Skip to main content
Erschienen in: Pediatric Nephrology 2/2015

01.02.2015 | Original Article

Urinary CD80 levels as a diagnostic biomarker of minimal change disease

verfasst von: Chen Ling, Xiaorong Liu, Ying Shen, Zhi Chen, Jianfeng Fan, Yeping Jiang, Qun Meng

Erschienen in: Pediatric Nephrology | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

Abstract

Background

Early diagnosis of minimal change disease (MCD) in nephrotic syndrome (NS) patients remains challenging. Doctors often make a diagnosis of MCD using invasive renal biopsy. CD80, a transmembrane protein, is present on podocytes in a number of experimental models of NS. Urinary CD80 levels are significantly elevated in MCD but not in focal segmental glomerulosclerosis (FSGS) or other glomerulopathies. The purpose of this study was to investigate the feasibility of using urinary CD80 levels as a biomarker for the diagnosis of MCD.

Materials and methods

A total of 165 subjects, 129 men and 36 women, were enrolled in this study. Urinary samples were collected from 37 patients with MCD, 27 patients with FSGS, 30 patients with other glomerulopathies, and 71 healthy people. Using ELISA, experimental values were compared with those produced by kidney biopsy samples.

Results

The concentration of urinary CD80 was significantly higher in the active MCD group (689.66 ± 378.21 ng/g creatinine) than in the FSGS group (123.49 ± 167. 88 ng/g creatinine, P < 0.00), other glomerulopathies group (152.37 ± 220. 14 ng/g creatinine, P < 0.001) and the control group (81.83 ± 23.01 ng/g creatinine; P < 0.001). A cutoff value of 328.98 (ng/g creatinine) was proposed, with a sensitivity of 81.1 % and specificity of 94.4 %. The area under the receiver operating characteristic (ROC) curve for the urinary CD80 to diagnose MCD was 0.925 (95 % confidence interval: 0.873–0.978).

