Serum AKR1A1 Levels Predict eGFR Decline Rate in Black Americans with Type 2 Diabetes.

KEY POINTS: AKR1A1 depletion impairs tubule cell function. Higher serum AKR1A1 predicts slower eGFR decline rate. AKR1A1 could be a potential therapeutic target.

BACKGROUND

Black Americans have disproportionately high rates of diabetic kidney disease (DKD). Identification of biomarkers predicting early DKD progression is essential to prescribe protective treatments before the development of irreversible histologic lesions and markedly reduced kidney function.

METHODS

We tested whether AKR1A1 was a marker of early DKD progression through knock-out of AKR1A1 in a human kidney proximal tubule cell line and by measuring serum AKR1A1 concentrations in Black patients with type 2 diabetes (T2D).

RESULTS

AKR1A1 knockout cells had reduced cell viability, and the effect was aggravated by administering high-dose palmitate. In addition, higher serum AKR1A1 concentrations in Black patients with T2D and preserved kidney function predicted slower decline rate in eGFR over time.

CONCLUSIONS

AKR1A1 seems to play a critical role in countering toxic effects of fatty acid metabolism and may prevent rapid decline of kidney function in Black patients with T2D.