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Abstract: PO1892

Cellular Senescence Is Associated with Faster Progression of Renal Disease in Adults with Focal Segmental Glomerulosclerosis: A 6-Year Prospective Cohort Study

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Verzola, Daniela, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Saio, Michela, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Picciotto, Daniela, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Viazzi, Francesca, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Russo, Elisa, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Cipriani, Leda, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Carta, Annalisa, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Costigliolo, Francesca, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Gaggero, Gabriele, Division of Pathology IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Esposito, Pasquale, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Garibotto, Giacomo, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
  • Poggi, Laura, Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genova and IRCCS Ospedale Policlinico San Martino, Genova, Italy
Background

A current hypothesis is that an acceleration of cellular senescence, a state of irreversible cell cycle arrest mediated by cyclin-dependent kinase inhibitors, is involved in impaired renal repair and in the progression of renal diseases. The functional role of the senescent changes observed in patients with glomerular diseases are unknown and if senescence is really associated with more disease progression is still not understood.

Methods

The hypothesis that cell senescence represents a proximate mechanism by which the kidney is damaged in focal segmental glomerulosclerosis (FSGS) was investigated in 26 consecutive kidney biopsies from FSGS patients (Age 50 ± 3, M/F 12/14, eGFR 72 ± 3.7, proteinuria 2.3 ± 0.6) who were incident in a Northern Italy Nephrology Centre. All biopsies were classified as the not otherwise specified (NOS) FSGS subtype.

Results

Cell senescence (p16INK4A, SA-b-galattosidase stains) was upregulated both in glomeruli (mainly in podocytes) and tubule cells in FSGS as compared to controls (p<=.05-0.01).Tubular p16INK4A correlated with tubulointerstitial fibrosis. Baseline proteinuria, eGFR, interstitial fibrosis and p16INK4A expression in the tubular compartment were associated with eGFR loss at follow up (6.5 ± 2 years). In multiple regression analysis, loss of renal function was predicted by interstitial fibrosis and tubular p16INK4A only. No association with faster eGFR decline was observed for SA-b-galattosidase stain.

Conclusion

These results indicate that an elevated cell senescence rate at the time of initial biopsy represents an independent predictor of progression to ESRD in adult patients at an early stage FSGS .