背景:常染色体隐性遗传性多囊肾病(ARPKD)导致纤维囊性肾病,先天性肝纤维化,和门静脉高压症。血清半乳糖凝集素-3(Gal-3)和肠脂肪酸结合蛋白(I-FABP)是肾纤维化和门脉高压的潜在生物标志物,分别。我们检查了血清Gal-3是否与肾脏疾病严重程度相关,血清I-FABP是否与ARPKD中的肝脏疾病严重程度相关。
方法:对29名患有ARPKD(0.2-21岁)且存在天然肾脏的参与者进行横断面研究(Gal-3分析,n=18)和/或天然肝脏(I-FABP分析,n=21)。采用酶联免疫吸附试验分析血清Gal-3和I-FABP。肾脏疾病严重程度变量包括估计的肾小球滤过率(eGFR)和高度调整的总肾脏体积(htTKV)。使用超声弹性成像测量肝纤维化来表征肝脏疾病的严重程度,脾脏长度和血小板计数是门静脉高压症的标志物。简单和多变量线性回归检查Gal-3和肾脏疾病严重程度之间的关联(调整为肝脏疾病严重程度)以及I-FABP和肝脏疾病严重程度之间的关联(调整为eGFR)。
结果:血清Gal-3与eGFR呈负相关;1标准差(SD)较低的eGFR与0.795SD较高的Gal-3水平相关(95%CI-1.116,-0.473;p<0.001)。当调整肝脏疾病严重程度时,这种关联仍然很重要。在校正分析中血清Gal-3与htTKV无关。整体I-FABP水平升高,但在未校正或校正模型中,I-FABP与肝脏疾病严重程度之间无线性关系.
结论:血清Gal-3与ARPKD的eGFR相关,提示其作为肾脏疾病严重程度的可能新型生物标志物的价值。我们发现血清I-FABP与ARPKD肝病严重程度之间没有关联,尽管I-FABP水平总体升高。
Autosomal recessive polycystic kidney disease (ARPKD) causes fibrocystic kidney disease, congenital hepatic fibrosis, and portal hypertension. Serum galectin-3 (Gal-3) and intestinal fatty acid binding protein (I-FABP) are potential biomarkers of kidney fibrosis and portal hypertension, respectively. We examined whether serum Gal-3 associates with kidney disease severity and serum I-FABP associates with liver disease severity in ARPKD.
Cross-sectional study of 29 participants with ARPKD (0.2-21 years old) and presence of native kidneys (Gal-3 analyses, n = 18) and/or native livers (I-FABP analyses, n = 21). Serum Gal-3 and I-FABP were analyzed using enzyme linked immunosorbent assay. Kidney disease severity variables included estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV). Liver disease severity was characterized using ultrasound elastography to measure liver fibrosis, and spleen length and platelet count as markers of portal hypertension. Simple and multivariable linear regression examined associations between Gal-3 and kidney disease severity (adjusted for liver disease severity) and between I-FABP and liver disease severity (adjusted for eGFR).
Serum Gal-3 was negatively associated with eGFR; 1 standard deviation (SD) lower eGFR was associated with 0.795 SD higher Gal-3 level (95% CI - 1.116, - 0.473; p < 0.001). This association remained significant when adjusted for liver disease severity. Serum Gal-3 was not associated with htTKV in adjusted analyses. Overall I-FABP levels were elevated, but there were no linear associations between I-FABP and liver disease severity in unadjusted or adjusted models.
Serum Gal-3 is associated with eGFR in ARPKD, suggesting its value as a possible novel biomarker of kidney disease severity. We found no associations between serum I-FABP and ARPKD liver disease severity despite overall elevated I-FABP levels.