Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function
Larger Nephron Size and Nephrosclerosis Predict Progressive CKD and Mortality after Radical Nephrectomy for Tumor and Independent of Kidney Function
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DOI：
10.1681/asn.2020040449
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发表时间：
2020-11-01
影响因子：
13.6
通讯作者：
Rule, Andrew D.
中科院分区：
文献类型：
--
作者：
Denic, Aleksandar;Elsherbiny, Hisham;Rule, Andrew D.
背景肾小球肥大和肾硬化可能是慢性肾脏病和死亡率的重要决定因素。然而，与这些微结构特征相关的结果研究仅限于来自肾脏健康状况良好或已知肾脏疾病的患者的小组织样本。方法为了确定微结构特征是否可以预测进展的CKD和死亡结果，我们研究了因肿瘤而接受根治性肾切除术的患者。肿瘤远端肾实质的大楔形切片被染色并扫描成高分辨率图像；我们对皮质和所有肾小球进行注释，以计算肾小球体积、每个肾小球的皮质体积和整体硬化肾小球的百分比。形态计量学测量还包括动脉管腔狭窄和皮质间质纤维化/肾小管萎缩(IF/TA)的百分比。在每6-12个月的随访中，我们确定哪些患者经历了进展性CKD(定义为透析、肾移植或肾切除后EGFR下降40%)。这些结果的Cox模型根据年龄、性别、体重指数、高血压、糖尿病、吸烟、EGFR和蛋白尿进行了调整。结果在936例患者(平均年龄为；肾切除后基线EGFR为48ml/min/1.73m(2))中，117例发生进展性慢性肾脏病，183例非肿瘤死亡，116例肿瘤死亡。较大的肾小球体积、较大的每个肾小球皮质和较高的整体硬化性肾小球百分比或IF/TA预测进展性CKD。更高比例的IF/TA也可以预测非癌症死亡率。微结构特征并不能预测癌症的死亡率或复发。结论在根治性肾切除术后，较大的肾单位和肾硬化预示着进展性CKD，IF/TA预示着非癌症死亡率。肾实质的形态计量学分析可以预测根治性肾切除术后长期患者的非癌症临床事件。根据肾组织学预测根治性肾切除术后结果的意义陈述仅限于样本量小、随访时间短和仅有组织学描述性特征的研究。在这项研究中，936名患者在建立了根治性肾切除术后新的基线肾功能后平均随访6.4年，作者使用形态计量学方法定量描述了大肾楔形切片上的微结构特征。较大的肾脏和更广泛的肾小球硬化和间质纤维化的结果预测进展性CKD；间质纤维化也预测癌症以外的其他原因的死亡率。这些发现有助于深入了解非特定肾脏疾病患者中“普通”CKD的重要微观结构特征，并支持使用定量方法评估根治性肾切除术后的肾组织学，以确定患者的长期风险。
Background Nephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease. Methods To determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6-12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or a 40% decline from postnephrectomy eGFR). Cox models for these outcomes were adjusted for age, sex, body mass index, hypertension, diabetes, smoking, eGFR, and proteinuria. Results Among 936 patients (mean age, 64 years; postnephrectomy baseline eGFR, 48 ml/min per 1.73 m(2)), 117 progressive CKD events, 183 noncancer deaths, and 116 cancer deaths occurred during a median follow-up of 6.4 years. Larger glomerular volume, larger cortex per glomerulus, and higher percentage of globally sclerotic glomeruli or IF/TA predicted progressive CKD. Higher percentage IF/TA also predicted noncancer mortality. Microstructural features did not predict cancer mortality or recurrence. Conclusions After a radical nephrectomy, larger nephrons and nephrosclerosis predicted progressive CKD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.Significance Statement Predicting outcomes on the basis of renal histology after a radical nephrectomy has been limited to studies with small sample sizes, short follow-ups, and only a descriptive characterization of histology. In this study of 936 patients followed up for a median of 6.4 years after establishing a new baseline kidney function following radical nephrectomy, the authors used morphometric methods to quantitatively characterize microstructural features on large renal wedge sections. Findings of larger nephrons and more extensive glomerulosclerosis and interstitial fibrosis predicted progressive CKD; interstitial fibrosis also predicted mortality from causes other than cancer. These findings provide insight into the important microstructural features of "generic" CKD in patients without a specific kidney disease and support the use of quantitative methods to evaluate renal histology after a radical nephrectomy to determine patients' long-term risks.