Paragas Neal, Nickolas Thomas L, Wyatt Christina, Forster Catherine S, Sise Meghan, Morgello Susan, Jagla Bernd, Buchen Charles, Stella Peter, Sanna-Cherchi Simone, Carnevali Maria Luisa, Mattei Silvia, Bovino Achiropita, Argentiero Lucia, Magnano Andrea, Devarajan Prasad, Schmidt-Ott Kai M, Allegri Landino, Klotman Paul, D'Agati Vivette, Gharavi Ali G, Barasch Jonathan
College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
J Am Soc Nephrol. 2009 Aug;20(8):1687-92. doi: 10.1681/ASN.2009010065. Epub 2009 Jul 23.
Nephrosis and a rapid decline in kidney function characterize HIV-associated nephropathy (HIVAN). Histologically, HIVAN is a collapsing focal segmental glomerulosclerosis with prominent tubular damage. We explored the expression of neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular injury, to determine whether this protein has the potential to aid in the noninvasive diagnosis of HIVAN. We found that expression of urinary NGAL was much higher in patients with biopsy-proven HIVAN than in HIV-positive and HIV-negative patients with other forms of chronic kidney disease. In the HIV-transgenic mouse model of HIVAN, NGAL mRNA was abundant in dilated, microcystic segments of the nephron. In contrast, urinary NGAL did not correlate with proteinuria in human or in mouse models. These data show that marked upregulation of NGAL accompanies HIVAN and support further study of uNGAL levels in large cohorts to aid in the noninvasive diagnosis of HIVAN and screen for HIVAN-related tubular damage.
肾病和肾功能迅速下降是HIV相关性肾病(HIVAN)的特征。从组织学上看,HIVAN是一种伴有显著肾小管损伤的塌陷性局灶节段性肾小球硬化。我们探究了肾小管损伤标志物中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的表达,以确定该蛋白是否有潜力辅助HIVAN的无创诊断。我们发现,经活检证实患有HIVAN的患者尿NGAL表达水平明显高于患有其他形式慢性肾病的HIV阳性和HIV阴性患者。在HIVAN的HIV转基因小鼠模型中,NGAL mRNA在肾单位扩张的微囊性节段中大量存在。相比之下,在人类或小鼠模型中,尿NGAL与蛋白尿均无相关性。这些数据表明,HIVAN伴有NGAL的显著上调,并支持在大型队列中进一步研究尿NGAL水平,以辅助HIVAN的无创诊断并筛查与HIVAN相关的肾小管损伤。