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

Abstract

AQP5 has been shown to be upregulated in kidney biopsies from patients with diabetic nephropathy.Here we investigate whether urinary baseline AQP5 is independently associated with eGFR decline in patients with type 2 diabetes and nephropathy. Baseline urine samples (n=997) from patients with type 2 diabetes and nephropathy recruited in the Sun-MACRO randomized placebo controlled double blind clinical trial were used for AQP5 measurement, using human AQP5-specific enzyme linked immunosorbent kits. Pearson correlation and multiple linear regression between AQP5 with eGFR slope (calculated by ≥3 serum creatinine during followup) was performed, and association with fast renal function decline, defined as eGFR slope less than 3.0 mL/min/1.73m 2 /year, was determined by logistic regression. Followup eGFR data over 1.4 years from n=700 were available for analysis. 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 r = -0.12, p<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<0.004). Furthermore, AQP5 was significantly associated with fast eGFR decline (OR = 1.03 (95%CI 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.Running title: Urine AQP5 as a prognostic marker of diabetic nephropathy.

Streptozotocin induces alpha-2u globulin nephropathy in male rats during diabetic kidney disease

“…Upregulation of AQP-2 and -5 is closely related to the progression of diabetic nephropathy in diabetic patients and are good candidates to use for diagnosis [21,27]. Recently, Go and Zhang also reported that an increase in AQP-5 in patients with diabetic nephropathy is independently associated with a reduction in the glomerular ltration rate [28]. In addition, a STZ-induced diabetic rat model exhibits a high level of anti-diuretic hormone, leading to upregulation of AQP-2 as a compensatory mechanism [29].…”

Aquaporins in insulin resistance and diabetes: More than channels!

“…AQP5 is a possible marker of tubular dysfunction and its basal levels were analyzed in two studies: one with a limited number of samples from T2D and T2D with diabetic nephropathy patients and the second with almost 1000 urine samples from patients with T2D with diabetic nephropathy. Both the studies candidate AQP5 as a prognostic marker for diabetic nephropathy progression and suggest an association between AQP5 baseline expression and the estimated glomerular filtration rate (eGFR) [ 136 , 137 ].…”