Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Abstract

Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m2; n = 10) or advanced (8.9±4.5 mL/min/1.73 m2; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = −0.8031; p<0.0001 and ρ = −0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (ρ = −0.6557; p = 0.0001 and ρ = −0.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (ρ = −0.7752; p<0.0001 and ρ = −0.8400; p<0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In conclusion, we found excellent association of plasma and urinary metabolites and urinary peptides with kidney function, and disease progression, but no added value in combining the different biomarkers data.

Metabolic biomarkers for chronic kidney disease

“…5A). The same effect was observed in a cross-sectional study on CKD patients; both in diabetic nephropathy and in non-diabetic CKD, later stages of the disease were significantly associated with higher plasma levels of SDMA (Lundin et al, 2011;Duranton et al, 2014; Fig. 5B).…”

“…Of course, many of these studies also find elevated ADMA levels in patients with impaired renal function (Fleck et al, 2001;Kielstein et al, 2006;Duranton et al, 2014) but this goes back to the chicken-and egg problem discussed earlier: CKD and CVD are closely intertwined, and so changes of their most prominent markers often coincide. There is, however, clinical evidence that clearly backs the biochemical reasoning linking SDMA to kidney function and ADMA to cardiovascular risk: in ESRD patients after kidney transplantation, i.e.…”

Alzheimer's disease–like pathology has transient effects on the brain and blood metabolome

“…Quantitative mass spectrometry-based metabolomic profiling was performed using the Biocrates AbsoluteIDQ p180 (BIOCRATES, Life Science AG, Innsbruck, Austria), as previously described (Nkuipou-Kenfack et al, 2014;Roemisch-Margl et al, 2012). The AbsoluteIDQ p180 kit provides simultaneous quantification of amino acids, acylcarnitines, SPHs, PCs, hexose (glucose), and biogenic amines in many biological samples.…”

Biomarker – vom Sein und Wesen

“…Die nächste Abstraktionsstufe stellt die Kombination von Pattern aus unterschiedlichen "-omics"-Disziplinen, z.B. Metabolomics und Proteomics und Genomics [7], zu neuen Meta-Markern dar, die an sich wiederum als "Biomarker" bezeichnet werden können, selbst wenn die komplexen Assoziationen innerhalb dieser Compound-Marker unaufgeklärt bleiben. Weitere Disziplinen bieten sich hier als Kombinationspartner an, z.B.…”