Association Between Obesity and Chronic Kidney Disease: Multivariable Mendelian Randomization Analysis and...

Area of Science:

• Nephrology
• Metabolic Disorders
• Bariatric Surgery

Background:

• Obesity is a suspected independent risk factor for chronic kidney disease (CKD), even when accounting for type 2 diabetes (T2D) and hypertension.
• Sub-diabetic dysglycemia, common in obesity, also elevates CKD risk.
• The independent contribution of obesity to CKD, separate from dysglycemia and hypertension, remains unclear, impacting optimal weight loss (WL) targets for CKD reduction.

Purpose of the Study:

• To investigate the independent causal relationship between increased body mass index (BMI) and chronic kidney disease (CKD) using Mendelian randomization.
• To evaluate the impact of varying degrees of WL after bariatric surgery (BS) on CKD progression and hospitalization rates.

Main Methods:

• Bidirectional inverse variance weighted Mendelian randomization (IVWMR) was employed to assess the causal links between BMI and CKD indicators (eGFR decline, microalbuminuria).
• A cohort of 5,337 bariatric surgery patients was analyzed to determine the association between WL percentages and CKD outcomes (eGFR decline, CKD hospitalization).

Main Results:

• Initial IVWMR suggested increased BMI causally linked to CKD (reduced eGFR and microalbuminuria).
• However, after adjusting for hypertension and fasting glucose, these associations were no longer significant, indicating obesity may not be an independent driver of CKD.
• WL of 30% to <40% after BS significantly reduced the primary outcome (eGFR decline), and greater WL (≥40%) showed significant reductions in CKD hospitalizations.

Conclusions:

• The findings suggest that obesity is unlikely to be an independent cause of CKD.
• Weight loss thresholds associated with improved glycemic control and blood pressure normalization appear crucial for mitigating CKD risk post-bariatric surgery.
• Achieving substantial WL (30-40% or more) is associated with significant reductions in CKD progression and hospitalization after BS.