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Kidney Volume and Molecular Processes are Dynamic in ADPKD
Journal article   Peer reviewed

Kidney Volume and Molecular Processes are Dynamic in ADPKD

Ali Tug, Jamie Zheng, Yahya Alsawaf, Jared Lutsic, Athreya Rangavajhula, Nalin Sharma, Youwen Zhang, Ivan Vuckovic, Slobodan Macura, Christian Hanna, …
Kidney international reports, Vol.11(6), p.106376
06/01/2026
DOI: 10.1016/j.ekir.2026.106376
PMID: 42058116
url
https://doi.org/10.1016/j.ekir.2026.106376View
Published (Version of record) Open Access

Abstract

Although progress has been made toward elucidating cellular pathways related to initial cystogenesis in autosomal dominant polycystic kidney disease (ADPKD), the mechanisms that contribute to disease progression and the timing of transitions remain largely unclear. We hypothesized that the predominant kidney biological processes in Pkd1RC/RC and other ADPKD models are highly dynamic throughout the disease, providing insights into the resulting kidney phenotype and conform well to those observed in human ADPKD. Kidney volume changes by class and age were determined in a large, well-characterized cohort of individuals with ADPKD and long follow-up. Similarly, Pkd1RC/RC and wild-type (WT) mice were studied longitudinally, and their kidney volume changes and function analyzed. Kidney mRNA profiles (mRNA-sequencing [mRNA-seq]) of Pkd1RC/RC mice were investigated at early, mid, and late stages, compared with those reported in other ADPKD models and humans with ADPKD. In most individuals with ADPKD, kidney volume continues to increase; however, the rate of growth differs between classes and within severe classes by age. Kidney volume and function changes in Pkd1RC/RC mice conform well to the kidney volume changes in class 1C patients during adulthood. The kidney transcriptomic profile in Pkd1RC/RC mice evolves over the course of the disease, underscoring their highly dynamic kidney phenotype, presents several commonalities with other ADPKD models, and is relevant to human ADPKD. Our study suggests that, in ADPKD, different therapeutic strategies might be beneficial at different disease stages and identifies target candidate pathways for biomarker discovery that could be further investigated in humans. [Display omitted]
 cell cycle and proliferation cell metabolism inflammation kidney volume mRNA polycystic kidney disease

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