Incidence of acute kidney disease after receiving hematopoietic stem cell transplantation: a single-center retrospective study

Background Previous reports have shown that acute kidney injury (AKI) is common after hematopoietic stem cell transplantation (HSCT), which is a crucial treatment for patients with hematological disorders. AKI could increase mortality and induce adverse effects including the development of chronic kidney disease. The incidence of AKI in association with HSCT reportedly varies significantly because several definitions of AKI have been adopted. Acute kidney disease (AKD) is a new concept that can clinically define both AKI and persistent decreases in glomerular filtration rate (GFR) state. We conducted a retrospective cohort study to determine the incidence of AKD after HSCT. Methods This study included 108 patients aged between 16 and 70 years undergoing HSCT. In this study, AKD included clinical condition of AKI or subacute decreases in GFR. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines based on serum creatinine. However, urine output data were not included to define AKI because the database lacked some of these data. Comparisons were made between groups using the Mann–Whitney U test. Results Acute kidney disease occurred in 17 patients (15.7%). There were significant differences between the AKD and non-AKD with respect to ABO-incompatible HSCT (p = 0.001) and incidence of acute graft versus host disease (GVHD) after HSCT (p < 0.001). The 100-day overall survival of patients with AKD and without AKD after HSCT was 70.6% and 79.8%, respectively (p = 0.409). Discussion ABO-incompatible HSCT and acute GVHD after HSCT were risk factors for the incidence of AKD. However, we could not find a significant association between AKD after HSCT and mortality

〈Cases Reports〉Successful treatment with intravenous colistin of sepsis caused by metallo-beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa in a patient with acute myeloid leukemia

[Abstract] In recent years, multidrug-resistant Pseudomonas aeruginosa (MDRP) has been detected in patients undergoing chemotherapy for hematological malignancies. MDRP can cause life-threatening infections such as sepsis and pneumonia, being a major concern for physiciansand patients. Here, we report the case of a patient with acute myeloid leukemia (AML ; FAB classification M2) who developed septic shock from MDRP infection during leukopenia induced by the first cycle of consolidation therapy, and in whom the combination of colistin administration and steroid pulse therapy promptly improved the septic shock symptoms and cleared MDRP from the blood. Although a transient nephrotoxic effect was observed, itsubsided rapidly on discontinuation of treatment. MDRP in stool samples fell to undetectable levels following oral doses of polymyxin B sulfate. The patient could continue consolidation chemotherapy and has remained in remission

Reaction Intermediates of Nitric Oxide Synthase from <i>Deinococcus radiodurans</i> as Revealed by Pulse Radiolysis: Evidence for Intramolecular Electron Transfer from Biopterin to Fe^II–O₂ Complex

Nitric oxide synthase (NOS) is a cytochrome P450-type mono-oxygenase that catalyzes the oxidation of l-arginine (Arg) to nitric oxide (NO) through a reaction intermediate <i>N</i>-hydroxy-l-arginine (NHA). The mechanism underlying the reaction catalyzed by NOS from <i>Deinococcus radiodurans</i> was investigated using pulse radiolysis. Radiolytically generated hydrated electrons reduced the heme iron of NOS within 2 μs. Subsequently, ferrous heme reacted with O₂ to form a ferrous-dioxygen intermediate with a second-order rate constant of 2.8 × 10⁸ M^–1 s^–1. In the tetrahydrofolate (H₄F)-bound enzyme, the ferrous-dioxygen intermediate was found to decay an another intermediate with a first-order rate constant of 2.2 × 10³ s^–1. The spectrum of the intermediate featured an absorption maximum at 440 nm and an absorption minimum at 390 nm. In the absence of H₄F, this step did not proceed, suggesting that H₄F was reduced with the ferrous-dioxygen intermediate to form a second intermediate. The intermediate further converted to the original ferric form with a first-order rate constant of 4 s^–1. A similar intermediate could be detected after pulse radiolysis in the presence of NHA, although the intermediate decayed more slowly (0.5 s^–1). These data suggested that a common catalytically active intermediate involved in the substrate oxidation of both Arg and NHA may be formed during catalysis. In addition, we investigated the solvent isotope effects on the kinetics of the intermediate after pulse radiolysis. Our experiments revealed dramatic kinetic solvent isotope effects on the conversion of the intermediate to the ferric form, of 10.5 and 2.5 for Arg and NHA, respectively, whereas the faster phases were not affected. These data suggest that the proton transfer in DrNOS is the rate-limiting reaction of the intermediate with the substrates

