AT1 receptor antagonism before ischemia prevents the transition of acute kidney injury to chronic kidney disease

Rodríguez-Romo, Roxana; Benítez, Kenia; Barrera‐Chimal, Jonatan; Pérez‐Villalva, Rosalba; Gómez, Armando Torres; Aguilar‐León, Diana; Rangel-Santiago, Jesus; Huerta, Sara; Gamba, Gerardo; Uribe, Norma; Bobadilla, Norma A.

doi:10.1038/ki.2015.320

Cited by 83 publications

(81 citation statements)

References 48 publications

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“…Since none of the ATN patients in this study were being treated with RAS inhibitors at the time of biopsy, the effect of RAS blockade on urinary AGT and ATN severity was unknown. However, animal studies have already shown a correlation between RAS blockade and improved AKI outcomes [22,23]. Further studies to investigate the role of RAS inhibition in various AKI populations would be helpful to extend our observations, and to confirm the role of intrarenal RAS in the pathogenesis of AKI.…”

Section: Discussionsupporting

confidence: 53%

“…Urinary AGT could potentially be added to these biomarkers to form a biomarker panel, and would probably be particularly A linkage between intrarenal RAS and kidney injury has been increasingly recognized. Animal studies have noted an association between inhibition of the RAS and improved outcomes of AKI [22,23]. Clinical studies have described urinary AGT as a novel predictive and prognostic biomarker of AKI [18,19].…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of Intrarenal Renin-Angiotensin System in Human Acute Tubular Necrosis

Cao

Jin²,

Zhou³

et al. 2016

Kidney Blood Press Res

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Background/Aims: Acute tubular necrosis (ATN), a leading cause of acute kidney injury (AKI), is associated with decreased survival and increased progression of chronic kidney disease. A barrier to improving the clinical outcomes is the incomplete understanding of the pathogenesis of AKI. Our objective is to test the hypothesis that intrarenal renin-angiotensin system (RAS) is overexpressed in patients with ATN and could be an indicator of ATN severity. Methods: A transversal study was conducted in patients with biopsy-proven ATN. Intrarenal expression of angiotensinogen and angiotensin II, and urinary angiotensinogen were measured. Results: Patients with ATN demonstrated upregulation of intrarenal RAS, evidenced by upregulation of intrarenal angiotensinogen and angiotensin II. Patients with ATN also have elevated urinary angiotensinogen level that correlated with the overexpressed intrarenal RAS. Moreover, this increase in intrarenal RAS expression and urinary angiotensinogen was associated with the extent of acute tubular injury and urinary albumin excretion, respectively. Conclusions: We demonstrate that the intrarenal RAS is upregulated in patients with ATN and is associated with the severity of ATN. Urinary angiotensinogen reflects intrarenal RAS status, and is of value to assess the severity of ATN.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Overexpression of Intrarenal Renin-Angiotensin System in Human Acute Tubular Necrosis

Cao

Jin²,

Zhou³

et al. 2016

Kidney Blood Press Res

View full text Add to dashboard Cite

show abstract

“…Many clinical trials have proved the specific renoprotective effect of RAS inhibition by ACE inhibitor/ARB for patients with diabetic or proteinuric non-diabetic CKD to reduce disease progression and mortality515253. However, RAS inhibition is usually avoided during the acute phase of AKI patients, and the role of RAS activity in acute phase and injury severity is not clear indeed212254. Based on findings that intrarenal RAS was activated in repairing kidneys in spite of complete recovery of plasma parameters for renal function assessment one month after acute injury, our previous study has shown that RAS inhibition with losartan in mouse AKI survivors can prevent the development of ensuing CKD and mortality20.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, animal studies have demonstrated that activation of intrarenal renin–angiotensin system (RAS) after AKI underlies the possible mechanism for development and progression of ensuing CKD202122. To get insight into the clinical application of RAS inhibitor and its impact on development of ensuing CKD in AKI survivors with complete renal recovery, we studied the outcomes and relevant risk factors of cardiac surgery–associated AKI (CSA-AKI) patients who did not have CKD history before surgery in our prospectively collected observational cohort.…”

mentioning

confidence: 99%

Renin-Angiotensin System Inhibitor is Associated with Lower Risk of Ensuing Chronic Kidney Disease after Functional Recovery from Acute Kidney Injury

