Background: Preterm infants with a low birth weight (LBW) show reduced numbers of nephrons at birth and a higher risk of developing kidney dysfunction during their lifetime. They demonstrate oligonephronia and focal segmental glomerulosclerosis (FSGS) lesions in their glomeruli. We examined the association between mitochondrial disorders and the pathological characteristics of LBW-related nephropathy.
Methods: We retrospectively evaluated the renal pathology in 8 infants including pairs of twins and 2 LBW infants demonstrating renal dysfunction. In addition to routine staining, the kidney biopsy specimens were analyzed using cytochrome c oxidase subunit IV (COX IV) and transcription factor A (TFAM) staining.
Results: FSGS was diagnosed in 4 and oligonephronia in 6 patients. Granular swollen epithelial cells (GSECs), which have previously been reported exclusively in patients with mitochondrial cytopathy, were observed in the distal tubules and/or collecting ducts in all 6 infants. Electron microscopic examination revealed that these GSECs included an increased number of enlarged mitochondria. Furthermore, we observed unbalanced expression patterns of COX IV and low expression of TFAM in the glomeruli and a part of the tubular cells.
Discussion: FSGS, a characteristic feature of glomerular involvement in patients with mitochondrial cytopathy is very commonly observed in LBW infants. In our study, all infants did not show FSGS lesions because a renal biopsy was performed in the early stages of the disease in contrast to previous reports. However, most patients revealed similar pathological changes of mitochondrial cytopathy such as unbalanced expression of TFAM, which plays a role in maintaining the mitochondrial DNA. This finding suggests that these lesions could appear during early childhood, resulting in the development of FSGS in the future.
Conclusions: These findings could suggest the application of a new approach targeting mitochondrial DNA to prevent the development of LBW-related nephropathy