Clinicopathologic Features of Mitochondrial Nephropathy

Abstract

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Renal involvement is frequent in adults with primary mitochondrial disorders: an observational study

“…Considering the high frequency of low muscle mass in patients suffering from neuromuscular manifestations, estimating GFR using serum creatinine clearance equations may fail to assess kidney disease correctly [ 25 ]. Indeed, Imasawa et al [ 22 ] recently provided evidence through a cohort of 81 patients with MIDAN showing that proteinuria is more common than decreased GFR. Thus great care was taken regarding blood analyses of electrolytes and urinalyses, both available for all included patients, to ensure that MIDANs were not misestimated.…”

“…These are huge differences compared with the paediatric population in which specific tubulopathies (e.g. Fanconi, Gitelman-like and Bartter-like tubulopathies) and nephrotic syndrome are predominant [ 22 , 33 , 34 ]. The metabolism of the renal tubular segments is highly dependent on OXPHOS to ensure ion homeostasis [ 12 ].…”

“…Glomerular diseases observed in MID-affected patients are thus the direct consequence of energy inadequacy within podocytes, which compromises the glomerular filtration barrier. Indeed, numerous studies have shown the relation between MID and glomerular affections both in paediatric and adult populations [ 15 , 20 , 22 , 34 ]. The prevalence of glomerular disease and tubulointerstitial nephritis has to be mitigated, as the two types can merge.…”

“…Researchers have provided evidence that kidney diseases are more likely to be MIDANs rather than diabetes mellitus complications [ 21 , 24 ]. In contrast, analysis of a large population of patients with MIDANs underscored the fact that 10% of biopsied patients presented diabetic nephropathy lesions [ 22 ]. It might be challenging to ascertain the pathogenic connection between MID and kidney disease occurrence.…”

“…Most of them are tubulointerstitial nephropathy and glomerular diseases with focal segmental glomerulosclerosis (FSGS) [ 13–20 ]. Clinical manifestations are heterogeneous, often referring to systemic manifestations such as mitochondrial encephalopathy, lactic acidosis, stroke-like episode syndrome (MELAS) [ 15 , 17 ] and maternal inherited diabetes and deafness syndrome [ 21 ], deafness, developmental disabilities and cardiomyopathies [ 16 , 22 ]. Nevertheless, a significant number of different types of MIDANs have been isolated at diagnosis [ 16 , 18 , 23 ].…”