Proteomics and metabolomics in renal transplantation-quo vadis?

Abstract

The improvement of long-term transplant organ and patient survival remains a critical challenge following kidney transplantation. Proteomics and biochemical profiling (metabolomics) may allow for the detection of early changes in cell signal transduction regulation and biochemistry with high sensitivity and specificity. Hence, these analytical strategies hold the promise to detect and monitor disease processes and drug effects before histopathological and pathophysiological changes occur. In addition they will identify enriched populations and enable individualize drug therapy. However, proteomics and metabolomics have not yet lived up to such high expectations. Renal transplant patients are highly complex, making it difficult to establish cause-effect relationships between surrogate markers and disease processes. Appropriate study design, adequate sample handling, storage and processing, quality and reproducibility of bioanalytical multi-analyte assays, data analysis and interpretation, mechanistic verification and clinical qualification (=establishment of sensitivity and specificity in adequately powered prospective clinical trials) are important factors for the success of molecular marker discovery and development in renal transplantation. However, a newly developed and appropriately qualified molecular marker can only be successful if it is realistic that it can be implemented in a clinical setting. The development of combinatorial markers with supporting software tools is an attractive goal.

Biomarkers in Transplantation—Proteomics and Metabolomics

“…Metabolomics studies have assessed the biochemical effects of immunosuppressants and their combinations on the kidney, the assessment of donor organ quality, storage and ischemia/reperfusion injury as well as relevant therapeutic interventions, and kidney transplant function in patients. These studies have been reviewed in reference 54 . More recent studies include the effect of calcineurin inhibitors 55 and allo-immune response on urine metabolite profiles after kidney transplantation 56,57 as well as the metabolic profiling of transplant liver biopsies 58 .…”

Metabolomics and renal disease

“…This article provides an update on publications within the last ~18 months that illustrate these points, reviewing both clinical and experimental renal metabolomics studies as well as select non-metabolomics studies that are of interest to the field. With the goal of providing a coherent synthesis primarily anchored around adult CKD, metabolomics studies of renal transplantation [5, 6], renal cell carcinoma [7], and pediatric nephrology [8] are not discussed.…”

Urine Metabolite Profiles Predictive of Human Kidney Allograft Status

“…1 However, despite the progress toward noninvasive characterization of kidney allograft status by mRNA profiling of urine from kidney graft recipients, 1,2 there remains huge potential for further progress by probing the small molecule composition of these urines for ascertaining kidney allograft status. 3 Metabolomics aims to measure all relevant small molecules (metabolites), [3][4][5][6][7][8] and nontargeted metabolite profiling allows for the relative quantification of hundreds of metabolites in small volumes of biologic specimens such as urine. As both intermediate and end point markers of diverse biologic processes in the human body, observations of altered metabolite concentrations provide access to functionally relevant read-outs of perturbed disease-associated pathways in human metabolism.…”