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1.
Am J Physiol Endocrinol Metab ; 326(6): E791-E806, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38630049

ABSTRACT

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.


Subject(s)
Diabetic Nephropathies , Drug Development , Humans , Diabetic Nephropathies/drug therapy , Angiotensin Receptor Antagonists/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Therapies, Investigational/trends , Therapies, Investigational/methods , Mineralocorticoid Receptor Antagonists/therapeutic use , Renin-Angiotensin System/drug effects , Hypoglycemic Agents/therapeutic use
2.
Genes (Basel) ; 15(1)2024 01 11.
Article in English | MEDLINE | ID: mdl-38254980

ABSTRACT

Renal cystic diseases (RCDs) can arise from utero to early adulthood and present with a variety of symptoms including renal, hepatic, and cardiovascular manifestations. It is well known that common RCDs such as autosomal polycystic kidney disease and autosomal recessive kidney disease are linked to genes such as PKD1 and PKHD1, respectively. However, it is important to investigate the genetic pathophysiology of how these gene mutations lead to clinical symptoms and include some of the less-studied RCDs, such as autosomal dominant tubulointerstitial kidney disease, multicystic dysplastic kidney, Zellweger syndrome, calyceal diverticula, and more. We plan to take a thorough look into the genetic involvement and clinical sequalae of a number of RCDs with the goal of helping to guide diagnosis, counseling, and treatment.


Subject(s)
Polycystic Kidney Diseases , Humans , Adult , Kidney , Genes, Regulator , Transcription Factors , Inheritance Patterns
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