Introduction: Current treatment strategies for chronic kidney disease ( CKD ) focus on controlling risk factors, and diabetes is the main cause of CKD progression to end-stage renal disease. SZ-A, a natural medicine for type 2 diabetes approved by the China National Products Administration in 2020, exerts protective effects against the development of diabetic nephropathy. However, the mechanism and whether SZ-A has an effect on kidney damage independent of its glucose-lowering effect have not been thoroughly elucidated. This study aims to evaluate the efficacy of SZ-A in slowing the progression of nondiabetic CKD.

Methods: A rat model of chronic kidney disease induced by adenine was established, and treated with SZ-A or control medication: acarbose or dapagliflozin, daily oral gavage for four weeks. Kidneys from all groups of rats were functionally evaluated and harvested for transcriptome sequencing analysis at the end of the experiment.

Results: Chronic adenine dosing resulted in severe CKD in vehicle-treated rats, as evidenced by significant increases in serum creatinine and UACR. SZ-A dose-dependently attenuated renal injury independent of glucose-lowering effects. This effect of the highest dose of SZ-A was comparable to that of dapagliflozin, whereas acarbose had no effect. In addition, renal fibrosis and inflammation were improved in the SZ-A treatment group compared to the model group. Transcriptomic analysis showed that the renoprotective effect of SZ-A was associated with the upregulation of PPAR signaling pathway and the inhibition of inflammation; in addition, the PPAR signaling pathway was closely related to FAO and mitochondrial homeostasis, and the ameliorative effect of SZ-A on both was verified at both tissue and cellular levels of rat kidney.

Conclusions: The fact that SZ-A is able to attenuate CKD progression in the adenine-induced model corroborates its potential as a therapeutic renoprotector.

Disclosure

J. Song: None. J. Ye: None. Y. Tang: None. X. Xiao: None. Y. Liu: None.

Funding

CAMS Innovation Fund for Medical Sciences (CIFMS, no. 2021-I2M-1-028)

© 2024 by the American Diabetes Association
2024
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