Kidney Week Educational Symposia-Update on Genetic Architecture and Therapy of Polycystic Kidney Diseases

Video Transcription

Video Summary

The symposium “Update on Genetic Architecture and Therapy of Polycystic Kidney Diseases” featured Dr. Lisa Guay-Woodford on PKD genetics and Dr. Vicente Torres on treatment advances.<br /><br />Guay-Woodford reviewed autosomal dominant PKD (ADPKD; ~1/800–1/1000), most commonly caused by PKD1, less often PKD2, and rarely GANAB, DNAJB11, or ALG9. Disease severity reflects “gene dosage,” including hypomorphic alleles and digenic inheritance (e.g., PKD1+PKD2), plus modifier genes, somatic variation, environment, and kidney injury. She noted emerging links between PKD and mitochondrial dysfunction/metabolic reprogramming. Genetic testing is useful for unclear diagnoses, early severe disease, donor evaluation, suspected phenocopies, and trial enrollment. Genotype contributes to prognostic models (e.g., PRO-PKD), with newer imaging/genotype approaches improving prediction, especially for younger patients.<br /><br />For autosomal recessive PKD (ARPKD; ~1/26,500), most cases involve PKHD1, with rarer DZIP1L and CYS1. Missense-variant position in PKHD1 correlates with renal versus hepatic severity; truncating variants often predict worse outcomes. Phenocopies (notably PKD1 and HNF1B) complicate diagnosis, supporting broader gene panels and future ARPKD prognostic scoring.<br /><br />Torres summarized therapies targeting cAMP/calcium pathways. Tolvaptan (TEMPO, REPRISE) slows kidney growth and eGFR decline, with evidence of benefit even in advanced CKD and suggestive pediatric results. Somatostatin analogs reduce kidney and liver volume growth, with mixed eGFR effects. Many other trials were negative/limited. Emerging strategies include PDE activation, PKA/CREB inhibition, microRNA targeting, NRF2/redox modulation, and metabolic interventions, requiring larger, well-powered clinical trials.

Asset Subtitle

Moderators: Rasheed Gbadegesin

Speakers:

Introduction - Rasheed Gbadegesin
Genetic Architecture of PKD - Lisa Guay-Woodford
Recent Advances in the Treatment of PKD - Vicente Torres

Meta Tag

Date 11/4/2021

Pathway 1 Genetic Diseases of the Kidneys

Session ID 408979

Session Type ES - Educational Symposium

Keywords

polycystic kidney disease

ADPKD genetics

ARPKD PKHD1

PKD1 PKD2 variants

gene dosage and modifier genes

genetic testing and prognostic models

tolvaptan therapy

somatostatin analogs

cAMP calcium signaling targets