Obesity creates challenges for patients with CKD
Click Here to Manage Email Alerts
The goal of Advancing American Kidney Health is clear. By 2030, HHS is asking the nephrology community to reduce the number of ESKD diagnoses by 25%. That means slowing the progress of kidney disease in the early stages before a patient’s GFR starts to descend and either dialysis or a transplant is necessary. Obesity, a growing problem in the general population, is also an issue among patients with chronic kidney disease.
“The latest research tells us that about one of two people in the United States will be obese by 2030, and one in four will be severely obese,” Allon N. Friedman, MD, a nephrologist and an associate professor of medicine at Indiana University School of Medicine, told Nephrology News & Issues. “Overall, 40% of people in this country are currently obese. It is arguably the greatest public health threat in the U.S.,” as well as in developing countries, Friedman said, who has researched and written extensively on the topic of obesity and kidney disease.
Problem that keeps growing
Friedman cited a paper published in the New England Journal of Medicine in December 2019 by Zachary J. Ward, MPH, a programmer/analyst for the Center for Health Decision Science at the Harvard T.H. Chan School of Public Health. Ward and his colleagues studied the projected growth in the number of cases of obesity during the next decade. In the paper, the researchers predicated the following:
By the year 2030, the prevalence of obesity (defined as a BMI at or greater than 30 kg/m2) will be above 50% in 29 states;
Nearly one in four adults is projected to have severe obesity defined as a BMI at or greater than 40 kg/m2 by the year 2030;
Among the remaining states, none will have a prevalence of obesity less than 35%; and
Source: Allon Friedman, MD
The hardest hit for obesity will be Alabama, Arkansas, Mississippi, Oklahoma and West Virginia.
Obesity prevalence is projected to reach 58% in those states, according to the study.
The authors noted obesity rates varied significantly by race.
“In general, we found a higher prevalence of obesity among non-Hispanic black and Hispanic adults than among non-Hispanic white adults ... we also found a large gradient in the prevalence of obesity according to income,” Ward and colleagues wrote. “Our analysis indicates that the prevalence of adult obesity and severe obesity will continue to increase nationwide, with large disparities across states and demographic subgroups.”
Obesity and risk for CKD
Obesity can be the trigger for jump-starting CKD, leading to the risk of diabetes, cardiovascular disease and hypertension, which are the hallmarks of kidney injury.
“Certainly, the link between cardiovascular disease and obesity is strong because it substantially increases the risk for diabetes,” Janani Rangaswami, MD, FACP, FCRS, FAHA, associate chair (research) in the department of medicine (nephrology) at Albert Einstein Medical Center in Philadelphia, told Nephrology News & Issues. “Obesity causes several inflammatory changes and neural-hormonal changes that are risk factors for heart failure.”
It also is the “common link in the chain” as an independent predictor for the progression for CKD, Rangaswami said. “You can’t show causality but when you see the combination of diabetes, heart failure, hypertension and kidney disease, invariable obesity is tied in with that equation.”
Research has shown that obesity can lead to a decline in eGFR. A study by Chang and colleagues that included 178 collaborators with the CKD Prognosis Consortium looked at associations between adiposity measures (BMI, waist circumference and waist-to-height ratio) with decline in GFR and with all-cause mortality. Data were collected from 40 countries between 1970 and 2017.
“Elevated body mass index, waist circumference and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR,” the authors concluded.
Louisa Sukkar, MD, MBBS, FRACP, from the George Institute for Global Health in Australia and colleagues wrote in Diabetes Care that obesity status played a role in renal function. Compared with adults with a normal-range BMI (<24.9 kg/m²), adults with obesity class I were 32% more likely to develop an eGFR of less than 60 mL/min/ 1.73 m2 with risk rising to 44% for adults with obesity class III.
Other comorbidities that influenced the risk for renal decline were hypertension, coronary heart disease, cancer and depression or anxiety, as did having diabetes for at least 5 years.
“All clinicians need to be looking for kidney disease among people with diabetes to maximize the opportunity to put in place measures to halt its progression and thus lessen the burden on individuals and the health system,” Sukkar and colleagues wrote.
Source: Obesity Fact Sheet; WHO; 2019. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
Patients with metabolic syndrome, a cluster of factors that increases the risk for heart disease and type 2 diabetes, may also be more at risk to develop kidney disease than people without this syndrome. Characteristics of metabolic syndrome include the following:
a large waist size, or having a lot of fat around the middle of the body;
a high level of triglycerides in the blood;
a low HDL or “good” cholesterol level;
high blood pressure; and
high blood sugar.
“It is not an exaggeration to state that, in modern times, CKD is to a great degree a complication of obesity,” Friedman said.
The CDC reports obesity has not only led to increases in mortality among Americans – wiping out gains seen from a reduction in deaths due to smoking – but hospitalizations for patients have been costly. Obesity-related medical care costs the American public $147 billion a year, the agency reported.
“Roughly half of all medical costs associated with obesity are financed by Medicare and Medicaid. In terms of government spending, the cost of treating obesity in our health care system is greater than what all U.S. governments (federal, state, local, etc.) combined spend on public health in a typical year,” the CDC noted.
