PubMed · 9280824
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T H Hostetter, C L Manske, M S Paller. 1997-09-04. Continuous hemofiltration.. https://pubmed.ncbi.nlm.nih.gov/9280824/
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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.
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The most serious forms of acute renal failure (ARF) are nowadays encountered in the intensive care unit (ICU), where up to 25% of new patients are reported to develop ARF. Lethality rates may reach 50 to 90% when the ARF is part of a multiple organ dysfunction syndrome. A multitude of extracorporeal procedures have been introduced into intensive care medicine. Applied with adequate skills and experience, most of these techniques will suffice to replace excretory renal function. However, because of low efficacy arterio-venous procedures (CAVH and CAVHD) have been abandoned for the veno-venous, pump-driven techniques (CVVH and CVVHD). Up to now, there is no consensus whether continuous or intermittent renal replacement therapy is more advantageous. In many cases, oliguric patients with circulatory instability will be treated by CVVH, even though there is no prospective study to show that in terms of outcome continuous treatment is superior to intermittent hemodialysis. It is equally conceivable to treat such patients with daily, prolonged (intermittent) hemodialysis. Apparently, the dose of replacement therapy, be it continuous filtration (36 to 48 l/24 h) or intermittent hemodialysis (daily 3 to 4 h) with a target BUN of less than 50 mg/dl, is more important than the modality of treatment. Moreover, there is good evidence that the use of biocompatible membranes (no complement- or leukocyte activation) is preferable and that with high-volume hemofiltration bicarbonate-containing replacement fluids should be used. However, despite all the technical advances, we firmly believe that the skills and the experience of those physicians and nurses who actually perform renal replacement therapy in the ICU are more important than the modality of treatment applied.