Chou

Huang

Pan

et al. 2017

Sci Rep

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Acute kidney injury (AKI) is an independent risk factor for ensuing chronic kidney disease (CKD). Animal studies have demonstrated that renin-angiotensin system (RAS) inhibitor can reduce ensuing CKD after functional recovery from AKI. Here we study the association between ensuing CKD and use of RAS inhibitor including angiotensin converting enzyme inhibitor or angiotensin II type 1a receptor blocker starting after renal functional recovery in our prospectively collected observational AKI cohort. Adult patients who had cardiac surgery–associated AKI (CSA-AKI) are studied. Patients with CKD, unrecovered AKI, and use of RAS inhibitor before surgery are excluded. Among 587 eligible patients, 94 patients are users of RAS inhibitor which is started and continued after complete renal recovery during median follow-up period of 2.99 years. The users of RAS inhibitor show significantly lower rate of ensuing CKD (users vs. non-users, 26.6% vs. 42.2%) and longer median CKD-free survival time (users vs. non-users, 1079 days vs. 520 days). Multivariate Cox regression analyses further demonstrate that use of RAS inhibitor is independently associated with lower risk of ensuing CKD (hazard ratio = 0.46, P < 0.001). We conclude that use of RAS inhibitor in CSA-AKI patients after renal functional recovery is associated with lower risk of ensuing CKD development.

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“…40 Losartan-treated mice were shown to have less renal injury by suppressing transdifferentiation and the resultant ECM synthesis. 41 Notably, Ang II can induce transdifferentiation and ECM deposition, albeit less efficaciously than TGF-b1. 6 Angiotensin II incubation for 24 hours significantly increased the expression of TGF-b1.…”

Section: Discussionmentioning

confidence: 99%

Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy

Shi

Wang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To examine the effects of losartan on scar formation after trabeculectomy and on fibrotic changes of human Tenon's fibroblasts (HTFs). METHODS.Trabeculectomy was performed on New Zealand rabbits. They were randomized to receive one of the following treatments: 0.9% normal saline, mitomycin-C, or one of the three doses of losartan. Bleb morphology, IOP, and histopathology examination were performed. Primary cultured HTFs were treated with losartan or vehicle, with or without angiotensin II (Ang II). Cell proliferation was assessed by Cell Counting Kit-8 assay, and cell migration was detected by scratch wound and transwell assay. Transdifferentiation was evaluated through the expression of a-smooth muscle actin (a-SMA) by immunofluorescence, real-time PCR, and Western blot. The expression of fibronectin (FN) was evaluated by real-time PCR and Western blot.RESULTS. An amount of 5 mg/mL of losartan subconjunctival injection significantly decreased IOP postoperatively and attenuated wound healing of the filtering bleb in the rabbit model. Immunostaining results showed less myofibroblast and collagen deposition around the bleb area in the losartan-treated eyes. Losartan (10 À5 M) in vitro significantly attenuated Ang II's stimulatory effects on proliferation and migration of HTFs. Expressions of a-SMA and FN in these cells were also decreased by losartan pretreatment.CONCLUSIONS. Losartan attenuates scar formation of filtering bleb after trabeculectomy likely via decreasing proliferation, migration, transdifferentiation, and extracellular matrix deposition of Tenon's fibroblasts. These results indicate that losartan may be an effective therapeutic agent in preventing bleb scar formation and in improving surgical outcome after trabeculectomy.

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AT1 receptor antagonism before ischemia prevents the transition of acute kidney injury to chronic kidney disease

Cited by 83 publications

References 48 publications

Overexpression of Intrarenal Renin-Angiotensin System in Human Acute Tubular Necrosis

Overexpression of Intrarenal Renin-Angiotensin System in Human Acute Tubular Necrosis

Renin-Angiotensin System Inhibitor is Associated with Lower Risk of Ensuing Chronic Kidney Disease after Functional Recovery from Acute Kidney Injury

Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy

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