Key Event Title
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|Complex I inhibition leads to Fanconi syndrome||AdverseOutcome|
Key Event Description
Fanconi syndrome (FS) is characterized by a lack of reabsorption at the proximal tubule that can have genetic or non-genetic origins. As the proximal tubule is the place of extensive reabsorption from the glomerular filtrate in the nephron, this lack of transport results in dramatic consequences for electrolyte homeostasis. In particular, high levels of glucose, amino acids, bicarbonate, and phosphate are excreted instead of returning to the circulation.
How It Is Measured or Detected
The main features of FS are detected in the urine:
hyperphosphaturea, glycosurea and proteinurea are typical clinical features of FS, together with polyuria.
The lack in reabsorption of bicarbonate results in renal tubular acidosis, characterised by polyurea, hypokalemia and hyperchloremia.
Effects on bone mineralisation (adults) and development (children) is another characteristic of FS. The lack of reabsorption of phosphate leads to bone disorders (hypophosphatemic rickets in children and bone demineralisation in adults).
Association studies have linked several pharmacological drugs with the induction of non-congenital forms of FS (Hall, Bass, and Unwin 2014).
At the tissue level, a marked effect of these chemicals is the induction of mitochondrial cytopathy (swollen and dysmorphic mitochondria without cristae) (Herlitz et al. 2010).
Domain of Applicability
Regulatory Significance of the Adverse Outcome
Hall, A. M., P. Bass, and R. J. Unwin. 2014. “Drug-Induced Renal Fanconi Syndrome.” Qjm 107(4):261–69.
Herlitz, Leal C. et al. 2010. “Tenofovir Nephrotoxicity: Acute Tubular Necrosis with Distinctive Clinical, Pathological, and Mitochondrial Abnormalities.” Kidney International 78(11):1171–77. Retrieved (http://dx.doi.org/10.1038/ki.2010.318).