Bariatric Surgery and Chronic Renal Disease

NCT ID: NCT05240443

Last Updated: 2022-02-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2023-06-01

Brief Summary

Obesity can be a major driver for the development of chronic kidney disease (CKD), which is a leading cause of death and significant loss in quality of life. A growing body of evidence has shown bariatric (metabolic) surgery as a novel approach to reduce the progression of CKD and reduce morbidity with sustained weight loss. This pilot trial will inform the design and execution of a large RCT that could determine the efficacy of bariatric surgery in the treatment of patients with CKD in the context of obesity. Ultimately, the results have the potential to influence guidelines that may deem bariatric surgery as a viable treatment option for CKD and reduce the morbidity from this chronic condition and inform clinical practice.

Detailed Description

Obesity is a major driver for the development of CKD, which is a leading cause of death and greatly reduces one's quality of life. With a global prevalence of 9.1% (7.2% in Canada), CKD affects an estimated 13.6% of the American population and was associated with over $50 billion in healthcare costs, with an additional $30 billion in costs associated with end-stage renal disease (ESRD). Moreover, with an aging Canadian population, the prevalence of CKD is expected to rise over the coming years with patients progressing to higher disease burdens. This, in part, has led to a substantial increase in renal replacement therapy by means of dialysis or kidney transplant by 43.1% since 1990. Obesity is also an important modulatory factor in the development of poor outcomes as a result of CKD and has been linked to an increased rate of progression from CKD towards kidney failure. The most common comorbidities in patients with CKD were hypertension, diabetes, heart failure, chronic pulmonary disease, and atrial fibrillation and in Canada, 25% of patients with CKD have at least 3 or more comorbidities which too are associated with an increased risk of hospitalization and early death. Most worryingly, unlike other non-communicable diseases today, the age-standardized mortality for CKD has not declined over the past decades. Therefore, innovative strategies are of timely importance to reduce mortality and morbidity in patients with CKD and thus urgently needed, especially in patients with multiple comorbidities and targeting weight loss is a promising avenue to find novel treatment options.

Bariatric surgery has been shown to not only facilitate sustained weight loss in patients with obesity, but also independently improve cardiac risk factors such as dyslipidemia, hypertension, and type 2 diabetes mellitus. It has also been shown to reverse glomerular hyperfiltration and lower proteinuria in patients with obesity and normal kidney function and delay the need for renal transplantation in patients with ESRD. Moreover, the protective benefit of bariatric surgery has been shown to reduce risk of CKD progression for up to seven years after intervention in observational studies. However, current guidelines do not address a role for bariatric surgery in the management of patients with obesity and CKD.

Given the poor outcomes with patients with obesity and CKD, a RCT to assess the efficacy and safety of bariatric surgery as an intervention for patients with CKD is of timely importance. The present proposed pilot RCT of bariatric surgery versus medical management alone for patients with morbid obesity and CKD in order to assess whether a large, multi-centre, efficacy trial is feasible. The results of the proposed pilot study will thus inform the design of a larger RCT in this patient population.

Conditions

Bariatric Surgery; Chronic Kidney Diseases; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bariatric Surgery + Medical Management for Chronic Kidney Disease

The intervention group will include medical management and bariatric surgery, which will consist of Roux-en-Y gastric bypass or sleeve gastrectomy performed according to local practice standards. Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of \<140/90 mmHg (\<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein \<2mmol/L for the treatment of CKD.

Group Type: EXPERIMENTAL

Bariatric Surgery + Medical Management of CKD.

Intervention Type: PROCEDURE

The intervention group will include medical management and bariatric surgery, which will consist of Roux-en-Y gastric bypass or sleeve gastrectomy performed according to local practice standards. Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of \<140/90 mmHg (\<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein \<2mmol/L for the treatment of CKD.

Medical Management for Chronic Kidney Disease

Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of \<140/90 mmHg (\<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein \<2mmol/L for the treatment of CKD.

Group Type: ACTIVE_COMPARATOR

Medical Management for CKD

Intervention Type: OTHER

Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of \<140/90 mmHg (\<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein \<2mmol/L for the treatment of CKD.

Interventions

Bariatric Surgery + Medical Management of CKD.

The intervention group will include medical management and bariatric surgery, which will consist of Roux-en-Y gastric bypass or sleeve gastrectomy performed according to local practice standards. Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of \<140/90 mmHg (\<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein \<2mmol/L for the treatment of CKD.

