By 2030, it is estimated that nearly 50 percent of the adult population in the United States will have obesity. Concurrently, the incidence rate of end-stage renal disease is projected to increase 11 to 18 percent in that same period depending on obesity trends. Today, nearly 10 percent of adults in the U.S. are considered to have class 3 obesity – a body-mass index (BMI) ≥40 kg/m2– which is a common upper limit for placement on the waiting list at kidney transplant centers.
Dr. Babak Orandi
Obesity and chronic kidney disease (CKD) are inextricably linked. “Obesity and its related comorbidities of hypertension and diabetes accelerate the pathway to end-stage renal disease,” says Babak J. Orandi, MD, a transplant surgeon who recently joined the Division of Endocrinology, Diabetes, and Metabolism at NewYork-Presbyterian/Weill Cornell Medicine to pursue a fellowship in obesity medicine. “More and more, there is very compelling evidence that, with weight loss, we can halt the progression of kidney disease and, in some cases, even reverse it. From my vantage point as a transplant surgeon, I was very interested in spending the year with the team here at Weill Cornell to learn how to help patients lose weight, make them eligible for transplant, and ideally maybe even preclude the need for transplant altogether.”
In 2021, the Chronic Kidney Disease Epidemiology Collaboration updated its estimated glomerular filtration rate (eGFR) formula, removing race from the previously established 2009 formula. However, the update may have unintended consequences.
“What motivated the push for this new formula was to help correct well-documented disparities in end-stage kidney disease care and transplant opportunities, but in some ways, it may actually exacerbate them,” notes Dr. Orandi. “It is widely acknowledged that Black patients are disproportionately burdened by the twin epidemics of chronic kidney disease and obesity. The change in the eGFR formula was meant to remove race from the equation with the idea that race is a social construct rather than a biological one and that this change would support earlier referral of Black patients to nephrology care and kidney transplant. While this is a very laudable goal, the downside of the modification meant that essentially overnight not only would more Black patients now be categorized as having chronic kidney disease, but the revised eGFR formula might also impact the pharmacotherapy options for patients with obesity.”
Dr. Louis Aronne
With this in mind, Dr. Orandi, Louis J. Aronne, MD, Director of the Center for Weight Management and Metabolic Clinical Research at NewYork-Presbyterian/Weill Cornell Medicine, and colleagues from the University of Alabama at Birmingham conducted a study to estimate the number of patients nationwide who would require a dosage reduction or would no longer be eligible for specific anti-obesity medications based on the new eGFR formula (2021 CKD-EPI).
“Obesity is a chronic disease that often does not receive the same standard of care as other conditions, despite its impact on physical, psychological, and metabolic health," says Dr. Aronne. “Now that we can treat obesity safely and effectively, it makes sense to treat obesity first, which in the past has often been secondary to treatments for dyslipidemia, hypertension, and diabetes.”
“We are now in what I would call a golden age of anti-obesity medication development, which will bring the treatment of obesity into the mainstream of care,” adds Dr. Aronne. “Many of the chronic diseases that we spend our time treating in internal medicine are driven by an increase in body weight and treating obesity makes the most sense. The problem with that treatment paradigm is that until recently, we haven't had effective and safe treatments that resulted in weight loss producing improvements in outcomes. Now we do.”
“There are currently 10 FDA-approved medications that we can use in the daily practice of obesity medicine,” says Dr. Orandi. “However, if a patient has comorbidities and impaired renal function it limits the arsenal of what you have to use in their treatment. Arguably this is a patient population – people with obesity and chronic kidney disease – that really needs aggressive treatment for their obesity to help prevent them from progressing to dialysis. Weight loss can prevent the need for a transplant and that is a powerful tool that we have to help patients. This benefits not just that individual patient, but the other people on the wait list who also need a very scarce resource.”
For the study, the research team culled data between 2017 and March 2020 from the National Health and Nutrition Evaluation Survey (NHANES) to estimate how many people might be eligible for weight loss pharmacotherapy.
“Applying the different exclusion criteria based on comorbidities and other factors, we looked at how the newer formula might impact the number of people who are eligible for these medications. We were interested, from an epidemiologic point of view, in identifying the potential ramifications for patients whose medications might have to be adjusted or become contraindicated based on kidney function and how many people might be affected,” says Dr. Orandi. “Ironically, we considered that one consequence of the change could lead to some patients not getting the care they need to prevent their kidney disease from progressing.”
Their findings, published in the November 2022 issue of Obesity, included the following:
- 16,412,571 Black people and 109,654,751 non-Black people in the NHANES survey were eligible for anti-obesity medication (estimated from a sample of 4,498 people eligible for anti-obesity medications on the basis of obesity and obesity-related co-morbidities)
- 911,336 (6.1 percent) Black people and 6,925,492 (6.6 percent) non-Black people had ≥CKD stage 3 according to the 2009 CKD-EPI eGFR formula
- 1,260,969 (8.5 percent) Black people and 4,989,919 (4.7 percent) non-Black people had ≥CKD stage 3 according to the 2021 CKD-EPI eGFR formula
- Additionally, the 2021 CKD-EPI eGFR formula increased the number of Black people eligible for anti-obesity pharmacotherapy with CKD stage 3 or higher by approximately 350,000 compared with the 2009 CKD-EPI eGFR formula
- When applying the 2021 formula related to anti-obesity medications requiring renal adjustment, the number of Black people who would require a lower dose or be precluded from using a medication increased by 24.7 percent to 50.2 percent
Is the New Formula Change Counterproductive?
Dr. Orandi explains that the formula change resulted in 350,000 Black people being upgraded to having a higher stage of kidney disease. Additionally, the number of people who required a lower dose or might be precluded from using an obesity medication nearly doubled.
“The way in which the formula changed also slightly increased the estimated GFR for non-Black patients,” says Dr. Orandi. “All of a sudden, there were more non-Black patients eligible for obesity medications. With more Black patients ineligible and more non-Black patients eligible, the disparity gap that already existed may widen even more.”
In addition to quantifying how many people might be impacted by the 2021 CPK-EPI, the findings by the research team raised awareness that estimated GFR formulas are very convenient, but they’re not perfectly accurate. “These findings highlight the importance of measuring – rather than estimating – GFR in Black people with CKD when considering many anti-obesity pharmacotherapy options that might be contraindicated or prescribed at a lower dose in the setting of kidney insufficiency,” says Dr. Orandi. “If you have a patient who is on the borderline, then it may make sense to actually measure their GFR rather than estimate it as this may open up therapeutic possibilities for patients. The challenge is that while estimating is easy, as it shows up automatically in a basic metabolic panel, measuring an individual’s GFR is a cumbersome procedure and therefore is not routinely performed.”
In addition, Dr. Orandi notes, elevated BMI precludes some patients from being candidates for a kidney transplant. “There are three different aspects to this issue,” he says. “The first is if we identify patients early enough, we may forestall the need for a transplant altogether or at least delay it potentially for years. Secondly, if patients do need a transplant, helping them lose weight will facilitate access to one. The third is that post-transplant, many patients gain weight, particularly with the medications needed for immunosuppression. We know that weight gain, whether it’s before or after the transplant, puts patients at increased risk of metabolic syndrome, cardiac events, and other health problems. Therefore, helping patients lose weight enables them to be as healthy as possible so they can enjoy the survival and quality of life benefits of a kidney transplant.”
“We have an enormous burden of kidney disease and an enormous burden of obesity in this country,” adds Dr. Orandi. “Weight loss presents an important opportunity to rectify disparities in care for patients with obesity and chronic kidney disease or end-stage renal disease.”