Abstract
Background: Mitochondrial disorders can present as kidney disease in children and be difficult to diagnose. Measurement of mitochondrial function in kidney tissue may help diagnosis. This study was to assess the feasibility of obtaining renal samples and analysing them for respiratory chain enzyme activity. Methods: The subjects were children undergoing a routine diagnostic renal biopsy, in whom a clinical condition of renal inflammation, scarring and primary metabolic disorder was unlikely. A fresh sample of kidney was snap frozen and later assayed for the activities of respiratory chain enzyme complexes I, II/III, and IV using spectrophotometric enzyme assay, and expressed as a ratio of citrate synthase activity. Results: The range of respiratory chain enzyme activity for complex I was 0.161 to 0.866 (mean 0.404, SD 0.2), for complex II/III was 0.021 to 0.318 (mean 0.177, SD 0.095) and for complex IV was 0.001 to 0.025 (mean 0.015, SD 0.006). There were correlations between the different activities but not between them and the age of the children or a measure of the amount of chronic damage in the kidneys. Conclusion: It is feasible to measure respiratory chain enzyme activity in routine renal biopsy specimens.
Highlights
Mitochondrial disorders are difficult to diagnose clinically because of phenotypic variation.Renal presentations include the renal Fanconi syndrome and steroid unresponsive nephrotic syndrome as a result of glomerular damage; progression to chronic kidney disease is described [1,2,3]
There were no significant correlations between age and index of chronic damage, age and any respiratory chain enzyme activity (RCEA), or index of chronic damage and any RCEA
The inter-assay coefficient of variation values for the RCEA and citrate synthase (CS) enzyme measurements calculated from the in-house QC human skeletal muscle homogenate data are as follows: Complex I: 9.11% (n = 29); Complex II/III: 10.70% (n = 29); Complex IV: 8.9% (n = 29); CS: 5.6% (n = 29)
Summary
Mitochondrial disorders are difficult to diagnose clinically because of phenotypic variation.Renal presentations include the renal Fanconi syndrome (tubular wasting of bicarbonate, sodium and potassium, glucose and amino acids) and steroid unresponsive nephrotic syndrome as a result of glomerular damage; progression to chronic kidney disease is described [1,2,3]. A clue to the diagnosis may come from clinical abnormalities of other organs that require a high rate of oxidative metabolism, such as the brain (encephalopathy, retinopathy or stroke), skeletal muscle (myopathy), heart (cardiomyopathy) and liver; a full review of the clinical features of mitochondrial diseases is beyond the scope of this paper, but is extensively reviewed by Gorman et al [4]. Without these other features, diagnosis may be difficult in children who have a predominantly renal presentation. Results: The range of respiratory chain enzyme activity for complex I was 0.161 to 0.866 (mean 0.404, SD 0.2), for complex II/III was 0.021 to 0.318
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