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Renal Fanconi syndrome: taking a proximal look at the nephron

Klootwijk, ED; Reichold, M; Unwin, RJ; Kleta, R; Warth, R; Bockenhauer, D; (2015) Renal Fanconi syndrome: taking a proximal look at the nephron. Nephrology Dialysis Transplantation , 30 (9) pp. 1456-1460. 10.1093/ndt/gfu377. Green open access

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Abstract

Renal Fanconi syndrome (RFS) refers to the generalized dysfunction of the proximal tubule (PT) (Kleta R. Fanconi or not Fanconi? Lowe syndrome revisited. Clin J Am Soc Nephrol 2008; 3: 1244-1245). In its isolated form, RFS only affects the PT, but not the other nephron segments. The study of isolated RFS can thus provide specific insights into the function of the PT. In a recent paper, Klootwijk et al. investigated one such form of isolated RFS and revealed the underlying molecular basis (Klootwijk ED, Reichold M, Helip-Wooley A et al. Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome. N Engl J Med 2014; 370: 129-138). The affected family had been described previously, demonstrating the typical features of RFS, such as low-molecular weight proteinuria, aminoaciduria, glycosuria and phosphaturia with consequent rickets; yet, importantly, patients had no evidence of impaired glomerular filtration (Tolaymat A, Sakarcan A, Neiberger R. Idiopathic Fanconi syndrome in a family. Part I. Clinical aspects. J Am Soc Nephrol 1992; 2: 1310-1317). Inheritance was consistent with an autosomal dominant mode. Klootwijk et al. discovered a surprising explanation: a heterozygous missense mutation causing partial mistargeting of the peroxisomal enzyme EHHADH to the mitochondria. Notably, disease causing was not the absence of the enzyme in the peroxisome, but its interference with mitochondrial function. The discovery of this novel disease mechanism not only confirmed the importance of mitochondrial function for PT transport, but also demonstrated the critical dependence of PT on fatty acid metabolism for energy generation.

Type: Article
Title: Renal Fanconi syndrome: taking a proximal look at the nephron
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/ndt/gfu377
Publisher version: http://dx.doi.org/10.1093/ndt/gfu377
Language: English
Additional information: This is a pre-copyedited, author-produced PDF of an article accepted for publication in Nephrology Dialysis Transplantation following peer review. The version of record Klootwijk, ED; Reichold, M; Unwin, RJ; Kleta, R; Warth, R; Bockenhauer, D; (2015) Renal Fanconi syndrome: taking a proximal look at the nephron. Nephrology Dialysis Transplantation , 30 (9) pp. 1456-1460, is available online at: http://dx.doi.org/10.1093/ndt/gfu377
Keywords: EHHADH, acute kidney injury, proximal tubule, renal Fanconi syndrome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1458509
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