Supplementary Material for: The Impact of Primary Renal Diagnosis on Prognosis and the Varying Predictive Power of Albuminuria in the NURTuRE-CKD Study

Introduction
The definition of CKD is broad, which neglects the heterogeneity of risk across primary renal diseases.

Methods
The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD is an ongoing UK, prospective multicentre cohort study of 2996 adults with an eGFR of 15–59 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73 m2 with a uACR >30 mg/mmol. Outcomes and predictive performance of eGFR and uACR were subcategorized by ERA-EDTA primary renal diagnosis (PRD) codes.

Results
2638 participants were included, with baseline median eGFR of 33.5ml/min/1.73m2 and uACR 29.8 mg/mmol. Over a median 49.2 months follow-up, 630 (23.9%) experienced kidney failure (KF), and 352 (13.3%) died before KF, the median eGFR slope was -1.97 ml/min/1.73m2/year. There were significant differences in risk across the PRD, persisting after adjustment for age, sex, baseline eGFR and modifiable risk factors (Blood pressure, HbA1c and renin-angiotensin-aldosterone system inhibitors (RAASi). Diabetic kidney disease, glomerulonephritis and familial/hereditary nephropathy were associated with the greatest risk, while tubulointerstitial disease and vasculitis carried a low risk of KF. eGFR had good predictive accuracy across all PRD. However, the addition of uACR showed variable benefit, depending on the PRD. The largest benefit was seen in vasculitis, renal vascular, and DKD groups, but uACR added no predictive value to the familial/hereditary group.

Conclusion
Significant differences in the risk of kidney related outcomes occurred across the various primary renal diagnoses persisting after adjustment for age, sex, baseline eGFR and modifiable risk factors. Albuminuria's discriminatory ability as a biomarker of progression varies by diagnosis. CKD care should, therefore, take a personalized approach that always considers the primary renal diagnosis.

引言
慢性肾脏病（Chronic Kidney Disease, CKD）的定义较为宽泛，忽略了不同原发性肾脏疾病之间的风险异质性。

方法
国家统一肾脏转化研究企业（National Unified Renal Translational Research Enterprise, NURTuRE）-CKD是一项正在英国开展的前瞻性多中心队列研究，共纳入2996名成年受试者，其估算肾小球滤过率（estimated Glomerular Filtration Rate, eGFR）为15~59 mL/min/1.73m²，或eGFR≥60 mL/min/1.73m²且尿白蛋白肌酐比（urinary albumin-to-creatinine ratio, uACR）＞30 mg/mmol。研究根据欧洲肾移植协会-欧洲透析与移植协会（European Renal Association-European Dialysis and Transplant Association, ERA-EDTA）的原发性肾脏诊断（Primary Renal Diagnosis, PRD）编码，对eGFR与uACR的临床结局及预测性能进行亚组分层分析。

结果
最终纳入2638名受试者，基线时中位eGFR为33.5 mL/min/1.73m²，中位uACR为29.8 mg/mmol。经过中位49.2个月的随访，630例（23.9%）发生肾衰竭（Kidney Failure, KF），其中352例（13.3%）在发生KF前死亡；受试者的中位eGFR年下降速率为-1.97 mL/min/1.73m²。不同PRD组间的肾衰竭风险存在显著差异，且在校正年龄、性别、基线eGFR及可干预危险因素（血压、糖化血红蛋白（glycated hemoglobin A1c, HbA1c）、肾素-血管紧张素-醛固酮系统抑制剂（renin-angiotensin-aldosterone system inhibitors, RAASi））后，该差异依然存在。糖尿病肾病（Diabetic Kidney Disease, DKD）、肾小球肾炎及家族性/遗传性肾病患者的肾衰竭风险最高，而肾小管间质性疾病与血管炎患者的KF风险较低。eGFR在所有PRD组中均表现出良好的预测准确性，但加入uACR后的获益程度因PRD组而异：在血管炎、肾血管疾病及DKD组中，uACR的预测增益最为显著；而在家族性/遗传性肾病组中，uACR未提供额外的预测价值。

结论
在校正年龄、性别、基线eGFR及可干预危险因素后，不同原发性肾脏疾病患者的肾脏相关结局风险仍存在显著差异。白蛋白尿作为疾病进展生物标志物的鉴别能力因诊断类型而异。因此，慢性肾脏病CKD的临床诊疗应采用个体化方案，且需始终结合原发性肾脏诊断进行决策。