Multiple approaches for understanding the metabolic changes in chronic kidney disease — ASN Events

Multiple approaches for understanding the metabolic changes in chronic kidney disease (#161)

Naama Karu 1 , Mitra Nouri Koupaei 1 , Thomas Rodemann 2 , Richard Wilson 2 , Esme Candish 1 , Robert A Shellie 1 , Matthew D Jose 3 4 , Emily F Hilder 1
  1. ACROSS, UTAS, Hobart, TAS, Australia
  2. Central Science Laboratory, UTAS, Hobart, Tasmania, Australia
  3. Royal Hobart Hospital, Hobart, Tasmania, Australia
  4. Menzies Research Institute Tasmania, UTAS, Hobart, Tasmania, Australia

Tasmania has a high occurrence of chronic kidney disease (CKD), which progresses to end-stage kidney failure (ESKF) requiring treatment with dialysis or a kidney transplant. CKD is commonly accompanied by neuropsychiatric conditions, diabetes and premature cardiovascular disease which do not correspond with the traditional risk factors. Kidney malfunction causes accumulation of many compounds in the blood instead of excretion via urine, known as uraemic syndrome. Unlike the symptomatic markers currently used for evaluating kidney function, some uremic molecules may hold the key to understanding and treating the predicted consequences of CKD.

The presented work investigates the overall picture of uraemia in biofluids using HPLC - Mass Spectrometry (Thermo LTQ-Orbitrap; Bruker µTOF) and FTIR spectrometry (Bruker Vertex 70). FTIR provided a rapid method for general profiling of the differences between sera of healthy, pre and post-dialysis patients, as well as the dialysate flowing out of the haemodialysis machine. Metabolomics approach using LC-MS was employed to find potential molecules of interest (<1 kDa) in serum or urine specimens collected from people with CKD, dialysis patients and healthy controls. Putative uremic toxins were also traced in serum and urine and related to the pathology of the samples, to test the agreement with the current concepts in nephrology. According to the findings in this preliminary stage, a set of target molecules will be constructed for LC-MS/MS analysis in a wider set of samples currently under collection.