Abstract
Background
CD44 is a marker of activated parietal epithelial cells (PECs), and is expressed in glomerular visceral epithelial cells (VECs) during development of segmental sclerosis. We explored the significance of glomerular epithelial CD44 expression in relation to segmental sclerosis in patients with mild IgA nephropathy (IgAN).
Methods
A total of 126 cases of IgAN were divided into three groups based on glomerular morphology: normal (group A, n = 30), mild mesangial proliferation without segmental sclerosis or synechia (SS) (group B, n = 31), or mild mesangial proliferation with SS (group C, n = 65). The number of CD44-expressing PECs and VECs was counted in each glomerulus and expressed as the mean number per case.
Results
CD44 staining was positive in VECs in 59.5 %, in PECs in 79.4 % and in both cell types in 56.3 % of cases. The number of CD44+ PECs or VECs was significantly higher in group C than in groups A or B. Cases with >1 CD44+ cell (PECs and VECs) per glomerulus were associated with increased urine protein/creatinine ratio (UPCr) at last follow-up. The presence of >1 CD44+ VEC/glomerulus was associated with increased UPCr and serum creatinine levels, and decreased estimated glomerular filtration rate (eGFR) even in the absence of SS at the time of biopsy.
Conclusion
CD44 was expressed in PECs and VECs in association with SS in IgAN. Increased CD44 expression in VECs is a sign of active glomerular injury and dysfunction in these patients.
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References
Matsusaka T, Xin J, Niwa S, Kobayashi K, Akatsuka A, Hashizume H, et al. Genetic engineering of glomerular sclerosis in the mouse via control of onset and severity of podocyte-specific injury. J Am Soc Nephrol. 2005;16(4):1013–23.
Laurens WE, Vanrenterghem YF, Steels PS, Van Damme BJ. A new single nephron model of focal and segmental glomerulosclerosis in the Munich-Wistar rat. Kidney Int. 1994;45(1):143–9.
Wharram BL, Goyal M, Wiggins JE, Sanden SK, Hussain S, Filipiak WE, et al. 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.
Smeets B, Kuppe C, Sicking EM, Fuss A, Jirak P, van Kuppevelt TH, et al. Parietal epithelial cells participate in the formation of sclerotic lesions in focal segmental glomerulosclerosis. J Am Soc Nephrol. 2011;22(7):1262–74.
Kriz W. The pathogenesis of ‘classic’ focal segmental glomerulosclerosis-lessons from rat models. Nephrol Dial Transplant. 2003;18(6):39–44.
Asanuma K, Mundel P. The role of podocytes in glomerular pathobiology. Clin Exp Nephrol. 2003;7(4):255–9.
Smeets B, Te Loeke NA, Dijkman HB, Steenbergen ML, Lensen JF, Begieneman MP, et al. The parietal epithelial cell: a key player in the pathogenesis of focal segmental glomerulosclerosis in Thy-1.1 transgenic mice. J Am Soc Nephrol. 2004;15(4):928–39.
Sarioglu S, Sis B, Tuncer C, Celik A, Zeybel M, Soylu A, et al. Tubular CD44 expression in renal allograft biopsies. Transplant Proc. 2004;36(1):92–4.
Zhang J, Pippin JW, Krofft RD, Naito S, Liu ZH, Shankland SJ. Podocyte repopulation by renal progenitor cells following glucocorticoids treatment in experimental FSGS. Am J Physiol Renal Physiol. 2013;304(11):F1375–89.
Fatima H, Moeller MJ, Smeets B, Yang HC, D’Agati VD, Alpers CE, et al. Parietal epithelial cell activation marker in early recurrence of FSGS in the transplant. Clin J Am Soc Nephrol. 2012;7(11):1852–8.
Kuppe C, Grone HJ, Ostendorf T, van Kuppevelt TH, Boor P, Floege J, et al. Common histological patterns in glomerular epithelial cells in secondary focal segmental glomerulosclerosis. Kidney Int. 2015;88(5):990–8.
Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfels AB, et al. Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study. Am J Kidney Dis. 2000;35(1):157–65.
Lee H, Kim DK, Oh KH, Joo KW, Kim YS, Chae DW, et al. Mortality and renal outcome of primary glomerulonephritis in Korea: observation in 1,943 biopsied cases. Am J Nephrol. 2013;37(1):74–83.
Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. 1997;29(6):829–42.
The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification, Cattran DC, Coppo R, Cook HT, Feehally J, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76(5):534–45.
Hishiki T, Shirato I, Takahashi Y, Funabiki K, Horikoshi S, Tomino Y. Podocyte injury predicts prognosis in patients with iga nephropathy using a small amount of renal biopsy tissue. Kidney Blood Press Res. 2001;24(2):99–104.
Kodama F, Asanuma K, Takagi M, Hidaka T, Asanuma E, Fukuda H, et al. Translocation of dendrin to the podocyte nucleus in acute glomerular injury in patients with IgA nephropathy. Nephrol Dial Transplant. 2013;28(7):1762–72.
El Karoui K, Hill GS, Karras A, Moulonguet L, Caudwell V, Loupy A, et al. Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies. Kidney Int. 2011;79(6):643–54.
Gutierrez E, Zamora I, Ballarin JA, Arce Y, Jimenez S, Quereda C, et al. Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J Am Soc Nephrol. 2012;23(10):1753–60.
Lemley KV, Lafayette RA, Safai M, Derby G, Blouch K, Squarer A, et al. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 2002;61(4):1475–85.
Kabgani N, Grigoleit T, Schulte K, Sechi A, Sauer-Lehnen S, Tag C, et al. Primary cultures of glomerular parietal epithelial cells or podocytes with proven origin. PLoS One. 2012;7(4):e34907.
Sakamoto K, Ueno T, Kobayashi N, Hara S, Takashima Y, Pastan I, et al. The direction and role of phenotypic transition between podocytes and parietal epithelial cells in focal segmental glomerulosclerosis. Am J Physiol Renal Physiol. 2014;306(1):F98–104.
Nam KH, Kie JH, Lee MJ, Chang TI, Kang EW, Kim DW, et al. Optimal proteinuria target for renoprotection in patients with IgA nephropathy. PLoS One. 2014;9(7):e101935.
Herlitz LC, Bomback AS, Stokes MB, Radhakrishnan J, D’Agati VD, Markowitz GS. IgA nephropathy with minimal change disease. Clin J Am Soc Nephrol. 2014;9(6):1033–9.
Smeets B, Stucker F, Wetzels J, Brocheriou I, Ronco P, Grone HJ, et al. Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease. Am J Pathol. 2014;184(12):3239–48.
Park KS, Han SH, Kie JH, Nam KH, Lee MJ, Lim BJ, et al. Comparison of the Haas and the Oxford classifications for prediction of renal outcome in patients with IgA nephropathy. Hum Pathol. 2014;45(2):236–43.
Qiaoling Z, Xiaoyun J, Wei W, Shuhong D, Yaqin P, Xiaoqing G. Altered P-selectin and CD44 expression in the renal tissues and peripheral blood of children with IgA nephropathy. Int Urol Nephrol. 2009;41(3):703–11.
Florquin S, Nunziata R, Claessen N, van den Berg FM, Pals ST, Weening JJ. CD44 expression in IgA nephropathy. Am J Kidney Dis. 2002;39(2):407–14.
Sano N, Kitazawa K, Sugisaki T. Localization and roles of CD44, hyaluronic acid and osteopontin in IgA nephropathy. Nephron. 2001;89(4):416–21.
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Kim, S., Kim, Y.H., Choi, K.H. et al. Glomerular epithelial CD44 expression and segmental sclerosis in IgA nephropathy. Clin Exp Nephrol 20, 871–877 (2016). https://doi.org/10.1007/s10157-015-1222-z
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DOI: https://doi.org/10.1007/s10157-015-1222-z