Published in Cardiovascular Research, the findings – based on big data and a unique kidney tissue resource funded by – suggest that tackling obesity could have a powerful impact on kidney health.¹

Using data from around 300,000 participants in the – one of the world’s largest biomedical databases and previous genome-wide association studies – the scientific team extracted information on the two most common measures of obesity, body mass index (BMI) and waist circumference (WC), and different measures of kidney function.

Most of the previous studies have been unable to explain if the relationship between obesity and renal disease was little more than an association.

However, through a technique called Mendelian Randomisation – which groups people according to a genetic code randomly assigned at birth and removes any bias – they found that increasing values of genetically predicted BMI and WC were causally associated with the measures of kidney function.

The team were able to show that the causal effect of obesity on the kidney is only partly mediated by high blood pressure and type 2 diabetes.

Through analysis of 467 kidney tissue samples, the study also uncovered the signatures of obesity on the human kidney – groups of genes and pathways that may potentially explain the effects of obesity on the kidney.

First author, Dr Xiaoguang Xu from The University of Manchester, said: “Obesity and kidney disease are common complex disorders with an increasing clinical and economic impact on healthcare around the globe.

“Our evidence substantiates the value of weight loss as a strategy of preventing or reversing a decline in kidney health, as well as decreasing the risk of renal disease.

“So, we hope our findings will help to stimulate further research and drive the development of public health policies to improve kidney health and prevent kidney disease through encouraging weight loss.”

Principal Investigator Professor Maciej Tomaszewski from The University of Manchester is also a Consultant Physician based at 91ֱ�� Royal Infirmary, part of MFT.

He said: “Chronic kidney disease affects more than 10 per cent of adults worldwide and is predicted to become a global threat to public health. With the use of Mendelian Randomisation, we were able to demonstrate a potentially causal effect excessive weight has on kidney health and the risk of chronic kidney disease and several other kidney disorders.

“Through the analysis of one of the largest collection of the human kidney samples, we have uncovered the specific renal pathways associated with body mass index/waist circumference – they are the most likely biological connections between obesity and kidney health and disease.”

Dr Aisling McMahon, Executive director: research, innovation and policy at Kidney Research UK said: “Studies like this from the University of Manchester, are adding to a growing body of evidence suggesting that obesity is a direct cause of kidney disease.

“Three million people in the UK are already living with kidney disease. With levels of obesity on the increase, this figure could be set to rise rapidly. The 91ֱ�� team’s findings demonstrate the need to promote healthy lifestyles in order to improve kidney health. Once someone becomes a kidney patient, they are a kidney patient for life because there is no cure. As the UK’s largest kidney disease research charity, finding new and transformative treatments and ways to prevent kidney disease are our core priorities. This means that our endeavours to help prevent people developing kidney disease are just as critical as finding new ways to treat it.”

1.  Xu X, Eales JM, Jiang X, Sanderson S, Drzal M, Saluja S, Scannali D, Williams B, Morris AP, Guzik TJ, Charchar FJ, Holmes MV, and Tomaszewski M. Contributions of obesity to kidney health and disease: insights from Mendelian randomization and the human kidney transcriptomics. Cardiovascular Research. 2022. doi:10.1093/cvr/cvab357.

91ֱ�� is available  

A new research programme dedicated to the study and treatment of Alport syndrome will begin work in early 2022, with a physical hub based at the University of Manchester. The Stoneygate and Kidney Research UK – Alport Research Hub aims to accelerate research, transform early diagnosis, and develop specific treatments for the disease.

Alport syndrome is a rare genetic disorder, but it is the second most common cause of inherited chronic kidney disease. It is caused by faults in the genetic code for a particular type of collagen protein essential to the normal structure and function of the kidney’s filtering system. Disruption of this protein causes progressive loss in kidney function. It can also cause hearing loss and eye problems.

With support from Kidney Research UK and a £2.55 million investment from the Stoneygate Trust, the 91ֱ��-based hub will be fronted by Professor Rachel Lennon from the University of Manchester, in collaboration with Professor Daniel Gale from University College London and Professor Neil Turner from the University of Edinburgh. Researchers are hopeful that the Alport Research Hub can be used as a model to tackle many different kidney diseases and conditions in the future.

The Hub will have a physical base in 91ֱ�� at the . Here a platform of new technologies will be used to test treatments in in kidney organoids and other models of Alport syndrome. A virtual aspect of the hub will use a database of over 850 patients with abnormal Alport genes to help understand both the genetic and environmental factors that affect, and may predict, how quickly Alport syndrome progresses.

Professor Rachel Lennon, Professor of Nephrology at the University of Manchester said: “Rare diseases have an enormous impact on an individual’s life, and they do not attract the critical mass of researchers required to enable rapid improvements in treatment. This Kidney Research UK-Stoneygate award to establish a UK hub for Alport Research is fabulous news and it will transform our ability to increase awareness, improve understanding of the condition and to accelerate new treatment options for patients. By bringing together expertise in cell and matrix biology, genetics and clinical practice, we aim to improve genetic testing and to progress a range of therapy options to extend kidney survival in patients with Alport syndrome.”

Sandra Currie, chief executive of Kidney Research UK said: “Rare diseases offer a unique challenge to charities such as ours and the overall scientific community. Often, there are limited resources attributed to sourcing new treatments as well as an overall lack of understanding into the causes, impacts and ways to treat them. Embarking on this new collaborative way of working, we are tackling this issue head on by bringing together a wealth of facilities and expertise. With this new Hub, we have the potential to accelerate the discovery and testing of new treatments and possibly even a cure through gene therapy.”

The diagnosis and treatment of Alport syndrome have improved in the last decade. However, more progress is urgently needed. With the additional resources and funding, researchers are optimistic that results and transformative treatments could begin to emerge from the hub within the next five years.