验证 IgA 肾病 CKD 进展理论的某些病理生理机制和结局预测。
Validation of some pathophysiological mechanisms of the CKD progression theory and outcome prediction in IgA nephropathy.
机构信息
D'Amico Foundation for Renal Diseases Research, Milan, Italy.
出版信息
J Nephrol. 2012 Sep-Oct;25(5):810-8. doi: 10.5301/jn.5000069.
BACKGROUND
The "remnant kidney" chronic kidney disease (CKD) progression theory based on hemodynamic, proteinuric and inflammatory mechanisms consequent to nephron loss has not been confirmed in a human disease. The aim of this study was to evaluate whether some of these mechanisms are present in IgA nephropathy (IgAN) and predict functional outcome.
METHODS
In 132 IgAN patients (68 untreated, 64 angiotensin-converting enzyme inhibitor [ACEi]-treated) fractional excretion of IgG (FEIgG) and α1-microglobulin, proteinuria/day and β-NAG excretion were divided by percentage of nonglobally sclerotic glomeruli ("surviving glomeruli" [SG]) to assess the effective glomerular loss and tubular load of proteins in surviving nephrons. Proteinuric markers were compared between 4 SG groups: group 1: ≤50%; group 2: >50% and <80%; group 3: ≥80% and <100%; and group 4: 100%. The outcome prediction (estimated glomerular filtration rate [eGFR] improvement and stability, progression) was assessed comparing low- and high-risk groups for each marker.
RESULTS
Proteinuric markers showed increasing values in parallel with reduction of percentages of SG (p<0.0001). FEIgG/SG, 40-fold higher in patients with SG ≤50% vs. SG=100% (0.00040 ± 0.00039 vs. 0.00001 ± 0.00002, p<0.0001), was the most powerful outcome predictor: in ACEi-untreated patients, FEIgG/SG less or greater than 0.00010 predicted eGFR improvement and stability (88% vs. 12%, p<0.0001) and end-stage renal disease (ESRD) + eGFR reduction ≥50% (2% vs. 87.5%, p<0.0001); ACEi treatment reduced ESRD+eGFR reduction ≥50%: 36% vs. 87.5% (p=0.002). In patients with FEIgG/SG <0.00010 the eGFR increase is significantly higher in ACEi-treated for ≥70 months versus ACEi-untreated with follow up ≥70 months (+35% ± 23% vs. +13% ± 8%, p=0.004).
CONCLUSIONS
In IgAN, progressive nephron loss is associated with an increase of proteinuric markers of glomerular and tubular damage. FEIgG/SG is the best outcome predictor. These data represent the first validation in a human disease of some pathophysiological mechanisms of CKD progression theory.
背景
基于肾单位丢失导致的血流动力学、蛋白尿和炎症机制的“残余肾脏”慢性肾脏病（CKD）进展理论尚未在人类疾病中得到证实。本研究旨在评估这些机制中的某些机制是否存在于 IgA 肾病（IgAN）中，并预测其功能结局。
方法
在 132 例 IgAN 患者（68 例未治疗，64 例血管紧张素转换酶抑制剂[ACEi]治疗）中，通过肾小球总数（“存活肾小球”[SG]）的百分比评估 IgG （FEIgG）和α1-微球蛋白、蛋白尿/天和β-NAG 排泄的分数排泄，以评估存活肾单位中的有效肾小球丢失和蛋白质管状负荷。在 4 个 SG 组之间比较蛋白尿标志物：组 1：≤50%；组 2：>50%且<80%；组 3：≥80%且<100%；组 4：100%。通过比较每个标志物的低危和高危组来评估预后预测（估计肾小球滤过率[eGFR]改善和稳定性、进展）。
结果
蛋白质标志物的数值随着 SG 百分比的降低而呈递增趋势（p<0.0001）。SG≤50%的患者 FEIgG/SG 比 SG=100%的患者高 40 倍（0.00040±0.00039 比 0.00001±0.00002，p<0.0001），是最强的预后预测指标：在 ACEi 未治疗的患者中，FEIgG/SG 小于或大于 0.00010 预测 eGFR 改善和稳定性（88%比 12%，p<0.0001）和终末期肾脏疾病（ESRD）+eGFR 下降≥50%（2%比 87.5%，p<0.0001）；ACEi 治疗降低了 ESRD+eGFR 下降≥50%：36%比 87.5%（p=0.002）。在 FEIgG/SG<0.00010 的患者中，ACEi 治疗≥70 个月的 eGFR 增加明显高于 ACEi 未治疗且随访≥70 个月的患者（+35%±23%比+13%±8%，p=0.004）。
结论
在 IgAN 中，进行性肾单位丢失与肾小球和肾小管损伤的蛋白尿标志物增加相关。FEIgG/SG 是最好的预后预测指标。这些数据代表了在人类疾病中对 CKD 进展理论的一些病理生理机制的首次验证。
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