Abstract
Background
Dent disease is an X-linked recessive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure (MIM 300009). A recent case series identified four patients with CLCN5 mutations who presented with nephrotic-range proteinuria, histologic evidence of focal segmental and/or global sclerosis, and low molecular weight proteinuria.
Case-Diagnosis/Treatment
We characterize the clinical, genetic, and histopathological features of seven unrelated adolescent males with nephrotic-range proteinuria and CLCN5 mutations. Six patients underwent renal biopsy prior to assessing tubular proteinuria. All biopsied patients had either segmental sclerosis (3/6) or segmental increase in mesangial matrix (3/6). Five patients revealed some degree of foot process effacement, but only one patient biopsy revealed >50 % foot process effacement. The attenuated foot process effacement suggests the glomerulosclerosis is not due to a primary podocytopathy.
Conclusions
These data suggest that clinicians should consider a diagnostic evaluation for Dent disease in young males presenting with high-grade proteinuria.
This is a preview of subscription content, log in via an institution to check access.
References
Frishberg Y, Dinour D, Belostotsky R, Becker-Cohen R, Rinat C, Feinstein S, Navon-Elkan P, Ben-Shalom E (2009) Dent’s disease manifesting as focal glomerulosclerosis: is it the tip of the iceberg? Pediatr Nephrol 24:2369–2373
Copelovitch L, Nash MA, Kaplan BS (2007) Hypothesis: Dent disease is an underrecognized cause of focal glomerulosclerosis. Clin J Am Soc Nephrol 2:914–918
Scheinman SJ (1998) X-linked hypercalciuric nephrolithiasis: clinical syndromes and chloride channel mutations. Kidney Int 53:3–17
Frymoyer PA, Scheinman SJ, Dunham PB, Jones DB, Hueber P, Schroeder ET (1991) X-linked recessive nephrolithiasis with renal failure. N Engl J Med 325:681–686
Marshansky V, Bourgoin S, Londono I, Bendayan M, Maranda B, Vinay P (1997) Receptor-mediated endocytosis in kidney proximal tubules: recent advances and hypothesis. Electrophoresis 18:2661–2676
Piwon N, Gunther W, Schwake M, Bosl MR, Jentsch TJ (2000) ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent’s disease. Nature 408:369–373
Devuyst O, Jouret F, Auzanneau C, Courtoy PJ (2005) Chloride channels and endocytosis: new insights from Dent’s disease and ClC-5 knockout mice. Nephron 99:69–73
Lloyd SE, Pearce SH, Gunther W, Kawaguchi H, Igarashi T, Jentsch TJ, Thakker RV (1997) Idiopathic low molecular weight proteinuria associated with hypercalciuric nephrocalcinosis in Japanese children is due to mutations of the renal chloride channel (CLCN5). J Clin Invest 99:967–974
Ovunc B, Otto EA, Vega-Warner V, Saisawat P, Ashraf S, Ramaswami G, Fathy HM, Schoeb D, Chernin G, Lyons RH, Yilmaz E, Hildebrandt F (2011) Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuria. J Am Soc Nephrol 22:1815–1820
Blanchard A, Vargas-Poussou R, Peyrard S, Mogenet A, Baudouin V, Boudailliez B, Charbit M, Deschesnes G, Ezzhair N, Loirat C, Macher MA, Niaudet P, Azizi M (2008) Effect of hydrochlorothiazide on urinary calcium excretion in dent disease: an uncontrolled trial. Am J Kidney Dis 52:1084–1095
Acknowledgments
The authors thank Amber K. O’Connor PhD of akoWriting LLC for editorial services. The authors state that there are no commercial affiliations or conflicts of interest to disclose.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary Figure 1
(DOCX 4450 kb)
Rights and permissions
About this article
Cite this article
Cramer, M.T., Charlton, J.R., Fogo, A.B. et al. Expanding the phenotype of proteinuria in Dent disease. A case series. Pediatr Nephrol 29, 2051–2054 (2014). https://doi.org/10.1007/s00467-014-2824-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-014-2824-5