Association Between Urinary VEGFA and Renal Pathology of IgA Nephropathy Patients

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2021 Sep 9

PMID 34498313

Citations 4

Authors

Shaozhen Feng

Naya Huang

Miaorong Xue

Puhua Zhang

Zhong Zhong

Qunying Guo

Zhijian Li

Affiliations

Soon will be listed here.

Abstract

Background: Renal biopsy remains the golden standard for diagnosing and monitoring IgA nephropathy (IgAN). Vascular endothelial growth factor A (VEGFA) was crucial for the survival of glomerular cells. Our aim was to screen the expression pattern of urinary, circulating and renal VEGFA in IgAN patients to reveal their relationship with renal pathology and outcomes.

Methods: Baseline VEGFA levels were determined with ELISA, real-time PCR and immunohistochemistry. Associations between VEGFA expression and clinical-pathological parameters, and renal outcomes were evaluated.

Results: Compared with healthy controls, urinary VEGFA level was obviously elevated in IgAN patients (76.19 ± 63.67 pg/mg Cr vs 146.67 ± 232.71 pg/mg Cr, p = 0.0291) and not correlated with serum VEGFA level. Baseline urinary VEGFA was significantly associated with gender and tubular atrophy/interstitial fibrosis by stepwise multivariate regression analysis. Urinary VEGFA was higher in male patients accompanied with higher serum creatinine, larger proportion of hypertension and recurrent hematuria than in female patients. In the kidney of IgAN patients, VEGFA were robustly expressed in the parietal epithelial cells, podocytes, mesangial cells and tubular epithelial cells. After a follow-up duration of 38.53 ± 27.14 months, IgAN patients with higher urinary VEGFA level were found to have a poorer renal outcome of renal replacement therapy (HR = 1.027, p = 0.037) or composite outcome (HR = 1.023, p = 0.039) after adjusting for confounders.

Conclusions: Increased urinary VEGFA might reflect certain renal pathology and, although not fully specific, still could be served as a valuable noninvasive indicator in predicting renal progression of IgAN.

Citing Articles

Notoginsenoside R1 can inhibit the interaction between FGF1 and VEGFA to retard podocyte apoptosis.

Li C, Zhong H, Ma J, Liang Z, Zhang L, Liu T BMC Endocr Disord. 2023; 23(1):140.

PMID: 37415174 PMC: 10324173. DOI: 10.1186/s12902-023-01402-6.

Independent Prognostic and Predictive Role of Interstitial Macrophages in Kidney Biopsies of IgA Nephropathy Patients.

Aiello F, Ranelletti F, Liberatore M, Felaco P, De Luca G, Lamolinara A J Pers Med. 2023; 13(6).

PMID: 37373924 PMC: 10302965. DOI: 10.3390/jpm13060935.

Diagnostic model constructed by five EMT-related genes for renal fibrosis and reflecting the condition of immune-related cells.

Guo Y, Yuan Z, Hu Z, Gao Y, Guo H, Zhu H Front Immunol. 2023; 14:1161436.

PMID: 37266443 PMC: 10229861. DOI: 10.3389/fimmu.2023.1161436.

Association between urinary VEGFA and renal pathology of IgA nephropathy patients.

Feng S, Huang N, Xue M, Zhang P, Zhong Z, Guo Q J Clin Lab Anal. 2021; :e23995.

PMID: 34498313 PMC: 8551689. DOI: 10.1002/jcla.23995.

References

Feng S, Huang N, Xue M, Zhang P, Zhong Z, Guo Q . Association between urinary VEGFA and renal pathology of IgA nephropathy patients. J Clin Lab Anal. 2021; :e23995. PMC: 8551689. DOI: 10.1002/jcla.23995. View

Li L, Liu Z . Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies. Kidney Int. 2004; 66(3):920-3. DOI: 10.1111/j.1523-1755.2004.00837.x. View

Huang P, Shu D, Su Z, Luo S, Xu F, Lin F . Association between lifestyle, gender and risk for developing end-stage renal failure in IgA nephropathy: a case-control study within 10 years. Ren Fail. 2019; 41(1):914-920. PMC: 6781456. DOI: 10.1080/0886022X.2019.1635029. View

Lopes T, de Souza M, da Silva V, Santos M, da Silva W, Itaquy T . Markers of renal fibrosis: How do they correlate with podocyte damage in glomerular diseases?. PLoS One. 2019; 14(6):e0217585. PMC: 6586273. DOI: 10.1371/journal.pone.0217585. View

Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N . Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. 2003; 111(5):707-16. PMC: 151905. DOI: 10.1172/JCI17423. View

Neugarten J, Golestaneh L . Gender and the prevalence and progression of renal disease. Adv Chronic Kidney Dis. 2013; 20(5):390-5. DOI: 10.1053/j.ackd.2013.05.004. View

Trimarchi H, Barratt J, Cattran D, Cook H, Coppo R, Haas M . Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017; 91(5):1014-1021. DOI: 10.1016/j.kint.2017.02.003. View

Avgustin N, Rotar Z, Pajek J, Kovac D, Osredkar J, Lindic J . The predictive value of urinary vascular endothelial growth factor (VEGF) on worsening kidney function in proteinuric chronic kidney disease. Clin Nephrol. 2017; 88(13):10-13. DOI: 10.5414/CNP88FX03. View

Moran S, Cattran D . Recent advances in risk prediction, therapeutics and pathogenesis of IgA nephropathy. Minerva Med. 2019; 110(5):439-449. DOI: 10.23736/S0026-4806.19.06165-2. View

10.

Ma Y, Zuo L, Chen J, Luo Q, Yu X, Li Y . Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol. 2006; 17(10):2937-44. DOI: 10.1681/ASN.2006040368. View

11.

Burt L, Forbes M, Thornhill B, Kiley S, Minor J, Chevalier R . Renal vascular endothelial growth factor in neonatal obstructive nephropathy. II. Exogenous VEGF. Am J Physiol Renal Physiol. 2006; 292(1):F168-74. DOI: 10.1152/ajprenal.00294.2005. View

12.

Namikoshi T, Satoh M, Horike H, Fujimoto S, Arakawa S, Sasaki T . Implication of peritubular capillary loss and altered expression of vascular endothelial growth factor in IgA nephropathy. Nephron Physiol. 2005; 102(1):p9-16. DOI: 10.1159/000088405. View

13.

Kikuchi R, Yasuda Y, Nakatochi M, Shibata Y, Hara T, Suzuki A . Urinary and circulating levels of the anti-angiogenic isoform of vascular endothelial growth factor-A in patients with chronic kidney disease. Clin Chim Acta. 2017; 475:102-108. DOI: 10.1016/j.cca.2017.10.014. View

14.

Nitta K, Uchida K, Honda K, Horita S, Hayashi T, Ishizuka T . Serum vascular endothelial growth factor concentration in rapidly progressive glomerulonephritis. Nephron. 1998; 80(3):357-8. DOI: 10.1159/000045201. View

15.

Gnudi L, Benedetti S, Woolf A, Long D . Vascular growth factors play critical roles in kidney glomeruli. Clin Sci (Lond). 2015; 129(12):1225-36. DOI: 10.1042/CS20150403. View

16.

Burt L, Forbes M, Thornhill B, Kiley S, Chevalier R . Renal vascular endothelial growth factor in neonatal obstructive nephropathy. I. Endogenous VEGF. Am J Physiol Renal Physiol. 2006; 292(1):F158-67. DOI: 10.1152/ajprenal.00293.2005. View

17.

Veron D, Reidy K, Bertuccio C, Teichman J, Villegas G, Jimenez J . Overexpression of VEGF-A in podocytes of adult mice causes glomerular disease. Kidney Int. 2010; 77(11):989-99. DOI: 10.1038/ki.2010.64. View

18.

Ohashi R, Shimizu A, Masuda Y, Kitamura H, Ishizaki M, Sugisaki Y . Peritubular capillary regression during the progression of experimental obstructive nephropathy. J Am Soc Nephrol. 2002; 13(7):1795-805. DOI: 10.1097/01.asn.0000018408.51388.57. View

19.

Wen D, Tang Y, Tan L, Tan J, Chen D, Zhang Y . Sex disparities in IgA nephropathy: a retrospective study in Chinese patients. Int Urol Nephrol. 2020; 53(2):315-323. DOI: 10.1007/s11255-020-02631-7. View

20.

Eremina V, Cui S, Gerber H, Ferrara N, Haigh J, Nagy A . Vascular endothelial growth factor a signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival. J Am Soc Nephrol. 2006; 17(3):724-35. DOI: 10.1681/ASN.2005080810. View