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The Role of Bariatric Surgery in Prevention of Kidney Disease Progression in Moderately Obese Patients With Type 2 Diabetes—Reply

The Role of Bariatric Surgery in Prevention of Kidney Disease Progression in Moderately Obese... In Reply The Microvascular Outcomes After Metabolic Surgery (MOMS) study demonstrated that Roux-en-Y gastric bypass (RYGB) can be used to place early stages of chronic kidney disease (CKD) in patients with type 2 diabetes into remission.1 Patoulias et al suggested that remission of albuminuria was enhanced by RYGB because more of these patients at baseline received glucagon-like peptide-1 receptor agonist (GLP-1RA). A subanalysis of patients undergoing RYGB according to presurgery treatment with a GLP-1RA found that the treatment did not predict albuminuria response. It should be remembered that GLP-1RA were stopped immediately after RYGB, although metformin, angiotensin-converting enzyme inhibitors, and statins were continued where possible. Rees et al questioned why microalbuminuria was chosen as the primary outcome and not glycemia. This is a fundamental advantage of MOMS because the focus is shifting from weight loss and reduction in glycemia to health gain. The MOMS study was the first to show that complications of obesity and diabetes, such as CKD, can be reversed. They also pointed to the patients who were either at higher than or lower than the body mass index inclusion criteria when the interventions started. This is a challenge in all studies of bariatric surgery because when patients were recruited, they did fulfill the inclusion criteria, but when the study started, their weight may have crept higher than or lower than the inclusion criteria. We reviewed all the data, and there were no biases either way regarding group allocation, so this change was unlikely to bias the outcomes. Rees et al also commented on the risk of cross over from the best medical arm to the RYGB arm. Our protocol did not allow cross over between treatment groups. Ramos et al questioned the decision to proceed with an intention-to-treat (ITT), “modified” ITT, or per protocol analysis. We used a bona fide ITT analysis, which is the gold-standard approach for the analysis of superiority trials.2 Data from all participants were included (in the groups they were randomized), regardless of protocol deviations or the intervention they actually received. The ITT analyses measure the “use-effectiveness,”3 which is the effect of prescribing RYGB compared with the best medical treatment (BMT). Ramos et al described a more clinically focused estimate, the method efficacy, which is the effect of actually undergoing RYGB compared with BMT. The ITT analyses jointly preserve baseline prognostic factors4 and assume that not all patients accept bariatric surgery as a therapeutic option. The ITT analysis can underestimate the magnitude of the clinical benefit of RYGB compared with BMT. However, compelling evidence indicates that ITT-based analyses provide the least biased estimate than other approaches such as modified ITT and per protocol analyses4 Ganesananthan et al were concerned about external validity, because the surgery was undertaken by a single, highly experienced surgeon in a single center. This is a valid point, but we are reassured that RYGB performed across the world is standardized, with subtle technical changes that do not interfere with safety or efficacy. Thus, it is very likely that any experienced bariatric surgeon would be able to reproduce these results. The concerns regarding long-term adverse effects in both groups will be addressed during the 5-year follow-up, but we hope that as CKD will decrease in both groups, harmful effects will not be amplified by CKD. The longer-term follow-up will also address concerns regarding meaningful kidney outcomes and the financial implications of treating patients similar to the cohort studied. Back to top Article Information Corresponding Author: Ricardo Vitor Cohen, MD, Oswaldo Cruz German Hospital, Rua Cincinato Braga 37, 5th Floor, São Paulo, 01333-010 SP, Brazil (ricardo.cohen@haoc.com.br). Published Online: November 18, 2020. doi:10.1001/jamasurg.2020.5192 Conflict of Interest Disclosures: Dr le Roux reported other support from Novo Nordisk, Herbalife, GI Dynamics, Keyron, and Johnson and Johnson during the conduct of the study. No other disclosures were reported. References 1. Cohen RV, Pereira TV, Aboud CM, et al. Effect of gastric bypass vs best medical treatment on early-stage chronic kidney disease in patients with type 2 diabetes and obesity: a randomized clinical trial.  JAMA Surg. Published online June 3, 2020. doi:10.1001/jamasurg.2020.0420PubMedGoogle Scholar 2. DeMets DL, Cook T. Challenges of non-intention-to-treat analyses.  JAMA. 2019;321(2):145-146. doi:10.1001/jama.2018.19192PubMedGoogle ScholarCrossref 3. Sheiner LB. Is intent-to-treat analysis always (ever) enough?  Br J Clin Pharmacol. 2002;54(2):203-211. doi:10.1046/j.1365-2125.2002.01628.xPubMedGoogle ScholarCrossref 4. Detry MA, Lewis RJ. The intention-to-treat principle: how to assess the true effect of choosing a medical treatment.  JAMA. 2014;312(1):85-86. doi:10.1001/jama.2014.7523PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Surgery American Medical Association

The Role of Bariatric Surgery in Prevention of Kidney Disease Progression in Moderately Obese Patients With Type 2 Diabetes—Reply

