Nonsteroidal Mineralocorticoid Receptor Antagonist Research Articles

Finerenone in patients with heart failure with mildly reduced or preserved ejection fraction: Rationale and design of the FINEARTS-HF trial.

Steroidal mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, are strongly recommended in the treatment of patients with chronic heart failure (HF) with reduced left ventricular ejection fraction (LVEF), but the balance of efficacy and safety in those with higher LVEF has not been well established. Broad use of steroidal MRAs has further been limited in part due to safety concerns around risks of hyperkalaemia, gynecomastia, and kidney dysfunction. These risks may be mitigated by the unique pharmacological properties of the non-steroidal MRA finerenone. The FINEARTS-HF trial is designed to evaluate the long-term efficacy and safety of the selective non-steroidal MRA finerenone among patients with HF with mildly reduced or preserved ejection fraction. FINEARTS-HF is a global, multicentre, event-driven randomized trial evaluating oral finerenone versus matching placebo in symptomatic patients with HF with LVEF ≥40%. Adults (≥40 years) with HF with New York Heart Association class II-IV symptoms, LVEF ≥40%, evidence of structural heart disease, and diuretic use for at least the previous 30 days were eligible. All patients required elevated natriuretic peptide levels: for patients in sinus rhythm, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml (or B-type natriuretic peptide [BNP] ≥100 pg/ml) were required, measured within 30 days (in those without a recent worsening HF event) or within 90 days (in those with a recent worsening HF event). Qualifying levels of NT-proBNP or BNP were tripled if a patient was in atrial fibrillation at screening. Estimated glomerular filtration rate <25 ml/min/1.73 m2 or serum potassium >5.0 mmol/L were key exclusion criteria. Patients were enrolled irrespective of clinical care setting (whether hospitalized, recently hospitalized, or ambulatory). The primary endpoint is the composite of cardiovascular death and total (first and recurrent) HF events. The trial started on 14 September 2020 and has validly randomized 6001 participants across 37 countries. Approximately 2375 total primary composite events are targeted. The FINEARTS-HF trial will determine the efficacy and safety of the non-steroidal MRA finerenone in a broad population of hospitalized and ambulatory patients with HF with mildly reduced or preserved ejection fraction. ClinicalTrials.gov NCT04435626 and EudraCT 2020-000306-29.

Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

Mineralocorticoid receptor antagonists and reno-protection: What's the evidence & where do they fit? A guide for non-specialists.

The role of aldosterone has yet to be well appreciated in chronic kidney disease (CKD). Two variables define CKD: an estimated glomerular filtration rate of <60 ml/min/1.73 m2 and a spot urine albumin-creatinine ratio of >30 mg/g. Both are needed for an accurate diagnosis. The presence of CKD at this level is associated with an elevated risk of cardiovascular death and a greater risk of CKD progression to kidney failure and subsequent dialysis. This paper presents an overview of aldosterone's importance in CKD and its contribution to the inflammatory processes involved in CKD development. Data on outcomes, both surrogate and hard, related to outcomes on CKD progression will also be discussed in the context of mineralocorticoid blockade. Based on recent epidemiological data as well as data examining markers of diabetic kidney disease progression, it is clear that use of both renin-angiotensin system inhibitors and aldosterone receptor antagonists have a significant role in altering the natural history of kidney disease progression itself, as well as reducing the risk of cardiovascular events that generally accompany long-standing kidney disease. This paper will discuss these issues and the management of consequent hyperkalaemia when both steroidal and non-steroidal mineralocorticoid receptor antagonists are used in detail.

Detecting and managing the patient with chronic kidney disease in primary care: A review of the latest guidelines.

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes. During the early stages, CKD is asymptomatic, and many people are unaware that they are living with the disease. Despite the lack of symptoms, CKD is associated with elevated risks of cardiovascular disease, progressive kidney disease, kidney failure and premature mortality. Risk reduction strategies are effective and cost-effective but require early diagnosis through testing of the estimated glomerular filtration rate and albuminuria in high-risk populations. Once diagnosed, the treatment of CKD centres around lifestyle interventions, blood pressure and glycaemic control, and preventative treatments for cardiovascular disease and kidney disease progression. Most patients with CKD should be managed with statins, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. Additional treatment options to reduce cardiorenal risk are available in patients with diabetes, including glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists. The Kidney Failure Risk Equation is a new tool that can support the identification of patients at high risk of progressive kidney disease and kidney failure and can be used to guide referrals to nephrology. This review summarizes the latest guidance relevant to managing adults with, or at risk of, CKD and provides practical advice for managing patients with CKD in primary care.

