People whose genetics predispose them towards obesity are more likely to develop chronic kidney disease (CKD), a new study indicates.
Notably, the findings suggest that obesity can cause CKD primarily by increasing the risk of high blood pressure and type 2 diabetes.
The study, “Conventional and Genetic Evidence on the Association between Adiposity and CKD,” was published in the Journal of the American Society of Nephrology.
The kidneys are critical for human health as they are responsible for filtering waste and excess fluid out of the blood to be disposed of in urine. CKD (also called chronic kidney failure) is when the kidneys start to lose their function.
Previous research has indicated that people who are obese are at increased risk of CKD. However, it was not clear whether obesity itself causes CKD, or whether other factors — for instance, differences in dietary salt content — might instead explain the association.
In the new study, researchers at the University of Oxford used data from the UK Biobank, a national database of medical and genetic information in the United Kingdom, to investigate the association between CKD and two measurements of obesity: body mass index (BMI), which is a ratio of weight to height, and waist-to-hip ratio, which is indicative of the amount of fat around abdominal organs.
In total, the researchers analyzed data for 281,228 people (53% women, mean age 56.6 years).
The scientists conducted two separate analyses. In the conventional analysis, they looked for statistical associations between BMI or waist-to-hip ratio and CKD. In the genetic analysis, the investigators used data from previous research to calculate genetic risk scores for BMI and waist-to-hip ratio. Then, they looked for statistical links between these genetic risk scores and CKD.
In both analyses, BMI and waist-to-hip ratio were significantly associated with CKD risk.
Every 5 kilogram per square meter (kg/m2) increase in BMI was associated with a 58% increased CKD risk in the conventional analysis and a 49% higher risk in the genetic analysis. In turn, every 0.06 increase in waist-to-hip ratio was associated with a 69% greater likelihood of CKD in the conventional assessment and a 29% greater risk in the genetic analysis.
Importantly, the finding that obesity-related genetics are significantly associated with CKD risk indicates that obesity is a cause of CKD.
“Using a genetic approach meant we could be more rigorous than with a conventional approach and rule out other factors,” Will Herrington, MD, a study co-author from Oxford’s Medical Research Council Population Health Research Unit, said in a press release.
Also, the results indicated that excess body fat increases CKD risk independently of where on the body that fat is distributed.
“In some diseases linked to obesity, such as heart disease, fat deposited around the abdominal organs (tummy fat) is worse than fat that accumulates around the buttocks,” Herrington said. “But our results clearly show that regardless of where it is deposited in the body, fat increases the risk of kidney disease.”
Further statistical analyses (both genetic and conventional) suggested that the correlation between obesity and CKD could largely be explained by high blood pressure and type 2 diabetes — conditions that have well-established links to obesity.
“This is good news,” said Herrington, “because we already know a lot about diabetes and high blood pressure, and we have treatments for them. If we can prevent diabetes and control blood pressure in those who are overweight or obese, we may be able to prevent many cases of kidney disease from developing in the first place. Ultimately, these results give us all more incentive to manage our weight.”
The researchers concluded: “genetic approaches show increased central adiposity and general adiposity both seem to be independent and important causes of CKD.”
This association may have implications for treatment, suggested Herrington.
“A new class of drugs called gliflozins reduce the kidney’s ability to retain sugar and salt, meaning the body is more able to get rid of excess sugar and salt,” he said. “This helps people with diabetes control their weight and blood pressure, and recent trials are revealing they are particularly effective at treating diabetic kidney disease.”
Added Aisling McMahon, PhD, executive director of research, innovation, and policy at Kidney Research UK, who was not involved in the study: “We’re watching the gliflozin trials with interest — if clinical trials reveal these drugs can benefit an even wider group of patients, we would like to see these research findings brought into clinical practice quickly so they can benefit patients across the country.”