August 28, 2023  Print

A world first study has successfully developed a preclinical model that provides groundbreaking insights into the complex, two-way interactions between chronic kidney disease (CKD) and osteoarthritis (OA). The findings pave the way for the development of transformative new treatment strategies.

The number of patients that suffer with both CKD and OA is on the rise worldwide, presenting a significant healthcare challenge. Despite sharing common risk factors like ageing, obesity, type 2 diabetes and hypertension, the mechanisms predisposing to simultaneous occurrence of CKD and OA remain unclear.

In Australia, about one in 10 adults have signs of CKD.  Aboriginal and Torres Strait Islander peoples are twice as likely to have CKD than non-Indigenous Australians.[1]  Osteoarthritis is the most common type of arthritis in Australia, affecting one in five Australians aged over 45 and one in three aged over 75.[2]

The study, conducted by a team of researchers from The Westmead Institute for Medical Research (WIMR) and the University of Sydney’s Kolling Institute, aimed to address the knowledge gap surrounding the interaction between CKD and OA. The results have just been published in a leading Rheumatology journal RMD Open, which is affiliated with the British Medical Journal (BMJ) and the European Alliance of Associations for Rheumatology (EULAR).

This preclinical model accurately replicated key features of CKD as they present in patients, including loss of bone volume and density. These CKD-induced bone changes affected the severity of the cartilage loss in a joint impacted by OA.
Interestingly, the researchers found that the introduction of OA resulted in changes to CKD-induced metabolic abnormalities, and even directly impacted renal pathology including, dilation of renal tubules and interstitial fibrosis as seen in the image.  
The study's lead researcher and first author Dr Sohel Julovi, Senior Research Scientist at WIMR’s Kidney Injury Group, emphasised the significance of these findings.

                                   IMAGE: OA induced renal tubular dilation and collagen 1 deposition (fibrosis-red).

"Our world first study has uncovered previously unknown interactions between these two conditions. The bidirectional effects underscore the complexity of these diseases and emphasise the need for a comprehensive approach to their management."

Joint senior author Professor Natasha Rogers, Nephrologist and Head of WIMR’s Kidney Injury Group, acknowledged the challenges ahead, but expressed optimism about the potential benefits for patients.
"Our research opens the door to a new era of targeted treatments that could offer relief for individuals battling both chronic kidney disease and osteoarthritis. By uncovering the underlying mechanisms, we're paving the way for transformative therapeutic strategies that address both conditions simultaneously.”

Joint Senior author of the study Professor Christopher B Little of the University of Sydney’s Kolling Institute, emphasised the study's significance, stating, "We’ve known for a while that CKD alters bone and joint tissue metabolism. Identifying that the crosstalk goes in both directions and that OA can alter kidney function, sheds an entirely new light on the potential whole body impact of this already common and increasing joint disease. The next steps are to identity the precise molecular pathways and messengers responsible for the bi-directional disease interaction, which will provide potential new opportunities to treat both conditions.”
What is chronic kidney disease?
Chronic kidney disease (also known as chronic renal disease) is a general term used to describe health conditions that damage kidneys and reduce their ability to filter wastes from blood and make urine.  This leads to wastes building up in blood, resulting in symptoms including high blood pressure, anaemia, weak bones, poor nutritional health and nerve damage.
What is osteoarthritis?
Osteoarthritis is a long-term condition where joints become inflamed and damaged. It is a complex disease that affects the entire joint, and its progress and impact is worsened by the presence of other chronic conditions.  Osteoarthritis is the most common joint disease and leading cause of pain, disability and early retirement.
Funding bodies
This work is funded by:
Betty Schofield and Joyce Anderson Bequest Grant 2018
The Westmead Medical Research Foundation
National Heart Foundation Vanguard Grant.