Biomarkers in Primary Focal Segmental Glomerulosclerosis in Optimal Diagnostic-Therapeutic Strategy

Overview

Journal J Clin Med

Specialty General Medicine

Date 2022 Jun 24

PMID 35743361

Authors

Aleksandra Musiala

Piotr Donizy

Hanna Augustyniak-Bartosik

Katarzyna Jakuszko

Miroslaw Banasik

Katarzyna Koscielska-Kasprzak

Magdalena Krajewska

Dorota Kaminska

Affiliations

Soon will be listed here.

Abstract

Focal segmental glomerulosclerosis (FSGS) involves podocyte injury. In patients with nephrotic syndrome, progression to end-stage renal disease often occurs over the course of 5 to 10 years. The diagnosis is based on a renal biopsy. It is presumed that primary FSGS is caused by an unknown plasma factor that might be responsible for the recurrence of FSGS after kidney transplantation. The nature of circulating permeability factors is not explained and particular biological molecules responsible for inducing FSGS are still unknown. Several substances have been proposed as potential circulating factors such as soluble urokinase-type plasminogen activator receptor (suPAR) and cardiolipin-like-cytokine 1 (CLC-1). Many studies have also attempted to establish which molecules are related to podocyte injury in the pathogenesis of FSGS such as plasminogen activator inhibitor type-1 (PAI-1), angiotensin II type 1 receptors (AT1R), dystroglycan(DG), microRNAs, metalloproteinases (MMPs), forkheadbox P3 (FOXP3), and poly-ADP-ribose polymerase-1 (PARP1). Some biomarkers have also been studied in the context of kidney tissue damage progression: transforming growth factor-beta (TGF-β), human neutrophil gelatinase-associated lipocalin (NGAL), malondialdehyde (MDA), and others. This paper describes molecules that could potentially be considered as circulating factors causing primary FSGS.

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References

Schenk H, Muller-Deile J, Schmitt R, Brasen J, Haller H, Schiffer M . Removal of focal segmental glomerulosclerosis (FSGS) factor suPAR using CytoSorb. J Clin Apher. 2017; 32(6):444-452. DOI: 10.1002/jca.21538. View

Wada T, Nangaku M . A circulating permeability factor in focal segmental glomerulosclerosis: the hunt continues. Clin Kidney J. 2015; 8(6):708-15. PMC: 4655796. DOI: 10.1093/ckj/sfv090. View

Kuo H, Kuo M, Chiu Y, Chang J, Guh J, Chen H . Increased glomerular and extracellular malondialdehyde levels in patients and rats with focal segmental glomerulosclerosis. Eur J Clin Invest. 2005; 35(4):245-50. DOI: 10.1111/j.1365-2362.2005.01488.x. View

Schena F . Survey of the Italian Registry of Renal Biopsies. Frequency of the renal diseases for 7 consecutive years. The Italian Group of Renal Immunopathology. Nephrol Dial Transplant. 1997; 12(3):418-26. DOI: 10.1093/ndt/12.3.418. View

Chang H, Kuo W, Hsieh Y, Yang S, Lin C, Lee M . Circulating matrix metalloproteinase-2 is associated with cystatin C level, posttransplant duration, and diabetes mellitus in kidney transplant recipients. Transl Res. 2008; 151(4):217-23. DOI: 10.1016/j.trsl.2007.12.004. View

Ribeiro-Resende V, Ribeiro-Guimaraes M, Lemes R, Nascimento I, Alves L, Mendez-Otero R . Involvement of 9-O-Acetyl GD3 ganglioside in Mycobacterium leprae infection of Schwann cells. J Biol Chem. 2010; 285(44):34086-96. PMC: 2962507. DOI: 10.1074/jbc.M110.147272. View

Korzeniecka-Kozerska A, Wasilewska A, Tenderenda E, Sulik A, Cybulski K . Urinary MMP-9/NGAL ratio as a potential marker of FSGS in nephrotic children. Dis Markers. 2013; 34(5):357-62. PMC: 3810364. DOI: 10.3233/DMA-130980. View

