PubMed · 15699863
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
Narayana S Murali, Swaminathan Sundararaman. 2005. Diametrically opposite result?. https://doi.org/10.1097/01.ccm.0000153588.03608.dd
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
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.
BACKGROUND: Cigarette smoking has been associated with accelerated renal dysfunction among patients with chronic renal disease. Conceivably, repeated parenchymal hypoxic injury, induced by nicotine-related vasomotor changes, might contribute to the progression of renal failure in smokers. METHODS: Renal blood flow and selective cortical and outer medullary blood flows were determined in anesthetized rats. Changes in total renal, cortical and medullary vascular resistance were calculated. Nicotine was repeatedly infused at rising doses (50-200 microg/kg) to intact (CTR) animals and to rats chronically administered with nicotine in their drinking water (NIC). In a complementary study, nicotine-treated and control rats were subjected to medullary hypoxic stress, induced by radiocontrast and indomethacin. RESULTS: Chronic nicotine exposure led to lower baseline renal blood flow and creatinine clearance. Nicotine infusion induced a transient dose-dependent rise in blood pressure, renal blood flow and cortical flow, with a corresponding decline in renal vascular resistance and cortical resistance in both experimental groups. However, while medullary flow increased in CTR by up to 16 +/- 6%, it remained unchanged or even somewhat declined in the NIC group. Calculated medullary resistance reciprocally declined in CTR while it rose in the NIC group (p < 0.001). In animals subjected to radiocontrast and indomethacin, nicotine intensified renal dysfunction, associated with focal medullary hypoxic damage. CONCLUSIONS: Chronic exposure to nicotine selectively compromises the outer medullary microcirculation, blunting a local vasodilatory response to acute nicotine administration. Repeated acute-on-chronic exposure to nicotine may predispose to hypoxic medullary injury.