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Article ; Online: Obesity and the kidney: mechanistic links and therapeutic advances.

Yau, Kevin / Kuah, Rachel / Cherney, David Z I / Lam, Tony K T

2024

Abstract: Obesity is strongly associated with the development of diabetes mellitus and chronic kidney disease (CKD), but there is evidence for a bidirectional relationship wherein the kidney also acts as a key regulator of body weight. In this Review, we highlight ...

Abstract	Obesity is strongly associated with the development of diabetes mellitus and chronic kidney disease (CKD), but there is evidence for a bidirectional relationship wherein the kidney also acts as a key regulator of body weight. In this Review, we highlight the mechanisms implicated in obesity-related CKD, and outline how the kidney might modulate feeding and body weight through a growth differentiation factor 15-dependent kidney-brain axis. The favourable effects of bariatric surgery on kidney function are discussed, and medical therapies designed for the treatment of diabetes mellitus that lower body weight and preserve kidney function independent of glycaemic lowering, including sodium-glucose cotransporter 2 inhibitors, incretin-based therapies and metformin, are also reviewed. In summary, we propose that kidney function and body weight are related in a bidirectional fashion, and that this interrelationship affects human health and disease.
Language	English
Publishing date	2024-02-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2489381-X
ISSN	1759-5037 ; 1759-5029
ISSN (online)	1759-5037
ISSN	1759-5029
DOI	10.1038/s41574-024-00951-7
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Zs.A 6336: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 93: Show issues

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Article ; Online: Novel Therapies in Diabetic Kidney Disease and Risk of Hyperkalemia: A Review of the Evidence From Clinical Trials.

Albakr, Rehab B / Sridhar, Vikas S / Cherney, David Z I

American journal of kidney diseases : the official journal of the National Kidney Foundation

2023 Volume 82, Issue 6, Page(s) 737–742

Abstract: Concerns about hyperkalemia may result in the underuse of established and novel therapies that improve kidney and/or cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Hyperkalemia-related ... ...

Abstract	Concerns about hyperkalemia may result in the underuse of established and novel therapies that improve kidney and/or cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Hyperkalemia-related issues are of particular relevance in patients with CKD, who are commonly receiving other hyperkalemia-inducing agents such as renin-angiotensin-aldosterone system inhibitors and nonsteroidal mineralocorticoid receptor antagonists. In contrast, sodium/glucose transporter 2 (SGLT2) inhibitors mitigate the risk of serious hyperkalemia in clinical trials. We aim to review recent evidence surrounding the risk of hyperkalemia in patients with T2DM and CKD treated with established and novel therapies for diabetic kidney disease, focusing on SGLT2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists. We conclude that SGLT2 inhibitors can be used safely in patients with T2DM at high CV risk with CKD without increasing the risk of hyperkalemia. Routine potassium monitoring is generally required when finerenone is used as a kidney- and CV-protective agent in patients with T2DM. Based on existing data, when added to the standard of care, combining SGLT2 inhibitors with finerenone is safe and has the potential to exert additional cardiorenal benefits in patients with diabetic kidney disease. The use of potassium binders should be considered to enable optimal doses of guideline-based therapies for patients with diabetic kidney disease to maximize the kidney and CV benefits.
MeSH term(s)	Humans ; Hyperkalemia/etiology ; Hyperkalemia/drug therapy ; Mineralocorticoid Receptor Antagonists/therapeutic use ; Mineralocorticoid Receptor Antagonists/pharmacology ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Nephropathies/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/chemically induced ; Potassium
Chemical Substances	Mineralocorticoid Receptor Antagonists ; Sodium-Glucose Transporter 2 Inhibitors ; Potassium (RWP5GA015D)
Language	English
Publishing date	2023-07-29
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2023.04.015
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Zs.A 1669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 468: Show issues

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Article ; Online: DAPA-CKD: The Beginning of a New Era in Renal Protection.

Cherney, David Z I / Verma, Subodh

JACC. Basic to translational science

2021 Volume 6, Issue 1, Page(s) 74–77

Language	English
Publishing date	2021-01-25
Publishing country	United States
Document type	Journal Article
ISSN	2452-302X
ISSN (online)	2452-302X
DOI	10.1016/j.jacbts.2020.10.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Predictive Enrichment in Kidney RCTs: Is Albuminuria the Answer?

Odutayo, Ayodele / Cherney, David Z I

Journal of the American Society of Nephrology : JASN

2021 Volume 32, Issue 11, Page(s) 2689–2691

MeSH term(s)	Albuminuria ; Glomerular Filtration Rate ; Humans ; Kidney
Language	English
Publishing date	2021-10-25
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2021091235
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Zs.A 3344: Show issues

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Article ; Online: Proximal versus distal diuretics in congestive heart failure.

Nardone, Massimo / Sridhar, Vikas S / Yau, Kevin / Odutayo, Ayodele / Cherney, David Z I

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

2024

Abstract: Volume overload represents a hallmark clinical feature linked to the development and progression of heart failure (HF). Alleviating signs and symptoms of volume overload represents a foundational HF treatment target that is achieved using loop diuretics ... ...

