Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Panel A Pkd1-flox mice were bred with Cdh16-CreERT2 mice, followed by tamoxifen induction to establish an ADPKD mouse model with kidney-specific Pkd1 knockout. Phenotype validation data were collected as shown in the study design.

Panel B By 85 days (~12 weeks) post tamoxifen induction, serum BUN and CREA levels were significantly increased in Pkd1:fl/fl Cdh16-CreER(T2):ki/wt male mice, indicating impaired renal function.

Panel C Urine mALB and UACR (mALB/CREA) levels were significantly increased in Pkd1:fl/fl Cdh16-CreER(T2):ki/wt mice, with levels increasing with age, indicating impaired renal function.

Panel D At day 50, renal volumes were significantly increased in Pkd1:fl/fl Cdh16-CreER(T2):ki/wt female mice. Renal volumes in Pkd1:fl/fl Cdh16-CreER(T2):ki/wt male mice exceeded the upper limit of ultrasound detection (data not shown).

Panel E Significant pathological phenotypes, including the presence of multiple cysts, protein casts, and tubular atrophy, were observed in Pkd1:fl/fl Cdh16-CreERT2:ki/wt model mice.

Statistical analysis was performed using one‑way ANOVA, and all data presented as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001，****p<0.0001

E

Panel A  The efficacy of tolvaptan was evaluated in male diseased mice according to the study design.

Panel B Serum BUN and CREA levels were elevated 86 days after tamoxifen induction, and tolvaptan significantly reduced these parameters.

Panel C Renal ultrasonography revealed increased renal volume, and tolvaptan ameliorated the renal phenotype.

Panel D The kidney cystic index was markedly increased in the disease group at the study endpoint, while tolvaptan rescued this phenotype.

Panel E Intrarenal administration technology enables precise drug delivery.

Statistical analysis was performed using one‑way ANOVA, and all data are presented as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001，****p<0.0001