Proteinuria Is Independently Associated with Impaired Gallbladder Emptying in Biopsy-Proven Glomerular Disease with...

Background/Objectives: Gallbladder emptying is primarily regulated by postprandial cholecystokinin release. In proteinuric glomerular diseases, renal loss of peptide hormones, hormone-binding proteins, or related regulatory proteins may affect biliary motility. However, gallbladder function has not been adequately investigated in individuals with proteinuric glomerular disease. This study evaluated the association between proteinuria and gallbladder emptying in patients with preserved kidney function and biopsy-proven glomerular disease. Methods: This single-center ultrasonographic case-control study with prospective participant enrollment and data collection included 106 participants: 52 patients with biopsy-proven proteinuric glomerular disease and 54 healthy controls without proteinuria. The proteinuric patient group consisted of individuals diagnosed with primary glomerulonephritis or amyloid A (AA) amyloidosis. Acute kidney injury, estimated glomerular filtration rate <60 mL/min/1.73 m², cholelithiasis, liver disease, diabetes mellitus, previous upper gastrointestinal surgery, pregnancy, oral contraceptive use, and recent rapid weight loss were considered exclusion criteria. After an overnight fast of at least 8 h, fasting gallbladder volume was measured by ultrasonography and recorded as baseline volume (V0). Gallbladder volume was measured again 45 min after stimulation with a standardized 40 g chocolate meal and recorded as postprandial volume (V45). Gallbladder volume was calculated using the ellipsoid formula, and gallbladder ejection fraction (GBEF) was calculated as [(V0 - V45)/V0] × 100. GBEF <40% was used as a predefined clinical threshold for impaired gallbladder emptying. In the primary analysis, the association between proteinuria status and GBEF as a continuous outcome was evaluated using a multivariable linear regression model adjusted for age, sex, body mass index, and family history of gallstones. Impaired gallbladder emptying, operationally defined as GBEF <40% for the supportive secondary binary outcome, was examined using multivariable logistic regression model adjusted for the same covariates. Results: Compared with controls, proteinuric patients had significantly higher postprandial gallbladder volume at 45 min: 15,614.04 ± 9148.35 mm³ versus 10,346.89 ± 5254.17 mm³ (p = 0.0003). GBEF was significantly lower in the proteinuria group than in healthy controls: 41.76% ± 19.64 versus 53.10% ± 20.22; mean difference, -11.34 percentage points (95% confidence interval, -19.02 to -3.66; p = 0.0042). Impaired gallbladder emptying was more frequently observed in the proteinuria group: 48.1% versus 27.8% (p = 0.031). In unadjusted analysis, the presence of proteinuria was associated with a 2.41-fold increase in the odds of impaired gallbladder emptying. This association remained statistically significant after adjustment for age, sex, and body mass index: adjusted odds ratio, 2.95 (95% confidence interval, 1.17-7.47; p = 0.022). Among proteinuric patients, GBEF did not differ significantly according to nephrotic versus non-nephrotic proteinuria, serum albumin level, serum total protein level, or histopathological diagnostic subgroup. Conclusions: In individuals with preserved kidney function and biopsy-proven glomerular disease, proteinuria was associated with impaired postprandial gallbladder emptying, and this association persisted after multivariable adjustment. These findings suggest that gallbladder dysmotility may represent a potentially relevant functional feature of proteinuric kidney disease; however, its biological basis and clinical consequences remain to be established. Prospective studies incorporating cholecystokinin measurements, duration of proteinuria, and longitudinal clinical follow-up are needed to clarify these issues.