Metabolic shifts in plasma amino acids and related metabolites in response to SGLT2 inhibition and hyperglycemia in type 1 diabetes.

Regulated kidney function is dependent on maintaining efficient energy utilization. Our aim in this study was to determine the effects of acute, ambient hyperglycemia and sodium-glucose cotransporter-2 (SGLT2) inhibition on plasma amino acid metabolism in patients with type 1 diabetes (T1D). The ATIRMA trial, a single-arm study, evaluated the effects of 8 weeks of oral empagliflozin (25 mg/day) in 40 young adults with T1D.

Advancing kidney protection in type 1 diabetes: insights from emerging therapies in type 2 diabetes and chronic kidney disease.

Introduction: For decades, the first-line treatment for kidney protection in people with type 1 diabetes (T1D) and chronic kidney disease (CKD) has been limited to intensive glycemic control, renin-angiotensin system blockers and managing modifiable risk factors. Accordingly, risk of CKD progression has remained unacceptably high, emphasizing the need for novel kidney protective therapies in T1D.

Areas Covered: This review summarizes the recent evidence supporting the use of existing treatments used for kidney protection in people with type 2 diabetes (T2D) for potential repurposing for people with T1D.

Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Emergency Department Visits and Hospitalization in Patients With Chronic Kidney Disease.

Objective: The aim of this study was to evaluate the effect of glucagon-like peptide 1 receptor agonist (GLP-1RA) versus dipeptidyl peptidase 4 inhibitor (DPP4i) initiation on emergency department (ED) visits and all-cause hospitalizations across the spectrum of kidney disease.

Research Design And Methods: This was a retrospective population-based observational cohort study in adults with an estimated glomerular filtration rate <90 mL/min/1.73 m2 using inverse probability of treatment weighting.

Effects of dapagliflozin on sodium excretion, blood pressure and volume status in patients with type 2 diabetes and/or chronic kidney disease: The DAPASALT trial.

Aims: We assessed the effects of dapagliflozin on natriuresis and blood pressure in patients with type 2 diabetes and chronic kidney disease (CKD) and evaluated the consistency of these effects across patients with type 2 diabetes without CKD and CKD without type 2 diabetes.

Materials And Methods: We conducted a mechanistic, nonrandomised, open-label study to evaluate the effects of dapagliflozin on sodium excretion and blood pressure in patients with type 2 diabetes and CKD under a standardised sodium intake (150 mmol/day). Evaluations were performed at baseline (average of Days -3 to -1), treatment start (average of Days 2-4; hereafter referred to as Day 4), treatment end (average of Days 12-14; hereafter referred to as Day 14) and washout (average of Days 15-17).

Mechanistic evaluation of ertugliflozin in patients with type 2 diabetes and heart failure.

The effect of sodium-glucose cotransporter-2 (SGLT2) inhibitor ertugliflozin on fluid volume and kidney function was assessed in patients with type 2 diabetes and heart failure. Thirty-four participants were randomized in this double-blind, placebo-controlled, parallel-group, multicenter study. Physiologic measurements were obtained under clamped euglycemia at baseline, 1 week, and 12 weeks of treatment.

Kidney hemodynamic effects of sodium-glucose cotransporter 2 inhibitors in diabetes: physiology and clinical implications.

The progressive loss of kidney function in diabetes mellitus is partly attributable to the occurrence of glomerular hyperfiltration. Consequently, therapeutic interventions that lower intra-glomerular pressure are a cornerstone of treatment in diabetic kidney disease. Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently reduce glomerular filtration rate (GFR) and calculated intraglomerular pressures across studies.

Modeling Cardiorenal Protection with Sodium-Glucose Cotransporter 2 Inhibition in Type 1 Diabetes: An Analysis of DEPICT-1 and DEPICT-2.

Key Points: Risk modelling analysis of DEPICT trials show that dapagliflozin reduced estimated cardiovascular and kidney disease risk in T1D persons. Greatest reduction in estimated ESKD risk was accompanied by an expected rise in eGFR, after 4 weeks post drug discontinuation. Dedicated outcome trials with SGLT2 inhibitors are warranted in T1D persons with CKD or CVD for best determination of efficacy and risks.

Upcoming drug targets for kidney protective effects in chronic kidney disease.

