Urinary AQP5 is independently associated with eGFR decline in patients with type 2 diabetes and nephropathy

Intrarenal Aquaporin 5 (AQP5) is upregulated in patients with diabetic nephropathy. Here we investigate whether urinary AQP5 is independently associated with estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes and nephropathy.

Baseline urine samples (n = 997) from patients with type 2 diabetes and nephropathy of the sulodexide macroalbuminuria trial were measured for AQP5 through enzyme-linked immunosorbent assays. Pearson correlation and multiple linear regression between AQP5 with eGFR slope (calculated by ≥3 serum creatinine during follow-up) was performed, and association with fast renal function decline, defined as eGFR slope less than 3.0 mL/min/1.73 m²/year, was determined by logistic regression.

Follow-up eGFR data >1.4 years from n = 700 were available for analyses. AQP5 was undetectable in 138 patients. Tertiles of AQP5 were 0.4 [0-2.2], 7.3 [5.9-9.1], and 16.0 [13.0-21.6] (ng/mL), respectively (p < 0.01). Patients in the highest tertile of AQP5 had significantly higher total cholesterol, lower baseline eGFR, and higher levels of albuminuria compared to the lowest tertile. AQP5 was inversely correlated with eGFR slope (Pearson's r = -0.12, p < 0.001), and independent of clinical risk factors age, sex, race, and baseline systolic and diastolic blood pressure, hemoglobin A1c, total cholesterol, eGFR, and urine albumin-to-creatinine ratio (β = -0.05, p < 0.004). Furthermore, AQP5 was significantly associated with fast eGFR decline (Odds Ratio = 1.03 (95% Confidence Interval 1.003-1.06), p < 0.03).

Our data suggest that baseline AQP5 is independently associated with the progression of eGFR decline in patients with type 2 diabetes and nephropathy.