Endocrinology Research Analysis
September’s endocrinology literature (limited weekly coverage) converged on kidney-centric endocrine–cardiometabolic axes. A microbiota-derived peptide (corisin) linked to cellular senescence emerged as a druggable mediator of diabetic kidney fibrosis with monoclonal antibody proof-of-concept in mice. A mechanistic study connected branched-chain amino acid dysmetabolism to podocyte PKM2-driven apoptosis, nominating metabolic restoration strategies for DKD. Clinically, a phase 3 RCT of the aldost
Summary
September’s endocrinology literature (limited weekly coverage) converged on kidney-centric endocrine–cardiometabolic axes. A microbiota-derived peptide (corisin) linked to cellular senescence emerged as a druggable mediator of diabetic kidney fibrosis with monoclonal antibody proof-of-concept in mice. A mechanistic study connected branched-chain amino acid dysmetabolism to podocyte PKM2-driven apoptosis, nominating metabolic restoration strategies for DKD. Clinically, a phase 3 RCT of the aldosterone synthase inhibitor baxdrostat showed meaningful blood pressure reductions in uncontrolled/resistant hypertension, positioning a potential first-in-class add-on therapy.
Selected Articles
1. Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension.
In a phase 3, double-blind, multinational RCT (n=794), baxdrostat 1–2 mg achieved placebo-corrected seated systolic BP reductions of approximately 8.7–9.8 mmHg at 12 weeks in uncontrolled/resistant hypertension, with modestly increased hyperkalemia versus placebo.
Impact: Delivers high-level evidence for a first-in-class aldosterone synthase inhibitor with clinically meaningful BP lowering in difficult-to-control hypertension.
Clinical Implications: Supports a new add-on option for resistant hypertension, particularly in aldosterone-driven phenotypes; requires routine potassium monitoring and longer-term outcomes.
Key Findings
- Placebo-corrected seated SBP reduction of −8.7 to −9.8 mmHg at 12 weeks (P<0.001).
- Hyperkalemia rates were low but higher than placebo.
- Consistent BP lowering on top of multidrug backgrounds including diuretics.
2. Microbiota-derived corisin accelerates kidney fibrosis by promoting cellular aging.
Translational work identifies corisin as elevated in diabetic CKD and mechanistically linked to fibrosis via senescence, EMT, and apoptosis; an anti-corisin monoclonal antibody reduced nephropathy severity in diabetic mice.
Impact: Connects the microbiome to DKD pathogenesis and delivers a druggable target with in vivo antibody proof-of-concept.
Clinical Implications: Positions serum corisin for DKD risk stratification and supports early-phase development of anti-corisin biologics pending safety evaluation.
Key Findings
- Serum corisin correlates with DKD stage and renal function decline.
- Anti-corisin mAb attenuates inflammation and fibrosis in diabetic mice.
- Corisin binds albumin and promotes senescence, EMT, and apoptosis in kidney cells.
3. Branched-chain amino acids contribute to diabetic kidney disease progression via PKM2-mediated podocyte metabolic reprogramming and apoptosis.
Mechanistic work links podocyte BCAA catabolic defects to DKD initiation through PKM2 depolymerization, metabolic diversion, and DDIT3–Chac1/Trib3-driven apoptosis, suggesting restoration of BCAA catabolism and PKM2 activation as therapeutic strategies.
Impact: Defines an actionable metabolic axis (BCAA–PKM2) connecting nutrient excess to podocyte apoptosis and DKD progression.
Clinical Implications: Warns against high-dose BCAA supplementation in diabetes and prioritizes development of PKM2 activators or BCAA catabolism–restoring approaches.
Key Findings
- Human DKD podocytes and db/db mice exhibit BCAA catabolic defects.
- Podocyte PP2Cm knockout or BCAA excess induces DKD phenotypes in mice.
- BCAAs trigger PKM2 depolymerization and nuclear PKM2–DDIT3 signaling to activate apoptosis programs.