Abstract
BackgroundIn kidney transplantation, fibrosis represents the final and irreversible consequence of the pathogenic mechanisms that lead to graft failure, and in the late stages it irremediably precedes the loss of renal function. The invasiveness of kidney biopsy prevents this condition from being frequently monitored, while clinical data are rather unspecific. The objective of this study was to find noninvasive biomarkers of kidney rejection.MethodsWe carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF).ResultsShotgun mass spectrometry of uEV-proteins identified differential expression of several proteins among these different groups. Up to 23 of these proteins were re-evaluated using targeted proteomics in a new independent cohort of patients (n = 41) classified in the same diagnostic groups. Among other results, we found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA).ConclusionUrinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion.
Highlights
Kidney transplantation is the best renal replacement therapy for patients with end-stage kidney disease in terms of survival rates [1], cost-effectiveness [2] and patients’1 3 Vol.:(0123456789)Journal of Nephrology (2021) 34:861–874 quality of life [3]
Decades after the first kidney transplantation, the risk of acute rejection is well controlled by the use of immunosuppressive drugs [4, 5], while chronic processes are still the target of current research [6,7,8,9,10,11]
The study population was selected according to the following inclusion criteria: (1) male or female patients older than 18 years of age; (2) ability to give informed consent; (3) absence of urinary tract infection demonstrated by the presence of leukocyturia and/or bacteriuria; (4) absence of haematuria; (5) absence of donor-specific antibody (DSA) or either active or chronic antibody-mediated rejection
Summary
Kidney transplantation is the best renal replacement therapy for patients with end-stage kidney disease in terms of survival rates [1], cost-effectiveness [2] and patients’1 3 Vol.:(0123456789)Journal of Nephrology (2021) 34:861–874 quality of life [3]. Methods We carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF). We found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA). Conclusion Urinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion
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