Bariatric Surgery and Chronic Renal Disease

Obesity Clinical Trial

— BARICADE  

Official title:

Effect of Bariatric Surgery on Chronic Renal Disease (BARICADE): A Pilot Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05240443
• Other study ID #: 2022-14388-GRA
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2022
• Est. completion date: June 1, 2023

Study information

• Verified date: February 2022
• Source: McMaster University
• Contact: Yung Lee, MD
• Phone: 416 732 7306
• Email: yung.lee[@]medportal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: June 1, 2023
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Bariatric Surgery
• Chronic Kidney Diseases
• Kidney Diseases
• Kidney Failure, Chronic
• Obesity
• Renal Insufficiency, Chronic

Intervention

Procedure:
• 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.

Other:
• 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.

Locations

Country	Name	City	State
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
McMaster University	American College of Surgeons, McMaster Surgical Associates

Country where clinical trial is conducted

Canada, 

References & Publications (14)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. Erratum in: Am J Kidney Dis. 2017 May;69(5):712. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 6 months		Month 6
Primary	Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 12 months		Month 12
Primary	Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 18 months		Month 18
Primary	Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 6 months		Month 6
Primary	Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 12 months		Month 12
Primary	Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 18 months		Month 18
Primary	Creatine Clearance (units: mL/min) at 6 months		Month 6
Primary	Creatine Clearance (units: mL/min) at 12 months		Month 12
Primary	Creatine Clearance (units: mL/min) at 18 months		Month 18
Primary	Serum Creatinine (units: µmol/L) at 6 months		Month 6
Primary	Serum Creatinine (units: µmol/L) at 12 months		Month 12
Primary	Serum Creatinine (units: µmol/L) at 18 months		Month 18
Primary	Serum Cystatin C (units: mg/L) at 6 months		Month 6
Primary	Serum Cystatin C (units: mg/L) at 12 months		Month 12
Primary	Serum Cystatin C (units: mg/L) at 18 months		Month 18
Primary	Urine Albumin-Creatine Ratio (units: mg/g) at 6 months		Month 6
Primary	Urine Albumin-Creatine Ratio (units: mg/g) at 12 months		Month 12
Primary	Urine Albumin-Creatine Ratio (units: mg/g) at 18 months		Month 18
Secondary	Weight and height will be combined to report BMI in kg/m^2 at 6 months		Month 6
Secondary	Weight and height will be combined to report BMI in kg/m^2 at 12 months		Month 12
Secondary	Weight and height will be combined to report BMI in kg/m^2 at 18 months		Month 18
Secondary	Recruitment Rate (60 patients will be recruited at an average recruitment rate of 1.25 patients per site per month.)	60 patients will be recruited at an average recruitment rate of 1.25 patients per site per month.	Month 6
Secondary	Intervention Administration Rate	>80% of patients randomized to the intervention arm will undergo bariatric surgery within 30 days of randomization.	Month 6
Secondary	Crossover rate between control and intervention arm		Month 6
Secondary	Number of patients adhering to study treatments	Patients will be monitored and asked about adherence at follow-ups.	Month 6