Comparison of intrarenal renin‐angiotensin system activity in diabetic versus non‐diabetic patients with overt proteinuria

Park, Ji‐Hyeon; Jang, Hye Ryoun; Lee, Jong Ho; Lee, Jung Eun; Huh, Wooseong; Lee, Kyu Beck; Kwon, Young Joo; Young, Jun; Kim, Hye Young; Kim, Yoon Goo

doi:10.1111/nep.12383

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…-Lower eGFR is associated with higher UAGT (Terami et al, 2013;Satirapoj et al, 2014;Zhuang et al, 2015). -Lower eGFR is not associated with higher UAGT (Park et al, 2015b).…”

Section: Diabetic Kidney Diseasementioning

confidence: 89%

Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting

et al. 2022

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E.J.H.). A.N. has received consulting fees, speaking honoraria, or both from Daiichi-Sankyo, Taisho, AstraZeneca, Tanabe-Mitsubishi, and Kowa. A.N. received research funds from Boehringer-Ingelheim, Daiichi-Sankyo, Taisho, and Bayer. A.H.J.D. received research funds from Alnylam Pharmaceuticals. D.B. is coinventor of patents entitled "Active low molecular weight variants of angiotensin converting enzyme 2," "Active low molecular weight variants of angiotensin converting enzyme 2 (ACE2) for the treatment of diseases and conditions of the eye," and "Shorter soluble forms of angiotensin converting enzyme 2 (ACE2) for treating and preventing coronavirus infection." D.B. is founder of Angiotensin Therapeutics Inc. D.B. has received consulting fees from AstraZeneca, Relypsa, and Tricida, all unrelated to this work.1 H.L. and F.G. contributed equally to this work. dx.

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“…-Lower eGFR is associated with higher UAGT (Terami et al, 2013;Satirapoj et al, 2014;Zhuang et al, 2015). -Lower eGFR is not associated with higher UAGT (Park et al, 2015b).…”

Section: Diabetic Kidney Diseasementioning

confidence: 89%

Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting

et al. 2022

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“…Therefore, the intracellular degradation system may be important in maintaining podocyte homeostasis and integrity. At the same time, the proximal convolute tubular cells (PCT) [7][8][9] are also vulnerable to high glucose with increased production of reactive oxygen species (ROS) via increased deposition of iron in lysosomes (Proximal Tubular Theory). Podocytes and PCT cells have evolved several mechanisms to face stress and to maintain cellular homeostasis, such as the anti-oxidative stress response and the endoplasmic reticulum (ER) stress response.…”

Section: Introductionmentioning

confidence: 99%

Diabetic Nephropathy from RAAS to Autophagy: The Era for New Players

Nakhoul¹,

Nakhoul²,

Nakhoul³

2017

J Clin Exp Nephrol

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Diabetic nephropathy is a leading cause of end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality worldwide in patients with type 2 diabetes mellitus. The mechanisms behind the pathophysiology of DN are complex and continue to be not fully understood. Both metabolic (hyperglycaemia) and haemodynamic alterations interact synergistically, and have been reported to activate local RAAS resulting in increased angiotensin-2. In spite the early and chronic treatment with converting enzyme inhibitors and angiotensin receptor blocking drugs, the number of patients reaching end stage renal disease and replacement therapy are increasing.Recently different pathways were proposed to be involved in the pathogenesis of diabetic nephropathy, including the autophagy process, Klotho and the selective agonist vitamin D and his receptor. Under hyperglycemic stress especially in podocytes and proximal convolute tubule cells, there is decrease in the protective autophagic process and increase in cellular damage.α-Klotho is a multifunctional protein highly expressed in the kidney. The klotho protein has endogenous anti fibrotic function via antagonism of Wnt/β-catenin signaling, which promotes fibrogenesis, suggesting that loss of Klotho in early stage of diabetic nephropathy may contribute to the progression of DN by accelerated fibrogenesis.The selective vitamin D agonist and his receptor, play a protective pathway in diabetic nephropathy. A key renoprotective function of vitamin D is to reduce albuminuria or proteinuria, major risk factors for CKD progression, renal failure, cardiovascular events, and death. This antiproteinuric effect and the deceleration of DN progression is mediated primarily via the blocking of the renin angiotensin aldosterone system. In this review we will discuss the different new mechanisms involved in diabetic nephropathy and future therapeutic agents like the mTorc1 blocker, Rapamycin, that can upregulate the autophagy process, the new sodium-glucose transport inhibitors and Paricalcitol, the selective active vitamin D.

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“…[6] Several previous studies have shown the presence of RAS components in the kidney and demonstrated that uAGT and urinary rennin can directly reflect the activity of intrarenal RAS. [7][8][9][10] The role of intrarenal RAS in AKI remains unclear, thus, the aim of this work was to determine the effect of intrarenal RAS on the occurrence of AKI in patients undergoing cardiac surgery with cardiopulmonary bypass.…”

Section: Observational Studymentioning

confidence: 99%

Effect of intrarenal renin-angiotensin-aldosterone system on renal function in patients after cardiac surgery

Niu

Ren

et al. 2022

Medicine

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The aim of the study was to investigate the influence of intrarenal RAS on the decrease of renal function in patients undergoing cardiac surgery with cardiopulmonary bypass. This observational study investigated the activation of intrarenal RAS in 24 patients with AKI after cardiac surgery with cardiopulmonary bypass. The activation of intrarenal RAS was determined by urinary angiotensinogen (uAGT), which was measured at 12 hours before surgery, 0 and12 hours after surgery. The results were compared with those of 21 patients without AKI after cardiac surgery with cardiopulmonary bypass. Clinical and laboratory data were collected. Compared with baseline, all patients with cardiac surgery had activation of intrarenal RAS at 0 and 12 hours after surgery. The activation of intrarenal RAS was found significantly higher at both 0 and 12 hours after surgery in AKI group versus non AKI group (6.18 ± 1.93 ng/mL vs 3.49 ± 1.71 ng/mL, 16.38 ± 7.50 ng/mL vs 6.04 ± 2.59 ng/mL, respectively). There was a positive correlation between the activation of RAS at 0 hour after surgery and the decrease of renal function at 48 hours after surgery (r = 0.654, P = .001). These findings suggest that uAGT might be a suitable biomarker for prediction of the occurrence and severity of AKI after cardiac surgery. Inhibition of intrarenal RAS activation might be one the path of future treatment for this type of disease.

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Comparison of intrarenal renin‐angiotensin system activity in diabetic versus non‐diabetic patients with overt proteinuria

Abstract: Consistently elevated uRenin in DN, regardless of the amount of proteinuria, indicates that intrarenal RAS activity may be higher in DN compared to NDN in patients with overt proteinuria.

Cited by 11 publications

References 34 publications

Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting

Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting

Diabetic Nephropathy from RAAS to Autophagy: The Era for New Players

Effect of intrarenal renin-angiotensin-aldosterone system on renal function in patients after cardiac surgery

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