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Book: The role of SGLT2 inhibitors in the management of chronic kidney disease

Lambers Heerspink, Hiddo J.

(Nephrology, dialysis, transplantation ; volume 35, number S1 (February 2020))

2020

Author's details	guest edited by Hiddo J.L. Heerspink, Denis Fouque and Christoph Wanner
Series title	Nephrology, dialysis, transplantation ; volume 35, number S1 (February 2020)
Collection
Language	English
Size	i55 Seiten, Illustrationen
Publisher	Oxford University Press
Publishing place	Oxford
Publishing country	Great Britain
Document type	Book
HBZ-ID	HT020384334
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Insulin resistance, kidney outcomes and effects of the endothelin receptor antagonist atrasentan in patients with type 2 diabetes and chronic kidney disease.

Smeijer, J David / Kohan, Donald E / Rossing, Peter / Correa-Rotter, Ricardo / Liew, Adrian / Tang, Sydney C W / de Zeeuw, Dick / Gansevoort, Ron T / Ju, Wenjun / Lambers Heerspink, Hiddo J

Cardiovascular diabetology

2023 Volume 22, Issue 1, Page(s) 251

Abstract: Background: Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR ... ...

Abstract	Background: Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD. Methods: We used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD [eGFR 25-75 mL/min/1.73 m², urine albumin-to-creatinine ratio of 300-5000 mg/g]. IR was calculated using the homeostatic model assessment (HOMA-IR). The association between HOMA-IR and the pre-specified cardio-renal outcomes was assessed using multivariable Cox proportional hazards regression, and effects of atrasentan on HOMA-IR by a linear mixed effect model. Results: In the SONAR trial, each log-unit increase in HOMA-IR was associated with an increased risk of the composite cardio-renal outcome [hazard ratio 1.32 (95%CI 1.09,1.60; p = 0.004)], kidney outcome [hazard ratio 1.30 (95%CI 1.00,1.68; p-value = 0.048)], and the kidney or all-cause mortality outcome [hazard ratio 1.25 (95%CI 1.01,1.55; p-value = 0.037)]. After 12 weeks treatment in the RADAR trial (N = 123), atrasentan 0.75 mg/day and 1.25 mg/day compared to placebo reduced HOMA-IR by 19.1 (95%CI -17.4, 44.3) and 26.7% (95%CI -6.4, 49.5), respectively. In the SONAR trial (N = 1914), atrasentan 0.75 mg/day compared to placebo reduced HOMA-IR by 9.6% (95%CI 0.6, 17.9). Conclusions: More severe IR is associated with increased risk of cardio-renal outcomes. The endothelin receptor antagonist atrasentan reduced IR. Trial registration: RADAR trial (Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan): NCT01356849. SONAR trial (The Study Of Diabetic Nephropathy With AtRasentan) NCT01858532.
MeSH term(s)	Humans ; Atrasentan/adverse effects ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Insulin Resistance ; Kidney ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/epidemiology ; Endothelin Receptor Antagonists/adverse effects
Chemical Substances	Atrasentan (V6D7VK2215) ; Endothelin Receptor Antagonists
Language	English
Publishing date	2023-09-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2093769-6
ISSN	1475-2840 ; 1475-2840
ISSN (online)	1475-2840
ISSN	1475-2840
DOI	10.1186/s12933-023-01964-8
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Article ; Online: Clinical trials: New nonabsorbable potassium-exchange resins in hyperkalaemia.

Roscioni, Sara S / Lambers Heerspink, Hiddo J

Nature reviews. Nephrology

2015 Volume 11, Issue 4, Page(s) 205–206

MeSH term(s)	Cation Exchange Resins/therapeutic use ; Clinical Trials as Topic ; Humans ; Hyperkalemia/drug therapy ; Polymers/therapeutic use ; Potassium ; Silicates/therapeutic use
Chemical Substances	Cation Exchange Resins ; Polymers ; Silicates ; ZS-9 compound ; patiromer (1FQ2RY5YHH) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2015-04
Publishing country	England
Document type	News
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/nrneph.2014.252
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Article ; Online: Epidemiology of the diabetes-cardio-renal spectrum: a cross-sectional report of 1.4 million adults.

Schechter, Meir / Melzer Cohen, Cheli / Yanuv, Ilan / Rozenberg, Aliza / Chodick, Gabriel / Bodegård, Johan / Leiter, Lawrence A / Verma, Subodh / Lambers Heerspink, Hiddo J / Karasik, Avraham / Mosenzon, Ofri

Cardiovascular diabetology

2022 Volume 21, Issue 1, Page(s) 104

Abstract: Background: Type-2 diabetes (T2D), chronic kidney disease, and heart failure (HF) share epidemiological and pathophysiological features. Although their prevalence was described, there is limited contemporary, high-resolution, epidemiological data ... ...

