The Effects of Bariatric Surgery on Kidney Oxygenation in Obese Adults With Type 2 Diabetes and Hyperfiltration

Recruiting

• Conditions: Kidney Hypoxia; Diabetes Mellitus, Type 2
• Interventions: Procedure: Bariatric surgery

• Registration Number: NCT06284785
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

In this study the investigators will examine the effects of VAT reduction by bariatric surgery on kidney hypoxia and compare kidney oxygenation before- and after surgery in both sexes using BOLD-MRI and measures of kidney hemodynamic function. Furthermore, the investigators will assess whether kidney oxygenation is reduced in obese T2D men and women versus various controls as described below. This will determine whether kidney hypoxia can be appointed as a modifiable pathogenic factor in early DKD and non-surgical interventions targeting kidney hypoxia can be designed to slow DKD progression.

Detailed Description

DKD (diabetic kidney disease) is the leading cause of chronic kidney disease (CKD) and leading to significant morbidity and early mortality. Although multiple mechanisms underlying DKD have been proposed, the exact underlying mechanisms remain uncertain resulting in limited treatment options. Accumulating evidence, derived from animal and human studies has indicated that chronic kidney hypoxia is a key underlying determinant of DKD and recent studies in T2D patients have related truncal obesity to glomerular hyperfiltration and unfavorable kidney hemodynamic function that may drive kidney hypoxia. Hyperfiltration is defined as increased whole-kidney GFR or as single-nephron hyperfiltration in people with GFR in the normal range. Hyperfiltration is an early recognized key factor driving kidney disease progression in people with diabetes as it drives subsequent eGFR loss. Increased and dysfunctional (i.e., altered adipose tissue biology) visceral adipose tissue (VAT) present in central obesity is thought to disturb the balance between kidney oxygen- consumption and delivery through secretion of endocrine signals resulting in induction of insulin resistance, mitochondrial dysfunction and impaired substrate metabolism amongst others. In line with this theory, reduction of abdominal obesity following bariatric surgery has demonstrated to improve kidney outcomes in some but not in all individuals. In part this may be sex-specific. Since women have a lower risk for progression of DKD, the role of kidney hypoxia in DKD need to be studied in this regard individualized for sex. In this study, the investigators will address the effects of bariatric surgery on changes in kidney oxygenation using a sex-specific approach in people with hyperfiltration.

Study Timeline

• Study Start: 2023-08-01
• Study First Submitted: 2023-08-03
• Status Verified: 2024-02
• Study First Submitted QC: 2024-02-28
• Last Update Submitted: 2024-02-28
• Study First Posted: 2024-02-29
• Last Update Posted: 2024-02-29
• Primary Completion: 2026-01-01
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Obese patients	Bariatric surgery	Obese patients with T2D and hyperfiltration that will undergo bariatric surgery

Primary Outcome Measures

Name	Time	Method
Difference in kidney oxygenation before and after bariatric surgery	1 year	BOLD-MRI

Secondary Outcome Measures

Name	Time	Method
Difference in kidney oxygenation between men and women	baseline, 1 year	BOLD-MRI
Difference in kidney oxygenation between obese, hyperfiltering men and women with T2D versus non-diabetic lean controls	Baseline	BOLD-MRI

Trial Locations

Locations (1)

VU University Medical Center; 🇳🇱 Amsterdam, Noord-Holland, Netherlands