Could a better understanding of kidney development uncover mechanisms for forming new nephrons?
Dr Sayyid Ammar Raza from the University of Manchester has received a start-up grant of £40,000 to look at how new nephrons (the tiny filtration units of the kidney) are formed to improve our knowledge of how this process works. Ultimately, the team hope to look at whether this knowledge can be applied to kidney disease in humans.
The problem
Chronic kidney disease (CKD) impacts more than 7 million people in the UK, often with serious outcomes. Most cases of CKD cause the loss of nephrons, which results in decreased kidney function. At birth, humans have approximately 1-2 million nephrons, although this number varies between individuals. Nephrons are lost as part of the aging process and also during some diseases. This means that remaining nephrons must work harder to filter waste products, and this added strain can lead to further nephron loss. Currently we cannot replace lost nephrons.
Mesonephri
During human development in the womb, three ‘versions’ of the kidneys are formed. In each version the kidney tissue becomes more complex and specialised. The second version of the kidneys is called the mesonephros. In humans, the mesonephros is lost when it is replaced by the final version of the kidneys but can remain as the adult kidney in some types of animals, including fish.
This means that fish can form new nephrons in response to loss or damage, whereas humans cannot. Scientists have studied mesonephri in zebrafish and saw that when damaged, new nephrons formed as a result of expressing a particular gene. The genes and pathways expressed in cells of the human mesonephros are not well understood.
The solution
Dr Raza and the team previously studied human mesonephri using a technique called spatial transcriptomics - which identifies which genes are turned on or off in cells in different situations.
They found the same genes expressed in zebrafish when forming new nephrons were also expressed in human mesonephri. With our support, they will explore this further by studying human mesonephri with more advanced spatial transcriptomics.
This will allow a greater understanding of which genes are expressed by which cells during the development of new nephrons in the human mesonephros.
What does this mean for kidney patients?
Identifying the underlying mechanisms involved in the development of new nephrons in humans is the first step to understanding whether this approach could be developed and used in people living with CKD.
“Studying how new nephrons are formed in very early human development will give us the knowledge to better understand if and how we could in the future take this approach in people with damaged kidneys. I would like to thank Kidney Research UK for supporting this work and look forward to sharing my results with the kidney community.” Dr Sayyid Ammar Raza
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