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Renoprotective Effects of Metabolic Surgery Versus GLP1 Receptor Agonists on Progression of Kidney Impairment in Patients with Established Kidney Disease
Ali Aminian1, *Hamlet Gasoyan1, *Alexander Zajichek1, *Nicholas J. Casacchia1, *Mohammad H. Alavi1, *Rickesha Wilson1, *Xiaoxi Feng1, *Ricard Corcelles1, Stacy A. Brethauer2, Philip R. Schauer3, Matthew Kroh1, Raul J. Rosenthal4, *Hiddo L. Heerspink5, *Michael B. Rothberg1
1Cleveland Clinic, Cleveland, OH; 2Ohio State University Wexner Medical Center, Columbus, OH; 3Pennington Biomedical Research Center, Baton Rouge, LA; 4Cleveland Clinic Florida, Weston, FL; 5University Medical Center Groningen, Groningen, Netherlands

Objectives: The impact of metabolic surgery and glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with established chronic kidney disease (CKD) has not been fully characterized and directly compared.

Methods: Patients with obesity (BMI ≥30 kg/m2), type 2 diabetes (T2DM), and baseline eGFR 20-60 ml/min/1.73 m2 (based on the CKD-EPI equation) who underwent metabolic surgery at a large health system in the US (2010-2017) were compared with similar nonsurgical patients who continuously received GLP-1RA. Utilizing doubly robust estimation, combining the overlap weighting and multivariable-adjusted Cox regression models, the progression of CKD (defined as onset of ≥40% sustained decline in eGFR compared with baseline, onset of sustained eGFR <15 mL/min/1.73 m2, initiation of dialysis, or kidney transplant) was examined, with follow-up through December 2022.

Results: A total of 425 adult patients (258 [60.7 %] women; mean age, 61.9 years [SD 8.2]; median BMI, 42.3 [IQR, 35.2 - 47.2]), including 183 patients in the metabolic surgery group (including Roux-ex-Y gastric bypass [n=99] and sleeve gastrectomy [n=84]) and 242 patients in the GLP-1RA group, with a median follow-up of 5.8 years (IQR, 4.3-7.6 years) were analyzed. The median baseline eGFR in the surgical group was 49 (IQR, 40-54.5) and in the GLP-1RA group was 50 (IQR, 41-55). Patients in the surgical group compared with patients in the GLP-1RA group lost more weight (mean difference at 10 years from baseline: 11.3 [95% CI, 2.3%- 17.5%] percentage points; P < .001). The cumulative incidence of CKD progression at 10 years was 32.2% (95% CI, 18.7%-45.7%) in the metabolic surgery group and 73.4% (95% CI, 48.6%-98.1%) in the GLP-1RA group (adjusted absolute risk difference, 21.7% [95% CI, 3.9%-36.3%]; adjusted hazard ratio, 0.44 [95% CI, 0.24-0.81], P < .001) [Figure 1]. The number needed to treat with metabolic surgery to prevent one additional CKD progression over a 10-year time frame was 4.6 (95% CI, 2.7-25.6).

Conclusions: Among patients with obesity, T2DM, and established CKD, metabolic surgery, compared with GLP-1RA, was associated with a 56% lower risk of progression of kidney impairment.

Figure 1: 10-Year Cumulative Incidence Estimates (Kaplan-Meier) for Progression of CKD in the Overlap-Weighted Analysis
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