Abstract
Recently, disorders of the slit diaphragm have been considered as major causes of proteinuria in renal disease and the charge barrier function of the glomerular capillary wall has been given less attention. We evaluated the charge selectivity index (CSI) in 40 patients with podocyte disease (PD), 75 with chronic glomerulonephritis (CGN), and 8 with Dent disease, to reexamine the charge barrier function. We evaluated CSI in Dent disease because the urinary protein profile in Dent disease was assumed to be a concentrate of a normal glomerular filtrate. CSI was defined as the renal clearance ratio between IgA and IgG. CSI values (mean ± SD) in the CGN and PD groups and in Dent disease were 1.12 ± 0.25, 0.42 ± 0.31, and 0.16 ± 0.06, respectively, suggesting that the charge barrier function was defective in the CGN group and of reduced capacity in the PD group. The results suggest that functional interactions between the slit diaphragm and the glomerular basement membrane exist, and that a slit diaphragm disorder is accompanied by a decrease in the charge barrier function in PD, as argued by the conventional hypothesis.
This is a preview of subscription content, log in via an institution to check access.
References
Brenner BM, Hostetter TH, Humes HD (1978) Molecular basis of proteinuria of glomerular origin. N Engl J Med 298:826–833
Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K (1998) Positionally cloned gene for a novel glomerular protein–nephrin–is mutated in congenital nephrotic syndrome. Mol Cell 1:575–582
Ruotsalainen V, Ljungberg P, Wartiovaara J, Lenkkeri U, Kestilä M, Jalanko H, Holmberg C, Tryggvason K (1999) Nephrin is specifically located at the slit diaphragm of glomerular podocytes. Proc Natl Acad Sci U S A 96:7962–7967
Sako M, Nakanishi K, Obana M, Yata N, Hoshii S, Takahashi S, Wada N, Takahashi Y, Kaku Y, Satomura K, Ikeda M, Honda M, Iijima K, Yoshikawa N (2005) Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome. Kidney Int 67:1248–1255
Takahashi S, Kitamura T, Murakami H, Hashimoto K, Nagata M, Harada K (2005) Acute interstitial nephritis predisposed a six-year-old girl to minimal change nephrotic syndrome. Pediatr Nephrol 20:1168–1170
Takahashi S, Watanabe S, Wada N, Murakami H, Funaki S, Yan K, Kondo Y, Harada K, Nagata M (2006) Charge selective function in childhood glomerular diseases. Pediatr Res 59:336–340
Norden AG, Lapsley M, Lee PJ, Pusey CD, Scheinman SJ, Tam FW, Thakker RV, Unwin RJ, Wrong O (2001) Glomerular protein sieving and implications for renal failure in Fanconi syndrome. Kidney Int 60:1885–1892
Sörensson J, Björnson A, Ohlson M, Ballermann BJ, Haraldsson B (2003) Synthesis of sulfated proteoglycans by bovine glomerular endothelial cells in culture. Am J Physiol Renal Physiol 284:F373–380
Smithies O (2003) Why the kidney glomerulus does not clog: a gel permeation/diffusion hypothesis of renal function. Proc Natl Acad Sci U S A 100:4108–4113
Ohlson M, Sörensson J, Haraldsson B (2001) A gel-membrane model of glomerular charge and size selectivity in series. Am J Physiol Renal Physiol 280:F396–405
Takahashi S, Wada N, Harada K, Nagata M (2004) Cationic charge-preferential IgG reabsorption in the renal proximal tubules. Kidney Int 66:1556–1560
Wada N, Ueda Y, Iidaka K, Inage Z, Kikkawa Y, Kitagawa T (1990) Portions of basement membrane with decreased negative charge in various glomerulonephritis. Clin Nephrol 34:9–16
Sakagami Y, Nakajima M, Takagawa K, Ueda T, Akazawa H, Maruhashi Y, Shimoyama H, Kamitsuji H, Yoshioka A (2004) Analysis of glomerular anionic charge status in children with IgA nephropathy using confocal laser scanning microscopy. Nephron Clin Pract 96:c96–104
Lee HS, Choi Y, Lee JS, Yu BH, Koh HI (1989) Ultrastructural changes in IgA nephropathy in relation to histologic and clinical data. Kidney Int 35:880–886
Nomura Y, Ohya N, Shimada M (1989) A histopathological study on the prognosis of childhood IgA nephropathy and glomerular basement membrane lesions. Pediatr Nephrol 3:242–247
Acknowledgments
This study was presented at the 14th Congress of the International Pediatric Nephrology Association in Budapest, 2007.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Saito, H., Takahashi, S., Nagata, M. et al. Reevaluation of glomerular charge selective protein-sieving function. Pediatr Nephrol 24, 609–612 (2009). https://doi.org/10.1007/s00467-008-1013-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-008-1013-9