PubMed · 729513
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A Pasternack. 1978. [Acute renal failure].. https://pubmed.ncbi.nlm.nih.gov/729513/
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Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a "hub" protein for graft injury irrespective of causation. Sixty-nine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection.
BACKGROUND: The short- and long-term effects of prophylactic hemodialysis (HD) immediately after cardiovascular catheterizations on renal function in patients with severe baseline renal insufficiency remain unknown though previous studies reported non-beneficial very-short-term effect in less severe patients. METHODS AND RESULTS: Patients who had pre-procedural serum creatinine (Scr) between 2.5 and 5.5 mg/dl were retrospectively studied. Twenty of them (14 M/6 F, aged 69 +/- 2 years) had received prophylactic HD after radiocontrast exposure and constituted the HD group. Another 20 patients were case-matched to the baseline demographics of the HD group and served as the non-HD group. The baseline Scr were 3.9 +/- 0.2 and 3.5 +/-0.2 mg/dl, respectively (p = NS). Although the Scr at 3 months was significantly higher in the HD group (4.3 +/- 0.3 vs. 3.4 +/- 0.2 mg/dl, p = 0.02), the absolute and percentage increments from baseline to 3 months (0.4 +/- 0.2 vs. 0.0 +/- 0.2 mg/dl, p = NS, and 11 +/- 5% vs. 1 +/- 7%, p = NS, respectively) and 6 months (0.6 +/- 0.3 vs. 0.4 +/- 0.4 mg/dl, p = NS, and 18 +/- 8% vs. 8 +/- 10%, p = NS, respectively) were not statistically different. Patients who developed end-stage renal disease requiring permanent HD at 1 year were also similar in both groups (four vs. three, respectively, p = NS). CONCLUSIONS: Our study confirmed that prophylactic HD immediately after contrast media administration in catheterizations failed to affect the short- and long-term renal and clinical outcomes even in patients with severe baseline renal insufficiency.
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