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

Mitochondrial functions are controlled by genes of both mitochondrial and nuclear DNA. Pathogenic variants affecting any of these are responsible for primary mitochondrial disorders (MIDs), which can be diagnosed during adulthood. Kidney functions are highly dependent on mitochondrial respiration. However, the prevalence of MID-associated nephropathies (MIDANs) is unknown in the adult population. We aimed to address this point and to provide a full characterization of MIDANs in this population.

We retrospectively included for observational study adults (≥16 years of age) with genetically diagnosed MID between 2000 and 2020 in our tertiary care academic centre when they had a chronic kidney disease (CKD) evaluation. MIDANs were ascertained by CKD occurring in MIDs. The phenotypic, biological, histopathological and genotypic characteristics were recorded from the medical charts.

We included 80 MID-affected adults and ascertained MIDANs in 28/80 (35%). Kidney diseases under the care of a nephrologist occurred in only 14/28 (50%) of the adults with MIDAN. MIDANs were tubulointerstitial nephropathy in 14/28 patients (50%) and glomerular diseases in 9/28 (32.1%). In adults with MID, MIDAN was negatively associated with higher albumin levels {odds ratio [OR] 0.79 [95% confidence interval (CI) 0.67-0.95]} and vision abnormalities [OR 0.17 (95% CI 0.03-0.94)] and positively associated with hypertension [OR 4.23 (95% CI 1.04-17.17)].

MIDANs are frequent among adult MIDs. They are mostly represented by tubulointerstitial nephropathy or glomerular disease. Vision abnormalities, hypertension and albumin levels were independently associated with MIDANs. Our results pave the way for prospective studies investigating the prevalence of MIDANs among undetermined kidney disease populations.