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Abstract: TH-PO883

Urinary Baseline AQP5 Is Independently Associated with eGFR Decline in Patients with Type 2 Diabetes and Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Gao, Chao, Albany Medical College, Albany, New York, United States
  • Pena, Michelle, University Medical Center Groningen, Groningen, Netherlands
  • Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • Zhang, Wenzheng, Albany Medical College, Albany, New York, United States
Background

Water channel AQP5 has been shown to be upregulated in kidney biopsies from patients with diabetic nephropathy, and may serve as a biomarker for tubular damage. Here we investigate whether urinary baseline water channel AQP5 is independently associated with eGFR decline in patients with type 2 diabetes and nephropathy.

Methods

Baseline urine samples (n=997) were used from the SUN-Macro randomized placebo controlled double blind clinical trial, which evaluated the renoprotective effects of sulodexide in patients with type 2 diabetes and nephropathy. Human AQP5-specific enzyme-linked immunosorbent assay was measured in baseline urine. Pearson correlation and multiple linear regression between baseline 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/1.73m2/year, was determined by logistic regression.

Results

Follow-up eGFR data over 1.4 years from n=700 were available for analysis. AQP5 was undetectable in 138 patients. Tertiles of baseline AQP5 were 0.4 [0 – 2.2], 7.3 [5.9 – 9.1], and 16.0 [13.0 – 21.6] (ng/mL), respectively (p-value <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. Baseline AQP5 was inversely correlated with eGFR slope (Pearson’s r = -0.12, p-value = 0.001), and independent of clinical risk factors age, sex, race, and baseline: SBP, DBP, HbA1c, Tot. Cholesterol, eGFR, and UACR (β = -0.05, p-value = 0.004). Furthermore, baseline AQP5 was significantly associated with fast eGFR decline (OR = 1.03 (95%CI 1.003 – 1.06), p-value = 0.03).

Conclusion

Our data suggest that baseline AQP5, a possible marker of tubular dysfunction, is independently associated with the progression of eGFR decline in patients with type 2 diabetes and nephropathy. Validation of these findings in an external cohort is necessary.

Funding

  • NIDDK Support