Successful initiation of hemodialysis for a hemophilia A patient with factor VIII inhibitor: a case report and literature review.

We report the first case of hemophilia A with factor VIII (FVIII) inhibitor who received hemodialysis via an arteriovenous (AV) fistula. Hemophilia A is a congenital deficiency of blood coagulation FVIII that is characterized by prolonged bleeding. Approximately 30% of patients with hemophilia develop allogeneic antibodies of FVIII. The inhibitors decrease the hemostatic effect of replacement therapy; thus, the prophylaxis strategy should be well designed. Prophylactic treatment with invasive procedures is needed to prevent excessive bleeding in patients with hemophilia undergoing hemodialysis. On the contrary, hemodialysis requires attention to the development of intracircuit coagulation during dialysis. Peritoneal dialysis or hemodialysis with a long-term tunneled central venous catheter has mainly been selected as the dialysis modality for patients with hemophilia and end-stage renal disease requiring renal replacement therapy because hemodialysis with an arteriovenous fistula may result in bleeding from the puncture site after each hemodialysis session. In our patient, hemodialysis was safely performed without any anticoagulant agents, and replacement therapy with FVIII concentrates prevented bleeding after puncture of the AV fistula.

Soluble Interleukin-2 Receptor Predicts Treatment Outcome in Patients With Autoimmune Tubulointerstitial Nephritis. A Preliminary Study.

Background: Autoimmune tubulointerstitial nephritis (TIN) is characterized by immune-mediated tubular injury and requires immunosuppressive therapy. However, diagnosing TIN and assessing therapeutic response are challenging for clinicians due to the lack of useful biomarkers. Pathologically, CD4+ T cells infiltrate to renal tubulointerstitium, and soluble interleukin-2 receptor (sIL-2R) has been widely known as a serological marker of activated T cell. Here, we explored the usefulness of serum sIL-2R to predict the treatment outcome in patients with autoimmune TIN. Methods: Study Design: Single-center retrospective observational study. Participants: 62 patients were diagnosed of TIN from 2005 to April 2018 at Hokkaido University Hospital. Among them, 30 patients were diagnosed with autoimmune TIN and treated with corticosteroids. We analyzed the association between baseline characteristics including sIL-2R and the change of estimated glomerular filtration rate (eGFR) after initiation of corticosteroids. Results: The serum sIL-2R level in patients with autoimmune TIN was significantly higher than that in chronic kidney disease patients with other causes. Mean eGFR in autoimmune TIN patients treated with corticosteroids increased from 43.3 ± 20.4 mL/min/1.73 m2 (baseline) to 50.7 ± 19.9 mL/min/1.73 m2 (3 months) (ΔeGFR; 22.8 ± 26.0%). Multivariate analysis revealed that higher sIL-2R (per 100 U/mL, ß = 1.102, P < 0.001) level was independently associated with the renal recovery. In ROC analysis, sIL-2R had the best area under the curve value (0.805) and the cutoff point was 1182 U/mL (sensitivity = 0.90, 1-specificity = 0.45). Conclusions: Our study showed that elevated serum sIL-2R levels might become a potential predictive marker for therapeutic response in autoimmune TIN.

Comparison of administration of single- and triple-course steroid pulse therapy combined with tonsillectomy for immunoglobulin A nephropathy.

