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Abstract: TH-PO433

Omics Profiling of Tolvaptan-Treated Autosomal Dominant Polycystic Kidney Disease Patients

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic


  • Lu, Tzongshi, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Huang, Jiun-Chi, Brigham and Women's Hospital, Boston, United States
  • Li, Yi, Brigham and Women's Hospital, Boston, Massachusetts, United States

Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening genetic kidney disease and the fourth leading cause of kidney failure. Dialysis or transplant are current treatments for end-stage ADPKD patients, and no other ideal efficient therapeutic strategy exists. The selective vasopressin V2-receptor antagonist, Tolvaptan, was used to treat hyponatremia in heart failure but was approved by FDA for ADPKD treatment in 2018; however, there are limitations for ADPKD patients to receive Tolvaptan treatment and its significant side effects severely affect patient's life quality. In this study, we use omics tools to discover potential therapeutic targets with fewer side effects for ADPKD patients.


Tolvaptan was started with the 45-0-15 dose, then titrated to 60-0-30 after two months. Blood and urine were collected before Tolvaptan treatment and 2, 3, 6, 9, and 12 months after treatment. Omics profiling was performed using SureSelect XT HS2 mRNA Library Preparation kit (Agilent, USA) and sequenced on Nextseq. Differential expression analysis was performed using StringTie and DEseq2 with Welgene Biotech's in-house pipeline. Genes with p-value < 0.05 and > 2.0-fold changes were considered significantly differentially expressed. Functional enrichment assay was performed using cluster Profiler v3.6.


Our data indicate that cytoskeleton-regulating proteins and junctional proteins: NBPF10, RGPD2, MYH1, NPIPB9, SLC9B1P1, and TUBB7P were involved in the regulation of cystogenesis in Tolvaptan-treated ADPKD patients. In addition, the downstream junctional and cytoskeleton regulating genes of the above proteins (Log2 ratio: CRB3, 11.01; CLDN10,10.09; MAPK10, 7.34; FGF17, 9.47; MYH14, 7.04) were significantly (p<0.05) preserved after Tolvaptan treatment that may be involved in the regulation of calcium, Rho GTPases, and PAK Pathway signaling. Furthermore, Hypoxanthine, Creatine, L-a-aminobutyric acid, and Trimethylamine N-oxide were significantly decreased in our metabolomics data analysis, showing paracellular transportation in kidney cells was inhibited.


Our data shows Tolvaptan treatment regulates the integrity of tight junctions and paracellular transportation of kidney cells. It elucidates the possible targets in inhibiting side effects and provides novel therapeutic targets that may be served in ADPKD treatments with fewer side effects.


  • Private Foundation Support