Abstract	Volume overload represents a hallmark clinical feature linked to the development and progression of heart failure (HF). Alleviating signs and symptoms of volume overload represents a foundational HF treatment target that is achieved using loop diuretics in the acute and chronic setting. Recent work has provided evidence to support guideline-directed medical therapies, such as sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor (MR) antagonists, as important adjunct diuretics that may act synergistically when used with background loop diuretics in people with chronic HF. Furthermore, there is growing interest in understanding the role of SGLT2 inhibitors, carbonic anhydrase inhibitors, thiazide diuretics, and MR antagonists in treating volume overload in patients hospitalized for acute HF, particularly in the setting of loop diuretic resistance. Thus, the current review demonstrates that: 1) SGLT2 inhibitors and MR antagonists confer long-term cardioprotection in chronic HF patients but it is unclear if natriuresis or diuresis represents the primary mechanisms for this benefit, 2) SGLT2 inhibitors, carbonic anhydrase inhibitors, and thiazide diuretics increase natriuresis in the acute HF setting, but implications on long-term outcomes remain unclear and warrants further investigation, and 3) a multi-nephron segment approach, using agents that act on distinct segments of the nephron, potentiate diuresis to alleviate signs and symptoms of volume overload in acute HF.
Language	English
Publishing date	2024-02-29
Publishing country	England
Document type	Journal Article
ZDB-ID	90594-x
ISSN	1460-2385 ; 0931-0509
ISSN (online)	1460-2385
ISSN	0931-0509
DOI	10.1093/ndt/gfae058
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Zs.A 2198: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 329: Show issues

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Article ; Online: SGLT2 Inhibitors: The Sweet Success for Kidneys.

Dharia, Atit / Khan, Abid / Sridhar, Vikas S / Cherney, David Z I

Annual review of medicine

2023 Volume 74, Page(s) 369–384

Abstract: Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) were originally developed as antidiabetic agents, with cardiovascular (CV) outcome trials demonstrating improved CV outcomes in patients with type 2 diabetes mellitus (T2D). Secondary analyses ... ...

Abstract	Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) were originally developed as antidiabetic agents, with cardiovascular (CV) outcome trials demonstrating improved CV outcomes in patients with type 2 diabetes mellitus (T2D). Secondary analyses of CV outcome trials and later dedicated kidney outcome trials consistently reported improved kidney-related outcomes independent of T2D status and across a range of kidney function and albuminuria. Importantly, SGLT2 inhibitors are generally safe and well tolerated, with clinical trials and real-world analyses demonstrating a decrease in the risk of acute kidney injury. The kidney protective effects of SGLT2 inhibitors generally extend across different members of the class, possibly on the basis of hemodynamic, metabolic, anti-inflammatory, and antifibrotic mechanisms. In this review, we summarize the effects of SGLT2 inhibitors on kidney outcomes in diverse patient populations.
MeSH term(s)	Humans ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Diabetes Mellitus, Type 2/metabolism ; Cardiovascular Diseases/metabolism ; Kidney/metabolism ; Hypoglycemic Agents/therapeutic use
Chemical Substances	Sodium-Glucose Transporter 2 Inhibitors ; Hypoglycemic Agents
Language	English
Publishing date	2023-01-26
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	207930-6
ISSN	1545-326X ; 0066-4219
ISSN (online)	1545-326X
ISSN	0066-4219
DOI	10.1146/annurev-med-042921-102135
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Ua VI Zs.321: Show issues

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Article ; Online: Biology and Clinical Use of Glucagon-Like Peptide-1 Receptor Agonists in Vascular Protection.

Yau, Kevin / Odutayo, Ayodele / Dash, Satya / Cherney, David Z I

The Canadian journal of cardiology

2023 Volume 39, Issue 12, Page(s) 1816–1838

Abstract: Glucagon-like peptide-1 receptor agonists (GLP1RA) are incretin agents initially designed for the treatment of type 2 diabetes mellitus but because of pleiotropic actions are now used to reduce cardiovascular disease in people with type 2 diabetes ... ...

Abstract	Glucagon-like peptide-1 receptor agonists (GLP1RA) are incretin agents initially designed for the treatment of type 2 diabetes mellitus but because of pleiotropic actions are now used to reduce cardiovascular disease in people with type 2 diabetes mellitus and in some instances as approved treatments for obesity. In this review we highlight the biology and pharmacology of GLP1RA. We review the evidence for clinical benefit on major adverse cardiovascular outcomes in addition to modulation of cardiometabolic risk factors including reductions in weight, blood pressure, improvement in lipid profiles, and effects on kidney function. Guidance is provided on indications and potential adverse effects to consider. Finally, we describe the evolving landscape of GLP1RA and including novel glucagon-like peptide-1-based dual/polyagonist therapies that are being evaluated for weight loss, type 2 diabetes mellitus, and cardiorenal benefit.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Glucagon-Like Peptide-1 Receptor Agonists ; Incretins/therapeutic use ; Incretins/pharmacology ; Cardiovascular Diseases/prevention & control ; Cardiovascular Diseases/drug therapy ; Biology
Chemical Substances	Hypoglycemic Agents ; Glucagon-Like Peptide-1 Receptor Agonists ; Incretins
Language	English
Publishing date	2023-07-08
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	632813-1
ISSN	1916-7075 ; 0828-282X
ISSN (online)	1916-7075
ISSN	0828-282X
DOI	10.1016/j.cjca.2023.07.007
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Zs.A 2150: Show issues

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Article ; Online: Cardiorenal mechanisms of action of glucagon-like-peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors.