Intervention Type: PROCEDURE

Medical Management for CKD

Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of \<140/90 mmHg (\<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein \<2mmol/L for the treatment of CKD.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patient age >18
• Body mass index > 40 (or > 35 kg/m2 for patients with comorbidities)
• Diagnosis of CKD stage III (G3a or A2) defined as the presence of any of the following:

1. glomerular filtration rate (GFR) under 60 mL/min/1.73 m2 as estimated from serum creatinine or cystatin C with the CKD-EPI equation

2. ACR > 30 mg/g

• Patient is deemed eligible to undergo bariatric surgery according to Ontario Bariatric Network (OBN) guidelines [contradictions to OBN guidelines include non-Ontario resident, age >70 years, history of cancer <2 years, current substance use disorder, accessed palliative care, previous organ transplant (liver, heart, or lungs), active cardiac disease, major revascularization procedures within 6 months, or severe liver disease with ascites <1 year]

Exclusion Criteria

• Hospital admission for kidney failure or acute kidney injury within 30 days of enrollment
• Documented GFR > 60 mL/min/1.73 m2 or ACR < 30 mg/g within 30 days of enrollment
• Documented confounders of kidney function measurement such as urinary tract infection or use of creatinine elevating medications or use of medications which interfere with measurement
• Contradiction to OBN guidelines including non-Ontario resident, age >70 years, history of cancer <2 years, current substance use disorder, accessed palliative care, previous organ transplant (liver, heart, or lungs), active cardiac disease, major revascularization procedures within 6 months, or severe liver disease with ascites <1 year
• Life expectancy <2 years due to non-CKD causes OR Untreated or inadequately treated psychiatric illness OR Risk of general anesthesia deemed too excessive OR Inability to provide informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American College of Surgeons

OTHER

Sponsor Role: collaborator

McMaster Surgical Associates

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Dennis Hong MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dennis Hong, MD MSc FRCSC

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Countries

Canada

Central Contacts

Yung Lee, MD

Role: CONTACT

yung.lee@medportal.ca

416 732 7306

Facility Contacts

Yung Lee, MD

Role: primary

yung.lee@medportal.ca

4167327306

Dennis Hong, MD

Role: backup

dennishong70@gmail.com

9055221155 ext. 35148

References

Saran R, Robinson B, Abbott KC, Agodoa LY, Albertus P, Ayanian J, Balkrishnan R, Bragg-Gresham J, Cao J, Chen JL, Cope E, Dharmarajan S, Dietrich X, Eckard A, Eggers PW, Gaber C, Gillen D, Gipson D, Gu H, Hailpern SM, Hall YN, Han Y, He K, Hebert H, Helmuth M, Herman W, Heung M, Hutton D, Jacobsen SJ, Ji N, Jin Y, Kalantar-Zadeh K, Kapke A, Katz R, Kovesdy CP, Kurtz V, Lavalee D, Li Y, Lu Y, McCullough K, Molnar MZ, Montez-Rath M, Morgenstern H, Mu Q, Mukhopadhyay P, Nallamothu B, Nguyen DV, Norris KC, O'Hare AM, Obi Y, Pearson J, Pisoni R, Plattner B, Port FK, Potukuchi P, Rao P, Ratkowiak K, Ravel V, Ray D, Rhee CM, Schaubel DE, Selewski DT, Shaw S, Shi J, Shieu M, Sim JJ, Song P, Soohoo M, Steffick D, Streja E, Tamura MK, Tentori F, Tilea A, Tong L, Turf M, Wang D, Wang M, Woodside K, Wyncott A, Xin X, Zang W, Zepel L, Zhang S, Zho H, Hirth RA, Shahinian V. US Renal Data System 2016 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2017 Mar;69(3 Suppl 1):A7-A8. doi: 10.1053/j.ajkd.2016.12.004. No abstract available.

Reference Type: BACKGROUND

PMID: 28236831 (View on PubMed)

Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of chronic kidney disease in the United States. JAMA. 2007 Nov 7;298(17):2038-47. doi: 10.1001/jama.298.17.2038.