Electron Transfer Reactions of Candidate Tumor Suppressor 101F6 Protein, a Cytochrome <i>b</i>₅₆₁ Homologue, with Ascorbate and Monodehydroascorbate Radical

The candidate tumor suppressor 101F6 protein is a homologue of adrenal chromaffin granule cytochrome <i>b</i>₅₆₁, which is involved in the electron transfer from cytosolic ascorbate to intravesicular monodehydroascorbate radical. Since the tumor suppressor activity of 101F6 was enhanced in the presence of ascorbate, it was suggested that 101F6 might utilize a similar transmembrane electron transfer reaction. Detailed kinetic analyses were conducted on the detergent-solubilized recombinant human 101F6 for its electron transfer reactions with ascorbate and monodehydroascorbate radical by stopped-flow and pulse radiolysis techniques. The reduction of oxidized 101F6 with ascorbate was found to be independent of pH in contrast to those observed for chromaffin granule and <i>Zea mays</i> cytochromes <i>b</i>₅₆₁ in which both cytochromes exhibited very slow rates at pH 5.0 but faster at pH 6.0 and 7.0. The absence of the inhibition for the electron acceptance from ascorbate upon the treatment with diethyl pyrocarbonate suggested that 101F6 might not utilize a “concerted proton/electron transfer mechanism”. The second-order rate constant for the electron donation from the ascorbate-reduced 101F6 to the pulse-generated monodehydroascorbate radical was found to be 5.0 × 10⁷ M^–1s^–1, about 2-fold faster than that of bovine chromaffin granule cytochrome <i>b</i>₅₆₁ and about five times faster than that of <i>Zea mays</i> cytochrome <i>b</i>₅₆₁, suggesting that human 101F6 is very effective for regenerating ascorbate from monodehydroascorbate radical in cells. Present observations suggest that 101F6 employs distinct electron transfer mechanisms on both sides of the membranes from those of other members of cytochrome <i>b</i>₅₆₁ protein family

〈Original〉Quality of life of chronic myelogenous leukemia patients following BCR-ABL inhibitor therapy: A multicenter study in Nara Japan using SF-8

[Abstract]Chronic myelogenous leukemia (CML) is caused by chromosomal translocation t (9;22) (q34;q11.2) forming a BCR-ABL fusion gene. Treatment of CML patients with tyrosine kinase inhibitor (TKI) led to a marked improvement in the survival rate. However, when treating CML patients, adverse events of TKI may reduce the QOL. When we were able to use only Imatinib, we continued to use despite adverse events. However, we can now use Dasatinib, Nilotinib, Bosutinib, and Ponatinib. Therefore, to examine the effects of TKI on the QOL of CML patients, we conducted a QOL survey at three major facilities in Nara Prefecture. For the QOL survey, we used SF-8. The results of the survey showed that there was no difference between the pretreatment QOL score and QOL score at the time of the survey. However, the QOL scores showed improved physical functioning, bodily pain, vitality, role-emotional, and mental health summary scores in the TKI switch group. The main reason for switching TKI was adverse events. Therefore, these adverse events reduce the QOL of CML patients. Switching TKI improved the QOL. Presently, five TKI are available, expanding the range of options. When adverse events appear, switching TKI and adverse event management are also important to maintain a patient’s QOL and continue the therapy