Cherney, David Z I / Udell, Jacob A / Drucker, Daniel J

Med (New York, N.Y.)

2022 Volume 2, Issue 11, Page(s) 1203–1230

Abstract: Cardiovascular and renal outcome trials (CVOTs) for glucagon-like-peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) highlight new options for people with and without type 2 diabetes (T2D). Drugs within these ... ...

Abstract	Cardiovascular and renal outcome trials (CVOTs) for glucagon-like-peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) highlight new options for people with and without type 2 diabetes (T2D). Drugs within these classes reduce rates of major adverse cardiovascular events (MACE), with SGLT2i simultaneously attenuating decline in kidney function. SGLT2i reduce rates of heart failure in people with and without T2D, whereas GLP1RA lower rates of myocardial infarction and stroke in people with T2D with or without preexisting cardiovascular disease. Mechanistically, SGLT2 and the GLP-1 receptor are expressed at low levels in the heart, and within some blood vessels and immune cells, implying indirect mechanisms of action for the preservation of ventricular function, and reduction of atherosclerosis. SGLT2i likely preserve renal function through the alteration of glomerular hemodynamics. These two drug classes enable organ protection and reduced mortality in people with T2D and represent promising therapies for some people without T2D.
MeSH term(s)	Diabetes Mellitus, Type 2/complications ; Glucagon/therapeutic use ; Glucagon-Like Peptide-1 Receptor/agonists ; Glucose/therapeutic use ; Humans ; Myocardial Infarction/chemically induced ; Sodium/therapeutic use ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology
Chemical Substances	Glucagon-Like Peptide-1 Receptor ; Sodium-Glucose Transporter 2 Inhibitors ; Glucagon (9007-92-5) ; Sodium (9NEZ333N27) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-03-31
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2021.10.004
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Liraglutide for the Treatment of Type 2 Diabetes and Safety in Diabetic Kidney Disease: Liraglutide and Diabetic Kidney Disease.

Cherney, David Z / Tuttle, Katherine R

Clinical journal of the American Society of Nephrology : CJASN

2020 Volume 15, Issue 4, Page(s) 444–446

MeSH term(s)	Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Humans ; Hypoglycemic Agents ; Liraglutide ; Renal Insufficiency, Chronic
Chemical Substances	Hypoglycemic Agents ; Liraglutide (839I73S42A)
Language	English
Publishing date	2020-03-04
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.01260120
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Zs.A 6584: Show issues

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Article ; Online: Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations.

Yau, Kevin / Dharia, Atit / Alrowiyti, Ibrahim / Cherney, David Z I

Kidney international reports

2022 Volume 7, Issue 7, Page(s) 1463–1476

Abstract: SGLT2 inhibitors have emerged as a key disease-modifying therapy to prevent the progression of chronic kidney disease (CKD). These agents prevent decline in kidney function through reduction in glomerular hypertension mediated through tubuloglomerular ... ...

Abstract	SGLT2 inhibitors have emerged as a key disease-modifying therapy to prevent the progression of chronic kidney disease (CKD). These agents prevent decline in kidney function through reduction in glomerular hypertension mediated through tubuloglomerular feedback independent of their effect on glycemic control. The proliferation of clinical trials on SGLT2 inhibitors has rapidly expanded the approved clinical indications for these agents beyond patients with diabetes mellitus (DM). We review the current indications for SGLT2 inhibitors in patients with and without diabetic kidney disease, including new evidence for use in patients with heart failure with or without reduced ejection fraction, stage 4 CKD, and chronic glomerulonephritis. The EMPA-KIDNEY trial was recently stopped early for efficacy suggesting that SGLT2 inhibitors may soon be indicated for patients with CKD without albuminuria. We review practical considerations for prescription of SGLT2 inhibitors, including the anticipated acute decline in estimated glomerular filtration rate (eGFR) on initiation, initiating the lowest dosage used in clinical trials, volume status considerations, and adverse event mitigation. Combination therapy in patients with DM may be considered with agents, including glucagon-like peptide-1 receptor agonists (GLP-1-RAs), novel mineralocorticoid receptor antagonists, and selective endothelin receptor antagonists to reduce residual albuminuria and cardiovascular risk.
Language	English
Publishing date	2022-05-05
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2022.04.094
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