Soluble urokinase plasminogen activator receptor (suPAR) and glomerular disease in children: a narrative review

Springer Science and Business Media LLC
Phuong Anh Le Thy1, Thuy Yen Hoang Thi1, Tran Kiem Hao2,3, Hữu Sơn Nguyễn2
1Pediatric Department, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam
2Pediatric Center, Hue Central Hospital, Hue, Vietnam
3Department of Health, Thua Thien Hue Provincial People’s Committee, Hue, Vietnam

Tóm tắt

Abstract Background Focal segmental glomerulosclerosis (FSGS) is a chronic glomerular disease that responds poorly to treatment, with a large proportion of patients progressing to end-stage renal disease in spite of initial aggressive treatment. It is worth emphasizing that the FSGS group has still a high recurrence rate after kidney transplantation. Therefore, understanding the factors involved in the pathogenesis of FSGS will help nephrologists better understand the pathogenesis as well as find out specific targeted therapies. Circulating immune factors have long been implicated in the pathogenesis of FSGS, and recent studies have suggested that soluble urokinase plasminogen activator receptor (suPAR) is one of the good candidates for this hypothesis. The aim of this review study was to analyze the value of suPAR in glomerular disease, especially in clinical studies. Methods In this review study, the PubMed database was searched using relevant keywords (suPAR, circulating permeability factors Children, FSGS, and children). Descriptive and cross-sectional studies were reviewed in the current study with the main focuses on the role of suPAR in FSGS, nephrotic syndrome, and the relation to progression of renal failure, especially the research in children. Results Overall, 32 studies from different countries were selected. These clinical studies on suPAR have shown the following: (i) the role of suPAR in the diagnosis of FSGS has not yet been confirmed, and (ii) there is strong evidence demonstrating a significant relationship between suPAR and the severity of kidney disease as well as a high value of suPAR in predicting the steroid responsiveness of nephrotic syndrome. Conclusion Researching on circulating permeability factors in FSGS is a current trend, which opens new avenues in targeted diagnosis and treatment. suPAR is a promising candidate, and urinary suPAR has also shown advantages over serum suPAR; therefore, more research on this issue is needed in the future.

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Tài liệu tham khảo

Tesar V, Zima T (2008) Recent progress in the pathogenesis of nephrotic proteinuria. Crit Rev Clin Lab Sci 45(2):139–220

Rood IM, Deegens JK, Wetzels JF (2012) Genetic causes of focal segmental glomerulosclerosis: implications for clinical practice. Nephrol Dial Transplant 27(3):882–890

McCarthy ET, Sharma M, Savin VJ (2010) Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 5(11):2115–2121

Savin VJ, Sharma M, Zhou J et al (2015) Renal and hematological effects of CLCF-1, a B-cell-stimulating cytokine of the IL-6 family. J Immunol Res 2015:714964

Pukajło-Marczyk A, Zwolińska D (2021) Involvement of hemopexin in the pathogenesis of proteinuria in children with idiopathic nephrotic syndrome. J Clin Med 10(14):3160

Kim EY, Hassanzadeh Khayyat N, Dryer SE (2018) Mechanisms underlying modulation of podocyte TRPC6 channels by suPAR: role of NADPH oxidases and Src family tyrosine kinases. Biochim Biophys Acta Mol Basis Dis 1864(10):3527–3536

Wei C, Möller CC, Altintas MM et al (2008) Modification of kidney barrier function by the urokinase receptor. Nat Med 14(1):55–63

Thunø M, Macho B, Eugen-Olsen J (2009) suPAR: the molecular crystal ball. Dis Markers 27(3):157–172

Kronbichler A, Saleem MA, Meijers B, Shin JI (2016) Soluble urokinase receptors in focal segmental glomerulosclerosis: a review on the scientific point of view. J Immunol Res 2016:2068691

Xu Y, Berrou J, Chen X et al (2001) Induction of urokinase receptor expression in nephrotoxic nephritis. Exp Nephrol 9(6):397–404

Maas RJ, Deegens JKJ, Wetzels JFM (2013) Serum suPAR in patients with FSGS: trash or treasure? Pediatr Nephrol 28:1041–1048

Ishimoto T, Shimada M, Gabriela G et al (2013) Toll-like receptor 3 ligand, polyIC, induces proteinuria and glomerular CD80, and increases urinary CD80 in mice. Nephrol Dial Transplant 28(6):1439–1446

Shimada M, Ishimoto T, Lee PY et al (2012) Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-κB-dependent pathway. Nephrol Dial Transplant 27(1):81–89

Winn MP, Conlon PJ, Lynn KL et al (2005) A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308(5729):1801–1804

Möller CC, Wei C, Altintas MM et al (2007) Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J Am Soc Nephrol 18(1):29–36

Kim EY, Yazdizadeh Shotorbani P, Dryer SE (2018) Trpc6 inactivation confers protection in a model of severe nephrosis in rats. J Mol Med (Berlin, Germany) 96(7):631–644

Kopp JB, Heymann J (2019) c-Src is in the effector pathway linking uPAR and podocyte injury. J Clin Investig 129(5):1827–1829

Wei C, El Hindi S, Li J et al (2011) Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 17(8):952–960