Tracking the early stages of obesity begins with screenings and education of primary care physicians, Hernan Rincon-Choles, MD, a nephrologist in the Glickman Urological & Kidney Institute at the Cleveland Clinic, told Nephrology News & Issues.
“One of the things that made identifying chronic renal insufficiency more confusing in the past was a lack of uniformity among lab tests,” he said.
Rangaswami said it is important to note that pharmacotherapy also can play a role in obesity. Patients with diabetes or with a transplant often take drugs that cause weight gain.
“Some of it is chicken and the egg. In some cases, we cause the problem; in other cases, it is patient related. But either way, it is huge part of the problem for both cardiovascular disease and kidney disease.”
Potential of new therapies
The goal of treating obesity is to lessen its impact on other conditions like diabetes and slow the progression of kidney disease. “Many of my patients are not just obese; they are morbidly obese,” Lance Sloan, MD, MS, FASN, FACE, FACP, chief medical officer of the Texas Institute for Kidney and Endocrine Disorders, told Nephrology News & Issues. “My goal is to prevent them from advancing to dialysis, reduce the risk of heart failure, atherosclerotic cardiovascular disease and manage their diabetes.” Sloan treats what he calls the total body visceral insulin-resistant adiposity syndrome (VIRAS) in patients who are at early stages of CKD. “VIRAS is driven by the dangers of visceral fat, which can increase your risk of heart and kidney disease even without having diabetes,” he said.
There are some promising results from drugs like sodium-glucose cotransporter-2 (SGLT2) inhibitors, Sloan said. They are a class of FDA-approved drugs that help with weight loss and lower blood sugar in adults with type 2 diabetes. “Diabetes is not just a disease of high blood sugar; it is also a disease of high total body sodium,” Sloan said. “If your blood sugar is high, then you have too much sodium. If you have too much sodium, you will have too much intravascular volume” that increases the workload on the kidney and the heart. “This is simplified, but by using an SGLT2 we are treating many of the underlying abnormalities that lead to cardiorenal disease and failure by reducing visceral fat, blood glucose, and total body sodium.”
Recently, the FDA approved canagliflozin (Invokana, Janssen) to reduce the risk of end-stage kidney disease, the doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria. “This is the first drug to treat type 2 diabetes to get this indication,” Sloan notes. Canagliflozin has previously been approved by the FDA to lower blood glucose in adults with type 2 diabetes and reduce major adverse cardiovascular events in adults with type 2 diabetes and established CVD.
On March 30, the Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) Phase 3 trial with dapagliflozin (Farxiga, AstraZeneca) was stopped early due to overwhelming efficacy in patients with CKD with type 2 diabetes and non-diabetes by the Data Monitoring Committee. In August 2019, the FDA granted Fast Track designation for Farxiga to delay the progression of CKD and death in patients with CKD.
Other than diabetes, cardiovascular disease, and systemic and pulmonary hypertension, patients with obesity may also face problems such as sleep apnea, a higher susceptibility to having kidney stones, depression and arthritis because of increased stress on joints.
While increased caloric intake and lack of exercise may be a large part of the problem that leads to obesity, “there may be other variables involved, including things like inadequate sleep, decreased smoking, changes in ambient temperature – which can affect metabolism – and chemicals added to the environment that have an impact on the endocrine system,” Friedman, of Indiana University Health, said. “We don’t have a clear answer as to why obesity rates have been climbing,” he said.
Geography also may play a role in who becomes obese. Findings from WalletHub, an personal finance website, showed the top five states with the most overweight and obese residents were in the South, with Mississippi, West Virginia and Kentucky leading the way. Nevada, Delaware and New Hampshire had the largest percentage of their population who were overweight; West Virginia, Mississippi and Oklahoma had the highest percentage of residents who were considered obese.
Some states hardest hit by obesity as reported by WalletHub also have a high prevalence of patients on dialysis, according to a data review by the National Kidney Foundation. Southern states make up the top 10 list of those hardest hit by kidney failure.
“These states have high rates of obesity and physical inactivity. Multiple chronic diseases are highly prevalent in this geographic area, also known as the ‘stroke belt.’ Yet healthy diet combined with physical activity to maintain a healthy body weight could change the levels of kidney failure,” Joseph Vassalotti, MD, chief medical officer for the NKF, said in a release.
Mississippi, one of the states with a high rate of obesity as identified by the WalletHub study, also has one of the highest rates for ESKD in the United States.
Treatment options
In addition to facing risks that include diabetes, cardiovascular disease, and hypertension, patients who are obese may also deal with sleep apnea, a higher susceptibility to having kidney stones, depression and arthritis because of increased stress on joints.
“Obesity touches on nearly every organ system in a negative way,” Friedman said.
Friedman also acknowledged the controversy about requiring prospective transplant candidates to lose weight.
“Many transplant sites have strict BMI cutoffs that prevent some patients from getting a kidney transplant. This is despite the fact that even patients who are obese live longer after receiving a transplant,” he said.
