Cross-Species Insights into Autosomal Dominant Polycystic Kidney Disease: Provide an Alternative View on Research Advancement

Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent hereditary disorder that affects the kidneys, characterized by the development of an excessive number of fluid-filled cysts of varying sizes in both kidneys. Along with the progression of ADPKD, these enlarged cysts displace normal kidney tissue, often accompanied by interstitial fibrosis and inflammation, and significantly impair renal function, leading to end-stage renal disease. Currently, the precise mechanisms underlying ADPKD remain elusive, and a definitive cure has yet to be discovered. This review delineates the epidemiology, pathological features, and clinical diagnostics of ADPKD or ADPKD-like disease across human populations, as well as companion animals and other domesticated species. A light has been shed on pivotal genes and biological pathways essential for preventing and managing ADPKD, which underscores the importance of cross-species research in addressing this complex condition. Treatment options are currently limited to Tolvaptan, dialysis, or surgical excision of large cysts. However, comparative studies of ADPKD across different species hold promise for unveiling novel insights and therapeutic strategies to combat this disease.

Keywords: ADPKD; cross-species research; therapeutic strategies.

Figure 1

Schematics of PC-1 and PC-2 with labeled domains. The schemas of PC-1 and PC-2 illustrate their complex structures and key domains. Both proteins interact through coiled-coil domains in their tails, critical for calcium signaling, which is disrupted in polycystic kidney disease. The pictures in this paper were created through the FigDraw website, https://www.figdraw.com/static/index.html#/ (accessed on 11 January 2024).

Figure 2

Hereditary mode of ADPKD. Autosomal dominant inheritance is a genetic pattern in which a trait or disorder is passed down through families. In this pattern, one copy of the altered gene in each cell is sufficient to increase the risk of developing a condition. Autosomal dominant conditions can occur in every generation of an affected family, and the risk of passing the condition from an affected parent to a child is 50%. Blue dots: normal genes; pink dots: pathogenic genes. The pictures in this paper were created through the FigDraw website, https://www.figdraw.com/static/index.html#/ (accessed on 13 January 2024).

Figure 3

Molecular mechanism of ADPKD. In ADPKD, altered levels of Ca²⁺ and elevated cAMP contribute to disease progression. Dysregulated calcium signaling can lead to increased cell proliferation and changes in extracellular matrix metabolism, promoting kidney cyst growth. Concurrently, increased cAMP levels activate PKA, which further stimulates cell proliferation and extracellular matrix secretion. The interplay between dysregulated calcium and elevated cAMP creates a harmful loop that intensifies renal damage in ADPKD, offering potential targets for therapeutic intervention to normalize these pathways and stop disease advancement. The pictures in this paper were created through the FigDraw website, https://www.figdraw.com/static/index.html#/ (accessed on 21 May 2024).

Figure 4

Ultrasonographic image of the felines’ kidneys. The first two images show the normal kidneys of felines. Red arrows indicate cysts in the kidney.

Figure 5

Contrast enhanced computed tomography of the pigs’ kidneys and livers. Red arrows indicate cysts in the kidney; blue arrows indicate cysts in the liver.