Reference Type: BACKGROUND

PMID: 17986697 (View on PubMed)

Bello AK, Ronksley PE, Tangri N, Kurzawa J, Osman MA, Singer A, Grill A, Nitsch D, Queenan JA, Wick J, Lindeman C, Soos B, Tuot DS, Shojai S, Brimble S, Mangin D, Drummond N. Prevalence and Demographics of CKD in Canadian Primary Care Practices: A Cross-sectional Study. Kidney Int Rep. 2019 Jan 21;4(4):561-570. doi: 10.1016/j.ekir.2019.01.005. eCollection 2019 Apr.

Reference Type: BACKGROUND

PMID: 30993231 (View on PubMed)

GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020 Feb 29;395(10225):709-733. doi: 10.1016/S0140-6736(20)30045-3. Epub 2020 Feb 13.

Reference Type: BACKGROUND

PMID: 32061315 (View on PubMed)

Eknoyan G. Obesity and chronic kidney disease. Nefrologia. 2011;31(4):397-403. doi: 10.3265/Nefrologia.pre2011.May.10963. Epub 2011 May 30.

Reference Type: BACKGROUND

PMID: 21623393 (View on PubMed)

Tonelli M, Wiebe N, Guthrie B, James MT, Quan H, Fortin M, Klarenbach SW, Sargious P, Straus S, Lewanczuk R, Ronksley PE, Manns BJ, Hemmelgarn BR. Comorbidity as a driver of adverse outcomes in people with chronic kidney disease. Kidney Int. 2015 Oct;88(4):859-66. doi: 10.1038/ki.2015.228. Epub 2015 Jul 29.

Reference Type: BACKGROUND

PMID: 26221754 (View on PubMed)

Cockwell P, Fisher LA. The global burden of chronic kidney disease. Lancet. 2020 Feb 29;395(10225):662-664. doi: 10.1016/S0140-6736(19)32977-0. Epub 2020 Feb 13. No abstract available.

Reference Type: BACKGROUND

PMID: 32061314 (View on PubMed)

Docherty NG, le Roux CW. Bariatric surgery for the treatment of chronic kidney disease in obesity and type 2 diabetes mellitus. Nat Rev Nephrol. 2020 Dec;16(12):709-720. doi: 10.1038/s41581-020-0323-4. Epub 2020 Aug 10.

Reference Type: BACKGROUND

PMID: 32778788 (View on PubMed)

Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012 Apr 26;366(17):1567-76. doi: 10.1056/NEJMoa1200225. Epub 2012 Mar 26.

Reference Type: BACKGROUND

PMID: 22449319 (View on PubMed)

Chagnac A, Weinstein T, Herman M, Hirsh J, Gafter U, Ori Y. The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol. 2003 Jun;14(6):1480-6. doi: 10.1097/01.asn.0000068462.38661.89.

Reference Type: BACKGROUND

PMID: 12761248 (View on PubMed)

Al-Bahri S, Fakhry TK, Gonzalvo JP, Murr MM. Bariatric Surgery as a Bridge to Renal Transplantation in Patients with End-Stage Renal Disease. Obes Surg. 2017 Nov;27(11):2951-2955. doi: 10.1007/s11695-017-2722-6.

Reference Type: BACKGROUND

PMID: 28500419 (View on PubMed)

Friedman AN, Wahed AS, Wang J, Courcoulas AP, Dakin G, Hinojosa MW, Kimmel PL, Mitchell JE, Pomp A, Pories WJ, Purnell JQ, le Roux C, Spaniolas K, Steffen KJ, Thirlby R, Wolfe B. Effect of Bariatric Surgery on CKD Risk. J Am Soc Nephrol. 2018 Apr;29(4):1289-1300. doi: 10.1681/ASN.2017060707. Epub 2018 Jan 15.

Reference Type: BACKGROUND

PMID: 29335242 (View on PubMed)

Friedman AN, Miskulin DC, Rosenberg IH, Levey AS. Demographics and trends in overweight and obesity in patients at time of kidney transplantation. Am J Kidney Dis. 2003 Feb;41(2):480-7. doi: 10.1053/ajkd.2003.50059.

Reference Type: BACKGROUND

PMID: 12552513 (View on PubMed)

Bolignano D, Zoccali C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrol Dial Transplant. 2013 Nov;28 Suppl 4:iv82-98. doi: 10.1093/ndt/gft302. Epub 2013 Oct 2.

Reference Type: BACKGROUND

PMID: 24092846 (View on PubMed)

Other Identifiers

2022-14388-GRA

Identifier Type: -

Identifier Source: org_study_id