Intellectual landscapes and emerging trends of non-steroidal mineralocorticoid receptor antagonists: a bibliometric and visual analysis.

With increasing studies, non-steroidal mineralocorticoid receptor (MR) antagonists have been increasingly recognized as a major novel dimension in cardiorenal disease therapy. This bibliometric analysis aimed to uncover current research status and identify future research directions in the study of non-steroidal MR antagonists to inform subsequent investigations. Relevant English-language literature was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection on January 10, 2024. Analyses of countries, institutions, authors, journals, documents, cited references and keywords were performed by the CiteSpace and VOSviewer software. Overall, 498 documents, including 297 articles and 201 reviews, were included and analyzed. The United States (n = 188), Bayer AG (n = 78), and Professor Peter Kolkhof (n = 59) were the most prolific country, institution, and author in this field, respectively. Cluster analysis of cited references identified major clusters like cardiovascular disease, chronic kidney disease, and omecamtiv mecarbil. Keyword analysis indicated that sodium-glucose transport protein (SGLT)-2 inhibitors, pharmacotherapy, clinical trial, and guideline have emerged recently. The field of non-steroidal MR antagonists is gradually gaining momentum as a novel pharmacotherapy in cardiorenal diseases, especially diabetic kidney disease, hypertension, and heart failure. Future studies will focus on add-on pharmacotherapy by combining non-steroidal MR antagonists with SGLT-2 inhibitors and the development and publication of clinical guidelines to facilitate patient management.

Cardiorenal Benefits of Finerenone in Different Races and Kidney Function in Patients with Chronic Kidney Disease.

The mineralocorticoid receptor plays an important pathophysiological role in cardiorenal diseases by causing inflammation and fibrosis. Mineralocorticoid receptor antagonists (MRAs) are well known in treating cardiovascular disease and diverse nephropathies. However, the first-generation MRA (spironolactone) and the second-generation MRA (eplerenone) remain underutilized because of the risk of inducing severe adverse events. As a selective nonsteroidal MRA, finerenone is safer and more effective and improves cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). However, the effect of finerenone on cardiorenal outcomes in patients of different races and kidney function (estimated glomerular filtration rate) is unclear. In this review, we summarized the impact of finerenone on patients with CKD and T2DM from randomized controlled trials. The synthesis of published data aims to address the questions pertaining to the cardiorenal benefits of finerenone among various racial groups and different levels of kidney function. Finerenone presents racial differences and effects associated with kidney function in CKD and T2DM patients. Due to the limited data for subgroups, it is prudent to approach the conclusion with caution.

Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease.

Diabetic kidney disease is a frequent microvascular complication of diabetes and is currently the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Although the prevalence of other complications of diabetes is falling, the number of diabetic patients with end-stage kidney disease in need of kidney replacement therapy is rising. In addition, these patients have extremely high cardiovascular risk. It is more than evident that there is a high unmet treatment need in patients with diabetic kidney disease. Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist used for treating diabetic kidney disease. It has predominant anti-fibrotic and anti-inflammatory effects and exhibits several renal and cardiac protective effects. This review article summarizes the current knowledge and future prospects of finerenone in treating patients with kidney disease.

Finerenone cardiovascular and kidney outcomes by age and sex: FIDELITY post hoc analysis of two phase 3, multicentre, double-blind trials

ObjectivesThis study aimed to evaluate the efficacy and safety of finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, on cardiovascular and kidney outcomes by age and/or sex.DesignFIDELITY post hoc analysis; median...

A New Hope on the Horizon for Kidney and Cardiovascular Protection with SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Mineralocorticoid Receptor Antagonists in Type 2 Diabetic and Chronic Kidney Disease Patients.

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD). In addition, the cardiovascular prevalence in diabetic patients is around 32.2%, with a two-fold increased mortality risk compared to those without diabetes. Recent investigations have shed light on the promising cardioprotective and nephroprotective benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and nonsteroidal mineralocorticoid receptor antagonists (nsMRAs) for individuals with T2D. The evidence robustly indicates that SGLT2i and GLP-1RA significantly reduce the risk of CKD and cardiovascular disease (CVD), all while effectively managing blood glucose levels. Furthermore, combining SGLT2i with nsMRAs amplifies the benefits, potentially offering a more profound reduction in cardiovascular and renal outcomes. The data analysis strongly supports the integration of these pharmacological agents in the management strategies for CKD and CVD prevention among T2D patients, highlighting the importance of awareness among nephrologists, especially in regions with limited healthcare resources.