Unlabelled: People with chronic kidney disease (CKD) are at a high risk of heart disease and end-stage kidney disease. This review describes how new medications, such as glucagon-like peptide-1 receptor agonists (GLP1RA), aldosterone synthase inhibitors (ASi), soluble guanylate cyclase (sGC) and endothelin receptor antagonists (ERA), can lower heart-kidney risk in people with CKD. GLP1RA are already recommended for managing blood sugar in people with CKD and type 2 diabetes and have been shown to lower the risk of developing end-stage kidney disease.

Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD.

Key Points: Poor glycemic control in type 1 diabetes and CKD is associated with a higher risk of CKD progression. In a subgroup of inTandem participants with type 1 diabetes and CKD, adding sotagliflozin to insulin reduced HbA1c, body weight, and systolic BP without increasing severe hypoglycemia, compared with adding placebo. In participants with type 1 diabetes and CKD, sotagliflozin did not significantly increase the risk of DKA, however, there were a small number of diabetic ketoacidosis events.

Effects of ertugliflozin on uric acid and gout-related outcomes in persons with type 2 diabetes and cardiovascular disease: Post hoc analyses from VERTIS CV.

Aim: To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout-related outcomes.

Materials And Methods: Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.

Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors for the treatment of diabetes mellitus in liver transplant recipients.

Aim: To investigate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors in liver transplant (LT) recipients with diabetes.

Methods: A single-centre, retrospective analysis of prospectively collected data from an LT recipient database (1990-2023) was conducted. We included adults with pre-existing diabetes and post-transplant diabetes, newly started on GLP-1RAs and/or SGLT2 inhibitors after LT.

Effect of hyperglycemia and empagliflozin on markers of cardiorenal injury and inflammation in patients with type 1 diabetes.

Aims: To investigate the effect of hyperglycemia and empagliflozin on cardiorenal injury and inflammation in patients with uncomplicated type 1 diabetes (T1D).

Methods: Serum cardiac (sST2, Gal-3, cTnT), kidney injury (KIM-1, NGAL), inflammatory (sTNFR1, sTNFR2), and hemodynamic (NT-proBNP, EPO) markers were assessed post-hoc in two separate T1D cohorts. The glycemic clamp trial (NCT02344602) evaluated 49 adults with T1D and 27 controls under euglycemic and acute hyperglycemic conditions.

Inflammation in heart failure: pathophysiology and therapeutic strategies.

A role for inflammation in the development and progression of heart failure (HF) has been proposed for decades. Multiple studies have demonstrated the potential involvement of several groups of cytokines and chemokines in acute and chronic HF, though targeting these pathways in early therapeutic trials have produced mixed results. These studies served to highlight the complexity and nuances of how pro-inflammatory pathways contribute to the pathogenesis of HF.

Proximal versus distal diuretics in congestive heart failure.

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.

Should Transplant Nephrology Pursue Recognition from the Accreditation Council for Graduate Medical Education (ACGME)?

Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology.

Minireview: Understanding and targeting inflammatory, hemodynamic and injury markers for cardiorenal protection in type 1 diabetes.

The coexistence of cardiovascular disease (CVD) and diabetic kidney disease (DKD) is common in people with type 1 diabetes (T1D) and is strongly associated with an increased risk of morbidity and mortality. Hence, it is imperative to explore robust tools that can accurately reflect the development and progression of cardiorenal complications. Several cardiovascular and kidney biomarkers have been identified to detect at-risk individuals with T1D.

Interactive Effects of Empagliflozin and Hyperglycemia on Urinary Amino Acids in Individuals With Type 1 Diabetes.

Optimizing energy use in the kidney is critical for normal kidney function. Here, we investigate the effect of hyperglycemia and sodium-glucose cotransporter 2 (SGLT2) inhibition on urinary amino acid excretion in individuals with type 1 diabetes (T1D). The open-label ATIRMA trial assessed the impact of 8 weeks of 25 mg empagliflozin orally once per day in 40 normotensive normoalbuminuric young adults with T1D.

Chronic kidney disease in type 1 diabetes: translation of novel type 2 diabetes therapeutics to individuals with type 1 diabetes.

Current management of chronic kidney disease (CKD) in type 1 diabetes centres on glycaemic control, renin-angiotensin system inhibition and optimisation of risk factors including blood pressure, lipids and body weight. While these therapeutic approaches have significantly improved outcomes among people with type 1 diabetes and CKD, this population remains at substantial elevated risk for adverse kidney and cardiovascular events, with limited improvements over the last few decades. The significant burden of CKD and CVD in type 1 diabetes populations highlights the need to identify novel therapies with the potential for heart and kidney protection.