Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor Michigan;
Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania.
J Am Soc Nephrol. 2019 Jul;30(7):1305-1313. doi: 10.1681/ASN.2018121227. Epub 2019 Jun 6.
Levels of soluble urokinase plasminogen activator receptor (suPAR), an inflammation marker, are strongly predictive of incident kidney disease. Patients with autosomal dominant polycystic kidney disease (ADPKD) experience progressive decline in renal function, but rates of decline and outcomes vary greatly. Whether suPAR levels are predictive of declining kidney function in patients with ADPKD is unknown.
We assessed suPAR levels in 649 patients with ADPKD who underwent scheduled follow-up for at least 3 years, with repeated measurements of height-adjusted total kidney volume and creatinine-derived eGFR. We used linear mixed models for repeated measures and Cox proportional hazards to characterize associations between baseline suPAR levels and follow-up eGFR or incident ESRD.
The median suPAR level was 2.47 ng/ml and median height-adjusted total kidney volume was 778, whereas mean eGFR was 84 ml/min per 1.73 m. suPAR levels were associated with height-adjusted total kidney volume (=0.02; 95% confidence interval, 0.01 to 0.03), independent of age, sex, race, hypertension, and eGFR. Patients in the lowest suPAR tertile (<2.18 ng/ml) had a 6.8% decline in eGFR at 3 years and 22% developed CKD stage 3, whereas those in the highest tertile (suPAR>2.83 ng/ml) had a 19.4% decline in eGFR at 3 years and 68% developed CKD stage 3. suPAR levels >2.82 ng/ml had a 3.38-fold increase in the risk of incident ESRD.
suPAR levels were associated with progressive decline in renal function and incident ESRD in patients with ADPKD, and may aid early identification of patients at high risk of disease progression.
可溶性尿激酶型纤溶酶原激活物受体（suPAR）水平是炎症标志物，与肾病的发生具有很强的预测性。常染色体显性多囊肾病（ADPKD）患者的肾功能逐渐下降，但下降速度和结果差异很大。suPAR 水平是否可预测 ADPKD 患者肾功能下降尚不清楚。
我们评估了 649 例 ADPKD 患者的 suPAR 水平，这些患者至少进行了 3 年的定期随访，反复测量身高校正的总肾体积和肌酐衍生的 eGFR。我们使用线性混合模型进行重复测量和 Cox 比例风险模型来描述基线 suPAR 水平与随访 eGFR 或终末期肾病（ESRD）的相关性。
suPAR 中位数为 2.47ng/ml，身高校正的总肾体积中位数为 778ml，平均 eGFR 为 84ml/min/1.73m。suPAR 水平与身高校正的总肾体积相关（=0.02；95%置信区间，0.01 至 0.03），与年龄、性别、种族、高血压和 eGFR 无关。suPAR 最低三分位数（<2.18ng/ml）的患者在 3 年内 eGFR 下降 6.8%，22%进展为 CKD3 期，而 suPAR 最高三分位数（suPAR>2.83ng/ml）的患者在 3 年内 eGFR 下降 19.4%，68%进展为 CKD3 期。suPAR 水平>2.82ng/ml 的患者发生 ESRD 的风险增加 3.38 倍。
suPAR 水平与 ADPKD 患者的肾功能进行性下降和 ESRD 的发生相关，可能有助于早期识别疾病进展风险较高的患者。
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