Kidney post-transplant monitoring of urinary glycosaminoglycans/proteoglycans and monokine induced by IFN-γ (MIG)

Abstract

Allograft rejection during the first year after renal transplantation can lead to persistent allograft dysfunction and reduced long-term graft survival. Thus, it is important to define early predictors of kidney damage, less invasive than allograft biopsy. Urinary glycosaminoglycan/proteoglycan concentration and distribution, N-acetyl-β-(D)-glucosaminidase (NAG), and monokine induced by IFN-γ (MIG) levels were evaluated in the immediate post-transplant and during a 1-year follow-up. We observed increased urinary levels of MIG, urinary trypsin inhibitor and its degradation products, the lack of urinary heparan sulfate excretion, and the decreased chondroitin sulfate relative content at day 1 post-transplant in most patients who developed complications in the postoperative period. Moreover, urinary MIG levels showed significant correlations with NAG, C-reactive protein, and GFR at day 1 post-transplant. The monitoring of glycosaminoglycan/proteoglycan urinary pattern and the levels of urine MIG could serve as useful markers for predicting possible complications of transplantation, unraveling an early inflammatory state, on whose basis the immunosuppressive therapy could be appropriately modified.

Selective Deletion of Heparan Sulfotransferase Enzyme, Ndst1, in Donor Endothelial and Myeloid Precursor Cells Significantly Decreases Acute Allograft Rejection

“…Early and ongoing activation of inflammatory immune cell responses, also termed innate or acute cellular rejection, are reported to induce ongoing organ damage and to be a significant driving force for late chronic transplant vasculitis, rejection and graft loss 36 – 44 . Late organ damage is also known to be caused by recurrent antibody-mediated immune rejection.…”

Development of a method for urine bikunin/urinary trypsin inhibitor (UTI) quantitation and structural characterization: Application to type 1 and type 2 diabetes

“…UTI purification is performed by two steps. The first one exploits the high negative charge density of the O ‐linked CS to capture this small PG, by anion exchange chromatography . The second one allows resolving the protein moiety, according to its molecular weight, by SDS‐PAGE.…”

“…According to a plethora of papers, bikunin can be considered a positive acute phase protein . Over the past few years we have described variations of UTI/glycosaminoglycans (GAGs) levels in some pathological conditions such as chronic glomerulonephritis , type 1 diabetes , kidney transplantation , and systemic lupus erythematosus , as well as during the physiological menstrual cycle in fertile women . Recently, we have reported that UTI may represent a useful marker for monitoring renal function in Fabry's disease .…”

“…The aim of the present work was to develop a sensitive method for both direct UTI quantitation and protein structural characterization by MS analysis, starting from very low quantities of specimen. To achieve this goal, we merged classical chromatographic methods, applied for GAGs/PGs purification , with image analysis of SDS‐PAGE profiles, which had been proven useful in quantifying protein microquantities from different sources . Furthermore, Nano‐LC‐MS/MS analysis on tryptic‐digested UTI bands was performed for protein identification and characterization.…”

Urine Bikunin as a Marker of Renal Impairment in Fabry's Disease

“…In urine, GAGs consist mainly of heparan sulfate (HS), CS, and, in negligible quantity, dermatan sulfate [6]. In the general population, bikunin has been reported to occur at higher levels in various pathological conditions exhibiting chronic inflammation, including cancer [11], chronic glomerulonephritis [12, 13], kidney transplantation [14], type 1 diabetes [15], and systemic lupus erythematosus [16]. Moreover, we reported variations of urine bikunin levels during the physiological menstrual cycle in fertile women [17].…”