PubMed · 14176460
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A M PARFITT. 1964-07-25. HYPERCALCAEMIC NEPHROPATHY.. https://doi.org/10.5694/j.1326-5377.1964.tb115035.x
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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.
The pharmacokinetic parameters of DA-7867 were compared after intravenous and oral administration at a dose of 10 mg/kg to control rats and rats with acute renal failure induced by uranyl nitrate (rats with U-ARF). After intravenous administration in rats with U-ARF, the time-averaged total body clearance (Cl) was significantly faster (2.45 versus 0.932 ml/min/kg) than controls due to significantly faster nonrenal clearance (2.25 versus 0.855 ml/min/kg) in rats with U-ARF. The faster nonrenal clearance could be due to significantly greater gastrointestinal (including biliary) excretion; the amount of unchanged DA-7867 recovered from the entire gastrointestinal tract at 24 h was significantly greater (30.3% versus 9.38% of intravenous dose) in rats with U-ARF. In rats with U-ARF, the Vss was significantly larger (1420 ml/kg compared with 580 ml/kg), but this was not due to a difference in plasma protein binding; the values were comparable between the two groups of rats. After oral administration to rats with U-ARF, the total area under the plasma concentration-time from time zero to time infinity (AUC) of DA-7867 was significantly smaller than the controls (2560 microg min/ml versus 7440 microg min/ml), and this was not due mainly to a decrease in absorption from the gastrointestinal tract in rats with U-ARF.
BACKGROUND: The outcome for patients presenting with acute renal failure and Burkitt lymphoma (BLARF) without dialysis is poor. This was a retrospective non-randomized comparative study designed to determine the outcome of two different treatment protocols. METHODS: One group of patients (TPA) received oral allopurinol, intravenous (IV) cyclophosphamide, vincristine, methotrexate, furosemide, 8.4% sodium bicarbonate, and intrathecal (IT) methotrexate; the other (TPB) alternate day IV infusion of low dose cyclosphosphamide (125 mg/m(2) x 4 doses), IT methotrexate (Days 1 and 5) and aggressive pre-emptive anti-tumor lysis syndrome therapy including oral allopurinol and calcium lactate, IV calcium gluconate, salbutamol, insulin and infusions of furosemide, sodium bicarbonate and glucose. RESULTS: Nine of 16 received TPA, 7 received TPB. Post chemotherapy anemia was more severe with TPA (P < 0.05). TPB patients received significantly more chemotherapy than those in TPA (P = 0.04). All 16 had tumor lysis syndrome (TLS). Six of nine patients with TPA died from this (three from other causes), two deaths in TPB were due to causes other than tumor lysis. Other evaluated outcome indices were similar in both groups. CONCLUSION: Slow IV infusion of low dose cyclophosphamide given on alternate days in addition to pre-emptive anti-TLS measures (TPB) were associated with better outcome in BLARF patients compared to a high dose multiple chemotherapy regimen (TPA).