Adaptive hyperfiltration in the aging kidney after contralateral nephrectomy

Abstract

We examined the magnitude of adaptive hyperfiltration in the remaining kidney of 16 aging (Ͼ57 yr) and 16 youthful (Ͻ55 yr) individuals who had undergone a contralateral nephrectomy. Healthy volunteers who were youthful (n ϭ 143) or aging (n ϭ 37) provided control values for the binephric condition. One-kidney glomerular filtration rate (GFR; ϩ42%), renal plasma flow (ϩ38%), plasma oncotic pressure (ϩ2.8 mmHg), and mean arterial pressure (ϩ7.0 mmHg) were all higher in youthful uninephric vs. binephric subjects. Corresponding excesses in aging uninephric vs. binephric subjects were by 38 and 36% and 1.4 and 14.0 mmHg, respectively. Modeling of these data revealed that an isolated increase in either the glomerular ultrafiltration coefficient (Kf) by 110% or in the transcapillary hydraulic pressure gradient (⌬P) by 7 mmHg, could account for the observed level of hyperfiltration in youthful uninephric subjects. Corresponding increases for aging uninephric subjects were 61% for Kf and 5 mmHg for ⌬P. We conclude that the magnitude of adaptive hyperfiltration is similar in aging to that in youthful uninephric subjects, albeit at a lower absolute GFR level. Isolated increases in either Kf or ⌬P or a combination of smaller increases in both can account for the hyperfiltration. Greater adaptive arterial hypertension in aging than youthful uninephric subjects raises the possibility of a disproportionate role for glomerular hypertension and ⌬P elevation in aging compared with youthful uninephric subjects. Glomerular hypertension could exacerbate the sclerosing glomerulopathy of senescence and lead to renal insufficiency. We recommend that living donors of a kidney transplantation in or beyond the seventh decade be used with caution.living kidney donor; uninephrectomy; glomerular filtration A SHORTAGE OF KIDNEYS FOR transplantation (Tx) in the United States has resulted in a recipient waiting list in excess of 50,000 and a median waiting time of 1,131 days (38). One measure adopted to lower the donor deficit has been the increasing use of unrelated, living donor transplants (35,36,38). Another recent source of additional donors has been deceased donors who meet the so-called "expanded" criteria for donation, the most prominent of which is a donor age in the seventh or even eighth decade (38). Although the expanded criteria have been recommended for deceased donors, the use of living donors over 60 yr of age has, in fact, more than doubled during the past decade (38), suggesting a possible trend toward the increasing use of aging donors, be they deceased or living.A large body of evidence indicates that both the short-term and long-term risks of living kidney donation are minimal and that the ensuing uninephric state is safe for the living donor (9,22,25,26). Donors above age 60 yr at the time of nephrectomy have been few, however, and a comparison between their course and outcome and those of younger donors has not been reported. A relative paucity of aging donors reflects an inverse relationship between graft survival and d...

Evaluation of Kidney Function and Structure in Potential Living Kidney Donors: Implications for the Donor and Recipient

“…In healthy subjects, unilateral nephrectomy is followed by a compensatory increase of the contralateral kidney function. This compensation is approximately a 20-40 % increase in GFR from baseline [16][17][18][19][20]. Velosa et al among others showed that as early as 1-week post-nephrectomy, renal function has recovered to levels slightly lower than those achieved at 6 months post-nephrectomy.…”

“…The mechanisms of this compensatory hyperfiltration are complex and determined by several factors [18]. Age and body size may be important determinants of the change in GFR following donation.…”

“…Studies by Velosa et al as well as by Saxena et al showed that, although aging subjects have a lower absolute baseline GFR, they do not necessarily lose the adaptive hyperfiltration capacity post-nephrectomy. This suggests that post-nephrectomy GFR appears to depend mostly on the pre-nephrectomy kidney function [18,19]. Furthermore, the work by Tan et al provides some mechanistic insights into this hypothesis.…”

Longitudinal study of living kidney donor glomerular dynamics after nephrectomy

“…Immediately following nephrectomy, an approximately 40% increase in renal plasma flow (RPF) and glomerular filtration rate (GFR) in the remaining kidney ensues (6,7). This is associated with glomerular hypertrophy, which may contribute to the adaptive hyperfiltration by enhancing the filtration surface area and hence the whole-kidney ultrafiltration coefficient (K f ) (7).…”

“…This is associated with glomerular hypertrophy, which may contribute to the adaptive hyperfiltration by enhancing the filtration surface area and hence the whole-kidney ultrafiltration coefficient (K f ) (7). Another hypothetical contribution to hyperfiltration is an increase in glomerular capillary -and hence ultrafiltration -pressure.…”