Sas-Strozik A, Donizy P, Koscielska-Kasprzak K, Kaminska D, Gawlik K, Mazanowska O . Angiotensin II Type 1 Receptor Expression in Renal Transplant Biopsies and Anti-AT1R Antibodies in Serum Indicates the Risk of Transplant Loss. Transplant Proc. 2020; 52(8):2299-2304. DOI: 10.1016/j.transproceed.2020.01.126. View

Zanoteli E, van de Vlekkert D, Bonten E, Hu H, Mann L, Gomero E . Muscle degeneration in neuraminidase 1-deficient mice results from infiltration of the muscle fibers by expanded connective tissue. Biochim Biophys Acta. 2010; 1802(7-8):659-72. PMC: 2906380. DOI: 10.1016/j.bbadis.2010.04.002. View

10.

Wu D, Bitzer M, Ju W, Mundel P, Bottinger E . TGF-beta concentration specifies differential signaling profiles of growth arrest/differentiation and apoptosis in podocytes. J Am Soc Nephrol. 2005; 16(11):3211-21. DOI: 10.1681/ASN.2004121055. View

11.

Schiffer M, Bitzer M, Roberts I, Kopp J, Ten Dijke P, Mundel P . Apoptosis in podocytes induced by TGF-beta and Smad7. J Clin Invest. 2001; 108(6):807-16. PMC: 200928. DOI: 10.1172/JCI12367. View

12.

Kim J, Han B, Choi S, Cha S . Secondary Focal Segmental Glomerulosclerosis: From Podocyte Injury to Glomerulosclerosis. Biomed Res Int. 2016; 2016:1630365. PMC: 4819087. DOI: 10.1155/2016/1630365. View

13.

Fogo A . Causes and pathogenesis of focal segmental glomerulosclerosis. Nat Rev Nephrol. 2014; 11(2):76-87. PMC: 4772430. DOI: 10.1038/nrneph.2014.216. View

14.

Kim J, Kim B, Moon K, Hong H, Lee H . Activation of the TGF-beta/Smad signaling pathway in focal segmental glomerulosclerosis. Kidney Int. 2003; 64(5):1715-21. DOI: 10.1046/j.1523-1755.2003.00288.x. View

15.

Iranzad R, Motavalli R, Ghassabi A, Pourakbari R, Etemadi J, Yousefi M . Roles of microRNAs in renal disorders related to primary podocyte dysfunction. Life Sci. 2021; 277:119463. DOI: 10.1016/j.lfs.2021.119463. View

16.

Wharram B, Goyal M, Wiggins J, Sanden S, Hussain S, Filipiak W . Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J Am Soc Nephrol. 2005; 16(10):2941-52. DOI: 10.1681/ASN.2005010055. View

17.

Catania J, Chen G, Parrish A . Role of matrix metalloproteinases in renal pathophysiologies. Am J Physiol Renal Physiol. 2006; 292(3):F905-11. DOI: 10.1152/ajprenal.00421.2006. View

18.

Takawira D, Budinger G, Hopkinson S, Jones J . A dystroglycan/plectin scaffold mediates mechanical pathway bifurcation in lung epithelial cells. J Biol Chem. 2010; 286(8):6301-10. PMC: 3057847. DOI: 10.1074/jbc.M110.178988. View

19.

Barabadi M, Shahbaz S, Foroughi F, Hosseinzadeh M, Nafar M, Yekaninejad M . High Expression of FOXP3 mRNA in Blood and Urine as a Predictive Marker in Kidney Transplantation. Prog Transplant. 2018; 28(2):134-141. DOI: 10.1177/1526924818765812. View

20.

Yamamoto T, Noble N, Cohen A, Nast C, Hishida A, Gold L . Expression of transforming growth factor-beta isoforms in human glomerular diseases. Kidney Int. 1996; 49(2):461-9. DOI: 10.1038/ki.1996.65. View