ABSTRACT: Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis that can cause end-stage renal disease. Recently, tonsillectomy combined with corticosteroid pulse (TSP) has been shown to be effective for achieving clinical remission and favorable renal outcome in patients with IgAN. However, the standard regimen of corticosteroid use in TSP has not been established. Herein, we compared the effect of single- or triple-course steroid pulse therapy combined with tonsillectomy in patients with IgAN.This retrospective, observational cohort study included 122 patients with IgAN enrolled from January 2004 to December 2018 at 2 independent institutions. We divided the patients into 2 groups; single-course (TSP1: n = 70) and triple-course (TSP3: n = 52) of corticosteroid pulse therapy (1 course comprised 3 consecutive days' infusion of 0.5 g methylprednisolone) combined with tonsillectomy. The primary outcome for renal survival was defined as the first occurrence of ≧30% decrease in estimated glomerular filtration rate from baseline. Secondary outcomes included the incidence of clinical remission and recurrence of the disease.Regarding clinical parameters and findings at baseline, there were no significant differences between the 2 groups. The 8-years renal survival in the 2 groups was not significantly different according to Kaplan-Meier curves (TSP1; 82.5% vs TSP3; 69.2%, log-rank test P = .39). The cumulative incidence rates of remission of hematuria (94.4% vs 85.4%, P = .56) and clinical remission (85.0% vs 64.8%, P = .07) were comparable in both groups, while those of proteinuria showed higher rates in TSP1 than TSP3 (88.4% vs 65.4%, P = .02). The cumulative incidence of relapse of hematuria (5.6% vs 2.3%, P = .42) and proteinuria (7.1% vs 3.3%, P = .41) showed no significant differences in the 2 groups. Cox regression analyses showed that the number of courses of corticosteroid pulse therapy was not significantly associated with renal outcome (TSP1 vs TSP3; Hazard ratios 0.69, 95% confidence intervals 0.29-1.64, P = .39).The effect of single-course corticosteroid pulse therapy is not statistically, significantly different from triple-course in TSP protocol for improving renal outcome and preventing relapse in patients with IgAN. Single-course corticosteroid pulse therapy may become a treatment option for patients with IgAN.

Establishment and intra-/inter-laboratory validation of a standard protocol of reactive oxygen species assay for chemical photosafety evaluation.

A reactive oxygen species (ROS) assay was previously developed for photosafety evaluation of pharmaceuticals, and the present multi-center study aimed to establish and validate a standard protocol for ROS assay. In three participating laboratories, two standards and 42 coded chemicals, including 23 phototoxins and 19 nonphototoxic drugs/chemicals, were assessed by the ROS assay according to the standardized protocol. Most phototoxins tended to generate singlet oxygen and/or superoxide under UV-vis exposure, but nonphototoxic chemicals were less photoreactive. In the ROS assay on quinine (200 µm), a typical phototoxic drug, the intra- and inter-day precisions (coefficient of variation; CV) were found to be 1.5-7.4% and 1.7-9.3%, respectively. The inter-laboratory CV for quinine averaged 15.4% for singlet oxygen and 17.0% for superoxide. The ROS assay on 42 coded chemicals (200 µm) provided no false negative predictions upon previously defined criteria as compared with the in vitro/in vivo phototoxicity, although several false positives appeared. Outcomes from the validation study were indicative of satisfactory transferability, intra- and inter-laboratory variability, and predictive capacity of the ROS assay.

Visualization by comprehensive microarray analysis of gene expression programs during transdifferentiation of mesophyll cells into xylem cells.

Plants have a unique transdifferentiation mechanism by which differentiated cells can initiate a new program of differentiation. We used a comprehensive analysis of gene expression in an in vitro zinnia (Zinnia elegans L.) culture model system to gather fundamental information about the gene regulation underlying the transdifferentiation of plant cells. In this model, photosynthetic mesophyll cells isolated from zinnia leaves transdifferentiate into xylem cells in a morphogenic process characterized by features such as secondary-wall formation and programmed cell death. More than 8,000 zinnia cDNA clones were isolated from an equalized cDNA library prepared from cultured cells transdifferentiating into xylem cells. Microarray analysis using these cDNAs revealed several types of unique gene regulation patterns, including: the transient expression of a set of genes during cell isolation, presumably induced by wounding; a rapid reduction in the expression of photosynthetic genes and the rapid induction of protein synthesis-associated genes during the first stage; the preferential induction of auxin-related genes during the subsequent stage; and the transient induction of genes closely associated with particular morphogenetic events, including cell-wall formation and degradation and programmed cell death during the final stage. This analysis also revealed a number of previously uncharacterized genes encoding proteins that function in signal transduction, such as protein kinases and transcription factors that are expressed in a stage-specific manner. These findings provide new clues to the molecular mechanisms of both plant transdifferentiation and wood formation.