Wu Qiaoyan, Troost Jonathan P, Dai Tiane, Nast Cynthia, Eddy Sean, Wei Boxian, Wang Ying, Gipson Debbie S, Dell Katherine M, Gibson Keisha L, Kretzler Matthias, Adler Sharon
Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-University of California, Torrance, CA.
Department of Nephrology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China.
Glomerular Dis. 2021 Jun;1(2):45-59. doi: 10.1159/000513166. Epub 2021 Mar 30.
Kidney injury molecule-1 (KIM-1) and periostin (POSTN) are proximal and distal tubule injury biomarkers. We tested whether baseline urine KIM-1/creatinine (uKIM-1/cr) and/or uPOSTN/cr correlated with disease severity or improved a remission prediction model.
Baseline uKIM1/cr and uPOSTN/cr were measured on spot urine samples from immunosuppression-free patients enrolled in Nephrotic Syndrome Study Network until December 15, 2014. Urine protein/creatinine (UPCR) and albumin/creatinine (UACR) were measured at baseline, 4 months, and until last follow-up. Glomerular and tubulointerstitial (TI) expression arrays were analyzed from a baseline research renal biopsy core collected during a clinically indicated biopsy.Renal diagnoses were centrally confirmed, sections scanned, and measured morphometrically. Correlations between baseline uKIM-1/cr and uPOSTN/cr and UPCR, UACR, histopathologic features, glomerular and TI KIM-1 and POSTN expression levels, and renal outcomes were assessed.
Baseline uKIM-1/cr correlated with UPCR and UACR, and were associated with complete remission after adjustment for proteinuria, histopathologic diagnosis, and treatment. Baseline uKIM-1/cr also correlated with degree of foot process effacement and acute tubular injury. Glomerular and TI KIM-1 expression levels correlated with UPCR and UACR. Higher TI KIM-1 expression levels correlated with interstitial fibrosis, tubular atrophy, and global glomerulosclerosis, while glomerular KIM-1 expression correlated with time to remission. Findings for POSTN were of lesser statistical strength.
DISCUSSION/CONCLUSION: Lower baseline uKIM-1/cr values were associated with more rapid time to complete remission after adjusting for proteinuria, histopathologic diagnosis, and treatment. Increased TI KIM-1 expression levels in proteinuric states were associated with chronic morphological injury; lower glomerular expression levels were associated with a greater potential for proteinuria reversibility.
肾损伤分子-1（KIM-1）和骨膜蛋白（POSTN）是近端和远端肾小管损伤的生物标志物。我们测试了基线尿KIM-1/肌酐（uKIM-1/cr）和/或uPOSTN/cr是否与疾病严重程度相关，或是否能改进缓解预测模型。
对2014年12月15日前纳入肾病综合征研究网络的未接受免疫抑制治疗患者的即时尿样进行基线uKIM1/cr和uPOSTN/cr检测。在基线、4个月及最后一次随访时检测尿蛋白/肌酐（UPCR）和白蛋白/肌酐（UACR）。从临床指征性活检时收集的基线研究肾活检核心样本中分析肾小球和肾小管间质（TI）表达阵列。肾诊断经集中确认，切片扫描并进行形态计量学测量。评估基线uKIM-1/cr和uPOSTN/cr与UPCR、UACR、组织病理学特征、肾小球和TI KIM-1及POSTN表达水平以及肾脏结局之间的相关性。
基线uKIM-1/cr与UPCR和UACR相关，并在调整蛋白尿、组织病理学诊断和治疗后与完全缓解相关。基线uKIM-1/cr也与足突消失程度和急性肾小管损伤相关。肾小球和TI KIM-1表达水平与UPCR和UACR相关。较高的TI KIM-1表达水平与间质纤维化、肾小管萎缩和全球肾小球硬化相关，而肾小球KIM-1表达与缓解时间相关。POSTN的研究结果统计学强度较低。
讨论/结论：在调整蛋白尿、组织病理学诊断和治疗后，较低的基线uKIM-1/cr值与更快达到完全缓解的时间相关。蛋白尿状态下TI KIM-1表达水平升高与慢性形态学损伤相关；较低的肾小球表达水平与蛋白尿可逆性的更大潜力相关。