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Publisher
American Medical Association
Copyright
Copyright 2020 American Medical Association. All Rights Reserved.
ISSN
2168-6254
eISSN
2168-6262
DOI
10.1001/jamasurg.2020.5192
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Abstract

In Reply The Microvascular Outcomes After Metabolic Surgery (MOMS) study demonstrated that Roux-en-Y gastric bypass (RYGB) can be used to place early stages of chronic kidney disease (CKD) in patients with type 2 diabetes into remission.1 Patoulias et al suggested that remission of albuminuria was enhanced by RYGB because more of these patients at baseline received glucagon-like peptide-1 receptor agonist (GLP-1RA). A subanalysis of patients undergoing RYGB according to presurgery treatment with a GLP-1RA found that the treatment did not predict albuminuria response. It should be remembered that GLP-1RA were stopped immediately after RYGB, although metformin, angiotensin-converting enzyme inhibitors, and statins were continued where possible. Rees et al questioned why microalbuminuria was chosen as the primary outcome and not glycemia. This is a fundamental advantage of MOMS because the focus is shifting from weight loss and reduction in glycemia to health gain. The MOMS study was the first to show that complications of obesity and diabetes, such as CKD, can be reversed. They also pointed to the patients who were either at higher than or lower than the body mass index inclusion criteria when the interventions started. This is a challenge in all studies of bariatric surgery because when patients were recruited, they did fulfill the inclusion criteria, but when the study started, their weight may have crept higher than or lower than the inclusion criteria. We reviewed all the data, and there were no biases either way regarding group allocation, so this change was unlikely to bias the outcomes. Rees et al also commented on the risk of cross over from the best medical arm to the RYGB arm. Our protocol did not allow cross over between treatment groups. Ramos et al questioned the decision to proceed with an intention-to-treat (ITT), “modified” ITT, or per protocol analysis. We used a bona fide ITT analysis, which is the gold-standard approach for the analysis of superiority trials.2 Data from all participants were included (in the groups they were randomized), regardless of protocol deviations or the intervention they actually received. The ITT analyses measure the “use-effectiveness,”3 which is the effect of prescribing RYGB compared with the best medical treatment (BMT). Ramos et al described a more clinically focused estimate, the method efficacy, which is the effect of actually undergoing RYGB compared with BMT. The ITT analyses jointly preserve baseline prognostic factors4 and assume that not all patients accept bariatric surgery as a therapeutic option. The ITT analysis can underestimate the magnitude of the clinical benefit of RYGB compared with BMT. However, compelling evidence indicates that ITT-based analyses provide the least biased estimate than other approaches such as modified ITT and per protocol analyses4 Ganesananthan et al were concerned about external validity, because the surgery was undertaken by a single, highly experienced surgeon in a single center. This is a valid point, but we are reassured that RYGB performed across the world is standardized, with subtle technical changes that do not interfere with safety or efficacy. Thus, it is very likely that any experienced bariatric surgeon would be able to reproduce these results. The concerns regarding long-term adverse effects in both groups will be addressed during the 5-year follow-up, but we hope that as CKD will decrease in both groups, harmful effects will not be amplified by CKD. The longer-term follow-up will also address concerns regarding meaningful kidney outcomes and the financial implications of treating patients similar to the cohort studied. Back to top Article Information Corresponding Author: Ricardo Vitor Cohen, MD, Oswaldo Cruz German Hospital, Rua Cincinato Braga 37, 5th Floor, São Paulo, 01333-010 SP, Brazil (ricardo.cohen@haoc.com.br). Published Online: November 18, 2020. doi:10.1001/jamasurg.2020.5192 Conflict of Interest Disclosures: Dr le Roux reported other support from Novo Nordisk, Herbalife, GI Dynamics, Keyron, and Johnson and Johnson during the conduct of the study. No other disclosures were reported. References 1. Cohen RV, Pereira TV, Aboud CM, et al. Effect of gastric bypass vs best medical treatment on early-stage chronic kidney disease in patients with type 2 diabetes and obesity: a randomized clinical trial.  JAMA Surg. Published online June 3, 2020. doi:10.1001/jamasurg.2020.0420PubMedGoogle Scholar 2. DeMets DL, Cook T. Challenges of non-intention-to-treat analyses.  JAMA. 2019;321(2):145-146. doi:10.1001/jama.2018.19192PubMedGoogle ScholarCrossref 3. Sheiner LB. Is intent-to-treat analysis always (ever) enough?  Br J Clin Pharmacol. 2002;54(2):203-211. doi:10.1046/j.1365-2125.2002.01628.xPubMedGoogle ScholarCrossref 4. Detry MA, Lewis RJ. The intention-to-treat principle: how to assess the true effect of choosing a medical treatment.  JAMA. 2014;312(1):85-86. doi:10.1001/jama.2014.7523PubMedGoogle ScholarCrossref

Journal

JAMA SurgeryAmerican Medical Association

Published: Feb 18, 2021

References