Friedman tells his patients with CKD there are three main options for reducing weight: lifestyle changes, including diet; pharmacotherapy and surgery.
“You can lose weight with lifetime intervention, and that should be your first step,” Friedman said. There are several FDA-approved drugs that can help with weight loss, but only Liraglutide (LGM Pharmacy), a glucagon-like peptide-1 receptor agonist, appears safe and relatively easy to use in patients with CKD, he said. Liraglutide was approved for diabetes care in the United States in 2010.
Surgical intervention, such as bariatric surgery, “is unquestionably the most effective of the three options because it leads to large weight loss that is sustainable over time and presents the best way of protecting against kidney disease based on what we currently know,” Friedman said, noting several observational studies that showed a slowing of progression of kidney disease after bariatric surgery.
However, “the evidence we do have in support of bariatric surgery is observational in nature. We would benefit from randomized trials in this area to solidify our evidence base,” he said.
In their paper looking at long-term outcomes in patients with obesity and renal disease after sleeve gastrectomy (SG), Kassam and colleagues prospectively collected data on patients with ESKD and CKD undergoing the procedure from 2011 to 2018. Not only did 72% and 48% in the patient groups achieve a BMI of at least 40 kg/m2 and equal to or less than 35 kg/m2, respectively, “the weight loss reduced hypertension (85.8% vs. 52.1%), decreased antihypertensive medication use (1.6 vs. 1) (P < .01 each), and reduced incidence of diabetes (59.6% vs. 32.5%, P < .01),” the authors noted. “Mortality rate after was 1.8 per 100 patient-years, compared with 7.3 for non-SG,” they wrote. “Patients with stage 3a or 3b CKD exhibited improved glomerular filtration rate (43.5 mL/ min vs. 58.4 mL/min, P = .01).”
Others agree that well-designed trials are needed to determine if bariatric surgery successfully reduces obesity risk in patients with CKD. In a white paper from the American Society of Transplant Surgeons’ Obesity in Transplantation Taskforce that looked at the benefits of bariatric surgery for organ transplant recipients, Tayyab Diwan, MD, and colleagues wrote, “Patients with obesity and concurrent end-stage organ failure face significant challenges in access to transplant as well as negative impacts on outcomes after solid organ transplant. Addressing obesity in select patients with bariatric surgery before transplant may improve access, facilitate an easier operation, as well as improve benefits of transplant.
Guidelines needed on obesity-CKD connection
For the future, there is a need for direction on how to determine the impact of obesity on CKD, Friedman said.
“There is a large gap in guidelines on obesity both for patients with CKD and their physicians,” he said. “This is a high-risk patient population to whom obesity is a topic of great clinical importance. We need to begin to focus more intently on how best to manage their obesity.” – by Mark E. Neumann
- References:
- CDC. Chronic Kidney Disease Surveillance System—United States. www.cdc.gov/ckd
- Chang A, et al. Kidney Int Rep. 2017;doi:10.1016/j.ekir.2017.01.010.
- Chang AR, et al. BMJ. 2019; doi:10.1136/bmj.k5301.
- Diwan T, et al. Am. Jrnl of Transplant. 2020;doi:10.1111/ajt.1578.
- https://srch.eurekalert.org/e3/query.html?col=ev3new&col=ev3oneyr&col=ev3rel&col=ev3rel1&qt=obesity+2020&charset=iso-8859-1&pw=100.101%25
- https://usafacts.org/articles/obesity-rate-nearly-triples-united-states-over-last-50-years/
- https://wallethub.com/edu/fattest-states/16585
- https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight
- Kassam AF, et al. Am Jrnl Transplant. 2020;doi:10.1111/ajt.15650.
- Sukkar L, et al. Diabetes Care. (ital) 2020;doi:10.2337/dc19-1803
- Ward Z, et al. New Engl Jrnl of Medicine. 2019;doi:10.1056/NEJMsa1909301.
- For more information:
- Allon Friedman, MD, can be reached at 550 University Blvd., Suite 6100, Indianapolis, IN 46202; email: allfried@iu.edu.
- Janani Rangaswami, MD, can be reached at Albert Einstein Medical Center, 5501 Old York Road, Philadelphia, PA 19141, email: rangaswJ@einstein.edu.
- Hernan Rincon-Choles, MD, can be reached at the Glickman Urological & Kidney Institute at the Cleveland Clinic, 12000 McCracken Road, Cleveland, OH 44125; phone: 216-444-5600.
- Lance Sloan, MD, FACE, FASN, can be reached at the Texas Institute for Kidney and Endocrine Disorders, 10 Medical Center Blvd. Suite A, Lufkin, TX 75904; phone: 936-632-4282
Disclosures: Friedman, Rangaswami, and Rincon-Choles report no relevant financial disclosures. Sloan has consulted, accepted speaker fees, and completed research for Janssen, AstraZeneca, Boehringer Ingelheim/Eli Lilly and Merck.
Collapse
Read more about
Click Here to Manage Email Alerts