Verdelho M, Carina Ferreira A, Céu Santos M et al (2018) Soluble urokinase-type plasminogen activator receptor as a biomarker for focal segmental glomerulosclerosis; a retrospective analysis. J Nephropathol 7(3):182–187

Franco Palacios CR, Lieske JC, Wadei HM et al (2013) Urine but not serum soluble urokinase receptor (suPAR) may identify cases of recurrent FSGS in kidney transplant candidates. Transplantation 96(4):394–399

Huang J, Liu G, Zhang Y-m et al (2014) Urinary soluble urokinase receptor levels are elevated and pathogenic in patients with primary focal segmental glomerulosclerosis. BMC Med 12(1):81

Weidemann DK, Abraham AG, Roem JL, Furth SL, Warady BA (2020) Plasma soluble urokinase plasminogen activator receptor (suPAR) and CKD progression in children. Am J Kidney Dis 76(2):194–202

Iversen E, Houlind MB, Kallemose T et al (2020) Elevated suPAR is an independent risk marker for incident kidney disease in acute medical patients. Front Cell Dev Biol 8:339

Mahmood N, Mihalcioiu C, Rabbani SA (2018) Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): diagnostic, prognostic, and therapeutic applications. Front Oncol 8:24

Winnicki W, Sunder-Plassmann G, Sengölge G et al (2019) Diagnostic and prognostic value of soluble urokinase-type plasminogen activator receptor (suPAR) in focal segmental glomerulosclerosis and impact of detection method. Sci Rep 9(1):13783

Wei C, Trachtman H, Li J et al (2012) Circulating suPAR in two cohorts of primary FSGS. J Am Soc Nephrol 23(12):2051–2059

Huang J, Liu G, Zhang YM et al (2013) Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis. Kidney Int 84(2):366–372

Chen JS, Chang LC, Wu CZ et al (2016) Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models. J Biomed Sci 23:24

Shuai T, Pei Jing Y, Huang Q et al (2019) Serum soluble urokinase type plasminogen activated receptor and focal segmental glomerulosclerosis: a systematic review and meta-analysis. BMJ Open 9(10):e031812

Peng Z, Mao J, Chen X et al (2015) Serum suPAR levels help differentiate steroid resistance from steroid-sensitive nephrotic syndrome in children. Pediatr Nephrol 30(2):301–307

Mousa S, Saleh S, Aly H, Amin M (2018) Evaluation of serum soluble urokinase plasminogen activator receptor as a marker for steroid-responsiveness in children with primary nephrotic syndrome. Saudi J Kidney Dis Transpl 29(2):290–296

Schaefer F, Trachtman H, Wühl E et al (2017) Association of serum soluble urokinase receptor levels with progression of kidney disease in children. JAMA Pediatr 171(11):e172914

Jhee JH, Nam BY, Lee CJ et al (2021) Soluble urokinase-type plasminogen activator receptor, changes of 24-hour blood pressure, and progression of chronic kidney disease. J Am Heart Assoc 10(1):e017225

Roca N, Jatem E, Martín ML et al (2020) Relationship between soluble urokinase-type plasminogen activator receptor and serum biomarkers of endothelial activation in patients with idiopathic nephrotic syndrome. Clin Kidney J 14(2):543–549

Jehn U, Schütte-Nütgen K, Henke U et al (2021) Soluble urokinase-type plasminogen activator receptor (suPAR) is a risk indicator for eGFR loss in kidney transplant recipients. Sci Rep 11(1):3713

Saleem MA (2018) What is the role of soluble urokinase-type plasminogen activator in renal disease? Nephron 139(4):334–341

Sinha A, Bajpai J, Saini S et al (2014) Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children. Kidney Int 85(3):649–658

Sun P, Yu L, Huang J et al (2019) Soluble urokinase receptor levels in secondary focal segmental glomerulosclerosis. Kidney Dis (Basel) 5(4):239–246

Fujimoto K, Imura J, Atsumi H et al (2015) Clinical significance of serum and urinary soluble urokinase receptor (suPAR) in primary nephrotic syndrome and MPO-ANCA-associated glomerulonephritis in Japanese. Clin Exp Nephrol 19(5):804–814

Fujimoto K, Kagaya Y, Fujii A et al (2020) P0221SOLUBLE urokinase receptor (suPAR) is a predictor of disease state and renal prognosis in primary nephrotic syndrome. Nephrol Dial Transplant 35(Supplement_3):gfaa142-P0221

Burcsár S, Toldi G, Kovács L et al (2021) Urine soluble urokinase plasminogen activator receptor as a potential biomarker of lupus nephritis activity. Biomarkers 26(5):443–449

Savin VJ, Sharma M, Zhou J et al (2017) Multiple targets for novel therapy of FSGS associated with circulating permeability factor. Biomed Res Int 2017:6232616

Schenk H, Müller-Deile J, Schmitt R et al (2017) Removal of focal segmental glomerulosclerosis (FSGS) factor suPAR using CytoSorb. J Clin Apher 32(6):444–452

Alachkar N, Li J, Matar D et al (2018) Monitoring suPAR levels in post-kidney transplant focal segmental glomerulosclerosis treated with therapeutic plasma exchange and rituximab. BMC Nephrol 19(1):361

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