Chronic renovascular hypertension is associated with elevated levels of neutrophil gelatinase-associated lipocalin

被引:51
作者
Eirin, Alfonso [1 ]
Gloviczki, Monika L. [1 ]
Tang, Hui [1 ]
Rule, Andrew D. [1 ]
Woollard, John R. [1 ]
Lerman, Amir
Textor, Stephen C. [1 ]
Lerman, Lilach O. [1 ]
机构
[1] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN 55905 USA
关键词
cytokines; inflammation; KIM-1; NGAL; renovascular hypertension; ACUTE KIDNEY INJURY; RENAL-ARTERY STENOSIS; URINARY BIOMARKERS; MOLECULE-1; KIM-1; CARDIAC-SURGERY; DISEASE; NGAL; ACTIVATION; MARKER; OUTCOMES;
D O I
10.1093/ndt/gfs370
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Renovascular hypertension (RVH) is characterized by chronic inflammation of the stenotic kidney and progressive renal dysfunction. Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein induced in inflammatory conditions and ischemia, is a novel biomarker for acute kidney injury. We hypothesized that chronic RVH would be associated with increased renal and circulating NGAL levels. We prospectively measured renal vein and inferior vena cava (IVC) levels of NGAL and inflammatory cytokines in essential hypertensive (EH) and RVH patients, during constant sodium intake and anti-hypertensive regimens, and compared them with systemic levels in age-matched normotensive subjects (n 22 each). In addition, we measured urinary NGAL and kidney injury molecule (KIM)-1 in all patients. Blood pressure, serum creatinine, estimated glomerular filtration rate (eGFR), lipid panels and medications were similar in RVH and EH. Systemic, stenotic and contralateral renal vein levels of NGAL were all similarly elevated in RVH versus normal hypertension and EH (P 0.05), as were renal vein levels of inflammatory markers like tumor necrosis factor-. Furthermore, renal vein NGAL levels inversely correlated with eGFR, and directly with renal vein (but not systemic) levels of inflammatory markers. Urinary levels of NGAL and KIM-1 were elevated in both EH and RVH, as were systemic levels of C-reactive protein. Chronic RVH is associated with elevated NGAL levels, likely due to ongoing kidney and systemic inflammation and ischemia. These findings may also imply the occurrence of the inflammation process in chronic RVH, which might contribute to the poorer outcomes of RVH compared with EH patients.
引用
收藏
页码:4153 / 4161
页数:9
相关论文
共 45 条
[11]   Clinical implication of plasma neutrophil gelatinase-associated lipocalin (NGAL) concentrations in patients with advanced carotid atherosclerosis [J].
Giaginis, Constantinos ;
Zira, Athina ;
Katsargyris, Athanasios ;
Klonaris, Chris ;
Theocharis, Stamatios .
CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 2010, 48 (07) :1035-1041
[12]   Preserved Oxygenation Despite Reduced Blood Flow in Poststenotic Kidneys in Human Atherosclerotic Renal Artery Stenosis [J].
Gloviczki, Monika L. ;
Glockner, James F. ;
Lerman, Lilach O. ;
McKusick, Michael A. ;
Misra, Sanjay ;
Grande, Joseph P. ;
Textor, Stephen C. .
HYPERTENSION, 2010, 55 (04) :961-966
[13]   Neutrophil gelatinase-associated lipocalin as a marker of acute renal disease [J].
Haase, Michael ;
Haase-Fielitz, Anja ;
Bellomo, Rinaldo ;
Mertens, Peter R. .
CURRENT OPINION IN HEMATOLOGY, 2011, 18 (01) :11-18
[14]   Platelet Activation in Patients with Atherosclerotic Renal Artery Stenosis Undergoing Stent Revascularization [J].
Haller, Steven ;
Adlakha, Satjit ;
Reed, Grant ;
Brewster, Pamela ;
Kennedy, David ;
Burket, Mark W. ;
Colyer, William ;
Yu, Haifeng ;
Zhang, Dong ;
Shapiro, Joseph I. ;
Cooper, Christopher J. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2011, 6 (09) :2185-2191
[15]   Urinary biomarkers in the early diagnosis of acute kidney injury [J].
Han, W. K. ;
Waikar, S. S. ;
Johnson, A. ;
Betensky, R. A. ;
Dent, C. L. ;
Devarajan, P. ;
Bonventre, J. V. .
KIDNEY INTERNATIONAL, 2008, 73 (07) :863-869
[16]   NGAL is an early predictive biomarker of contrast-induced nephropathy in children [J].
Hirsch, Russel ;
Dent, Catherine ;
Pfriem, Holly ;
Allen, Janene ;
Beekman, Robert H., III ;
Ma, Qing ;
Dastrala, Sudha ;
Bennett, Michael ;
Mitsnefes, Mark ;
Devarajan, Prasad .
PEDIATRIC NEPHROLOGY, 2007, 22 (12) :2089-2095
[17]   Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury [J].
Ichimura, T ;
Bonventre, JV ;
Bailly, V ;
Wei, H ;
Hession, CA ;
Cate, RL ;
Sanicola, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (07) :4135-4142
[18]   Atherosclerotic renovascular disease in United States patients aged 67 years or older: Risk factors, revascularization, and prognosis [J].
Kalra, PA ;
Guo, HF ;
Kausz, AT ;
Gilbertson, DT ;
Liu, JN ;
Chen, SC ;
Ishani, A ;
Collins, AJ ;
Foley, RN .
KIDNEY INTERNATIONAL, 2005, 68 (01) :293-301
[19]   Ischaemic nephropathy secondary to atherosclerotic renal artery stenosis: clinical and histopathological correlates [J].
Keddis, Mira T. ;
Garovic, Vesna D. ;
Bailey, Kent R. ;
Wood, Christina M. ;
Raissian, Yassaman ;
Grande, Joseph P. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2010, 25 (11) :3615-3622
[20]   Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition [J].
Ko, Gang Jee ;
Grigoryev, Dmitry N. ;
Linfert, Douglas ;
Jang, Hye Ryoun ;
Watkins, Tonya ;
Cheadle, Chris ;
Racusen, Lorraine ;
Rabb, Hamid .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2010, 298 (06) :F1472-F1483