Nephron Number, Single-Nephron Workload, and Podometrics as Predictors of Renal Function After Nephrectomy

Nephrectomy results in abrupt nephron loss and variability in postoperative estimated glomerular filtration rate (eGFR) trajectories that are incompletely explained by baseline clinical factors. Adaptive hyperfiltration has been hypothesized to increase single-nephron workload, with potential consequences for podocyte structure. However, nephron number, single-nephron filtration, and podocyte structural characteristics have rarely been examined jointly as determinants of functional adaptation after nephron loss. We therefore evaluated their association with eGFR compensation after uninephrectomy.

We retrospectively assessed nephron number, single-nephron filtration, and podometrics in patients undergoing nephrectomy for renal tumors, using imaging and stereology on nonneoplastic tissue. Renal compensation (ΔeGFR) was calculated at 1 year postsurgery, and structural-functional parameters were compared across ΔeGFR tertiles using analysis of variance.

A total of 54 patients (mean age: 67 ± 13 years; 43% female) were stratified into ΔeGFR tertiles. Presurgical baseline eGFR was 84 ± 15 ml/min per 1.73 m² and was similar across tertiles. Patients with the poorest compensation (most negative ΔeGFR) exhibited lower nephron number (0.81 ± 0.20 × 10⁶ vs. 1.12 ± 0.39 and 1.20 ± 0.42 × 10⁶ in the greater and intermediate compensation groups; P = 0.005), glomerular hypertrophy (3.0 ± 0.7 × 10⁶ μm³ vs. 2.2 ± 0.5 and 2.5 ± 0.6 × 10⁶ μm³ in the greater and intermediate compensation groups; P = 0.004), and higher single-nephron filtration (54 ± 15 nl/min per 1.73 m² vs. 42 ± 13 and 39 ± 13 nl/min per 1.73 m² in the greater and intermediate compensation groups; P = 0.005) preoperatively. Podocyte-specific metrics were similar across tertiles.

Together, these findings frame compensatory adaptation after nephrectomy as a function of nephron endowment, structural changes, and single-nephron workload, extending beyond conventional clinical risk profiles alone. By integrating parameters rarely examined together, this study provides a comprehensive view of post-nephrectomy functional adaptation.