The human kidney is a significant organ in the body, carrying out essential functions such as homeostasis and blood filtration through a network of many nephrons. Renal hormonal interactions also regulate other body physiological features. The kidney is prone to several chronic illnesses. This lack of renal activity can lead to anemia, cardiovascular risks, bone diseases, and dietary issues. Since the only available treatments are dialysis and kidney transplant, it has placed significant pressure on the healthcare system. Making methods to comprehend and model human kidney disorders has become a goal in medicine.
There hasn’t been a medication for Autosomal Dominant Polycystic Kidney Disease (ADPKD) sufferers until recently.
The drug tolvaptan, approved in 2018, proves effective in only a subset of ADPKD patients in reducing disease progression. Therefore, broader-acting drugs are required to combat cyst formation and growth in the kidney.
According to a recent study published online at Cell Stem Cell, scientists have created organoids, which are miniature kidney-like structures, to find possible medications for treating adult-onset polycystic kidney disease.
Organoids demonstrate disease processes and potential therapeutics for ADPKD
Chronic renal disease burdens the healthcare system. Despite these difficulties, the search for viable medications has made very little progress. One of the most prevalent autosomal dominant gene variants in the human population is ADPKD.
The adult-onset form of polycystic kidney disease, which affects 8 million people globally, has an “autosomal dominant” pattern of inheritance, which arises when a person gets a faulty copy of the PKD1 or PKD2 gene, and the function of the second good copy also disappears.
Large fluid-filled cysts develop in numerous parts of the kidney due to ADPKD, which also poses a significant risk to the liver, pancreas, and heart.
Human pluripotent stem cells, which may either divide to produce more stem cells or differentiate into a wide variety of specialized cells, were used as the study’s starting point. These pluripotent stem cells were employed to create organoids with one or more nephron-like structures, which are the filtering cells of the kidney.
These organoids are straightforward, repeatable, scalable, and reasonably priced. Most notably, the organoids can accurately mimic crucial features of both cyst formation in ADPKD and human kidney growth.
The researchers then conducted the initial screening to find possible treatment agents for ADPKD using gene-edited human organoids, concentrating on a group of enzyme inhibitors to provide a detailed understanding of the cellular mechanisms regulating cyst formation.
The researchers discovered nine compounds that slowed the formation of the cysts without impairing the organoids’ overall growth after they tested a collection of 247 enzyme inhibitor compounds on the organoids.
The findings of this new study are helpful in the search to develop broader-acting drugs for ADKPD. The limitations of the currently used medications, and the burden of dialysis and kidney transplanting, can be reduced significantly with newer drugs targeted at better therapeutic outcomes for chronic kidney conditions.
The study scientists successfully developed a mini kidney that allowed for an investigation into the mechanism of ADKDP. They also showed a potential for more effective drug discovery to treat patients with polycystic kidney diseases.