Serum Level of Polyubiquitinated PTEN and Loss of Kidney Function in American Indians With Type 2 Diabetes

Overview

Journal Am J Kidney Dis

Specialty Nephrology

Date 2021 Sep 25

PMID 34562525

Citations 4

Authors

Helen C Looker

Chunru Lin

Viji Nair

Matthias Kretzler

Michael Mauer

Behzad Najafian

Robert G Nelson

Affiliations

Soon will be listed here.

Abstract

Rationale & Objective: 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.

Study Design: Observational cohort study.

Setting & Participants: Southwest United States, American Indians (154 women, 80 men) with or at high risk for diabetic kidney disease (DKD).

Predictors: Serum level of PTEN.

Outcome: ≥40% loss of glomerular filtration rate (GFR) or onset of kidney failure. Kidney structural measures in a subset of study participants who underwent research kidney biopsies (n = 77).

Analytical Approach: Cox proportional hazards models adjusted for age, sex, diabetes duration, hemoglobin A (HbA), blood pressure, use of renin angiotensin system (RAS) blockers, measured GFR, and albuminuria. Spearman correlations for associations with structural measures.

Results: At baseline, the participants' mean age was 42.8 ± 10.5 (SD) years, diabetes duration 11.5 ± 7.1 years, mean arterial pressure 90.5 ± 9.5 mm Hg, HbA 9.3 ± 2.4%, GFR 152 ± 45 mL/min, and median urinary albumin-creatinine ratio 38 (interquartile range, 14-215) mg/g. RAS blockers were being used by 64 participants (27.4%). A higher PTEN value was associated with a greater risk of ≥40% loss of GFR during a median follow-up period of 6.3 years (HR for quartile 4 [Q4] vs Q1, 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 period of 15.8 years (HR for Q4 vs Q1, 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 (ρ = 0.370, P < 0.001) and mesangial fractional volume (ρ = 0.392, P < 0.001).

Limitations: Small study in single population.

Conclusions: Higher serum PTEN is associated with increased risk for GFR decline and kidney failure in American Indians with type 2 diabetes.

Citing Articles

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Looker H, Chang D, Baier L, Hanson R, Nelson R Presse Med. 2023; 52(1):104176.

PMID: 37783422 PMC: 10805453. DOI: 10.1016/j.lpm.2023.104176.

Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2.

Sun Z, Shao X, Wu H, Zhao Y, Cao Y, Li D Kidney Dis (Basel). 2023; 9(1):58-71.

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What's New in the Molecular Mechanisms of Diabetic Kidney Disease: Recent Advances.

Watanabe K, Sato E, Mishima E, Miyazaki M, Tanaka T Int J Mol Sci. 2023; 24(1).

PMID: 36614011 PMC: 9820354. DOI: 10.3390/ijms24010570.

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