SA-β-Gal in Kidney Tubules as a Predictor of Renal Outcome in Patients with Chronic Kidney Disease

Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of beta-galactosidase at pH 6 (SA-beta-Gal) is a classic maker of senescence in cellular biology; however, the predictive role of kidney tissue SA-beta-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectively studied the expression of SA-beta-Gal in kidney biopsies obtained in a cohort [n = 22] of incident patients who were followed up for 3 years as standard of care. SA-beta-Gal staining was approximately fourfold higher in the tubular compartment of patients with CKD vs. controls [26.0 +/- 9 vs. 7.4 +/- 6% positive tubuli in patients vs. controls; p < 0.025]. Tubular expressions of SA-beta-Gal, but not proteinuria, at the time of biopsy correlated with eGFR loss at the follow up; moreover, SA-beta-Gal expression in more than 30% of kidney tubules was associated with fast progressive kidney disease. In conclusion, our study shows that SA-beta-Gal is upregulated in the kidney tubular compartment of adult patients affected by CKD and suggests that tubular SA-beta-Gal is associated with accelerated loss of renal function.