Conclusions

This experiment has preliminarily confirmed urinary CD80 as a non-invasive diagnostic biomarker. It may have significant value in the diagnosis of MCD.
Literatur
1.
Zurück zum Zitat International Study of Kidney Disease in Children (1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int 13:159–165CrossRef International Study of Kidney Disease in Children (1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int 13:159–165CrossRef
2.
Zurück zum Zitat International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 98:561–564CrossRef International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 98:561–564CrossRef
3.
Zurück zum Zitat Rianthavorn P, Kerr SJ, Chiengthong K (2014) Safety of pediatric percutaneous native kidney biopsy and factors predicting bleeding complications. Nephrology (Carlton) 19:143–148CrossRef Rianthavorn P, Kerr SJ, Chiengthong K (2014) Safety of pediatric percutaneous native kidney biopsy and factors predicting bleeding complications. Nephrology (Carlton) 19:143–148CrossRef
4.
Zurück zum Zitat Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family revisited. Annu Rev Immunol 23:515–548PubMedCrossRef Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family revisited. Annu Rev Immunol 23:515–548PubMedCrossRef
5.
Zurück zum Zitat Chang JM, Hwang DY, Chen SC, Kuo MC, Hung CC, Hwang SJ, Tsai JC, Chen HC (2013) B7-1 expression regulates the hypoxia-driven cytoskeleton rearrangement in glomerular podocytes. Am J Physiol Renal Physiol 304:F127–F136PubMedCrossRef Chang JM, Hwang DY, Chen SC, Kuo MC, Hung CC, Hwang SJ, Tsai JC, Chen HC (2013) B7-1 expression regulates the hypoxia-driven cytoskeleton rearrangement in glomerular podocytes. Am J Physiol Renal Physiol 304:F127–F136PubMedCrossRef
6.
Zurück zum Zitat Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi MP, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, Sugimoto H, Kalluri R, Sharpe AH, Kreidberg JA, Mundel P (2004) Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 113:1390–1397PubMedCentralPubMedCrossRef Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi MP, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, Sugimoto H, Kalluri R, Sharpe AH, Kreidberg JA, Mundel P (2004) Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 113:1390–1397PubMedCentralPubMedCrossRef
7.
Zurück zum Zitat Garin EH, Diaz LN, Mu W, Wasserfall C, Araya C, Segal M, Johnson RJ (2009) Urinary CD80 excretion increases in idiopathic minimal-change disease. J Am Soc Nephrol 20:260–266PubMedCentralPubMedCrossRef Garin EH, Diaz LN, Mu W, Wasserfall C, Araya C, Segal M, Johnson RJ (2009) Urinary CD80 excretion increases in idiopathic minimal-change disease. J Am Soc Nephrol 20:260–266PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat Garin EH, Mu W, Arthur JM, Rivard CJ, Araya CE, Shimada M, Johnson RJ (2010) Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int 78:296–302PubMedCrossRef Garin EH, Mu W, Arthur JM, Rivard CJ, Araya CE, Shimada M, Johnson RJ (2010) Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int 78:296–302PubMedCrossRef
9.
Zurück zum Zitat Kistler AD, Reiser J (2010) Maximal ‘CD80-uria’ with minimal change. Kidney Int 78:236–238PubMedCrossRef Kistler AD, Reiser J (2010) Maximal ‘CD80-uria’ with minimal change. Kidney Int 78:236–238PubMedCrossRef
10.
Zurück zum Zitat Churg J, Habib R, White RH (1970) Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet 760:1299–1302PubMedCrossRef Churg J, Habib R, White RH (1970) Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet 760:1299–1302PubMedCrossRef
11.
Zurück zum Zitat Reiser J, Mundel P (2004) Danger signaling by glomerular podocytes defines a novel function of inducible B7-1 in the pathogenesis of nephrotic syndrome. J Am Soc Nephrol 15:2246–2248PubMedCrossRef Reiser J, Mundel P (2004) Danger signaling by glomerular podocytes defines a novel function of inducible B7-1 in the pathogenesis of nephrotic syndrome. J Am Soc Nephrol 15:2246–2248PubMedCrossRef
12.
Zurück zum Zitat Eto N, Wada T, Inagi R, Takano H, Shimizu A, Kato H, Kurihara H, Kawachi H, Shankland SJ, Fujita T, Nangaku M (2007) Podocyte protection by darbepoetin: preservation of the cytoskeleton and nephrin expression. Kidney Int 72:455–463PubMedCrossRef Eto N, Wada T, Inagi R, Takano H, Shimizu A, Kato H, Kurihara H, Kawachi H, Shankland SJ, Fujita T, Nangaku M (2007) Podocyte protection by darbepoetin: preservation of the cytoskeleton and nephrin expression. Kidney Int 72:455–463PubMedCrossRef
13.