The changing landscape of mineralocorticoid receptor antagonists – finerenone in cardiovascular and renal health

Finerenone is a novel non-steroidal mineralocorticoid receptor antagonist (MRA) with high selectivity and affinity to mineralocorticoid receptor (MR). Steroidal MRAs, like spironolactone and eplerenone, have been in use for decades. They have an established position in the management of hypertension and heart failure with reduced ejection fraction (HFrEF). There are studies showing that MR antagonism has anti-inflammatory and anti-fibrotic effects resulting in cardiovascular and renal protection. However, broader use of steroidal MRAs is seriously limited by antiandrogenic side effects and the risk of hyperkalemia. The differences in structure as well as pharmacokinetic and pharmacodynamic properties between steroidal and non-steroidal MRAs result in reduced risk of side effects while offering the benefit of cardiorenal protection. Finerenone is currently the only non-steroidal MRA approved by European Medicines Agency (EMA). It is indicated for patients with chronic kidney disease (CKD) with albuminuria and type 2 diabetes mellitus (DM2). Several studies showed a reduction of the risk of cardiovascular and renal events in this group of patients compared to placebo. The risk of hyperkalemia was increased resulting in discontinuation of treatment in more patients than placebo, but the risk of serious adverse events did not differ significantly. The other indications for finerenone, including heart failure (HF) management, are currently being researched.

Use of ACEi/ARBs, SGLT2 inhibitors and MRAs can help us reach the therapeutic ceiling in CKD

ABSTRACT Chronic kidney disease (CKD) is increasing in prevalence worldwide, posing major implications for public health such as kidney failure requiring dialysis, and increased risk of cardiovascular and all-cause mortality. Diabetic and hypertensive kidney disease represent the two most common causes of CKD. Until a few years ago, lifestyle modifications, blood pressure, glycaemic and lipid control, along with angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker monotherapy were the only measures for retarding these two diseases and were the cornerstone of treatment for CKD of any aetiology. Effective application of all these measures could reduce the estimated glomerular filtration rate (eGFR) decline in proteinuric CKD roughly from 10–12 to 5–6 mL/min/1.73 m2/year, hence leaving a large unmet need in CKD treatment. In recent years, major kidney outcome trials showed that the addition of sodium–glucose cotransporter-2 inhibitors (SGLT2i) in patients with CKD with or without type 2 diabetes (T2D) and of the non-steroidal mineralocorticoid receptor antagonist finerenone in patients with CKD with T2D can largely improve kidney and cardiovascular outcomes. Elegant analyses of these trials shed further light on these effects, showing that SGLT2i or finerenone use on top of standard-of-care treatment in patients with albuminuric CKD can further reduce chronic eGFR annual loss to 2–2.5 mL/min/1.73 m2, while SGLT2is in normoalbuminuric CKD can reduce this loss &amp;lt;0.5 mL/min/1.73 m2, i.e. well below the aging-related GFR loss. Therefore, current evidence suggests that available treatments, if properly implemented, can help us reach the therapeutic ceiling in the majority of CKD patients.

Kidney Fibrosis and Oxidative Stress: From Molecular Pathways to New Pharmacological Opportunities.

Kidney fibrosis, diffused into the interstitium, vessels, and glomerulus, is the main pathologic feature associated with loss of renal function and chronic kidney disease (CKD). Fibrosis may be triggered in kidney diseases by different genetic and molecular insults. However, several studies have shown that fibrosis can be linked to oxidative stress and mitochondrial dysfunction in CKD. In this review, we will focus on three pathways that link oxidative stress and kidney fibrosis, namely: (i) hyperglycemia and mitochondrial energy imbalance, (ii) the mineralocorticoid signaling pathway, and (iii) the hypoxia-inducible factor (HIF) pathway. We selected these pathways because they are targeted by available medications capable of reducing kidney fibrosis, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and HIF-1alpha-prolyl hydroxylase inhibitors. These drugs have shown a reduction in oxidative stress in the kidney and a reduced collagen deposition across different CKD subtypes. However, there is still a long and winding road to a clear understanding of the anti-fibrotic effects of these compounds in humans, due to the inherent practical and ethical difficulties in obtaining sequential kidney biopsies and the lack of specific fibrosis biomarkers measurable in easily accessible matrices like urine. In this narrative review, we will describe these three pathways, their interconnections, and their link to and activity in oxidative stress and kidney fibrosis.

