Obesity, more common now in young patients, adds to the burden of cardiorenal syndrome
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The Cover Story this month in Healio/ Nephrology News & Issues focuses on obesity and its relationship to chronic kidney disease and ultimately, cardiovascular disease and death.
CKD, particularly when diabetes is involved, is the number one risk factor for CVD and death, which frequently occurs prior to the development of chronic renal failure. Most cases of kidney disease in the world, but particularly in the United States, are metabolically driven from diabetes and hypertension.
The U.S. leads the world in obesity with a prevalence of 42.4%; another 31.8% of individuals are overweight. This means approximately 75% of our population is overweight or obese. The ratio of obesity to overweight is even worse in those with diabetes.
Childhood obesity
It is estimated that 9 million children older than 6 years are obese, and even more are diagnosed as being overweight. This has led to an increase in childhood diabetes, but more importantly a greater increase in diabetes in younger adults. Developing diabetes at a younger age means an increased risk of complications during the life of the individual, such as a high risk for CKD. We should expect to see individuals develop CKD and the need for renal replacement therapy at increasingly younger ages, based on current trends.
Obesity is more common in historically underrepresented populations, especially among Black individuals, and disproportionally increases their risk for obesity-related complications. This increase in metabolic disease is driven by the presence of visceral and ectopic fat in the abdomen and organs, such as the kidneys, heart, liver and in other tissues, that I call the visceral insulin-resistance adiposity syndrome, or VIRAS. This is also referred to as the metabolic syndrome.
VIRAS is the number one cause of death, not only from cardiorenal diseases, but also cancer and other viruses and infectious diseases, such as COVID-19 and pneumococcal pneumonia. This population needs to be immunized earlier due to their reduced immune function, usually seen at older ages.
Poor diets
The increase in visceral fat is due to our diet, which is high in processed carbohydrates, saturated and trans fats and sodium, and our decrease in physical activity and quality sleep. The overabundance of unhealthy processed foods leads to a buildup of white fat in places it should not be, resulting in release of pro-inflammatory cytokines, chemokines and hormones such as angiotensin II. This leads to systemic vascular inflammation including in the kidneys and heart, which are specialized organs of the vascular system. This inflammation leads to cardiovascular stiffening due to fibrosis and a decrease in microvascular perfusion, which leads to ischemia, more fibrosis and eventually organ failure and death.
This inflammatory response, or immune dysregulation, also leads to insulin resistance and eventually diabetes in genetically susceptible individuals who cannot maintain adequate beta cell pancreatic function to get past the resistance to insulin and maintain adequate blood sugar control. The increase in insulin resistance from obesity may also be driving the increase in type 1 diabetes by decreasing beta cell function, in addition to the immune destruction of the pancreatic beta cells, and by increasing pancreatic immune dysregulation and inflammation, potentially caused by visceral and pancreatic fat.
The VIRAS ultimately results in the perfect metabolic storm with positive unstable metabolic feedback loops leading ultimately to death.
Treatment
To disrupt these deleterious feedback loops and stop the storm, we need to get people to lose weight, particularly around the waist. This can be done with an improved diet containing more fruits and vegetables, less processed foods and red meat, more physical activity, medications and sometimes, bariatric surgery.
In general, drugs that cause weight loss without increasing sympathetic activity reduce mortality. We now have two classes of drugs that do this – SGLT2 inhibitors and the incretin agonists. The incretin agonists, including Ozempic and Wegovy (semaglutide, NovoNordisk), Trulicity (dulaglutide, Eli Lilly) and Mounjaro (tirzepatide, Eli Lilly) have been shown to successfully cause greater than a 15% decrease in weight, similar to bariatric surgery. In addition, these medications decrease proteinuria and have been shown to improve atherosclerotic CVD outcomes.
We are awaiting the results of the prospective randomized FLOW trial with semaglutide for more definitive data on the ability of this medication to reduce the loss of GFR. We, however, need more data on the effects of incretin agonist medication on lean body mass in a population with kidney disease that is prone to increased mortality associated with sarcopenia. In addition, the price of these drugs is prohibitive for many, particularly in the nondiabetic population for which insurance coverage is even worse.
National change
Ultimately, we will probably need a national change in our diet to immunize us against this killer metabolic VIRAS. This may require more regulations on the food industry, encouraging more physical activity, educating health care providers about nutrition counseling and incentivizing and paying for lifestyle counseling.
- References:
- Adult obesity facts. CDC. https://www.cdc.gov/obesity/data/adult.html. Accessed March 26, 2023.
- Childhood obesity. World Obesity Federation. https://www.worldobesity.org/about/about-obesity/prevalence-of-obesity. Accessed March 26, 2023.
- Rossing P, et al. Neph Dial Trans. 2023;doi:10.1093/ndt/gfad009.
- For more information:
- Lance Sloan, MD, MS, FACE, FASN, FACP, FEAA is the medical director of the Texas Institute for Kidney and Endocrine Disorders in Lufkin, Texas. He is also an Associate Editor for Healio | Nephrology News & Issues. He can be reached at tikedlufkin@gmail.com.
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