Diabetic nephropathy (DN) is a microangiopathic complication of diabetes (DM) affecting about one third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM, along with the possibility of glomerulonephritis independent from DM, make kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure with risk of major complications. For this reason, numerous studies have been conducted to identify a non-invasive biomarker of the disease, but none of these is considered to be sufficiently specific and sensitive.
Water channel aquaporins (AQP), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. Interestingly, apical membrane protein are excreted in the urinary space as nano-scale exosome vesicles thus allowing their quantitation in urine samples.
In this work we analyzed urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2) in 35 diabetic patients: 12 with histological diagnosis of DN, 12 with normal renal function and normoalbuminuric DM (D) and 11 with proteinuric non-diabetic nephropathy (NDRD).
ELISA and WB analysis independently showed that uAQP5 was significantly higher in DN patients (7458 ± 2576, p <0.05) compared to the other two groups (D 847,2 ± 70,51; NDRD1882 ± 215;). uAQP5 was not statistically different between D and NDRD patients. Interestingly, a strict correlation was found between uAQP5 and the histological severity of DN (p <0.05). The same analysis showed comparable results for uAQP2.
In conclusion our data showed, for the first time, that uAQP5 and uAQP2 dramatically and specifically increase in patients with DN and positively correlate with the histological class of DN. Taken together these data suggest a possible role of AQP5 and AQP2 as novel non-invasive biomarkers to help diagnosing DN and classifying its histological stage.
