Abstract
Background
Minimal change disease (MCD) is characterized by increased urinary excretion of CD80, whereas focal segmental glomerulosclerosis (FSGS) is associated with increased serum soluble urokinase-type plasminogen activator receptor (suPAR). The aim of the study was to assess whether the simultaneous measurement of urinary CD80 and serum suPAR helps differentiate MCD and FSGS.
Methods
Urine and sera were collected from patients with MCD in relapse or in remission, from FSGS patients with nephrotic syndrome, and from healthy individuals. CD80 and suPAR were measured by ELISA.
Results
Urinary CD80 was significantly increased in MCD patients in relapse compared with those in remission and with FSGS patients and control individuals. Serum suPAR levels were significantly higher in patients with FSGS when compared with MCD patients in relapse. Urinary suPAR showed a positive correlation with proteinuria in MCD in relapse and FSGS patients, whereas urinary CD80 correlated with proteinuria only in MCD patients in relapse.
Conclusion
Urinary CD80 is elevated in MCD patients in relapse compared with FSGS patients. In contrast, serum suPAR is significantly elevated in FSGS patients. The consistent pattern of these two biomarkers in MCD and FSGS suggests that these two conditions represent different entities rather than a continuum spectrum of one disease.
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References
Habib R, Kleinknecht C (1971) The primary nephrotic syndrome in childhood: classification and clinicopathologic study of 406 cases. Pathol Annu 6:417–474
Barisoni L, Schnaper HW, Kopp JB (2007) A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic diseases. Clin J Am Soc Nephrol 2:529–542
Kriz W, LeHir M (2005) Pathways to nephron loss starting from glomerular diseases-insights from animal models. Kidney Int 67:404–419
Ponticelli C, Glassock RJ (2010) Treatment of primary glomerulonephritis, 2nd edn. Oxford University Press, New York, p 181
Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 2:556–560
Sharma M, Sharma R, McCarthy ET, Savin VJ (1999) "The FSGS factor:" enrichment and in vivo effect of activity from focal segmental glomerulosclerosis plasma. J Am Soc Nephrol 10:552–561
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 15:2246–2248
Franceschini N, North KE, Kopp JB, McKenzie L, Winkler C (2006) NPHS2 gene, nephrotic syndrome and focal segmental glomerulosclerosis: a HuGE review. Genet Med 8:63–75
Clement LC, Avila-Casado C, Macé C, Soria E, Bakker WW, Kersten S, Chugh SS (2011) Podocyte-secreted Angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med 17:117–122
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 20:260–266
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 78:296–302
Wei C, El Hindi S, Li J, Fornoni A, Goes N, Sageshima J, Maiguel D, Karumanchi SA, Yap HK, Saleem M, Zhang Q, Nikolic B, Chaudhuri A, Daftarian P, Salido E, Torres A, Salifu M, Sarwal MM, Schaefer F, Morath C, Schwenger V, Zeier M, Gupta V, Roth D, Rastaldi MP, Burke G, Ruiz P, Reiser J (2011) Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 17:952–960
(1981) Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children. Kidney Int 20:765–771
D'Agati VD, Fogo AB, Bruijn JA, Jennette JC (2004) Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 43:368–382
Reiser J, von Gersdorff G, Loos M, Oh L, 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 113:1390–1397
Wei C, Möller CC, Altintas MM, Li J, Schwarz K, Zacchigna S, Xie L, Henger A, Schmid H, Rastaldi MP, Cowan P, Kretzler M, Parrilla R, Bendayan M, Gupta V, Nikolic B, Kalluri R, Carmeliet P, Mundel P, Reiser J (2008) Modification of kidney barrier function by the urokinase receptor. Nat Med 14:55–63
Wei C, Trachtman H, Li J, Dong C, Friedman AL, Gassman JJ, McMahan JL, Radeva M, Heil KM, Trautmann A, Anarat A, Emre S, Ghiggeri GM, Ozaltin F, Haffner D, Gipson DS, Kaskel F, Fischer DC, Schaefer F, Reiser J, PodoNet and FSGS CT Study Consortia (2012) Circulating suPAR in two cohorts of primary FSGS. J Am Soc Nephrol 23:2051–2059
Cara-Fuentes G, Araya C, Wei C, Rivard C, Ishimoto T, Reiser J, Johnson R, Garin EH (2013) CD80, suPAR and Nephrotic Syndrome in a case of NPHS2 mutation. Nefrologia 33:727–731
Shimada M, Ishimoto T, Lee PY, Lanaspa MA, Rivard CJ, Roncal-Jimenez CA, Wymer DT, Yamabe H, Mathieson PW, Saleem MA, Garin EH, Johnson RJ (2012) Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-kB-dependent pathway. Nephrol Dial Transplant 27:81–89
Acknowledgments
This study was supported by NIH R01DK080764 to EG and in part by grants from the National Institutes of Health DK073495 and DK089394 to JR
Disclosures
JR and CW are inventors of pending (JR, CW) and issued (JR) patents on novel technologies around proteinuric kidney diseases and stand to gain royalties from their commercialization. The other authors declare no conflict of interest.
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Cara-Fuentes, G., Wei, C., Segarra, A. et al. CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance. Pediatr Nephrol 29, 1363–1371 (2014). https://doi.org/10.1007/s00467-013-2679-1
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DOI: https://doi.org/10.1007/s00467-013-2679-1