Altered urinary excretion of aquaporin 2 in IgA nephropathy

Abstract

Objective: The intrarenal renin-angiotensin system (RAS) activation plays a pivotal role in immunoglobulin A nephropathy (IgAN) pathogenesis, which is still largely undefined. Recently, vasopressin (AVP) has been advocated to contribute to the genesis and progression of chronic kidney diseases (CKD) directly, and indirectly, via RAS activation. Our aim is to explore the intrarenal activity of AVP, its relationship with RAS activity, as well as its modulation by therapies in IgAN. Design: In this observational study, we measured plasma copeptin, a surrogate marker of AVP, the urine excretion of aquaporin 2 (AQP2), a protein reflecting renal AVP action, and angiotensinogen (AGT), a parameter of renal RAS activation, and their relationship with renal function in 44 IgAN patients at the time of renal biopsy, without any drug therapy, and after 6-month treatment with ACEi or steroidCACEi. Twenty-one patients with other CKD and 40 healthy subjects were recruited as controls. Methods: ELISAs were used to measure all variables of interest. Results: At baseline, IgAN patients showed higher urinary levels of AQP2, compared with controls and patients with other CKD. Urinary AQP2 and AGT levels strongly correlated with the presence of arterial hypertension. SteroidsCACEi caused the decrease of all the variables examined. The fall of urinary AQP2 and AGT following drug treatments was associated with the decrease of daily proteinuria. Conclusion: Our findings would support the involvement of AVP-AQP2 axis, interacting with the RAS, in the progression of IgAN and candidate AQP2 as a possible novel marker of the disease.

Urinary RKIP/p-RKIP is a potential diagnostic and prognostic marker of clear cell renal cell carcinoma

“…All the spectra were normalized by means of total ion current. The reproducibility of the SELDI analysis, assessed as previously described [20], was comparable to that in our previous works [22, 23]. Only mass peaks showing a statistically significant different expression (p<0.05) between cases and controls were considered for further analyses.…”

“…Urinary proteomics by the so-called profiling technologies may overcome some of the limitations of laborious gel-based approaches, thus resulting more appropriate for clinical proteomics studies [21]. Recent reports demonstrated that urinary peptides and proteins could serve as specific biomarkers for chronic kidney diseases (CKD) [22–23] and uro-genital cancers [24]. However, most of the studies carried out so far have primarily compared patients to healthy controls, making it difficult to ascertain the specificity and sensitivity of the potential biomarkers.…”

Low aquaporin-2 excretion in the nephrotic syndrome: an escape from the vasopressin regulating effect

“…6 The results of our study contradict the data of Rocchetti et al, who reported a rise in the renal excretion of AQP2 in untreated patients with immunoglobulin A (IgA) nephropathy. 11 Furthermore, patients with a greater deterioration of kidney function, higher proteinuria, and arterial hypertension displayed even higher urinary AQP2 excretion; moreover, a decrease of daily proteinuria following treatment was asso-ciated with a fall of the urinary AQP2 level. The authors suggested that an increase in the urinary excretion of AQP2 may reflect enhanced intrarenal AVP and renin-angiotensin system (RAS) activity, as well as the severity of renal damage.…”

Diagnosis and monitoring of IgA nephropathy: the role of biomarkers as an alternative to renal biopsy

“…For these reasons, different proteomics approaches have been carried out for biomarker discovery, which might be an important step forward to the noninvasive diagnosis of kidney diseases, including IgAN [83,87,88]. Among Using proteomic approaches, several potential urinary biomarkers have been identified for the diagnostic and prognostic evaluation of IgAN, including aquaporin 2 [89], laminin G-like 3 [90,91], free kappa light chains [90] and other peptides such as bradykinin, uromodulin and alpha-1-antitrypsin [88]. Other proteins have been suggested as potential prognostic biomarkers in IgAN including afamin, leucine-rich alpha-2-glycoprotein, ceruloplasmin, alpha-1-microgolbulin, hemopexin, apolipoprotein A-I, complement C3, vitamin D-binding protein, beta-2-microglobulin and retinolbinding protein 4.…”