Advancements in diabetic kidney disease management: integrating innovative therapies and targeted drug development.

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and affects approximately 40% of individuals with diabetes . Cases of DKD continue to rise globally as the prevalence of diabetes mellitus increases, with an estimated 415 million people living with diabetes in 2015 and a projected 642 million by 2040. DKD is associated with significant morbidity and mortality, representing 34% and 36% of all chronic kidney disease deaths in men and women, respectively. Common comorbidities including hypertension and ageing-related nephron loss further complicate disease diagnosis and progression. The progression of DKD involves several mechanisms including glomerular endothelial cell dysfunction, inflammation, and fibrosis. Targeting these mechanisms has formed the basis of several therapeutic agents. Renin-angiotensin-aldosterone system (RAAS) blockers, specifically angiotensin receptor blockers (ARBs), demonstrate significant reductions in macroalbuminuria. Sodium-glucose transporter type 2 (SGLT-2) inhibitors demonstrate kidney protection independent of diabetes control while also decreasing the incidence of cardiovascular events. Emerging agents including glucagon-like peptide 1 (GLP-1) agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, lixudebart, and tozorakimab; mesenchymal stem/stromal cell infusion; and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development.

Worsened short-term clinical outcomes in a cohort of patients with iNO-unresponsive PPHN: a case for improving iNO responsiveness.

OBJECTIVES: To identify distinguishing characteristics of neonates with persistent pulmonary hypertension of the newborn (PPHN) unresponsive to inhaled nitric oxide (iNO) and evaluate the use of milrinone in this cohort. STUDY DESIGN: Retrospective chart review of 99 neonates with PPHN treated with iNO over a five-year period at a quaternary neonatal intensive care unit. RESULTS: Neonates with iNO-unresponsive PPHN had an increased number of ventilator days (10 vs 7 days, p = 0.02), greater length of hospital stay (30 vs 22 days, p = 0.02), and increased risk of death or ECMO than iNO-responsive neonates (p = 0.03). Inhaled NO non-responders treated with milrinone had improved oxygenation (p < 0.03) and no change in systemic hemodynamics. CONCLUSION: Neonates with iNO-unresponsive PPHN had worse clinical outcomes than iNO responders. Milrinone may be a safe and effective adjuvant therapy, although large-scale studies are lacking. Identifying early predictors of iNO response and novel strategies to enhance iNO responsiveness should be prioritized.

Linking the Perinatal Environment to Neonatal Cardiovascular Outcomes.

Cases of high-risk pregnancies continue to rise throughout the United States and globally, increasing rates of maternal and neonatal morbidity. Common pregnancy complications and morbidities include preterm birth, hypertensive disorders, fetal growth restriction, diabetes mellitus, and chorioamnionitis. Exposure to these perinatal conditions contributes to cardiac morbidities in the fetus and neonate, including altered cardiac growth, congenital heart disease, and cardiac dysfunction. Significant research has demonstrated lasting effects of these pregnancy complications, with increased rates of cardiac morbidities seen in children and adults after these perinatal exposures. The link between the perinatal environment and long-term outcomes has not been fully elucidated. The aim of this review is to discuss the current understanding of the implications of a high-risk pregnancy on fetal and neonatal cardiac development.