#2564 Kidney Involvement in non-MELAS/MIDD mitochondrial diseases: a report on 58 patients

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Abstract Background and Aims Mitochondrial diseases, characterized by defects in oxidative phosphorylation (OXPHOS), can affect several organs. These disorders result from mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). While the most prevalent and well-documented syndromes include mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and maternally inherited diabetes and deafness (MIDD), many rarer and less well-characterized syndromes have also been identified. This study aims to describe kidney involvement in patients with mitochondrial diseases, excluding MELAS and MIDD syndromes. Method We conducted a retrospective multicenter study from 12 French hospitals of patients with genetically confirmed mitochondrial diseases, excluding MELAS and MIDD syndromes, who presented with kidney involvement. Results The cohort included 58 patients diagnosed with 21 distinct mitochondrial syndromes. The most common syndromes were Kearns-Sayre syndrome and CoQ10 deficiency, with 10 patients in each group. Four genes had never been described as causing kidney disease(COX15, TOP3A, PUS1 and MT-TE). Mutations in mtDNA were identified in 29 patients (50%), while the remaining 29 patients had mutations in nDNA. The median age at onset of the first symptom was 1 year [IQR: 0–6], with kidney manifestations developing at a median age of 10 years [IQR: 2–34]. Extrarenal manifestations were present in all but 4 patients and involved a median of 3 [IQR: 2–4] different organs. Proteinuria greater than 1 g/24 h was present in 18 of 44 patients (40.9%), and tubulopathy was observed in 23 of 38 patients (39.7%). Kidney biopsies were performed in 20 patients, revealing tubulointerstitial lesions as the most common finding (7 cases, 35%), followed by focal segmental glomerulosclerosis (FSGS) in 6 cases (30%) and vascular lesions in 5 cases (25%). The median follow-up period—defined as the time between the first kidney manifestation and either the last clinical follow-up or the onset of kidney failure (KF)—was 3.42 years [IQR: 0.500–6.623]. During this time, 24 patients (41.4%) developed KF at a median age of 12 years [IQR: 3–31.8]. Additionally, 13 patients (22.4%) died at a median age of 13 years [IQR: 9–66]. Patients with CoQ10 deficiency and those with proteinuria greater than 1 g/24 h had significantly worse kidney survival. Conclusion Kidney involvement in mitochondrial diseases other than MELAS and MIDD may manifest as a combination of tubular, glomerular, or vascular lesions, frequently progressing to kidney failure. Diagnosis of kidney involvement is delayed, indicating systematic screening for kidney involvement should be carried out in all patients with mitochondrial disorders, both at the time of diagnosis and during follow-up, to enable early intervention and optimize patient outcomes.

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