Glomerular Filtration Rate in Healthy Living Potential Kidney Donors: A Meta-Analysis Supporting the Construction of the Full Age Spectrum Equation

Abstract

Background: Normal kidney function or, more specifically, normal glomerular filtration rate (GFR) in men and women and its decline with age is still much debated today. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has gender (and race) multiplication factors, accounts for a decline that starts at very young age and assumes that the mean GFR is as high as 120-130 ml/min/1.73 m² from a young age. The full age spectrum (FAS) estimated mean GFR is about 107 ml/min/1.73 m² at a young age and remains constant until the age of 40 years and then starts to decline both in men and women. The aim of this research study was to give more insight into ‘normal' GFR levels and the physiological decrease of kidney function with age and to use a meta-analysis to evaluate the mathematical construction of the FAS and the CKD-EPI equation. Methods: We conducted a meta-analysis of published GFR measurements in healthy Caucasian living potential kidney donors (n = 5,482, 46.8% men). Only publications dating from 2000 were selected to avoid the possible influence of body surface area changes in the last decades on the indexed GFR, expressed in ml/min/1.73 m². Results: We found that the mean GFR ≈ 107 ml/min/1.73 m² up to the age of 40 years, but renal decline begins beyond 40 years. No evidence could be found for any difference between men and women in the separate age groups. Conclusions: The current meta-analysis supports the mathematical form of the FAS equation, which matches the age/sex dependency of measured GFR for healthy potential living kidney donors.

Age-dependent reference intervals for estimated and measured glomerular filtration rate

“…No difference was observed between males and females in the defined age groups younger than 50 years of age. However, we noticed a difference between males and females older than 50 years, with a faster decline in females than in males, an observation that we also found in our meta-analysis study [6]. …”

“…In this article we present original un published data from Lyon (France), Liège (Belgium) and Leuven (Belgium) for mGFR in healthy potential living kidney donors to confirm our results from the meta-analysis [6]. The goal of this work is to validate the correspondence between the FAS-eGFR reference limits derived from the upper and lower SCr reference limits, with reference limits for mGFR as obtained from the literature.…”

“…From the meta-analysis table, published previously [6], we calculated 2.5th and 97.5th percentiles for mGFR as mean ± 2× SD for 12 studies (males and females separately) and 6 different age groups. The means of the LRLs and URLs with their SDs obtained from these 12 studies are presented in Table 2.…”

“…This literature search resulted in 12 publications that have previously been presented in a meta-analysis study [6]. Mean mGFR and standard deviations (SDs) from this meta-analysis study were used to calculate lower (LRL) and upper (URL) reference limits as mean mGFR ± 2×SD.…”

“…Also, the currently recommended Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR equation [5] predicts a value of 124 mL/min/1.73 m 2 for an 18-year-old male with SCr = 0.90 mg/dL. However, a recent meta-analysis analysing publications on GFR measurements in healthy living potential kidney donors challenged these prior thresholds and confirmed 107 mL/min/1.73 m 2 as an acceptable normal reference value [6]. For the older average healthy adult (with SCr/ Q  = 1), a simple age-dependent decline of eGFR = 107.3 × 0.988 (Age − 40) is obtained from the FAS equation.…”