Longitudinal Study of the Decline in Renal Function in Healthy Subjects

Abstract

BackgroundChronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan.MethodsRetrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method.ResultsIn the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7ml/min/1.73m2. In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42ml/min/1.73m2/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6ml/min/1.73m2.ConclusionsThe present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.

High-Normal Estimated Glomerular Filtration Rate in Early-Onset Preeclamptic Women 10 Years Postpartum

“…A highnormal eGFR was defined as eGFR over 110 mL/min per 1.73 m 2 ; which is 2 SD above the mean eGFR of healthy women as reported in the population-based studies. 17,18 CKD was defined as eGFR <60 mL/min per 1.73 m 2 .…”

Glomerular Filtration Rate and Aging: Another Longitudinal Study - A Long Time Coming!

“…<60 ml/ min/1.73 m 2 ) and mortality (global or cardiovascular) has been used as an important justification for the choice of the unique GFR threshold for CKD definition in the KDIGO guidelines [16] . However, such a unique 'prognosis-based' threshold for CKD definition is questionable for several reasons [15] : (i) this leads to a large gap between eGFR sensed to be the breakpoint to predict mortality (or other events), that is, 60 ml/min/1.73 m 2 [22] and eGFR actually observed in healthy populations [6,7] . For example, in the healthy population described by van den Brand et al [6] , low normal eGFR value (defined as the percentile 5) is 94 and 85 ml/min/1.73 m 2 at 25-29 years, 67 and 70 ml/min/1.73 m 2 at 50-54 years and 44 and 51 ml/min/1.73 m 2 at 70-74 years for men and women, respectively.…”

“…More recent publications have amply confirmed that declining mGFR occurs in 'healthy' and even 'very-healthy' subjects, such as living related donors for kidney transplantation [4,5] . In addition, numerous epidemiological studies have described such declining GFR with aging in samples of apparently healthy populations studied with estimated GFR (eGFR) rather than mGFR [6,7] . The studies with mGFR were limited to a relatively small sample size, especially in the elderly, whereas the epidemiological studies may have been confounded by inaccuracies in the eGFR equations in elderly subjects.…”

Lifetime Risk of CKD

“…In the context of the well established GFR decline with healthy aging, the reference base of normality is also very important. Cross-sectional data with eGFR and mGFR have clearly shown that otherwise healthy people demonstrate a decline in GFR to values ,60 ml/min per 1.73 m 2 with aging, especially in women aged .65 years (3,(11)(12)(13)(14). Thus, it is not surprising that using the definitions of Inker et al, the lifetime risk (to age 85 years) of CKD is greater in women than in men; this is the opposite of what is seen from calculations of lifetime risk of treated ESRD, in which men have a greater (about 1.5-fold) risk than women (15).…”

“…The best scientific tool to define normality for such a "moving" parameter would be the use of percentiles, like pediatricians use every day for height and weight. Using such normograms available in the literature (11)(12)(13)(14) would avoid both false negative (in young people) and false positive (in elderly individuals) diagnoses of CKD. Because this strategy might be considered too complex or cumbersome for daily practice, the use of a specific threshold is favored; however, an age-calibrated threshold seems like good trade-off that is balanced between the two extremes (percentiles on one side and a unique threshold on the other side).…”