Therapeutic Advances in Diabetic Kidney Disease

Article Peripheral Vascular Disease

Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes

Rajiv Agarwal et al.

Summary: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, was found to reduce 24-hour, daytime, and nighttime systolic blood pressure in patients with chronic kidney disease and type 2 diabetes.

JOURNAL OF HYPERTENSION (2023)

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Article Transplantation

The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease

Peter Rossing et al.

Summary: This study aims to investigate the effects of semaglutide on kidney outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). The participants were found to be mostly at high risk for CKD progression. The study is expected to be completed in late 2024.

NEPHROLOGY DIALYSIS TRANSPLANTATION (2023)

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Article Transplantation

Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE)

Jennifer B. Green et al.

Summary: This study aims to investigate the efficacy of dual therapy with finerenone and an SGLT2i in reducing chronic kidney disease and type 2 diabetes. The results will provide important insights for improving treatment methods for kidney disease and cardiovascular risks.

NEPHROLOGY DIALYSIS TRANSPLANTATION (2023)

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Article Endocrinology & Metabolism

11. Chronic Kidney Disease and Risk Management: Standards of Medical Care in Diabetes-2022

Summary: The American Diabetes Association (ADA) Standards of Medical Care in Diabetes provide comprehensive guidelines and tools for diabetes care. These standards are regularly updated by a professional committee to ensure their relevance and accuracy.

DIABETES CARE (2022)

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Article Cardiac & Cardiovascular Systems

Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis

Rajiv Agarwal et al.

Summary: The study found that finerenone can reduce the risk of kidney disease and cardiovascular events in patients with type 2 diabetes. Screening patients for albuminuria can help reduce the burden of cardiovascular and kidney disease.

EUROPEAN HEART JOURNAL (2022)

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Article Transplantation

Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results

Rajiv Agarwal et al.

Summary: This study compares the effects of two clinical trials and highlights the similar cardiorenal benefits of finerenone and canagliflozin.

NEPHROLOGY DIALYSIS TRANSPLANTATION (2022)

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Article Urology & Nephrology

The Kidney Protective Effects of the Sodium-Glucose Cotransporter-2 Inhibitor, Dapagliflozin, Are Present in Patients With CKD Treated With Mineralocorticoid Receptor Antagonists

Michele Provenzano et al.

Summary: Dapagliflozin was equally safe and effective in reducing major adverse kidney outcomes in participants with CKD, regardless of whether they were prescribed MRAs at baseline.

KIDNEY INTERNATIONAL REPORTS (2022)

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Article Urology & Nephrology

Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy

Peter Rossing et al.

Summary: The FIDELIO-DKD study investigated the treatment effect of finerenone in patients with CKD and T2D, showing that finerenone can improve UACR and have beneficial effects on kidney and cardiovascular outcomes, regardless of whether patients were also using SGLT-2i.

KIDNEY INTERNATIONAL REPORTS (2022)

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Article Cardiac & Cardiovascular Systems

Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Hyperkalemia in People With Type 2 Diabetes: A Meta-Analysis of Individual Participant Data From Randomized, Controlled Trials

Brendon L. Neuen et al.

Summary: SGLT2 inhibitors reduce the risk of serious hyperkalemia in people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease without increasing the risk of hypokalemia.

CIRCULATION (2022)

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Review Biochemistry & Molecular Biology

Role of polyphenols in combating Type 2 Diabetes and insulin resistance

Moyad Shahwan et al.

Summary: Compromised carbohydrate metabolism leading to hyperglycemia is the primary metabolic disorder of non-insulin-dependent diabetes mellitus. Polyphenolic compounds play an important role in regulating insulin resistance and carbohydrate metabolism through inhibiting key enzymes and activating specific pathways to control blood glucose levels.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2022)

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Article Urology & Nephrology

Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial

Michele Provenzano et al.

Summary: This study assessed the efficacy and safety of SGLT2 inhibitors and mineralocorticoid receptor antagonists in patients with CKD. The results showed that changes in urinary albumin did not correlate between dapagliflozin and eplerenone, but the combination of these drugs resulted in a strong additive effect in lowering UACR.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2022)

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Review Urology & Nephrology

Molecular mechanisms and therapeutic targets for diabetic kidney disease

Katherine R. Tuttle et al.

Summary: Diabetic kidney disease is a global burden that increases the risk of kidney failure and cardiovascular events. There is a need to understand the molecular mechanisms of the disease and find new therapies. Inflammatory and fibrotic mediators play important roles in the pathophysiology of the disease. Recent clinical trials have shown promising drug therapies and dietary strategies for treating diabetic kidney disease.

KIDNEY INTERNATIONAL (2022)

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Article Endocrinology & Metabolism

Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium-Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis

Peter Rossing et al.

Summary: Finerenone reduces the risk of kidney and cardiovascular events in patients with CKD and type 2 diabetes, irrespective of SGLT2i use.

DIABETES CARE (2022)

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Article Urology & Nephrology

Kidney-Protective Effects of SGLT2 Inhibitors

Biff F. Palmer et al.

Summary: SGLT2 inhibitors, initially developed as antihyperglycemic drugs, have kidney-protective effects in patients with CKD. The mechanisms involve reducing workload of proximal tubular cells, lowering intraglomerular pressure, activating nutrient-sensing pathways, promoting weight loss, and improving adipose characteristics. These drugs also affect phosphate and magnesium reabsorption, as well as uric acid excretion.

CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2022)

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Article Cardiac & Cardiovascular Systems

Aldosterone in chronic kidney disease and renal outcomes

Ashish Verma et al.

Summary: The study found that higher serum aldosterone levels are independently associated with an increased risk for kidney disease progression in individuals with chronic kidney disease, regardless of concomitant diabetes. This suggests a potential role for mineralocorticoid receptor antagonists in delaying CKD progression even in those without diabetes.

EUROPEAN HEART JOURNAL (2022)

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Article Urology & Nephrology

Executive summary of the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease: an update based on rapidly emerging new evidence

Peter Rossing et al.

KIDNEY INTERNATIONAL (2022)

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Article Urology & Nephrology

Mechanisms Leading to Differential Hypoxia-Inducible Factor Signaling in the Diabetic Kidney: Modulation by SGLT2 Inhibitors and Hypoxia Mimetics

Milton Packer

Summary: SGLT2 inhibitors exert renoprotective effects in diabetic kidneys by modulating the balance of HIF-1α and HIF-2α activities, promoting erythropoiesis, alleviating cellular stress, and reducing inflammation and fibrosis.

AMERICAN JOURNAL OF KIDNEY DISEASES (2021)

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Review Cardiac & Cardiovascular Systems

Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine

Rajiv Agarwal et al.

Summary: This review covers the development of mineralocorticoid receptor antagonists (MRAs) over the last 80 years, discussing the differences in mechanisms and effects between nonsteroidal and steroidal MRAs. Nonsteroidal MRAs demonstrate important distinctions in distribution, binding mode, and gene expression compared to steroidal MRAs.

EUROPEAN HEART JOURNAL (2021)

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Review Urology & Nephrology

Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease

Panagiotis I. Georgianos et al.

Summary: The article discusses the detrimental effects of MR overactivation in CKD models on the heart, kidney, and blood vessels, as well as the potential of Finerenone as a novel MR antagonist to improve the progression of cardiorenal disease.

KIDNEY INTERNATIONAL REPORTS (2021)

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Review Pharmacology & Pharmacy

Mechanisms for Cardiorenal Protection of SGLT-2 Inhibitors

Panagiotis Georgianos et al.

Summary: SGLT-2 inhibitors have shown cardio-renal protective effects in patients with diabetic kidney disease (DKD), slowing the progression of DKD and improving cardiovascular outcomes. The premature termination of the CREDENCE trial showed impressive benefits of canagliflozin on kidney and cardiovascular outcomes.

CURRENT PHARMACEUTICAL DESIGN (2021)

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Article Medicine, General & Internal

Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease

Deepak L. Bhatt et al.

Summary: The trial involving 10,584 patients with diabetes and chronic kidney disease showed that sotagliflozin resulted in fewer deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure compared to placebo. However, there were adverse events such as diarrhea, mycotic infections, and diabetic ketoacidosis associated with sotagliflozin.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Urology & Nephrology

Effects of Finerenone Combined with Empagliflozin in a Model of Hypertension-Induced End-Organ Damage

Peter Kolkhof et al.

Summary: This study compared the effects of nonsteroidal MR antagonist finerenone and SGLT2 inhibitor empagliflozin as monotherapy and in combination in a preclinical model of hypertension-induced cardiorenal disease. The low-dose combination therapy showed superior outcomes in reducing proteinuria, blood pressure, plasma markers, and cardiorenal lesions compared to respective monotherapy dosages.

AMERICAN JOURNAL OF NEPHROLOGY (2021)

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Article Endocrinology & Metabolism

Effects of the SGLT2 inhibitor canagliflozin on plasma biomarkers TNFR-1, TNFR-2 and KIM-1 in the CANVAS trial

Taha Sen et al.

Summary: Higher plasma concentrations of TNFR-1, TNFR-2, and KIM-1 are associated with increased risk of kidney failure in individuals with type 2 diabetes. Canagliflozin can reduce these biomarkers, with early decreases in TNFR-1 and TNFR-2 independently associated with a lower risk of kidney disease progression.

DIABETOLOGIA (2021)

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Review Pharmacology & Pharmacy

Finerenone: First Approval

James E. Frampton

Summary: Finerenone, a first-in-class nonsteroidal mineralocorticoid receptor antagonist, has been approved in the USA for the treatment of CKD associated with T2D. It is currently undergoing regulatory assessment in the EU and China, with a phase III trial in HF patients with preserved ejection fraction underway. This milestone approval aims to reduce the risk of serious kidney and heart complications in adults with CKD and T2D.

DRUGS (2021)

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Article Medicine, General & Internal

Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes

Bertram Pitt et al.

Summary: Finerenone therapy improved cardiovascular outcomes in patients with type 2 diabetes and stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria, compared to placebo. The risk of the primary outcome event was significantly lower in the finerenone group, primarily driven by a reduction in hospitalization for heart failure.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Cardiac & Cardiovascular Systems

Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine

Rajiv Agarwal et al.

Summary: This review summarizes the development of mineralocorticoid receptor antagonists over the past 80 years, focusing on the mechanisms of action and advantages of nonsteroidal MRAs.

EUROPEAN HEART JOURNAL (2021)

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Review Transplantation