PubMed · 14171884
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R PATEL. 1964. URINARY CASTS IN EXERCISE.. https://doi.org/10.1111/imj.1964.13.2.170
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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.
Poly(vinylpyrrolidone-co-dimethyl maleic acid) (PVD) was found to have high renal-targeting capability and safety as a drug carrier. To optimize the renal drug delivery system using PVD, the relationship between the molecular weight of PVD and its renal accumulation were evaluated in mice by their intravenous injection. It was found that the molecular size of 6-8 kDa was associated with the highest renal accumulation. The specific bioactivity of PVD-conjugated superoxide dismutase (SOD) relative to that of unmodified SOD gradually decreased with an increase in the degree of modification to SOD with PVD6K. The conjugated SOD (L-PVD-SOD) with the molecular size of 73 kDa, which had comparable specific bioactivity with native SOD, showed longer plasma half-life than native SOD. About sixfold more L-PVD-SOD was distributed to the kidneys than native SOD 3 h after intravenous injection, whereas extensive PVD modification did not enhance the renal accumulation of SOD. This L-PVD-SOD effectively accelerated recovery from mercuric chloride-induced acute renal failure in vivo. These results suggest that L-PVD-SOD may be the optimal derivative as a potential therapeutic agent to various renal diseases.
OBJECTIVE: To determine the threshold of age that best discriminates the survival of mechanically ventilated patients and to estimate the outcome of mechanically ventilated older patients. DESIGN: International prospective cohort study. SETTING: Three hundred sixty-one intensive care units from 20 countries. PATIENTS AND PARTICIPANTS. Five thousand one hundred eighty-three patients mechanically ventilated for more than 12 h. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Recursive partitioning and logistic regression were used and an outcome model was derived and validated using independent subgroups of the cohort. Two age thresholds (43 and 70 years) were found, by partitioning recursive analysis, to be associated with outcome. This study focuses on the analysis of patients older than 43 years of age, divided in two subgroups: between 43 and 70 years (middle age group) and older than 70 years (elderly group). Survival in hospital was 45% (95% C.I.: 43-48) for the elderly group and 55% (53-57) for the middle age group ( p<0.001). Advanced age was not associated with prolongation of mechanical ventilation, weaning or length of stay in the ICU and in hospital ( p>0.05). Variables associated with mortality in the elderly were: acute renal failure, shock, Simplified Acute Physiology Score II and a ratio of PaO(2) to FIO(2) more than 150. CONCLUSIONS: Older mechanically ventilated patients (age >70 years) had a lower ICU and hospital survival, but the duration of mechanical ventilation, ICU and hospital stay were similar to younger patients. Factors associated with the highest risk of mortality in patients older than 70 were the development of complications during the course of mechanical ventilation, such as acute renal failure and shock.