Awardees
 

Award: KRESCENT Post-Doctoral Fellowship
Supervisor(s) :  Benjamin Humphreys, Kory Lavine
Institution: Washington University in St. Louis
Year: 2024 - 2027

Project Title:  The macrophage niche and its role in repair after ischemic AKI

Biography
Waleed Rahmani is an academic nephrologist focused on the immune system's role in kidney fibrosis after acute kidney injuries. He earned his BSc in Biochemistry and Microbiology from the University of Victoria and completed a joint MD/PhD in Stem Cell Biology and Regenerative Medicine from the University of Calgary in 2019. His thesis explored dermal stem cells and macrophages during skin and hair follicle regeneration. In 2024, he finished his Adult Nephrology Residency at the University of Calgary and will start a post-doctoral research fellowship at Washington University School of Medicine with Dr Benjamin Humphrey’s and Kory Lavine where he will learn cutting-edge multi-omic approaches while studying the innate immune system after ischemic kidney injuries.

Waleed has received several awards, including the Internal Medicine Research Award, the Helios Post-Fellowship award, and the Krescent Post-doctoral award. He has numerous publications, given multiple national and international conference presentations and hosts The Canadian Kidney Discoveries Network’s “Kidney Corner,” a video blog where Canadian leaders in kidney disease research are interviewed. Ultimately, he aims to establish a Regenerative Nephrology research program focused at understanding regenerative failure in kidney diseases and preventing end-stage kidney failure.

Lay Summary
Introduction: Chronic kidney disease affects approximately 4 million Canadians and nearly 13% of the global population. After a sudden kidney injury, the risk of developing chronic kidney disease rises by 30-40%. This is partly because the cells most susceptible to injury, tubular cells, have a limited ability to regenerate. Recent studies discovered a small number of tubular cells fail to repair after injury and remain inflammatory months after. It is thought that these inflammatory unrepaired cells cause the transition to chronic kidney disease by increasing the amount of scarring. We are just beginning to learn more about these cells.
 
Another important cell involved in healing after kidney injuries is a specific immune cell called a macrophage. These are diverse cells with many different roles in the kidney. In the first few days after injury, they help with healing by clearing the debris of damaged and dead cells. But in later stages, especially if their inflammatory signal lasts too long, they can worsen scarring and cause chronic kidney disease. A lot of research has been done in mice to understand how kidney macrophage react to injury, but little is known in human kidneys. Early results suggest that unrepaired tubular cells directly communicate with macrophage. In fact, it appears they can send alarm signals to recruit macrophage from the blood to the site of injury. We suspect that this relationship contributes to scarred healing and the risk for chronic kidney disease.
 
Purpose No medicine exists to stop scarring after an abrupt kidney injury. The goal of our research is to discover how macrophage and injured tubular cells conspire to create scar after a kidney injury. This is important so one day we can develop drugs that reprogram the relationship between these cells to prevent scarring and chronic kidney disease.
 
Method: To study injured tubular cells and macrophage after an acute kidney injury, we will injure mice kidneys by temporarily stopping blood flow to them. We will also use kidney biopsies from patients with similar injuries caused by reduced kidney blood flow. Like map makers, we will make high-resolution atlases of these injured kidneys using advanced biologic and statistical approaches. First, we will generate 3-dimensional coordinates that pinpoint the location of every cell within thin slices of kidneys. Then, we will layer genetic and epigenetic information of each cell on this map. It is like using Google maps “traffic view” or “terrain view”; each layer gives more information so pedestrians can navigate cityscapes. The atlas will allow us to zoom in on different parts of the kidney at very high-resolution and study how macrophage and injured tubular cells conspire to cause scarring and chronic disease after the acute injury. It is like using Google maps “street view” to investigate crime scenes in different neighbourhoods across a city.
 
Anticipated Outcomes: We hope to build high-resolution immune atlas of human and mouse kidneys during kidney injury and chronic kidney disease. We expect to find similarities and differences between the mice and human data. We hope to find a unique type of macrophage responsible for excessive scarring because of how it communicates with inflammatory tubular cells. If we identify this unique type of macrophage, we expect that removing it in mice would make them less susceptible to kidney scarring and chronic kidney disease after an acute injury.
 
Patient Engagement: We do not have a patient engagement plan because this work will focus on animal models and bio-banked human kidney biopsies.
 
Conclusion and Relevance to Community: Acute kidney injuries effect nearly 2% of Canadians every year. Nearly one-third will develop chronic kidney disease and we have no therapies to prevent this transition. Our work will help the scientific community understand why the immune system promotes scarred healing rather than true regeneration in the kidney. With this knowledge, we hope therapies can be developed so patients can fully recover after an acute kidney injury and avoid needing dialysis or a life-saving transplant.