Fibrosis is a major driver of chronic kidney disease and epithelial-mesenchymal transition (EMT) may contribute to its development. A polyubiquitinated form of phosphatase and tensin homolog (PTEN ) promotes EMT in vitro. Thus, it is a potentially useful biomarker of progressive kidney fibrosis and may predict loss of kidney function.
Observational cohort study.
Southwest USA. American Indians (154 women, 80 men) with or at high risk for diabetic kidney disease (DKD).
Serum PTEN .
≥40% loss of glomerular filtration rate (GFR) or onset of kidney failure. Kidney structural measures in a sub-set of study participants who underwent research kidney biopsies (n=77).
Cox proportional hazards models adjusted for age, sex, diabetes duration, HbA1c, blood pressure, use of renin angiotensin system (RAS) blockers, measured GFR and albuminuria. Spearman correlations for associations with structural measures.
At baseline, mean age was 42.8 ± 10.5 (SD) years, diabetes duration 11.5 ± 7.1years, mean arterial pressure 90.5 ± 9.5 mmHg, HbA1c 9.3 ± 2.4%, GFR 152 ± 45 ml/min and median albumin:creatinine ratio 38 mg/g (interquartile range 14-215). 64 (27.4%) participants were using RAS blockers. Higher PTEN was associated with greater risk of ≥40% loss of GFR during a median follow-up of 6.3 years (Hazard ratio [HR] for the 4 vs. 1 quartile = 3.95, 95% CI 2.23-6.98, p<0.001). Serum PTEN was associated with an increased risk of kidney failure over a median follow-up of 15.8 years (HR quartile 4 vs. 1 = 5.66, 95% CI 1.99-16.13, p=0.001). Baseline serum PTEN in the biopsy subset correlated with structural measures including glomerular basement membrane width (rho =0.370, p<0.001) and mesangial fractional volume (rho =0.392, p<0.001).
Small study in single population.
Higher serum PTEN is associated with increased risk for GFR decline and kidney failure in American Indians with type 2 diabetes.

Copyright © 2021. Published by Elsevier Inc.