Abstract	Background: Type-2 diabetes (T2D), chronic kidney disease, and heart failure (HF) share epidemiological and pathophysiological features. Although their prevalence was described, there is limited contemporary, high-resolution, epidemiological data regarding the overlap among them. We aimed to describe the epidemiological intersections between T2D, HF, and kidney dysfunction in an entire database, overall and by age and sex. Methods: This is a cross-sectional analysis of adults ≥ 25 years, registered in 2019 at Maccabi Healthcare Services, a large healthcare maintenance organization in Israel. Collected data included sex, age, presence of T2D or HF, and last estimated glomerular filtration rate (eGFR) in the past two years. Subjects with T2D, HF, or eGFR < 60 mL/min/1.73 m Results: Overall, 1,389,604 subjects (52.2% females) were included; 445,477 (32.1%) were 25- < 40 years, 468,273 (33.7%) were 40- < 55 years, and 475,854 (34.2%) were ≥ 55 years old. eGFR measurements were available in 74.7% of the participants and in over 97% of those with T2D or HF. eGFR availability increased in older age groups. There were 140,636 (10.1%) patients with T2D, 54,187 (3.9%) with eGFR < 60 mL/min/1.73m Conclusions: This large, broad-based study provides a contemporary, high-resolution prevalence of the DCR spectrum and its components. The results highlight differences in dominance and degree of congruence between T2D, HF, and kidney dysfunction across ages.
MeSH term(s)	Adult ; Aged ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Glomerular Filtration Rate/physiology ; Heart Failure ; Humans ; Kidney ; Male ; Middle Aged ; Renal Insufficiency ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/epidemiology
Language	English
Publishing date	2022-06-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2093769-6
ISSN	1475-2840 ; 1475-2840
ISSN (online)	1475-2840
ISSN	1475-2840
DOI	10.1186/s12933-022-01521-9
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Article ; Online: Rebuttal of the Con View: Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD.

Lambers Heerspink, Hiddo J / Gansevoort, Ron T

Clinical journal of the American Society of Nephrology : CJASN

2015 Volume 10, Issue 6, Page(s) 1099

Abstract: Our opponents in this debate state that there are insufficient data to consider albuminuria as a valid target for therapy in patients with CKD. They base their opinion predominantly on two arguments: first, a decrease in albuminuria is not always ... ...

Abstract	Our opponents in this debate state that there are insufficient data to consider albuminuria as a valid target for therapy in patients with CKD. They base their opinion predominantly on two arguments: first, a decrease in albuminuria is not always associated with renoprotection, and second, no prospective randomized controlled trial has been conducted that really targeted albuminuria.
MeSH term(s)	Albuminuria/therapy ; Humans ; Kidney/drug effects ; Renal Insufficiency, Chronic/therapy ; Serum Albumin/metabolism ; Urological Agents/therapeutic use
Chemical Substances	Serum Albumin ; Urological Agents
Language	English
Publishing date	2015-06-05
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.02760315
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Article ; Online: Therapeutic approaches in lowering albuminuria: travels along the renin-angiotensin-aldosterone-system pathway.

Heerspink, Hiddo J Lambers

Advances in chronic kidney disease

2011 Volume 18, Issue 4, Page(s) 290–299

Abstract: Achieving optimal blood pressure and albuminuria control is a major therapeutic treatment goal in patients with renal insufficiency. Angiotensin-converting enzyme-inhibitors (ACEIs) and angiotensin-receptor blockers (ARB) are the mainstay of therapy in ... ...

