Cardiorenal Syndrome

(A) Body weight: Lepr(-/-) groups gained more weight. (B) Blood glucose: severe hyperglycemia in the Lepr(-/-) groups. (C) UACR: marked increase, most severe in BKS-db+AAV-mREN and BKS-db+UNX+AAV-mREN group. (D) Survival curve of BSK+Vehicle, BKS-db+AAV-mREN and BKS-db+UNX+AAV-mREN.

H&E-stained sections at 5 and 8 weeks post-administration. Control (BKS) muscle shows normal architecture. The model group (BKS-Lepr-/- + AAV-mRenin) exhibits progressive fibrosis: interstitial, perivascular, and severe replacement fibrosis, which is more extensive at 8 weeks.

Kidney sections from three groups: Control (BKS), Model 1 (BKS-Lepr-/- + AAV-mRenin), and Model 2 (BKS-Lepr-/- + UNx + AAV-mRenin). H&E (shows inflammation, black arrows), PAS (highlights glomerulosclerosis, red arrows; and tubular casts, blue arrows), and Masson's trichrome (collagen/fibrosis in blue). Pathology severity increases in both models.

Bar graphs (5 & 8 wpa) for groups: BKS (●), BKS-Lepr-/- + AAV-mRenin (▼), BKS-Lepr-/- + UNx + AAV-mRenin (△). Parameters: glomerulopathy, tubular protein (cast), tubular basophilia, interstitial inflammation, and interstitial fibrosis scores.

Retatrutide, Lisinopril, and Empagliflozin all improved injury/fibrosis phenotypes. Empagliflozin reduced protein casts and glomerulosclerosis. Retatrutide showed no glomerulosclerosis and markedly fewer casts. Lisinopril nearly reversed the injury phenotype.

Empagliflozin significantly reduced glomerulosclerosis and inflammation scores. Retatrutide lowered all scores except interstitial fibrosis. Lisinopril restored all indices to near-control levels, with only interstitial fibrosis mildly elevated.

Retatrutide and Lisinopril effectively reversed hypertrophy, evidenced by reduced wall thickness and LV mass, with altered chamber volumes and function. Empagliflozin provided milder improvement.

(A) Experimental timeline. (B) Body weight: STZ+AAV-mREN group shows significant weight loss vs. control. (C) Induced group exhibits significantly reduced survival post-induction.

(A) Postprandial blood glucose, (B) Blood pressure, and (C-D) UACR levels are all significantly elevated in the experiemntal group compared to control. Data shows increased glycemia, BP, and renal injury markers.

(A) HW, KW, and HW/BW ratio are significantly elevated vs. control. (B) Gross morphology shows enlarged heart/kidney; HE staining reveals protein casts and glomerulosclerosis. (C) Renal pathology scores are significantly increased across all indices.