title: Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome.
abstract: BACKGROUND
  MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia.
  
  
  METHODS
  We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss.
  
  
  CONCLUSIONS
  Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.
authors.affiliation: SS Nephrology ASOU san Luigi, Orbassano, Torino, Italy. gbpiccoli@yahoo.it
authors.forename: Giorgina Barbara
authors.initials: GB
authors.lastname: Piccoli
authors.forename: Laura Davico
authors.initials: LD
authors.lastname: Bonino
authors.forename: Paola
authors.initials: P
authors.lastname: Campisi
authors.forename: Federica Neve
authors.initials: FN
authors.lastname: Vigotti
authors.forename: Martina
authors.initials: M
authors.lastname: Ferraresi
authors.forename: Federica
authors.initials: F
authors.lastname: Fassio
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brocheriou
authors.forename: Francesco
authors.initials: F
authors.lastname: Porpiglia
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
mesh_terms: D000328:Adult; D050379:Arteriolosclerosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D007680:Kidney Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D017241:MELAS Syndrome / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D012720:Severity of Illness Index
chemical_list: D004272:DNA, Mitochondrial