Skip to main content
Top
Published in: Pediatric Nephrology 11/2017

01-11-2017 | Brief Report

Is CD44 in glomerular parietal epithelial cells a pathological marker of renal function deterioration in primary focal segmental glomerulosclerosis?

Authors: Brunna Pinto Froes, Stanley de Almeida Araújo, Eduardo Alves Bambirra, Eduardo Araújo Oliveira, Ana Cristina Simões e Silva, Sérgio Veloso Brant Pinheiro

Published in: Pediatric Nephrology | Issue 11/2017

Login to get access

Abstract

Background

The search for risk factors for chronic kidney disease in children with focal segmental glomerulosclerosis (FSGS) is important in defining prognosis and individualized treatment. This study preliminarily investigated whether CD44 immunostaining in glomerular parietal epithelial cells (PECs) is a prognostic marker in pediatric FSGS.

Methods

In this retrospective study, 26 patients with FSGS, biopsied from 1985 to 2010, were evaluated. Immunohistochemistry for CD44 was performed in all cases. For analysis purposes, patients were grouped according to whether or not they were positive for CD44 in PECs. The primary outcome was a decline in baseline estimated glomerular filtration rate (eGFR) of 50% or more.

Results

Median follow-up was 6.9 years. Median renal survival was 14.5 years and probability of a 50% decline of eGRF was 30% in 10 years. Nine children exhibited the primary outcome and 7 developed end-stage renal disease (ESRD). In comparison with PEC CD44-negative patients (n = 18), PEC CD44-positive patients (n = 8) presented lower baseline eGFR (99 ± 41 versus 141 ± 44 ml/min/1.73 m2, p = 0.035) and a significant decline in eGFR (−38.6 ± 39.5 versus −5.6 ± 25.3 ml/min/1.73 m2/year, p = 0.018). No difference was observed in FSGS subtypes or other glomerular features. Presence of CD44 staining in PECs was significantly associated with the decline in baseline eGFR of 50% or more. Renal survival was significantly reduced in PEC CD44-positive patients (3.8 vs 14.6 years in C4d-negative, p < 0.05).