Abstract	Achieving optimal blood pressure and albuminuria control is a major therapeutic treatment goal in patients with renal insufficiency. Angiotensin-converting enzyme-inhibitors (ACEIs) and angiotensin-receptor blockers (ARB) are the mainstay of therapy in these patients. However, despite these therapies many patients remain at high risk of renal or cardiovascular disease that shows a relationship with albuminuria. Various approaches have been tested to maximize the efficacy of ACEI and ARB. Increasing the dose of an ACEI or ARB beyond the maximal registered antihypertensive dose causes a distinct decrease in albuminuria without additional effects on blood pressure. The combination of an ACEI and ARB is another possibility to further reduce albuminuria. However, the alleged beneficial effects on hard renal and cardiovascular outcome are not unambiguously demonstrated. Adding a direct renin inhibitor to an ACEI or ARB has been shown to lower albuminuria in patients with and without diabetes. Long-term trials are currently under way to determine the effects of direct renin inhibition on clinical outcomes. Volume excess has been shown to blunt the blood pressure and albuminuria response to ACEI or ARB therapy. Intervening in volume status by means of restricting dietary sodium intake or diuretic therapy has convincingly been shown to lower blood pressure and albuminuria. Whether this strategy translates into a reduction in the risk of renal or cardiovascular events has not (yet) been investigated in prospective randomized trials. Various options are at hand which have been shown to maximize the blood pressure and albuminuria response to ACEI and ARB treatment. However, long-term studies supporting the benefits of these strategies on hard renal and cardiovascular outcomes are warranted.
MeSH term(s)	Albuminuria/drug therapy ; Angiotensin Receptor Antagonists/administration & dosage ; Angiotensin Receptor Antagonists/adverse effects ; Angiotensin-Converting Enzyme Inhibitors/administration & dosage ; Angiotensin-Converting Enzyme Inhibitors/adverse effects ; Antihypertensive Agents/therapeutic use ; Cardiovascular Diseases/drug therapy ; Contraindications ; Diuretics/therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Male ; Mineralocorticoid Receptor Antagonists ; Renal Insufficiency, Chronic/drug therapy ; Renin/antagonists & inhibitors ; Renin-Angiotensin System/drug effects ; Renin-Angiotensin System/physiology ; Sodium, Dietary ; Treatment Outcome
Chemical Substances	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Antihypertensive Agents ; Diuretics ; Mineralocorticoid Receptor Antagonists ; Sodium, Dietary ; Renin (EC 3.4.23.15)
Language	English
Publishing date	2011-07
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1548-5609 ; 1548-5595
ISSN (online)	1548-5609
ISSN	1548-5595
DOI	10.1053/j.ackd.2011.04.001
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Zs.A 4627: Show issues

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Article ; Online: Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering.

BMJ open diabetes research & care

2023 Volume 11, Issue 3

Abstract: Introduction: Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.: Research design and methods: We analyzed 4395 individuals with prebaseline ... ...

Abstract	Introduction: Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain. Research design and methods: We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components. Results: HbA1c lowering was modified by baseline estimated glomerular filtration rate (eGFR). For baseline eGFR 60-90, 45-59, and 30-44 mL/min/1.73 m Conclusions: The glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22.
MeSH term(s)	Humans ; Canagliflozin/pharmacology ; Glucose ; Glycated Hemoglobin ; Kidney ; Kidney Failure, Chronic ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology
Chemical Substances	Canagliflozin (0SAC974Z85) ; Glucose (IY9XDZ35W2) ; Glycated Hemoglobin ; Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2023-06-13
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2732918-5
ISSN	2052-4897 ; 2052-4897
ISSN (online)	2052-4897
ISSN	2052-4897
DOI	10.1136/bmjdrc-2022-003270
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Article ; Online: Are post-trial observational studies useful?

Heerspink, Hiddo J Lambers / de Zeeuw, Dick

Journal of the American Society of Nephrology : JASN

2014 Volume 25, Issue 10, Page(s) 2148–2150

MeSH term(s)	Albuminuria/epidemiology ; Diabetes Mellitus, Type 1/complications ; Diabetic Nephropathies/epidemiology ; Female ; Humans ; Male
Language	English
Publishing date	2014-06-12
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.2014040410
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Article ; Online: Are renin-angiotensin-aldosterone system inhibitors lifesaving in chronic kidney disease?

Damman, Kevin / Lambers-Heerspink, Hiddo J

Journal of the American College of Cardiology

2014 Volume 63, Issue 7, Page(s) 659–660

MeSH term(s)	Angiotensin II Type 1 Receptor Blockers/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Female ; Humans ; Male ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/mortality
Chemical Substances	Angiotensin II Type 1 Receptor Blockers ; Angiotensin-Converting Enzyme Inhibitors
Language	English
Publishing date	2014-02-25
Publishing country	United States
Document type	Comment ; Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2013.10.051
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Article ; Online: Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease.

Lambers Heerspink, Hiddo J / Gaillard, Carlo J A M / Gansevoort, Ron T

Annals of internal medicine

2014 Volume 161, Issue 1, Page(s) 82–83

MeSH term(s)	Humans ; Mass Screening ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/drug therapy
Language	English
Publishing date	2014-07-01
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/L14-5013-3
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