Bazzi Claudio, Rizza Virginia, Olivieri Giulia, Casellato Daniela, D'Amico Giuseppe
D'Amico Foundation for Renal Diseases Research, Via Cherubini 6, 20145, Milan, Italy.
Biochemical Laboratory, San Carlo Borromeo Hospital, Milan, Italy.
J Nephrol. 2015 Oct;28(5):541-8. doi: 10.1007/s40620-014-0139-z. Epub 2014 Sep 17.
Proteinuria, the hallmark of glomerular diseases, is an independent predictor of end-stage renal disease (ESRD) progression. Proteinuria is a mixture of proteins of different molecular weight (MW) dependent on alterations of glomerular filtration barrier (GFB) and reabsorption impairment by proximal tubular epithelial cells (PTECs). We aimed to evaluate the excretion of different-MW proteins according to the tubulo-interstitial damage marker N-acetyl-β-D-glucosaminidase (NAG) in glomerulonephritides (GNs).
In 189 patients [idiopathic membranous nephropathy (IMN) n = 84, primary focal segmental glomerulosclerosis (FSGS) n = 48, crescentic IgA nephropathy (CIgAN) n = 37, minimal change disease (MCD) n = 20] several urinary proteins were measured at biopsy: α2-macroglobulin/creatinine ratio; fractional excretion of IgG, transferrin, albumin and α1-microglobulin, and the NAG/creatinine ratio divided by estimated glomerular filtration rate (eGFR) (NAG/C/eGFR), as NAG excretion is dependent on functioning nephron mass. Protein excretion was compared between 4th vs. 1st quartile of NAG/C/eGFR.
In IMN, FSGS and CIgAN high-MW proteins excretion (α2-macroglobulin, IgG) was greater than that of middle- (transferrin, albumin) and low-MW proteins (α1-microglobulin) in 4th vs. 1st quartile of NAG/C/eGFR; the mean fold excretion increase of high-MW proteins in 3 GNs was 74.9, higher than that of middle- (34.8) and low-MW proteins (12.0). Higher excretion of high-MW proteins may be dependent on lower reabsorption by PTECs. By contrast, in MCD the difference in excretion of different-MW proteins is probably due to high GFB selectivity.
High-MW protein excretion is dependent on GFB alteration and reduced reabsorption; its prognostic significance is ominous because in several glomerular diseases progression is associated with high-MW protein excretion.
蛋白尿是肾小球疾病的标志，是终末期肾病（ESRD）进展的独立预测指标。蛋白尿是不同分子量（MW）蛋白质的混合物，其取决于肾小球滤过屏障（GFB）的改变以及近端肾小管上皮细胞（PTECs）的重吸收受损情况。我们旨在根据肾小管间质损伤标志物N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）评估肾小球肾炎（GNs）中不同MW蛋白质的排泄情况。
在189例患者中[特发性膜性肾病（IMN）n = 84，原发性局灶节段性肾小球硬化（FSGS）n = 48，新月体性IgA肾病（CIgAN）n = 37，微小病变病（MCD）n = 20]，在活检时检测了几种尿蛋白：α2 - 巨球蛋白/肌酐比值；IgG、转铁蛋白、白蛋白和α1 - 微球蛋白的分数排泄率，以及NAG/肌酐比值除以估计肾小球滤过率（eGFR）（NAG/C/eGFR），因为NAG排泄取决于有功能的肾单位数量。比较了NAG/C/eGFR第4四分位数与第1四分位数之间的蛋白质排泄情况。
在IMN、FSGS和CIgAN中，NAG/C/eGFR第4四分位数与第1四分位数相比，高分子量蛋白质（α2 - 巨球蛋白、IgG）的排泄量大于中分子量（转铁蛋白、白蛋白）和低分子量蛋白质（α1 - 微球蛋白）；3种肾小球肾炎中高分子量蛋白质的平均排泄增加倍数为74.9，高于中分子量蛋白质（34.8）和低分子量蛋白质（12.0）。高分子量蛋白质排泄增加可能依赖于PTECs较低的重吸收。相比之下，在MCD中，不同分子量蛋白质排泄的差异可能归因于较高的GFB选择性。
高分子量蛋白质排泄依赖于GFB改变和重吸收减少；其预后意义不佳，因为在几种肾小球疾病中，进展与高分子量蛋白质排泄相关。
