Metabolomic fingerprinting for biomarker discovery in renal amyloidosis

Abstract

Background Minimal change disease (MCD), a glomerular disease subtype is characterised by no visible change in the glomerulus upon light microscopy except for the urinary excretion of excess proteins. The symptoms of minimal change disease and renal amyloidosis are mostly overlapping and thereby misdiagnosed. However, the possible linkage between these two disease types has not been documented. We hypothesised that amyloid formation could be one of the players promoting the pathology associated with minimal change disease, resulting in perturbations of the downstream cellular pathways. Methods One hundred glomerular diseased patients were identified in a two-year study, based on symptoms and biochemical markers. Histopathological analysis showed predominance of minimal change disease in twenty patients. Further, gold standard Congo red staining was performed in these patients to detect amyloid deposition followed by tracking its downstream effects on cellular pathways using mass-spectrometry-based untargeted approach. Results Congo red staining showed presence of amyloid deposits in eleven minimal change diseased patients. Further, plasma metabolomic fingerprinting revealed a total of fifteen biologically important metabolites altered in minimal change diseased patients having renal amyloidosis as compared to controls. Different classes of lipids, carnitines and amino acids were found to be dysregulated in these patients. Conclusion In the present study we have shown the onset of renal amyloidosis and associated pathogenesis in minimal change diseased patients. Additionally, we have identified novel altered metabolic signatures in these patients as compared to controls. This is the first study in context to the Indian population, depicting the potential of metabolomic fingerprinting to identify novel markers for early diagnosis of amyloid formation in minimal change disease, a glomerular disease type.