| Introduction: Most of IgA nephropathy(IgAN) are known as chronic and progressive disease which can not be evaluated by repeated renal biopsy. Urinary angiostatin and lyve-1 were identified distinct proteins by Raybiotech Protein Array and validated on a small samples. Angiostatin, a 38-kDa plasminogen fragment that was discovered in the serum and urine of tumor-bearing mice,has anti-angiogenic and anticancer effects and was found to be elevated in both non-diabetic nephropathy patients and animal models. Lyve-1 is a lymphatic endothelial cell hyaluronan receptor 1, a lymphoid endothelium-specific marker which is associated with tumor metastasis and plays a role in lymphatic hyaluronic acid (HA) transport. In the IgA nephropathy, HA is mainly deposited in the renal papilla, crescent and injured renal tubules, and associated with proteinuria, creatinine clearance and degree of renal function deterioration. The roles of lyve-1 playing on the overexpression of HA in injuryed kidney worth further studying. This study aimed to evaluated the value of angiostatin and lyve-1 level in urine supernatant for assessing disease severity and progression of IgAN.Methods: A total of 190 patients with IgAN and 173 patients with non-IgAN primary glomerulopathy(disease control, DC) were enrolled in the study. Among them, 177cases of IgAN were used to detect the level of urinary angiostatin and 107 cases of IgAN were used to detect urinary lyve-1 level, which both coincided with 94 cases of IgAN patients. Among them, 157 cases of DC were used to detect the level of urinary angiostatin and 46 cases of IgAN were used to detect urinary lyve-1 level,which both coincided with 30 cases of DC patients. The levels of angiostatin and lyve-1 were measured by enzyme-linked immunosorbent assay (ELISA). The prediction value of urinary biomarkers for disease severity and prognosis were further analyzed in IgAN patients with follow-up records.Results:Urinary levels of angiostatin and lyve-1 were adjusted by urinary creatitine.Urinary angiostatin levels were significantly lower in IgAN patients than lower than disease controls(113. 38(51.00,327.64) vs 620.61 (126. 00,1644. 93),P<0.01).Urinary lyve-1 levels were significantly lower in IgAN patients) than disease controls(634.5 (371.78,908.64) vs 888.37(569.82,1563.65), P<0.001).Compared with CKD stage1, the levels of urinary angiostatin were higher significantly with CKD stage≥3(CKDstage3: 182.68(70.38, 466.12) vs CKDstagel:82.15(34.80, 147.28), P<0.01; CKDstage4: 275.81(211.08,521.24) vs CKDstagel:82.15(34.80, 147.28) , P<0.001)). The levels of urinary lyve-1 were higher significantly with CKD 4(849.059684.27, 1363.38) vs 527.80(220.27, 682.04),P<0.01). No difference was found between in urinary lyve-1 and CKD stage.in DC.Urinary angiosatin levels in Lee’s grade Ⅳ-Ⅴ (220.14 (93.25,561.78) ng/mg) were significantly higher than those in Lee’s grade Ⅰ-Ⅱ(44.11 (29.07,247.53) ng/mg,P<0.01) and Ⅲ (73.68 (39.14,196.28) ng/mg, P<0.001) . Urinary lyve-1 levels in Lee’s grade Ⅳ-Ⅴ (733.35 (509.46,961.20)pg/mg) were significantly higher than those in Lee’s grade Ⅲ (446.11 (201.54,772.29),P<0.01). According to Oxford Classification,patients with mesangial proliferative score 1(M1: (192.30(71.82, 545.25)ng/mg) had higher urinary angiostatim level than that of M0(88.16(42.00, 223.37) ng/mg, P<0.01.Compared to patients with T0(66.75 (34.17,211.46)ng/mg), urinary angiostatin level in T1(103. 75 (63. 64, 198. 59)ng/mg, P<0.05) and T2 (247.53(103.75,589.02)ng/mg ,P<0.001)were significantly higher. Urinary lyve-1 levels were significantly higher in T2 than T0(754.23 (561.48,1048.69) vs 474.16 (218.77,729.05)pg/mg, P<0.01). No significantly difference was found between in urinary angiostatin or lyve-1 and endocapillary hypercellularity (E) or segmental glomerulosclerosis(S) lesion.The levels of urinary angiostatin and lyve-1 were positively correlated with the levels of 24-hour proteinuria and the percentage of sclerotic glomeruli in patients with IgAN.Moreover,a negative correlation was found between the levels of these markers and eGFR.To identify the independent clinical and pathology factors correlated with urinary angiostatin and lyve-1 level, we then applied a multivariable linear regression model to our data. We found 24 hour urinary protein, sex and T lesion wereassociated with urinary angiostatin and 24 hour urinary protein and sexwereassociated with urinay lyve-1 levels.To evaluate the prognostic effect of urinary angiostatin and lyve-1 on disease progression in IgAN, we divided IgAN patients into two groups according to meidan.Renal survival was significantly worse in patients withhigher urinary angiostatinlevel(>1109. 55ng/mg,P <0.01).No difference was found between in two groups according to median of urinary lyve-1 level.Conclusion: IgAN patients with severe clinical and pathological lesions are associated with higher urinary angiostatin or lyve-1 levels. Urinary angiostatin and lyve-1 may be a useful novel non-invasive biomarker toevaluate disease severity or progression of IgAN. |
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