Glomerular Function, Structure, and Number in Renal Allografts from Older Deceased Donors

Abstract

The 5-yr survival rate of renal allografts is significantly lower for grafts from older deceased donors than from younger deceased donors. For evaluation of the potential contribution of renal senescence in this shortened graft survival, glomerular function and structure were analyzed in allografts from deceased donors older than 55 yr ("aging") or younger than 40 yr ("youthful"). Aging donors had a significantly higher prevalence of sclerotic glomeruli (P Ͻ 0.002), and their nonsclerotic glomeruli tended to be larger, had a larger filtration surface area (P ϭ 0.02), and had a higher single-nephron ultrafiltration coefficient (K f ; P ϭ 0.07), suggesting a compensatory response to functional loss of glomeruli. After serum creatinine reached a stable nadir in the transplant recipients, GFR and its hemodynamic determinants were evaluated and the whole allograft K f was computed. Compared with the allografts from youthful donors, allografts from aging donors exhibited a 32% lower GFR, which was exclusively attributable to a 45% reduction in allograft K f (both P Ͻ 0.001). In addition, the number of functioning glomeruli per allograft was profoundly lower in grafts from aging donors than from youthful donors (3.6 Ϯ 2.1 ϫ 10 5 versus 8.5 Ϯ 3.4 ϫ 10 5 ; P Ͻ 0.01), and this could not be explained by the relatively modest 17% prevalence of global glomerulosclerosis in the aging group. The marked reduction in overall glomerular number in many aging donors may lead to a "remnant kidney" phenomenon, potentially explaining the shorter mean survival of these allografts.

Longitudinal study of living kidney donor glomerular dynamics after nephrectomy

“…Biopsy series suggest that glomerular obsolescence is unusual below the age of 40 years, but becomes increasingly prevalent after the age of 50 years (19,20). We have previously demonstrated an inverse relationship between glomerular number and age in both living and deceased donor kidneys (9,21). Human autopsy series have also shown a negative correlation between age and glomerular number (22,23).…”

“…Blood pressure was measured with a Dinamap (GE Healthcare). The K f was calculated using a mathematical model described by Deen et al (8,9). This requires knowledge of the GFR, RPF, π A , and ΔP.…”

“…A cortical wedge biopsy from the donated kidney was obtained from 19 subjects prior to transplantation. Each biopsy core was subjected to detailed light and electron microscopic analysis, as described in detail by us previously (9). Briefly, the percentage of global glomerular sclerosis, the fractional interstitial area, and the glomerular volume (V G ) were measured using light microscopy.…”

“…We used Deen's mathematical model (8,9) to estimate the single-kidney K f longitudinally. Since the MAP was similar at all 3 study time points, we first calculated the K f , assuming that the glomerular transcapillary hydraulic pressure gradient (ΔP) was fixed at 40 mmHg (Figure 2A).…”

Expanded Criteria Donors in Kidney Transplantation: The Role of Older Donors in a Setting of Older Recipients

“…In addition senescence of renal tissue is associated with impaired cellular repair mechanism [46]. The progressive loss of the renal mass and the decrease in the total number of functioning glomeruli cause a marked reduction of the functional reserve of the kidney, with the glomerulopenia being at the basis of a "remnant kidney" phenomenon causing progressive allograft failure [47]. Along with the changes caused by aging, "marginal kidney" has been defined not only those organs obtained from marginal donors, but also kidneys that, though collected from standard donors, have complex arterial anomalies (e.g., more than 2 arteries though on a single patch or separated in such a way to need a double anastomosis or a bench reconstruction), kidneys with noticeable parenchymal damage (macroscopic sclerosis areas or sutured polar branches accidentally damaged during removal), and kidneys with complex anomalies of the excretory tract (complete double district), all conditions causing a loss functional mass [29].…”