Longitudinal study of living kidney donor glomerular dynamics after nephrectomy

Abstract

Background: Over 5,000 living kidney donor nephrectomies are performed annually in the US. While the physiological changes that occur early after nephrectomy are well documented, less is known about the long-term glomerular dynamics in living donors.

Methods: We enrolled 21 adult living kidney donors to undergo detailed long-term clinical, physiological, and radiological evaluation pre-, early post- (median, 0.8 years), and late post- (median, 6.3 years) donation. A morphometric analysis of glomeruli obtained during nephrectomy was performed in 19 subjects.

Results: Donors showed parallel increases in single-kidney renal plasma flow (RPF), renocortical volume, and glomerular filtration rate (GFR) early after the procedure, and these changes were sustained through to the late post-donation period. We used mathematical modeling to estimate the glomerular ultrafiltration coefficient (Kf), which also increased early and then remained constant through the late post-donation study. Assuming that the filtration surface area (and hence, Kf) increased in proportion to renocortical volume after donation, we calculated that the 40% elevation in the single-kidney GFR observed after donation could be attributed exclusively to an increase in the Kf. The prevalence of hypertension in donors increased from 14% in the early post-donation period to 57% in the late post-donation period. No subjects exhibited elevated levels of albuminuria.

Conclusions: Adaptive hyperfiltration after donor nephrectomy is attributable to hyperperfusion and hypertrophy of the remaining glomeruli. Our findings point away from the development of glomerular hypertension following kidney donation.

Trial registration: Not applicable. FUNDING. NIH (R01DK064697 and K23DK087937); Astellas Pharma US; the John M. Sobrato Foundation; the Satellite Extramural Grant Foundation; and the American Society of Nephrology.

Figure 4. Schematic of glomerular filtration.

The GFR is dependent on RPF, P_UF, and the K_f. At a given RPF, the single-nephron GFR is a product of the P_UF and the K_f (GFR = P_UF × K_f). The P_UF is determined by Starling’s forces across the glomerular capillary and is the difference between the ΔP and the π_GC (P_UF = ΔP – π_GC). The amount of filtrate produced by a given pressure across the glomerular filtration barrier is described by the K_f, which is determined by its hydraulic permeability and surface area.

Figure 3. Relationship between renocortical volume and the K_f and implications for post-donation glomerular dynamics.

(A) Relationship between pre-donation renocortical volume and the K_f, assessed using Spearman’s rank-order correlation (n = 20). (B) Estimated change in ΔP, assuming that the K_f increases in proportion to the mean renocortical volume at each time point (n = 21). Statistical comparisons were made using Friedman’s test with Dunn’s post-test. In B, the boxes extend between the first and third quartiles, the line within the boxes represents the median value, and the lower and upper whiskers extend between the minimum and maximum values.

Figure 2. Glomerular dynamics before and after donor nephrectomy.

(A) Whole-kidney K_f values pre-, early post-, and late post-kidney donation, calculated assuming a fixed ΔP of 40 mmHg at all time points (n = 21). (B) Whole-kidney K_f values pre-, early post-, and late post-kidney donation, calculated using ΔP values of 40 mmHg or 43 mmHg for normotensive and hypertensive time points, respectively (n = 21). (C) Whole-kidney K_f values pre- early post-, and late post-kidney donation, calculated assuming a fixed ΔP of 40 mmHg at all time points, in subjects unexposed to antihypertensive medications (n = 11). (D) ΔP values pre-, early post-, and late post-kidney donation, calculated assuming a fixed whole-kidney K_f (n = 21). Statistical comparisons were made using Friedman’s test with Dunn’s post-test. *P < 0.05; **P < 0.01; ***P < 0.001. In each plot, the boxes extend between the first and third quartiles, the line within the boxes represents the median value, and the lower and upper whiskers extend between the minimum and maximum values, excluding outliers. ^aIn A, B, and C, a single outlier with a K_f value of 34.6 ml/(min × mmHg) early post-donation is not shown in the plots but is included in all statistical analyses.

Figure 1. Baseline clinical, physiological, and radiological parameters.

(A) Single-kidney GFR measured pre-, early post-, and late post-kidney donation (n = 21). (B) Single kidney RPF measured pre-, early post-, and late post-kidney donation (n = 21). (C) Renocortical volume measured pre-, early post-, and late post-kidney donation (n = 12). (D) MAP measured pre-, early post-, and late post-kidney donation (n = 21). (E) Serum creatinine measured pre-, early post-, and late post-kidney donation (n = 21). (F) Serum albumin measured pre-, early post-, and late post-kidney donation (n = 21). (G) Percentage of single-kidney GFR change over time plotted separately for each individual (n = 21). (H) Percentage of RPF change over time plotted separately for each individual (n = 21). Statistical comparisons made using repeated-measures ANOVA with Bonferroni’s post-test (B–F) or Friedman’s test with Dunn’s post-test (A). ***P < 0.001. In each plot, the boxes extend between the first and third quartiles, the line within the boxes represents the median value, and lower and upper whiskers extend between the minimum and maximum values.