Assessment of renal and cardiovascular risks in patients with type 2 diabetes when using non-steroidal mineralocorticoid receptor antagonists

Background. Given the proven excessive activation of the renin-angiotensin-aldosterone system and the clinical manifestations of hypertension, mostly of renal origin, there is a need to optimize antihypertensive therapy aimed at an active nephroprotection. The purpose of the study is to carry out a comprehensive assessment of kidney and heart risk factors in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) and to justify the administration of non-steroidal mineralocorticoid receptor antagonists to these patients. Materials and methods. In a prospective cohort study, 88 patients with type 2 diabetes were examined: group 1 — estimated glomerular filtration rate (eGFR) &lt; 60 ml/min/m2, group 2 — eGFR ≥ 60 ml/min/m2. eGFR was evaluated according to the CKD-EPI (Chronic Kidney Disease Epidemiology Colla­boration) formula based on serum creatinine. GFR category was defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The albumin-creatinine ratio was calcula­ted. The level of glycated hemoglobin (HbA1c) was assessed by the method of high-performance liquid chromatography. Aldosterone was evaluated by immunoenzymatic method. Results. In patients with eGFR &lt; 60 ml/min/m2, the albumin-creatinine ratio in daily urine is statistically significantly higher compared to group 2. Patients with eGFR &lt; 60 ml/min/m2 had an average uric acid level of 410.3 ± 98.8 μmol/l, which is statistically significantly higher than in those with eGFR ≥ 60 ml/min/m2 — 321.10 ± 74.54 μmol/l. A statistically significant correlation between the level of uric acid and markers of renal dysfunction was found only in patients with eGFR &lt; 60 ml/min/m2. Aldosterone levels were higher in the first group. No statistical difference was found between the average value of HbA1c in the studied groups. Conclusions. Numerous factors of unfavorable prognosis regarding kidney and heart risks have been identified: hypertension, increased albumin-creatinine ratio and cholesterol, unsatisfactory compensation of diabetes, obesity. There is an increase in the frequency of resistant hypertension, hyperuricemia, and hyperaldosteronism in patients with decreased eGFR. In patients with diabetic kidney damage on the background of type 2 diabetes, the administration of finerenone, a non-steroidal mine­ralocorticoid receptor antagonist, at a dose of 10–20 mg/day is pathogenetically justified.

A fluorescence chemo sensor approach for determination of finerenone in pharmaceutical formulation and human plasma: Method development and validation

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has gained recent approval for treating cardiovascular and kidney-related conditions. Herein, an innovative fluorescence chemo sensor was developed for the determination of finerenone in the pharmaceutical dosage form and the plasma matrix. The method is basically based on chemical transformation of finerenone into a fluorescent product through sequential reactions. This transformation occurs through a sequence of steps involving the interaction of finerenone with trimethylamine, resulting in the formation of a nucleophilic intermediate that subsequently reacts with bromoacetyl bromide to form fluorescent product, (S)-N-(2-bromoacetyl)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide. The formed fluorescent product exhibits defined emission peak at 338 nm when excited at 248 nm. Significant concentration-dependent fluorescence enhancement was obtained enabling precise finerenone determination in the pharmaceutical formulation and plasma matrix. The method was optimized and validated providing sensitive determination over linearity range of 1–200 ng/mL with a lower limit of detection at 0.280 ng/mL. This strategy provides an efficient, economical substitute and straightforward, more sensitive analytical method for finerenone assessment in various matrices, in contrast to the previously published method, high-performance liquid chromatography-tandem mass spectrometry, which is expensive and time-consuming.

Implications of Untreated Hypertension on Chronic Kidney Disease: A Literature Review

