Urinary excretion of angiogenesis factors in chronic glomerulonephritis patients: association with clinical activity and urinary biomarkers of kidney injuryтезисы доклада
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Дата последнего поиска статьи во внешних источниках: 8 февраля 2017 г.
Аннотация:Introduction and Aims: Although it is well proven that tubulointerstitial fibrosis (TIF) plays an important role in progression of chronic glomerulonephritis (CGN), there are no approaches for TIF monitoring in clinical practice for more precise control of the immunosuppressive and renoprotective treatment effectiveness. Uromoduline (UMOD) is a transmembrane glycoprotein produced by the thick ascending limb of the loop of Henle. As the most abundant protein excreted in normal human urine and highly specific for renal tubulocytes UMOD can be considered the candidate for urinary biomarker of TIF progression. The aim of the study was to investigate the urinary excretion of UMOD and collagen IV (COL4) in patients with CGN, its possible associations with proteinuria (PU) and other clinical signs of CGN activity, glomerular filtration rate, morphologic degree of nephrosclerosis.
Methods: 82 CGN patients (45% men, 55% women; mean age 36.5 (28.0; 55.0)) were examined. 69.% patients developed arterial hypertension; in 31.7% of the study patients the hypertension was sever or resistant (blood pressure (BP) ≥ 160/100 Hg mm before treatment or BP ≥ 140/90 Hg mm although 3 or more antihypertensive drugs are used). Nephrotic syndrome was revealed in 31.7%; glomerular filtration rate estimated using the CKD-EPI formula (eGFR) < 60 ml/min/1.73 m2 was found in 31.7% of the study patients. High degree of TIF (> 30%) was found in 38.2% patients. Morning
Nephrology Dialysis Transplantation 31 (Supplement 1): i38–i39, 2016 doi:10.1093/ndt/gfw134.4
urine samples were analyzed by ELISA to determine the excretion of biomarkers (UMOD and COL4). The results were adjusted to urinary creatinine concentrations. Results: Urinary excretion of UMOD positively correlated with eGFR (Rs = 0.37; p < 0.001), and negatively correlated with CKD duration (Rs = -0.43; p < 0.0001). High UMOD excretion (> 75th percentile) was revealed in 38% of patients with minimal or moderate degree of TIF, although in group with high degree of TIF nobody presented high level of UMOD. In contrast urinary excretion of COL4 positively correlated with age (Rs = 0.39; p < 0.001), CKD duration (Rs = 0.25; p < 0.05), systolic and diastolic blood pressure (Rs = 0.22; p < 0.05 and Rs = 0.25; p < 0.05), PU (Rs = 0,50; p < 0.0001), serum fibrinogen (Rs = 0.57; p < 0.0001), and negatively correlated with eGFR (Rs = -0.36; p < 0.001), hemoglobin (Rs = -0.32; p < 0.01).
Conclusions: While COL4 excretion can be considered the universal biomarker signing both CGN activity and progression, UMOD excretion is exclusively associated with TIF development. The combination of depleted UMOD and high COL4 excretion was found in the most sever cases of CGN; this combination can reflect tubulocytes transdifferentiation and apoptosis. Studying UMOD and COL4 urinary excretion complex can be useful for estimation of CGN stage and prognosis. But prospective studies are needed to verify it.