Mineralocorticoid antagonists in chronic kidney disease

Dhaybi, Omar Al; Bakris, George L.

doi:10.1097/mnh.0000000000000290

Cited by 26 publications

(11 citation statements)

References 52 publications

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“…Han et al previously demonstrated that spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats [ 24 ]. Randomized studies confirmed that the addition of MRAs to a renin–angiotensin system (RAS) blocker reduced albuminuria resulting from diabetic or nondiabetic causes [ 25 , 26 ]. Additionally, the use of spironolactone alone was similarly effective to the use of spironolactone and losartan combination in reducing albuminuria [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Spironolactone alleviates diabetic nephropathy through promoting autophagy in podocytes

Dong

Fan

et al. 2019

Int Urol Nephrol

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Purpose Podocytes are terminally differentiated cells lining the Bowman’s capsule. Podocytes are critical for the proper glomerular filtration barrier function. At the same time, autophagy is crucial for maintaining podocyte homeostasis and insufficient autophagy could cause podocyte loss and proteinuria that is commonly observed in diabetic nephropathy (DN). Methods In this study, we investigated the role of spironolactone in podocyte loss and autophagy. DN model was established in male Sprague–Dawley rats using high-fat diet and low-dose streptozotocin. The impact of spironolactone on metabolic and biochemical parameters were tested by automatic biochemical analyzer. The angiotensin converting enzyme 1 and 2 (ACE1 and ACE2) and aldosterone were examined by ELISA. We examined the kidney histology and autophagy in podocytes by histochemical staining and electron microscopy. Podocyte loss and autophagy were analyzed by anti-NPHS2 and anti-WT1 as well as anti-Beclin1 and anti-LC3B, respectively. Results Spironolacton decreased the urinary albumin excretion, lipids and fasting glucose levels, and alleviated kidney damage. Further, spironolactone increased the expression of the podocyte-specific markers WT1 and NPHS2, as well as the autophagic markers Beclin1 and LC3B ( P < 0.05). Additionally, spironolactone partially blocked the rennin angiotensin aldosterone system (RAAS) by regulating the ACE1, ACE2 and aldosterone levels. Conclusions In conclusion, spironolactone promoted autophagy in podocytes and further alleviated DN through partially blocking the RAAS.

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Section: Discussionmentioning

confidence: 99%

Spironolactone alleviates diabetic nephropathy through promoting autophagy in podocytes

Dong

Fan

et al. 2019

Int Urol Nephrol

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“…84 There are no long-term data from RCTs on clinical benefits. In addition, side effects, particularly hyperkalemia and acute reversible reduction in eGFR, 85 are a concern when added to background therapy with an ACEi or ARB or diuretic, particularly among patients with eGFR <45 ml/min per 1.73 m 2 . 86 Thus, blocking aldosterone may be particularly useful in patients with resistant hypertension without a history of high potassium, and GFR >45 ml/min per 1.73 m 2 .…”

Section: No Dosage Adjustment Necessary Poorly Removed By Hemodialysismentioning

confidence: 99%

KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease

Boer¹,

Caramori²,

Chan³

et al. 2020

Kidney International

822

549

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S20 Introduction S22 Summary of recommendation statements and practice points S30 Chapter 1: Comprehensive care in patients with diabetes and CKD S39 Chapter 2: Glycemic monitoring and targets in patients with diabetes and CKD S47 Chapter 3: Lifestyle interventions in patients with diabetes and CKD S58 Chapter 4: Antihyperglycemic therapies in patients with type 2 diabetes (T2D) and CKD S79 Chapter 5: Approaches to management of patients with diabetes and CKD S87 Methods for guideline development S96 Biographic and disclosure information S106 Acknowledgments S107 References The development and publication of this guideline were supported by KDIGO. The opinions or views expressed in this professional education supplement are those of the authors and do not necessarily reflect the opinions or recommendations of the International Society of Nephrology or Elsevier. Dosages, indications, and methods of use for products that are referred to in the supplement by the authors may reflect their clinical experience or may be derived from the professional literature or other clinical sources. Because of the differences between in vitro and in vivo systems and between laboratory animal models and clinical data in humans, in vitro and animal data may not necessarily correlate with clinical results.

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“…Mineralocorticoid receptor antagonists (MRAs) have a track record of benefit in cardiovascular complications of DKD, that is, heart failure risk reduction, and of efficacy in reducing albuminuria and treating resistant hypertension . Thus, with the advent of novel non‐steroidal MRAs with generally less hyperkalaemia risk, there is a renewed commitment, to investigate their effect on both slowing DKD progression and reducing cardiovascular risk in diabetes …”

Section: Introductionmentioning

confidence: 99%

Non‐steroidal mineralocorticoid antagonists: Prospects for renoprotection in diabetic kidney disease

Dhaybi

Bakris

2020

Diabetes Obesity Metabolism

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Diabetic kidney disease (DKD) is the major cause of kidney failure in the world and the combination of DKD and diabetes mellitus contributes to an additive incidence of worsening cardiovascular mortality rates. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) remain the mainstay of therapy and have reduced kidney function decline in DKD from 8 to 10 to~4 mL/min/y. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, in the presence of ACE inhibitors or ARB agents, further slowdown DKD progression by an additional 58% to 1.8 mL/min/y. Moreover, SGLT2 inhibitors reduce heart failure risk. However, the normal rate of kidney function decline in humans is between 0.7 and 0.9 mL/min/y, hence, there is still room for improvement. Mineralocorticoid receptor antagonists (MRAs) already have a track record of benefit in heart failure risk reduction, and efficacy in reducing albuminuria and treating resistant hypertension; however hyperkalaemia and other adverse effects preclude their routine use in DKD. Novel non-steroidal MRAs offer a reduced risk of hyperkalaemia, and yet have many benefits that they share with their steroidal cousins. This paper reviews the data for both steroidal and non-steroidal MRAs in DKD and presents some data from soon-to-becompleted ongoing renal and cardiovascular outcome trials in DKD.

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Mineralocorticoid antagonists in chronic kidney disease

Cited by 26 publications

References 52 publications

Spironolactone alleviates diabetic nephropathy through promoting autophagy in podocytes

Spironolactone alleviates diabetic nephropathy through promoting autophagy in podocytes

KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease

Non‐steroidal mineralocorticoid antagonists: Prospects for renoprotection in diabetic kidney disease

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