation of percentiles to individuals older than 65 is useful to define age-adapted GFR thresholds for older individuals.

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Unilateral nephrectomy causes an early abrupt decrease in plasma arginine and simultaneous reduction in glomerular filtration rate in living kidney donors

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2013.04.031 ◽

2013 ◽

Vol 46 (15) ◽

pp. 1394-1398 ◽

Cited By ~ 5

Author(s):

Gordana Žunić ◽

Aleksandar Tomić ◽

Slavica Spasić

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Unilateral Nephrectomy ◽

Kidney Donors ◽

Abrupt Decrease ◽

Simultaneous Reduction ◽

Living Kidney Donors ◽

Plasma Arginine

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A Modified TNM Classification for Primary Operable Colorectal Cancer

JNCI Cancer Spectrum ◽

10.1093/jncics/pkaa093 ◽

2020 ◽

Author(s):

Chundong Zhang ◽

Zubing Mei ◽

Junpeng Pei ◽

Masanobu Abe ◽

Xiantao Zeng ◽

...

Keyword(s):

Colorectal Cancer ◽

Validation Cohort ◽

Tnm Classification ◽

Characteristic Curve ◽

External Validation ◽

Model Fitting ◽

Information Criteria ◽

Stage I ◽

Internal Validation ◽

Clinical Benefits

Abstract Background The American Joint Committee on Cancer (AJCC) 8th tumor/node/metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis. Methods We included 45,379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (N =31,772) or an internal validation cohort (N =13,607). External validation was performed in 10,902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve (AUC) and Akaike information criteria (AIC) were applied for prognostic discrimination and model-fitting, respectively. Clinical benefits were further assessed by decision curve analyses. Results We created a modified TNM (mTNM) classification: stages I (T1-2N0-1a), IIA (T1N1b, T2N1b, T3N0), IIB (T1-2N2a-2b, T3N1a-1b, T4aN0), IIC (T3N2a, T4aN1a-2a, T4bN0), IIIA (T3N2b, T4bN1a), IIIB (T4aN2b, T4bN1b), and IIIC (T4bN2a-2b). In the internal validation cohort, compared to the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (AUC = 0.675 vs. 0.667, respectively; two-sided P <0.001) and better model-fitting (AIC = 70,937 vs. 71,238, respectively). Similar findings were obtained in the external validation cohort. Decision curve analyses revealed that the mTNM had superior net benefits over the AJCC 8th TNM classification in the internal and external validation cohorts. Conclusions The mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.

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P1718COMPARISON OF MEASURED GLOMERULAR FILTRATION RATE USING 24-HOUR URINE CREATININE CLEARANCE WITH 51-CHROMIUM EDTA IN A MALAYSIAN COHORT OF LIVING KIDNEY DONOR CANDIDATES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1718 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Chee Keong Thye ◽

Yee Wan Lee ◽

Maisarah Jalalonmuhali ◽

Soo Kun Lim ◽

Kok Peng Ng

Keyword(s):

Glomerular Filtration Rate ◽

Creatinine Clearance ◽

Glomerular Filtration ◽

Filtration Rate ◽

Urine Volume ◽

Kidney Donor ◽

Living Kidney Donor ◽

Kidney Donors ◽

Living Kidney Donors ◽

51Cr Edta

Abstract Background and Aims All living kidney donors undergo assessment of renal function by evaluation of Glomerular Filtration Rate (GFR). 51Cr-EDTA is one of the most widely used marker for measuring GFR but it is hampered by cost and laboriousness as well as not being widely available in Malaysia. Measuring 24-hour urine for creatinine clearance (Ccr) is a common alternative when exogenous filtration markers are not available. Ccr suffers from over/underestimation of measured GFR (mGFR) due to errors in urine collection and tubular secretion of creatinine. This is a study to compare the correlation of Ccr against 51Cr-EDTA in measuring GFR among the living donors in Malaysian population. Method This is a cross-sectional, single-centre study of a cohort of living kidney donor candidates from January 2007 to March 2019. All candidates who had mGFR done with both 51Cr-EDTA and Ccr in University Malaya Medical Centre were enrolled. Special consideration was taken to account for adequate urine sampling for Ccr. Clinical data was analysed for correlation, bias, precision and accuracy between Ccr and 51Cr-EDTA. Results A total of 83 living kidney donors with a mean age of 45.60 ± 11.06 years and body mass index (BMI) of 24.36 ± 4.03 were enrolled. Female comprised 74.7% of the donors while Chinese, Malay and Indian accounted for 67.5%, 20.5% and 7.2% of the donors respectively. The study group had a mean serum creatinine of 63.37 ± 16.00 umol/L with a urine volume of 2.03 ± 0.81 L (range 0.70 – 3.82). mGFR from 51Cr-EDTA was 125.56 ± 27.64 ml/min/1.73m2 (range 77.0 – 194.3) whereas calculated Ccr was 136.05 ± 36.15 ml/min/1.73m2 (range 75.32 – 280.06). The correlation coefficient between Ccr and 51Cr-EDTA is moderate (r = 0.43) (p < 0.01). Mean absolute bias between Ccr and 51Cr-EDTA was 10.59 ± 37.99 ml/min/1.73m2 (p < 0.05). The accuracy of Ccr within 30% of 51Cr-EDTA was 77.11%. Conclusion Our study showed that Ccr significantly overestimates mGFR compared to 51Cr-EDTA. However, there is a significantly moderate positive correlation between Ccr and 51Cr-EDTA. Thus, in the absence of 51Cr-EDTA, Ccr is a clinically acceptable alternative if utilized with care and understanding its limitations.

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