The untreated progression of hypertension holds significant implications for the development and progression of chronic kidney disease (CKD). Therefore, necessitating the implementation of strategic hypertension management measures to mitigate its impact on CKD. This review highlights the necessity of precise diagnostic methodologies that employ oscillometric equipment and advocates for pharmacological interventions, the incorporation of combination therapies such as the "Polypill" to effectively control hypertension, and lifestyle adjustments. The pivotal role of the renin-angiotensin-aldosterone system (RAAS) in hypertension is acknowledged, noting the importance of stringent blood pressure regulation and the utilization of RAAS-blocking agents to attenuate its association with CKD. A comprehensive analysis is provided on the effects of various classes of antihypertensive medications on renal function, encompassing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and nonsteroidal mineralocorticoid receptor antagonists. Additionally, both non-invasive and invasive therapeutic modalities for managing resistant hypertension in CKD patients are examined, alongside discussions on prognostic indicators and outcomes across different stages of CKD. Lifestyle modifications such as sodium restriction, weight management, and moderation of alcohol intake are assessed for their influence on CKD prognosis. The review also extensively delves into the impact of ethnicity on the prevalence and outcomes of hypertension-induced CKD, highlighting disparities and distinctive trends among diverse ethnic cohorts including Indian, African American, Middle Eastern, Chinese, Pacific Islander, Native American, and Hispanic populations. Additionally, this study addresses the intricate relationship between cardiovascular abnormalities and CKD, the significance of gastrointestinal disorders, and the importance of multidisciplinary approaches in CKD management. Furthermore, insights are provided into the significance of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for identifying renal injury and CKD progression, alongside factors influencing adverse prognosis and life expectancy in CKD patients. This study accentuates the importance of tailored treatment assessments and interventions to address varied patterns and obstacles within ethnic groups, with the aim of optimizing CKD management strategies and reducing health disparitie

Management of Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor: Strategies to Maintain Chronic Kidney Disease Patients with Type II Diabetes on Therapy.

According to the Centers for Disease Control and Prevention (CDC), diabetes affects approximately 37.3 million individuals in the USA, with another estimated 96 million people having a prediabetic state. Furthermore, one or two out of three adult Americans exhibit metabolic syndrome or an insulin-resistant state, depending on their age group. Chronic kidney disease (CKD) represents a complication often associated with type II diabetes or the insulin-resistant condition, typically identifiable through proteinuria. Proteinuria serves as both a marker and a contributing factor to kidney damage, and it significantly heightens the risk of cardiovascular (CV) events, including atherosclerosis, heart attacks, and strokes. Renin-angiotensin-aldosterone system inhibitors (RAASis) have demonstrated clinical efficacy in lowering blood pressure, reducing proteinuria, and slowing CKD progression. However, hyperkalemia is a common and serious adverse effect associated with using RAASi. It is imperative to establish personalized management strategies to enable patients to continue RAASi therapy while effectively addressing hyperkalemia risk. Healthcare professionals must be careful not to inadvertently create a low renal perfusion state, which can reduce distal nephron luminal flow or luminal sodium concentration while using RAASi. Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), such as finerenone, are demonstrated to delay CKD progression and reduce CV complications, all while mitigating the risk of hyperkalemia. Additionally, maintaining a routine monitoring regimen for serum potassium levels among at-risk patients, making dietary adjustments, and considering the adoption of newer potassium-binding agents hold promise for optimizing RAASi therapy and achieving more effective hyperkalemia management.

New advances in pediatric nephrology: ESPN 2023 results

On September 28 — October 1, 2023, the European Society for Paediatric Nephrology (ESPN) 55th Annual Meeting was held in Vilnius, Lithuania, where new achievements in the world of pediatric nephrology were presented. The program included 66 sessions with reports, continuing medical education courses, 117 invited speakers, meetings of working groups on various issues of pediatric nephrology were held, about 450 abstracts were printed and 292 poster presentations were discussed, inclu­ding two by authors from Ukraine. Courses for young doctors, preparing them for the international exam, and 5-minute reports by well-known specialists became interesting in the organization of continuing medical education, which significantly increased the amount of presented material. Among the innovative approaches in pediatric nephrology, the following drugs have been considered: finerenone (a selective non-steroidal mineralocorticoid receptor antagonist), sparsentan (an angiotensin/endothelin receptor antagonist) for Alport syndrome, focal segmental glomerulosclerosis, IgA nephropathy, dapagliflozin (a sodium-glucose cotransporter 2 inhibitor) for chronic kidney disease and pioglitazone for proteinuria. New approaches have been introduced: to IgA nephropathy — proteinuria control with angiotensin-converting enzyme inhibitors (ACEi), tonsillectomy, rituximab, eculizumab; to focal segmental glomerulosclerosis — plasmapheresis, rituximab (CD20), ofatumumab (CD20), abatacept (CD80/86), belatacept (CD80/86), daratumumab (CD38); to membranous nephropathy — proteinuria control with ACEi, rituximab, calcineurin inhibitors, glucocorticoids, cyclophosphamide; to membranoproliferative glomerulonephritis — proteinuria control with ACEi; to C3 glomerulopathy — proteinuria control with ACEi, eculizumab. Specific provisions of the BK polyomavirus (BKPyV) guidelines were considered, in particular, monthly screening for BKPyV-DNAemia in blood plasma is suggested until month 9, then every 3 months until month 24, after which additional screening every 3 months until the end of the third year after transplantation in pediatric kidney recipients (C, weak). In pediatric patients with stable renal function and high BKPyV-DNAemia, despite reduction in immunosuppressive therapy, we suggest consideration of renal allograft biopsy, as creatinine elevation may be decreased in children with significant renal involvement, including rejection (A, strong).