Conclusion

Our preliminary findings indicate, for the first time, that positivity for CD44 in PECs seems to be a pathological marker of renal function deterioration in pediatric patients with FSGS.
Appendix
Available only for authorised users
Literature
1.
go back to reference D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. N Engl J Med 365:2398–2411CrossRefPubMed D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. N Engl J Med 365:2398–2411CrossRefPubMed
2.
go back to reference Kitiyakara C, Kopp JB, Eggers P (2003) Trends in the epidemiology of focal segmental glomerulosclerosis. Semin Nephrol 23:172–182CrossRefPubMed Kitiyakara C, Kopp JB, Eggers P (2003) Trends in the epidemiology of focal segmental glomerulosclerosis. Semin Nephrol 23:172–182CrossRefPubMed
4.
go back to reference Staples AO, Greenbaum LA, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, Wong CS (2010) Association between clinical risk factors and progression of chronic kidney disease in children. Clin J Am Soc Nephrol 5:2172–2179CrossRefPubMedPubMedCentral Staples AO, Greenbaum LA, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, Wong CS (2010) Association between clinical risk factors and progression of chronic kidney disease in children. Clin J Am Soc Nephrol 5:2172–2179CrossRefPubMedPubMedCentral
5.
go back to reference Mendonça AC, Oliveira EA, Fróes BP, Faria LD, Pinto JS, Nogueira MM, Lima GO, Resende PI, Assis NS, Simões E, Silva AC, Pinheiro SV (2015) A predictive model of progressive chronic kidney disease in idiopathic nephrotic syndrome. Pediatr Nephrol 30:2011–2020CrossRefPubMed Mendonça AC, Oliveira EA, Fróes BP, Faria LD, Pinto JS, Nogueira MM, Lima GO, Resende PI, Assis NS, Simões E, Silva AC, Pinheiro SV (2015) A predictive model of progressive chronic kidney disease in idiopathic nephrotic syndrome. Pediatr Nephrol 30:2011–2020CrossRefPubMed
6.
go back to reference National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) Fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRef National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) Fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576CrossRef
7.
go back to reference 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
8.
go back to reference D’Agati VD, Fogo AB, Brujin JA, Charles Jennete J (2004) Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 43:368–382CrossRefPubMed D’Agati VD, Fogo AB, Brujin JA, Charles Jennete J (2004) Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis 43:368–382CrossRefPubMed
9.
go back to reference Taal MW, Brenner BM (2006) Predicting initiation and progression of chronic kidney disease: developing renal risk scores. Kidney Int 70:1694–1705CrossRefPubMed Taal MW, Brenner BM (2006) Predicting initiation and progression of chronic kidney disease: developing renal risk scores. Kidney Int 70:1694–1705CrossRefPubMed
10.
go back to reference Appel D, Kershaw DB, Smeets B, Yuan G, Fuss A, Frye B, Elger M, Kriz W, Floege J, Moeller MJ (2009) Recruitment of podocytes from glomerular parietal epithelial cells. J Am Soc Nephrol 20:333–343CrossRefPubMedPubMedCentral Appel D, Kershaw DB, Smeets B, Yuan G, Fuss A, Frye B, Elger M, Kriz W, Floege J, Moeller MJ (2009) Recruitment of podocytes from glomerular parietal epithelial cells. J Am Soc Nephrol 20:333–343CrossRefPubMedPubMedCentral
11.
go back to reference Lasagni L, Romagnani P (2010) Glomerular epithelial stem cells: the good, the bad, and the ugly. J Am Soc Nephrol 21:1612–1619CrossRefPubMed Lasagni L, Romagnani P (2010) Glomerular epithelial stem cells: the good, the bad, and the ugly. J Am Soc Nephrol 21:1612–1619CrossRefPubMed
12.
go back to reference Smeets B, Kuppe C, Sicking EM, Fuss A, Jirak P, van Kuppevelt TH, Endlich K, Wetzels JF, Gröne HJ, Floege J, Moeller MJ (2011) Parietal epithelial cells participate in the formation of sclerotic lesions in focal segmental glomerulosclerosis. J Am Soc Nephrol 22:1262–1274CrossRefPubMedPubMedCentral Smeets B, Kuppe C, Sicking EM, Fuss A, Jirak P, van Kuppevelt TH, Endlich K, Wetzels JF, Gröne HJ, Floege J, Moeller MJ (2011) Parietal epithelial cells participate in the formation of sclerotic lesions in focal segmental glomerulosclerosis. J Am Soc Nephrol 22:1262–1274CrossRefPubMedPubMedCentral
13.
go back to reference Smeets B, Stucker F, Wetzels J, Brocheriou I, Ronco P, Gröne HJ, D’Agati V, Fogo AB, van Kuppevelt TH, Fischer HP, Boor P, Floege J, Ostendorf T, Moeller MJ (2014) Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease. Am J Pathol 184:3239–3248CrossRefPubMed Smeets B, Stucker F, Wetzels J, Brocheriou I, Ronco P, Gröne HJ, D’Agati V, Fogo AB, van Kuppevelt TH, Fischer HP, Boor P, Floege J, Ostendorf T, Moeller MJ (2014) Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease. Am J Pathol 184:3239–3248CrossRefPubMed
14.
go back to reference Fatima H, Moeller MJ, Smeets B, Yang HC, D’Agati VD, Alpers CE, Fogo AB (2012) Parietal epithelial cell activation marker in early recurrence of FSGS in the transplant. Clin J Am Soc Nephrol 7:1852–1858CrossRefPubMedPubMedCentral Fatima H, Moeller MJ, Smeets B, Yang HC, D’Agati VD, Alpers CE, Fogo AB (2012) Parietal epithelial cell activation marker in early recurrence of FSGS in the transplant. Clin J Am Soc Nephrol 7:1852–1858CrossRefPubMedPubMedCentral
15.
go back to reference Hodgkins KS, Schnaper HW (2012) Tubulointerstitial injury and the progression of chronic kidney disease. Pediatr Nephrol 27:901–909CrossRefPubMed Hodgkins KS, Schnaper HW (2012) Tubulointerstitial injury and the progression of chronic kidney disease. Pediatr Nephrol 27:901–909CrossRefPubMed
Metadata
Title
Is CD44 in glomerular parietal epithelial cells a pathological marker of renal function deterioration in primary focal segmental glomerulosclerosis?
Authors
Brunna Pinto Froes
Stanley de Almeida Araújo
Eduardo Alves Bambirra
Eduardo Araújo Oliveira
Ana Cristina Simões e Silva
Sérgio Veloso Brant Pinheiro
Publication date
01-11-2017
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 11/2017
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-017-3775-4

Other articles of this Issue 11/2017

Pediatric Nephrology 11/2017 Go to the issue