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Abstract: TH-PO1070

Associations of Nephron Endowment, Single-Nephron Hyperfiltration and Podocyte Metrics with Postnephrectomy Kidney Function

Session Information

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Paschen, Christopher, Medical University of Vienna, Division of Nephrology and Dialysis, Vienna, Austria
  • Koeller, Maximilian Christian, Medical University of Vienna, Department of Pathology, Vienna, Austria
  • Hennenberg, Juliane, Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna, Austria
  • Nackenhorst, Maja Carina, Medical University of Vienna, Department of Pathology, Vienna, Austria
  • Oszwald, André, Medical University of Vienna, Department of Pathology, Vienna, Austria
  • Kammer, Michael, Medical University of Vienna, Division of Nephrology and Dialysis, Vienna, Austria
  • Pruijm, Menno, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland
  • Kozakowski, Nicolas, Medical University of Vienna, Department of Pathology, Vienna, Austria
  • Regele, Heinz, Medical University of Vienna, Department of Pathology, Vienna, Austria
  • Oberbauer, Rainer, Medical University of Vienna, Division of Nephrology and Dialysis, Vienna, Austria
Background

Uninephrectomy entails an immediate reduction in nephron mass. The transition from two kidney to one implies compensatory adaptations of the remnant kidney with interindividual differences in estimated glomerular filtration rate (eGFR) courses, not fully determined by traditional risk factors. As renal compensation after nephron loss requires increased single-nephron workload, imposing stress on glomeruli and podocytes, pre-existing hyperfiltration may limit adaptive capacity. Despite their central role, single-nephron filtration and podocyte metrics have seldom been investigated together. The aim of this study was to assess the effect of these structural-functional parameters on long-term nephrectomy outcomes.

Methods

Retrospective analysis of 54 patients who underwent tumor nephrectomy. Glomerular and podocyte metrics were ascertained in regions not affected by tumor. Nephron number and single-nephron filtration were estimated with CT-derived cortex volume of the remnant kidney. Outcome analysis included eGFR courses up to 5 years and was performed using linear mixed-effects models, adjusted for baseline kidney function, age, sex, and comorbidities.

Results

The cohort had a mean age of 67±13 years; 69% had hypertension, 28% diabetes, and 72% visceral obesity. Kidney samples contained a mean of 300±121 non-sclerotic glomeruli, with an average nephron number per kidney of 1.04±0.40 ×106, glomerular volume of 2.6±0.7 ×106 µm3, podocyte density of 207±64 per 106 µm3, podocyte nuclear volume of 218±32 µm3 and single-nephron eGFR of 45±15 nL/min/1.73m2. Single-nephron eGFR correlated with podocyte nuclear hypertrophy (RP: 0.44, p<0.001) and inversely with podocyte density (RP: -0.38, p=0.005). Lower post-nephrectomy eGFR trajectories were associated with reduced nephron endowment (-1.7 mL/min/1.73m2 per 100,000; p=0.002), glomerulomegaly (-0.9 mL/min/1.73m2 per 0.1×106 µm3; p=0.001), and higher single-nephron filtration at baseline (-3.7 mL/min/1.73m2 per 10 nL/min/1.73m2; p=0.003).

Conclusion

This study presents a comprehensive framework of structural-functional determinants of uninephrectomy outcomes. Low nephron reserve, glomerulomegaly, and pre-existing single-nephron hyperfiltration appear to represent key mechanisms underlying kidney functional adaptation following nephron loss.

Funding

  • Private Foundation Support