Association Between Obesity and Chronic Kidney Disease: Multivariable Mendelian Randomization Analysis and Observational Data From a Bariatric Surgery Cohort
Bibliographic record
Abstract
Obesity is postulated to independently increase chronic kidney disease (CKD), even after adjusting for type 2 diabetes (T2D) and hypertension. Dysglycemia below T2D thresholds, frequently seen with obesity, also increases CKD risk. Whether obesity increases CKD independent of dysglycemia and hypertension is unknown and likely influences the optimal weight loss (WL) needed to reduce CKD. T2D remission rates plateau with 20-25% WL after bariatric surgery (BS), but further WL increases normoglycemia and normotension. We undertook bidirectional inverse variance weighted Mendelian randomization (IVWMR) to investigate potential independent causal associations between increased BMI and estimated glomerular filtration rate (eGFR) in CKD (CKDeGFR) (<60 mL/min/1.73 m2) and microalbuminuria (MA). In 5,337 BS patients, we assessed whether WL influences >50% decline in eGFR (primary outcome) or CKD hospitalization (secondary outcome), using <20% WL as a comparator. IVWMR results suggest that increased BMI increases CKDeGFR (b = 0.13, P = 1.64 × 10-4; odds ratio [OR] 1.14 [95% CI 1.07, 1.23]) and MA (b = 0.25; P = 2.14 × 10-4; OR 1.29 [1.13, 1.48]). After adjusting for hypertension and fasting glucose, increased BMI did not significantly increase CKDeGFR (b = -0.02; P = 0.72; OR 0.98 [0.87, 1.1]) or MA (b = 0.19; P = 0.08; OR 1.21 [0.98, 1.51]). Post-BS WL significantly reduced the primary outcome with 30 to <40% WL (hazard ratio [HR] 0.53 [95% CI 0.32, 0.87]) but not 20 to <30% WL (HR 0.72 [0.44, 1.2]) and ≥40% WL (HR 0.73 [0.41, 1.30]). For CKD hospitalization, progressive reduction was seen with increased WL, which was significant for 30 to <40% WL (HR 0.37 [0.17, 0.82]) and ≥40% WL (HR 0.24 [0.07, 0.89]) but not 20 to <30% WL (HR 0.60 [0.29, 1.23]). The data suggest that obesity is likely not an independent cause of CKD. WL thresholds previously associated with normotension and normoglycemia, likely causal mediators, may reduce CKD after BS.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".