Zurück zum Zitat Shimada M, Araya C, Rivard C, Ishimoto T, Johnson RJ, Garin EH (2011) Minimal change disease: a “two-hit” podocyte immune disorder? Pediatr Nephrol 26(4):645–649PubMedCrossRef Shimada M, Araya C, Rivard C, Ishimoto T, Johnson RJ, Garin EH (2011) Minimal change disease: a “two-hit” podocyte immune disorder? Pediatr Nephrol 26(4):645–649PubMedCrossRef
14.
Zurück zum Zitat Kow NY, Mak A (2013) Costimulatory pathways: physiology and potential therapeutic manipulation in systemic lupus erythematosus. Clin Dev Immunol 2013:245928PubMedCentralPubMedCrossRef Kow NY, Mak A (2013) Costimulatory pathways: physiology and potential therapeutic manipulation in systemic lupus erythematosus. Clin Dev Immunol 2013:245928PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Merrill JT (2013) Co-stimulatory molecules as targets for treatment of lupus. Clin Immunol 148(3):369–375PubMedCrossRef Merrill JT (2013) Co-stimulatory molecules as targets for treatment of lupus. Clin Immunol 148(3):369–375PubMedCrossRef
16.
Zurück zum Zitat Wong CK, Lit LC, Tam LS, Li EK, Lam CW (2005) Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus. Rheumatology 44:989–994PubMedCrossRef Wong CK, Lit LC, Tam LS, Li EK, Lam CW (2005) Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus. Rheumatology 44:989–994PubMedCrossRef
17.
Zurück zum Zitat Meyrier A, Niaudet P (2005) Minimal changes and focal segmental glomerulosclerosis. In: Davison AM, Cameron SJ, Grunfeld JP, Ponticelli C, Ritz E, Winearls C, Van Ypersele C (eds) Textbook of clinical nephrology. Oxford University Press, Oxford, pp 439–469 Meyrier A, Niaudet P (2005) Minimal changes and focal segmental glomerulosclerosis. In: Davison AM, Cameron SJ, Grunfeld JP, Ponticelli C, Ritz E, Winearls C, Van Ypersele C (eds) Textbook of clinical nephrology. Oxford University Press, Oxford, pp 439–469
18.
Zurück zum Zitat Haas M, Yousefzadeh N (2002) Glomerular tip lesion in minimal change nephropathy: a study of autopsies before 1950. Am J Kidney Dis 39:1168–1175PubMedCrossRef Haas M, Yousefzadeh N (2002) Glomerular tip lesion in minimal change nephropathy: a study of autopsies before 1950. Am J Kidney Dis 39:1168–1175PubMedCrossRef
19.
Zurück zum Zitat Howie AJ, Brewer DB (1984) The glomerular tip lesion: a previously undescribed type of segmental glomerular abnormality. J Pathol 142:205–220PubMedCrossRef Howie AJ, Brewer DB (1984) The glomerular tip lesion: a previously undescribed type of segmental glomerular abnormality. J Pathol 142:205–220PubMedCrossRef
20.
Zurück zum Zitat Howie AJ, Lee SJ, Green NJ, Newbold KM, Kizaki T, Koram A, Richards NT, Michael J, Adu D (1993) Different clinicopathological types of segmental sclerosing glomerular lesions in adults. Nephrol Dial Transplant 8:590–599PubMed Howie AJ, Lee SJ, Green NJ, Newbold KM, Kizaki T, Koram A, Richards NT, Michael J, Adu D (1993) Different clinicopathological types of segmental sclerosing glomerular lesions in adults. Nephrol Dial Transplant 8:590–599PubMed
21.
Zurück zum Zitat D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. N Engl J Med 365:2398–2411PubMedCrossRef D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. N Engl J Med 365:2398–2411PubMedCrossRef
22.
Zurück zum Zitat Sinha A, Bajpai J, Saini S, Bhatia D, Gupta A, Puraswani M, Dinda AK, Agarwal SK, Sopory S, Pandey RM, Hari P, Bagga A (2014) Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children. Kidney Int 85:649–658PubMedCrossRef Sinha A, Bajpai J, Saini S, Bhatia D, Gupta A, Puraswani M, Dinda AK, Agarwal SK, Sopory S, Pandey RM, Hari P, Bagga A (2014) Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children. Kidney Int 85:649–658PubMedCrossRef
23.
Zurück zum Zitat Cara-Fuentes G, Wei C, Segarra A, Segarra A, Ishimoto T, Rivard C, Johnson RJ, Reiser J, Garin EH (2014) CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance. Pediatr Nephrol 29:1363–1371PubMedCrossRef Cara-Fuentes G, Wei C, Segarra A, Segarra A, Ishimoto T, Rivard C, Johnson RJ, Reiser J, Garin EH (2014) CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance. Pediatr Nephrol 29:1363–1371PubMedCrossRef
Metadaten
Titel
Urinary CD80 levels as a diagnostic biomarker of minimal change disease
verfasst von
Chen Ling
Xiaorong Liu
Ying Shen
Zhi Chen
Jianfeng Fan
Yeping Jiang
Qun Meng
Publikationsdatum
01.02.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 2/2015
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-014-2915-3

Weitere Artikel der Ausgabe 2/2015

Pediatric Nephrology 2/2015 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.