Nowak Kristen L, Copeland Timothy P, Ku Elaine, Sarnak Mark J, Gitomer Berenice, Abebe Kaleab Z, Chapman Arlene, Perrone Ronald, Rahbari-Oskoui Frederic F, Steinman Theodore, Yu Alan S L, Chonchol Michel
Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Division of Nephrology, Department of Medicine University of California-San Francisco, San Francisco, California.
Clin J Am Soc Nephrol. 2025 Apr 1;20(4):520-528. doi: 10.2215/CJN.0000000640. Epub 2025 Feb 19.
Higher body mass index increased risk of progression to ESKD in patients with early-stage autosomal dominant polycystic kidney disease. Higher body mass index did not increase the risk of progression to ESKD in patients with late-stage autosomal dominant polycystic kidney disease.
Prior research has linked higher body mass index (BMI) and greater visceral adiposity with more rapid progression of early-stage autosomal dominant polycystic kidney disease (ADPKD). We now evaluate the association between overweight and obesity in patients with early- and late-stage ADPKD with progression to ESKD.
Participants with early-stage ADPKD (study A; =556; eGFR: 91±17 ml/min per 1.73 m) and late-stage ADPKD (study B; =483; eGFR: 48±12 ml/min per 1.73 m) who participated in the Halt Progression of Polycystic Kidney Disease (HALT) polycystic kidney disease trials were categorized by BMI as normal weight (18.5–24.9 kg/m; ref; =357), overweight (25.0–29.9 kg/m; =384), or obese (≥30 kg/m; =298). Kaplan–Meier survival analysis and multivariate Cox proportional hazard models were used to determine the association of baseline BMI as a continuous and categorical variable with risk of ESKD (according to the United States Renal Data System) over a median (interquartile range) follow-up period of 12.2 (7.5–13.3; study A) and 7.3 (5.1–11.7; study B) years (primary outcome). All-cause mortality (National Death Index) was also considered as a competing risk (Fine and Gray method).
The number of ESKD events was greater with overweight (=24) and obesity (=23) in HALT study A versus normal weight (=12) but not in HALT study B (normal weight: =89, overweight: =102, obese: =92). In fully adjusted models, higher BMI was associated with risk of progression to ESKD in study A (hazard ratio [HR (95% confidence interval)], 1.09 [1.03 to 1.15] per unit higher BMI) but not in study B (HR, 0.98 [0.96 to 1.00]). Obesity was associated with increased risk of ESKD (HR, 2.71 [1.22 to 6.02] versus normal weight) in study A only. Results were similar when considering death as a competing risk.
Higher BMI, particularly obesity, increased the risk of progression to ESKD in patients with early-stage ADPKD but not in those with late-stage ADPKD.
较高的体重指数增加了早期常染色体显性多囊肾病患者进展为终末期肾病（ESKD）的风险。较高的体重指数并未增加晚期常染色体显性多囊肾病患者进展为ESKD的风险。
先前的研究已将较高的体重指数（BMI）和更大的内脏脂肪与早期常染色体显性多囊肾病（ADPKD）更快速的进展联系起来。我们现在评估早期和晚期ADPKD患者超重和肥胖与进展为ESKD之间的关联。
参与多囊肾病进展停止（HALT）多囊肾病试验的早期ADPKD患者（研究A；n = 556；估算肾小球滤过率：91±17 ml/（min·1.73 m²））和晚期ADPKD患者（研究B；n = 483；估算肾小球滤过率：48±12 ml/（min·1.73 m²））根据BMI被分类为正常体重（18.5 - 24.9 kg/m²；参照组；n = 357）、超重（25.0 - 29.9 kg/m²；n = 384）或肥胖（≥30 kg/m²；n = 298）。采用Kaplan - Meier生存分析和多变量Cox比例风险模型来确定基线BMI作为连续和分类变量与在中位数（四分位间距）为12.2（7.5 - 13.3；研究A）和7.3（5.1 - 11.7；研究B）年的随访期内进展为ESKD（根据美国肾脏数据系统）的风险之间的关联（主要结局）。全因死亡率（国家死亡指数）也被视为竞争风险（Fine和Gray方法）。
在HALT研究A中，超重（n = 24）和肥胖（n = 23）患者发生ESKD事件的数量多于正常体重患者（n = 12），但在HALT研究B中并非如此（正常体重：n = 89，超重：n = 102，肥胖：n = 92）。在完全调整模型中，较高的BMI与研究A中进展为ESKD的风险相关（风险比[HR（95%置信区间）]，每单位较高BMI为1.09[1.03至1.15]），但在研究B中并非如此（HR，0.98[0.96至1.00]）。仅在研究A中，肥胖与ESKD风险增加相关（HR，2.71[1.22至6.02]对比正常体重）。将死亡视为竞争风险时结果相似。
较高的BMI，尤其是肥胖，增加了早期ADPKD患者进展为ESKD的风险，但未增加晚期ADPKD患者的风险。
