Consider Weight Loss Surgery as a Treatment for Chronic Kidney Disease, Obesity

New research from Cleveland Clinic suggests that weight loss surgery, also known as metabolic and bariatric surgery, should be considered as a therapeutic option for patients with chronic kidney disease (CKD) and obesity. In a recently published study in Annals of Surgery, the authors compared the renoprotective effects of metabolic surgery and glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with established CKD. Their findings indicate that compared to GLP-1RA, metabolic surgery was associated with a 60% reduction in kidney impairment progression and 44% reduction in kidney failure or death among patients with Type 2 diabetes (T2DM), obesity and established CKD.

“We know that GLP-1RAs and metabolic surgery have potential renoprotective effects – both options can reduce body weight, blood glucose levels, blood pressure, inflammation and oxidative stress,” explains Ali Aminian, MD, Director of Bariatric and Metabolic Institute at Cleveland Clinic and lead author of the study. “However, our current management guidelines for CKD don’t consider metabolic surgery as a treatment option. Based on findings from this study, we believe this should change.”

Study design

The retrospective observational study included Cleveland Clinic patients with obesity, T2DM, and established CKD who either underwent metabolic surgery between 2010 and 2017 or continuously received GLP-1RA for a minimum of two years. The primary endpoint of the study was CKD progression, which the authors defined as the onset of ≥ 50% sustained decline in estimated glomerular filtration rate (eGFR) compared with baseline, development of sustained eGFR < 15 mL/min/1.73 m², initiation of dialysis, or kidney transplant during follow-up. A secondary endpoint was incident kidney failure (defined as the onset of sustained eGFR < 15 mL/min/1.73 m², initiation of dialysis or kidney transplant) or all-cause mortality during follow-up.

The study included 425 adult patients, 258 (60.7%) of which were women. The median age was 64 (IQR, 57-68), and the median body mass index (BMI) was 40 (IQR, 35-47). Of these patients, 183 were in the metabolic surgery group, and 242 patients were in the GLP-1RA group.

The patients in the metabolic surgical cohort underwent either Roux-en-Y gastric bypass (RYGB) (n=99; 54.1%) or sleeve gastrectomy (n=84; 45.9%).

In the nonsurgical group, the GLP-1RAs at baseline were liraglutide (n=143, 59.1%), exenatide (n= 74, 30.6%), dulaglutide (n=35, 14.5%), and albiglutide (n=6, 2.5%). During follow-up, 48 (19.8%) patients in the nonsurgical group received semaglutide or tirzepatide at some point.

The median follow-up was 5.8 years (IQR, 4.4-7.6 y); including 6.2 years (IQR, 2.1-8.7 y) for patients in the metabolic surgery group and 5.7 years (IQR, 5.0-6.8 y) for patients in the GLP-1RA group.

Findings

The authors recorded 36 patients from the surgical group and 67 patients from the nonsurgical group with CKD progression at the end of the study period. At eight years, the cumulative incidence rate of CKD progression was 21.7% (95% CI: 12.2 to 30.6) in the surgical group and 45.1% (95% CI: 27.7 to 58.4) in the nonsurgical group, an adjusted absolute risk difference of 18.5% (95% CI: 0.6 to 28.3), with an adjusted HR of 0.40 (95% CI: 0.21 to 0.76), P=.006.

In terms of their secondary endpoint, the authors found that 45 patients in the surgical group and 69 patients in the nonsurgical group developed kidney failure or died. The cumulative incidence of the secondary composite endpoint at eight years was 24.0% (95% CI: 14.1 to 33.2) in the surgical group and 43.8% (95% CI: 28.1 to 56.1) in the nonsurgical group, an adjusted absolute risk difference of 12.3% (95% CI: −5.4 to 21.4), with an adjusted HR of 0.56 (95% CI: 0.31 to 0.99), P = .048.

The study group also compared changes in body weight, diabetes control, and medication between the two groups. The mean body weight at eight years in patients in the surgical and nonsurgical groups was reduced by 21.6% (95% CI: 19.2% to 24.2%) and 8.1% (95% CI: 5.5% to 12.3%), respectively.

Metabolic surgery was also associated with a reduction in HbA1c level (mean between-group difference in changes from baseline at five years: 0.84% [95% CI: 0.44% to 1.19%], P < .001; and at eight years: 0.46% [95% CI: −0.15% to 1.0%], P = .14). Use of noninsulin diabetes medications, insulin, renin-angiotensin-aldosterone system (RAAS) inhibitors, other antihypertensive medications and lipid-lowering therapies was also significantly lower after metabolic surgery compared with nonsurgical care.

“In our study, both the surgical and nonsurgical groups lost weight,” says Dr. Aminian. “However, in the metabolic surgery group, not only did we see a greater reduction in body weight and HbA1c levels, but we also observed a significant reduction in medication use with this group as well. This could be a major additional benefit for patients.”

The study group did observe a higher-than-normal rate of adverse events following metabolic surgery, but Dr. Aminian says these numbers could be explained by the higher-than-average-risk population (median age of 61 years and already had major damage to their end organs at the time of surgery).

“Over the past two decades, the safety of metabolic surgery has improved tremendously,” says Dr. Aminian. “The cumulative risk of adverse events and death in the early-postoperative period is generally accepted to be around 5% and 0.1%, respectively. The rates we observed in this study — 12.6% and 1.6%, respectively — were much higher than this, and we believe this was likely due in part to this cohort being at a higher risk. But, despite this, the surgical patient group still had favorable outcomes after three to four years of follow-up.”

Takeaways

To the authors’ knowledge, this was the first study done comparing the renoprotective effects of metabolic surgery and GLP-1RA among patients with CKD stages 3 and 4. They believe their finding that metabolic surgery was associated with a 60% lower risk of kidney impairment progression and a 44% lower risk of kidney failure or death indicates that metabolic surgery should be considered as a therapeutic option for this patient population.

“We believe that these findings suggest that surgery is a superior option compared to the available medications that would typically be used to treat patients,” says Dr. Aminian. “However, patients and surgeons generally agree that in most cases it’s best to start with the least invasive option first. Medications are still an important tool for us, but communicating effectively and consistently with patients about their progress is also essential for determining when it might be time to consider surgery.”

He continues, “It’s also important to recognize that medicine continues to improve, so while the findings from this study support surgery, we need to continuously evaluate as new medications and more data and evidence become available.”