Urine AQP5 is a potential novel biomarker of diabetic nephropathy

Lu, Yongde; Chen, Lihe; Zhao, Bihong; Xiao, Zhou; Meng, Ting; Zhou, Qiaoling; Zhang, Wenzheng

doi:10.1016/j.jdiacomp.2016.03.026

Cited by 17 publications

(22 citation statements)

References 30 publications

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“…Our results about the upregulation of uAQP5 in DN patients are in line with previous findings from Wu et al [ 25 ] who reported that AQP5 was expressed in the collecting ducts of patients with DN. During the preparation of this manuscript, the same authors demonstrated, with a similar approach, that uAQP5 is upregulated in the urine of DN patients and positively correlated with the stage of DN [ 45 ]. In their study, however, they classified DN patients to stages III, IV, and V on the basis of microalbuminuria and macroalbuminuria and increased serum creatinine and limited their analysis to uAQP5 alone.…”

Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

Rossi

Nicoletti

Carmosino

et al. 2017

Journal of Diabetes Research

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Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN.

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Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

Rossi

Nicoletti

Carmosino

et al. 2017

Journal of Diabetes Research

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“…A growing body of evidence showed that the expression of AQPs was dysregulated in DN patients. AQP5 is obviously increased in the kidney tissue of DN patients and urine AQP2 and AQP5 have been identified as potential novel biomarkers of diabetic nephropathy with sensitivity, early appearance, and low invasiveness features [68,69,70]. A community-based cohort study involving 620 participants with chronic kidney disease (CKD) firstly revealed that AQP11 rs2276415 variant is associated with CKD progression [69].…”

Section: Aqps In Diabetic Nephropathymentioning

confidence: 99%

Aquaporins in Renal Diseases

Yang

2019

IJMS

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Aquaporins (AQPs) are a family of highly selective transmembrane channels that mainly transport water across the cell and some facilitate low-molecular-weight solutes. Eight AQPs, including AQP1, AQP2, AQP3, AQP4, AQP5, AQP6, AQP7, and AQP11, are expressed in different segments and various cells in the kidney to maintain normal urine concentration function. AQP2 is critical in regulating urine concentrating ability. The expression and function of AQP2 are regulated by a series of transcriptional factors and post-transcriptional phosphorylation, ubiquitination, and glycosylation. Mutation or functional deficiency of AQP2 leads to severe nephrogenic diabetes insipidus. Studies with animal models show AQPs are related to acute kidney injury and various chronic kidney diseases, such as diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma. Experimental data suggest ideal prospects for AQPs as biomarkers and therapeutic targets in clinic. This review article mainly focuses on recent advances in studying AQPs in renal diseases.

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“…First, the small size (27 kD) permits direct secretion of AQP5 into urine from tubular cells. Secondly, urinary AQP5 may result from a reduction in tubular reabsorption, given the correlation between urine and serum AQP5 levels 10 . The final likeliness of 11 high urine levels of AQP5 is the shedding of AQP5-expressing tubular cells, as evidenced by the detection of detached AQP5 + cells in the lumen of the tubules 7 .…”

Section: Discussionmentioning

confidence: 99%

“…Baseline urine samples were stored at −80°C from the time of collection. Human AQP5 was measured using an AQP5-specific ELISA kit, as we previously reported 10 . For each patient, AQP5 was blindly measured in triplicates, averaged, and log2 transformed.…”

Section: Aqp5 Measurementsmentioning

confidence: 99%

“…We found that patients with DN had significantly elevated urine AQP5/creatinine, compared with normal controls and patients with diabetic mellitus. AQP5/creatinine improved the clinical models in distinguishing DN from other two groups (normal controls and diabetic mellitus) 10 . However, if AQP5 is associated with fast eGFR decline remains unknown.…”

Section: Introductionmentioning

confidence: 96%

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

Gao

Zhang

2018

Preprint

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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.

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Urine AQP5 is a potential novel biomarker of diabetic nephropathy

Cited by 17 publications

References 30 publications

Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

Aquaporins in Renal Diseases

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

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