KDOQI Commentary on the KDIGO 2022 Update to the Clinical Practice Guideline for Diabetes Management in CKD

The Kidney Disease: Improving Global Outcomes (KDIGO) guideline for diabetes management in chronic kidney disease (CKD) was updated in 2022, just 2 years after the previous update. The need for this rapid update is reflective of the recent and unprecedented positive results of numerous clinical trials aimed at reducing kidney and cardiovascular morbidity and mortality in people with diabetes. The Kidney Disease Outcomes Quality Initiative (KDOQI) work group for diabetes in CKD, convened by the National Kidney Foundation, provides herein a commentary on these changes, particularly the implications for health care in the United States. Changes to the KDIGO guideline mirror the evolution of sodium/glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists from purely antihyperglycemic agents to cardiorenal-metabolic therapeutics, and the lower estimated glomerular filtration rate of≥20mL/min/1.73m2 for SGLT2 inhibitor initiation. New data have also brought the addition of the first-in-class, Federal Drug Administration-approved nonsteroidal mineralocorticoid receptor antagonist finerenone as an agent to reduce cardiorenal end points. While there has been significant progress in innovation, there remain serious challenges to implementation, particularly in the United States where inequities in insurance coverage and high costs limit their use, particularly in vulnerable populations, ultimately widening health care disparities.

Optimizing Finerenone Therapy: A Comprehensive Review Using the “Finerenone Pentad”

Chronic kidney disease (CKD) is a pressing global health concern, often intertwined with comorbid conditions such as type 2diabetes mellitus (T2DM) and cardiovascular complications. Managing CKD in T2DM patients requires a multifaceted approach,and emerging therapeutic options are increasingly essential. Finerenone, a selective nonsteroidal mineralocorticoid receptorantagonist, has shown considerable promise in addressing the intricate cardiorenal needs of these patients. To maximize theeffectiveness of this therapy, we propose the approach of “Finerenone Pentad” which can be utilized as a checklist while startingand subsequently monitoring the finerenone therapy. This structured approach offers guidance on patient selection, monitoringand outcome evaluation, ensuring a holistic approach to the care of individuals with T2DM and CKD. 

Esaxerenone Protects against Diabetic Cardiomyopathy via Inhibition of the Chemokine and PI3K-Akt Signaling Pathway.

(1) Background: Diabetic cardiomyopathy (DCM) is a unique form of cardiomyopathy that develops as a consequence of diabetes and significantly contributes to heart failure in patients. Esaxerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has demonstrated potential in reducing the incidence of cardiovascular and renal events in individuals with chronic kidney and diabetes disease. However, the exact protective effects of esaxerenone in the context of DCM are still unclear. (2) Methods: The DCM model was successfully induced in mice by administering streptozotocin (55 mg/kg per day) for five consecutive days. After being fed a normal diet for 16 weeks, echocardiography was performed to confirm the successful establishment of the DCM model. Subsequent sequencing and gene expression analysis revealed significant differences in gene expression in the DCM group. These differentially expressed genes were identified as potential targets for DCM. By utilizing the Swiss Target Prediction platform, we employed predictive analysis to identify the potential targets of esaxerenone. A protein-protein-interaction (PPI) network was constructed using the common targets of esaxerenone and DCM. Enrichment analysis was conducted using Metascape. (3) Results: Compared to the control, the diabetic group exhibited impaired cardiac function and myocardial fibrosis. There was a total of 36 common targets, with 5 key targets. Enrichment analysis revealed that the chemokine and PI3K-Akt signaling pathway was considered a crucial pathway. A target-pathway network was established, from which seven key targets were identified. All key targets exhibited good binding characteristics when interacting with esaxerenone. (4) Conclusion: The findings of this study suggest that esaxerenone exhibits a favorable therapeutic effect on DCM, primarily by modulating the chemokine and PI3K-Akt signaling pathway.