Abstract
IntroductionThe clinicopathologic characteristics of nephropathy associated with mitochondrial disease (MD) remain unknown. We retrospectively analyzed a cohort of patients with proteinuria, decreased glomerular filtration rate, or Fanconi syndrome who had a genetic mutation confirmed as the cause of MD, defined as mitochondrial nephropathy.MethodsThis nationwide survey included 757 nephrology sections throughout Japan, and consequently, data on 81 cases of mitochondrial nephropathy were collected.ResultsThe most common renal manifestation observed during the disease course was proteinuria. Hearing loss was the most common comorbidity; a renal-limited phenotype was observed only in mitochondrial DNA (mtDNA) point mutation and COQ8B mutation cases. We found a median time delay of 6.0 years from onset of renal manifestations to diagnosis. Focal segmental glomerular sclerosis (FSGS) was the most common pathologic diagnosis. We then focused on 63 cases with the m.3243A>G mutation. The rate of cases with diabetes was significantly higher among adult-onset cases than among childhood-onset cases. Pathologic diagnoses were more variable in adult-onset cases, including diabetic nephropathy, nephrosclerosis, tubulointerstitial nephropathy, and minor glomerular abnormalities. During the median observation period of 11.0 years from the first onset of renal manifestations in patients with m.3243A>G, renal replacement therapy (RRT) was initiated in 50.8% of patients. Death occurred in 25.4% of the patients during the median observation period of 12.0 years. The median estimated glomerular filtration rate (eGFR) decline was 5.4 ml/min per 1.73 m2/yr in the cases, especially 8.3 ml/min per 1.73 m2/yr in FSGS cases, with m.3243A>G.ConclusionHere, we described the clinicopathologic features and prognosis of mitochondrial nephropathy using large-scale data.
Highlights
The clinicopathologic characteristics of nephropathy associated with mitochondrial disease (MD) remain unknown
We propose that mitochondrial nephropathy is broadly defined as nephropathy with at least one of the following renal manifestations: proteinuria ($0.15 g/g Cre), reduced estimated glomerular filtration rate (eGFR) (
Nephropathy should occur by nongenetic mitochondrial dysfunction as reported by us and others,[18,24,25,26,27,28] here, we propose that such nephropathy with an acquired mitochondrial dysfunction should not be considered mitochondrial nephropathy, following the definition of MD, mitochondrial encephalopathy, mitochondrial cardiomyopathy, or mitochondrial myopathy.[1,2,6,7,8,9]
Summary
This nationwide survey included 757 nephrology sections throughout Japan, and data on 81 cases of mitochondrial nephropathy were collected. Survey Process As the first step to establish a cohort for the J-SMiN study, questionnaires pertaining to the total number of cases of nephropathy associated with MDs were sent to 757 nephrology sections registered with the Japan Renal Biopsy Registry (143 nephrology sections in Supplementary Summary S2) or certified as educational. In 91 nephrology sections among the 325 sections, there were 159 cases of nephropathy associated with MDs. As the final step in establishing a cohort of the J-SMiN study, against these 91 nephrology sections, we conducted surveys to collect detailed data of each patient, with the permission of the ethics committee of each institute.
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