CD80 and CTLA-4 As Diagnostic and Prognostic Markers in Adult-onset Minimal Change Disease: a Retrospective Study

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2018 Aug 8

PMID 30083478

Citations 6

Authors

Bing Zhao

Hui Han

Junhui Zhen

Xiaowei Yang

Jin Shang

Liang Xu

Rong Wang

Affiliations

Soon will be listed here.

Abstract

Background: Minimal change disease (MCD) is a form of idiopathic nephrotic syndrome. Compared to children, adult-onset MCD patients are reported to have delayed responses to glucocorticoid treatment. Several studies of children have suggested detecting urinary CD80 levels to diagnose MCD. There are no effective diagnostic methods to distinguish steroid-sensitive MCD from steroid-resistant MCD unless treatments are used.

Methods: In a total of 55 patients with biopsy-proven MCD and 26 patients with biopsy-proven idiopathic membranous nephropathy, CD80 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in serum, urine and renal tissue were analyzed.

Results: Steroid-sensitive MCD patients in remission had lower urinary CD80 levels and higher CTLA-4 levels than patients in relapse (156.65 ± 24.62 vs 1066.40 ± 176.76 ng/g creatinine; < 0.0001), (728.73 ± 89.93 vs 151.70 ± 27.01 ng/g creatinine; < 0.0001). For MCD patients in relapse, mean urinary CD80 level was higher, and CTLA-4 level was lower for those who were steroid-sensitive than those who were steroid-resistant (1066.40 ± 176.76 vs. 203.78 ± 30.65 ng/g creatinine; < 0.0001), but the mean urinary CTLA-4 level was lower (151.70 ± 27.01 vs. 457.83 ± 99.45 ng/g creatinine; < 0.0001). CD80 expression in glomeruli was a sensitive marker to diagnose MCD. The absent or minimal expression of CTLA-4 in glomeruli could distinguish steroid-sensitive MCD from steroid-resistant MCD.

Conclusions: Glucocorticoid treatment may result in complete remission for only MCD patients with strongly positive CD80 expression and negative CTLA-4 expression in glomeruli, or higher urinary CD80 level and lower CTLA-4 level.

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Usefulness of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset minimal change disease.

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References

Reiser J, Mundel P . Danger signaling by glomerular podocytes defines a novel function of inducible B7-1 in the pathogenesis of nephrotic syndrome. J Am Soc Nephrol. 2004; 15(9):2246-8. DOI: 10.1097/01.ASN.0000136312.46464.33. View

Kistler A, Reiser J . Maximal 'CD80-uria' with minimal change. Kidney Int. 2010; 78(3):236-8. DOI: 10.1038/ki.2010.148. View

Trimarchi H . Abatacept and Glomerular Diseases: The Open Road for the Second Signal as a New Target is Settled Down. Recent Pat Endocr Metab Immune Drug Discov. 2015; 9(1):2-14. DOI: 10.2174/1872214809666150302104542. View

Wong C, Lit L, Tam L, Li E, Lam C . Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2005; 44(8):989-94. DOI: 10.1093/rheumatology/keh663. View

Cara-Fuentes G, Wasserfall C, Wang H, Johnson R, Garin E . Minimal change disease: a dysregulation of the podocyte CD80-CTLA-4 axis?. Pediatr Nephrol. 2014; 29(12):2333-40. PMC: 4213236. DOI: 10.1007/s00467-014-2874-8. View

Norlin J, Fink L, Kvist P, Galsgaard E, Coppieters K . Abatacept Treatment Does Not Preserve Renal Function in the Streptozocin-Induced Model of Diabetic Nephropathy. PLoS One. 2016; 11(4):e0152315. PMC: 4824484. DOI: 10.1371/journal.pone.0152315. View

