Deletion of mitochondrial DNA in patient with chronic tubulointerstitial nephritis☆,☆☆,★
Section snippets
CASE REPORT
A boy born to unrelated healthy parents (birth weight 3 kg) did well during the first years of life except for persistent intestinal obstruction after appendectomy at 5 years of age. At 11 years of age he had anemia and polyuria (height 131 cm [-2 SD], weight 27 kg [-2 SD]). Blood pressure was 130/60 mm Hg. Moderate proteinuria (0.5 gm/day) with no sign of proximal tubulopathy or renal failure was noted; the serum creatinine concentration was 206 μmol/L (2.3 mg/dl), and creatinine clearance was
METHODS
Plasma lactate-pyruvate and ketone body molar ratios (3-hydroxybutyrate/acetoacetate) were determined in the patient and in control subjects as indexes of the oxidation-reduction status in cytoplasm and mitochondria, respectively.2 A needle biopsy of the kidney and an open biopsy of the deltoid were performed with local anesthesia and the specimens were processed for histologic studies and for spectrophotometric and polarographic analyses of mitochondrial respiratory enzymes. Enzyme activities
RESULTS
Histopathologic examination of the kidney showed prominent tubulointerstitial changes characterized by marked, and nearly diffuse, interstitial fibrosis with tubular lesions consisting of obstructions of the tubular lumen by hyaline casts. Moderate thickening of the tubular basement membrane around atrophic tubules was seen focally. Within these areas, glomeruli were totally sclerosed or had irregular thickening and wrinkling of the basement membrane and retraction of the tuft within thickened
DISCUSSION
We report here an mtDNA deletion in a patient with tubulointerstitial nephritis that resulted in a concentrating defect and chronic renal failure. Nephronophthisis was initially considered because it is the most frequent cause of tubulointerstitial nephritis in childhood, but this diagnosis remained questionable because specific thickening of the basement membrane in the tubules was not observed. The disease remained unexplained, and only when it progressed to involvement of the central nervous
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Cited by (62)
Mitochondria in Acute Kidney Injury
2016, Seminars in NephrologyCitation Excerpt :Güçer et al39 described 2 pediatric patients who were found to have focal segmental glomerular sclerosis owing to different mtDNA deletions. In addition, mitochondrial disease can show a pure tubulointerstitial nephritis without evidence of a proximal tubulopathy, as reported by Rötig et al.40 Characterization of these genetic disorders is made difficult by the lack of a consistent genotype–phenotype relationship.
Renal involvement in mitochondrial cytopathies
2013, Nephrologie et TherapeutiqueSolute Transport, Energy Consumption, and Production in the Kidney
2013, Seldin and Geibisch's The KidneySolute Transport, Energy Consumption, and Production in the Kidney
2012, Seldin and Giebisch's The Kidney: Physiology and PathophysiologyNovel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy
2011, Biochemical and Biophysical Research Communications
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From the Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U393, Unité de Recherches de Néphrologie Pédiatrique, INSERM U192 and Département de Pédiatrie, Hôpital des Enfants-Malades, Paris, France, and the Service d'Anatomopathologie, Hôpital Lariboisière, Paris, France
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Reprint requests: Arnold Munnich, MD, INSERM U393, Hôpital des Enfants Malades, 149 rue de Sèvres, 75743 Paris-Cedex 15, France.
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0022-3476/95/$3.00 + 0 9/22/61435