In:
American Journal of Nephrology, S. Karger AG, Vol. 51, No. 12 ( 2020), p. 950-958
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 A current, albeit unproven, hypothesis is that an acceleration of cellular senescence is involved in impaired renal repair and progression of glomerular diseases. Focal segmental glomerulosclerosis (FSGS) is a glomerular disease with a substantial risk for progression to ESRD. However, if and to what extent cell senescence predicts a negative outcome in FSGS is still unknown. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The hypothesis that cell senescence represents a proximate mechanism by which the kidney is damaged in FSGS (NOS phenotype) was investigated in 26 consecutive kidney biopsies from adult FSGS cases (eGFR 72 ± 4 mL/min, proteinuria 2.3 ± 0.6 g/day) who were incident for 2 years in a Northern Italian nephrology center and had a 6-year clinical follow-up. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Cell senescence (p16 〈 sup 〉 INK4A 〈 /sup 〉 , SA-β-galactosidase [SA-β-Gal]) was upregulated by ∼3- to 4-fold in both glomerular and tubular cells in kidney biopsies of FSGS as compared to age-matched controls ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.05–0.01). Tubular SA-β-Gal correlated with proteinuria and glomerulosclerosis, while only as a trend, tubular p16 〈 sup 〉 INK4A 〈 /sup 〉 was directly associated with interstitial fibrosis. At univariate analysis, basal eGFR, proteinuria, and tubular expression of SA-β-Gal and p16 〈 sup 〉 INK4A 〈 /sup 〉 were significantly directly related to the annual loss of eGFR. No correlation was observed between glomerular p16 〈 sup 〉 INK4A 〈 /sup 〉 and eGFR loss. However, at multivariate analysis, eGFR, proteinuria, and tubular p16 〈 sup 〉 INK4A 〈 /sup 〉 , but not SA-β-Gal, contributed significantly to the prediction of eGFR loss. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The results indicate that an elevated cell senescence rate, expressed by an upregulation of p16 〈 sup 〉 INK4A 〈 /sup 〉 in tubules at the time of initial biopsy, represents an independent predictor of progression to ESRD in adult patients with FSGS.
Type of Medium:
Online Resource
ISSN:
0250-8095
,
1421-9670
Language:
English
Publisher:
S. Karger AG
Publication Date:
2020
detail.hit.zdb_id:
1468523-1
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