Smith J, Martz K, Blydt-Hansen T . Pediatric kidney transplant practice patterns and outcome benchmarks, 1987-2010: a report of the North American Pediatric Renal Trials and Collaborative Studies. Pediatr Transplant. 2013; 17(2):149-57. DOI: 10.1111/petr.12034. View

Fiorina P, Vergani A, Bassi R, Niewczas M, Altintas M, Pezzolesi M . Role of podocyte B7-1 in diabetic nephropathy. J Am Soc Nephrol. 2014; 25(7):1415-29. PMC: 4073425. DOI: 10.1681/ASN.2013050518. View

Barbarino J, Staatz C, Venkataramanan R, Klein T, Altman R . PharmGKB summary: cyclosporine and tacrolimus pathways. Pharmacogenet Genomics. 2013; 23(10):563-85. PMC: 4119065. DOI: 10.1097/FPC.0b013e328364db84. View

10.

Grimm M, Rinaldi M, Yonan N, Arpesella G, Arizon Del Prado J, Pulpon L . Superior prevention of acute rejection by tacrolimus vs. cyclosporine in heart transplant recipients--a large European trial. Am J Transplant. 2006; 6(6):1387-97. DOI: 10.1111/j.1600-6143.2006.01300.x. View

11.

Szeto C, Lai F, Chow K, Kwan B, Kwong V, Leung C . Long-term outcome of biopsy-proven minimal change nephropathy in Chinese adults. Am J Kidney Dis. 2014; 65(5):710-8. DOI: 10.1053/j.ajkd.2014.09.022. View

12.

Collino F, Bussolati B, Gerbaudo E, Marozio L, Pelissetto S, Benedetto C . Preeclamptic sera induce nephrin shedding from podocytes through endothelin-1 release by endothelial glomerular cells. Am J Physiol Renal Physiol. 2008; 294(5):F1185-94. DOI: 10.1152/ajprenal.00442.2007. View

13.

Wu Q, Jinde K, Endoh M, Sakai H . Clinical significance of costimulatory molecules CD80/CD86 expression in IgA nephropathy. Kidney Int. 2004; 65(3):888-96. DOI: 10.1111/j.1523-1755.2004.00477.x. View

14.

Hara M, Yanagihara T, Kihara I, Higashi K, Fujimoto K, Kajita T . Apical cell membranes are shed into urine from injured podocytes: a novel phenomenon of podocyte injury. J Am Soc Nephrol. 2004; 16(2):408-16. DOI: 10.1681/ASN.2004070564. View

15.

Levey A, Stevens L, Schmid C, Zhang Y, Castro 3rd A, Feldman H . A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150(9):604-12. PMC: 2763564. DOI: 10.7326/0003-4819-150-9-200905050-00006. View

16.

Petermann A, Floege J . Podocyte damage resulting in podocyturia: a potential diagnostic marker to assess glomerular disease activity. Nephron Clin Pract. 2007; 106(2):c61-6. DOI: 10.1159/000101799. View

17.

Trimarchi H, Canzonieri R, Schiel A, Costales-Collaguazo C, Politei J, Stern A . Increased urinary CD80 excretion and podocyturia in Fabry disease. J Transl Med. 2016; 14(1):289. PMC: 5062834. DOI: 10.1186/s12967-016-1049-8. View

18.

Garin E, Mu W, Arthur J, Rivard C, Araya C, Shimada M . Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int. 2010; 78(3):296-302. DOI: 10.1038/ki.2010.143. View

19.

Cara-Fuentes G, Wei C, Segarra A, Ishimoto T, Rivard C, Johnson R . CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance. Pediatr Nephrol. 2013; 29(8):1363-71. PMC: 4136522. DOI: 10.1007/s00467-013-2679-1. View

20.

Ling C, Liu X, Shen Y, Chen Z, Fan J, Jiang Y . Urinary CD80 levels as a diagnostic biomarker of minimal change disease. Pediatr Nephrol. 2014; 30(2):309-16. DOI: 10.1007/s00467-014-2915-3. View