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

Year: 2026

Type: article

Abstract: Introduction Nephrectomy results in abrupt nephron loss and variability in postoperative estimated glomerular filtration rate (eGFR) trajectories that is 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 following nephron loss. We therefore evaluated their association with eGFR compensation after uninephrectomy. Methods We retrospectively assessed nephron number, single-nephron filtration, and podometrics in patients undergoing nephrectomy for renal tumors, using imaging and stereology on non-neoplastic tissue. Renal compensation (ΔeGFR) was calculated at 1-year post-surgery, and structural-functional parameters were compared across ΔeGFR tertiles using ANOVA. Results 54 patients (mean age 67±13 years; 43% female) were stratified into ΔeGFR tertiles. Presurgical baseline eGFR was 84±15 mL/min/1.73m 2 and was similar across tertiles. Patients with the poorest compensation (most negative ΔeGFR) exhibited lower nephron number (0.81±0.20 ×10 6 vs. 1.12±0.39 and 1.20±0.42 ×10 6 in the greater and intermediate compensation groups; P =0.005), glomerular hypertrophy (3.0±0.7 ×10 6 μm 3 vs. 2.2±0.5 and 2.5±0.6 ×10 6 μm 3 in the greater and intermediate compensation groups; P =0.004), and higher single-nephron filtration (54±15 nL/min/1.73m 2 vs. 42±13 and 39±13 nL/min/1.73m 2 in the greater and intermediate compensation groups; P =0.005) preoperatively. Podocyte-specific metrics were similar across tertiles. Conclusion 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.

Source: Kidney International Reports

DOI: 10.1016/j.ekir.2026.107099