Successful use of eculizumab in immediate ANCA vasculitis recurrence in a pediatric kidney transplant.

BACKGROUND: Kidney transplantation is an acceptable therapy end-stage kidney disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis with risk of disease recurrence ranging from 3% to 17%. Standard posttransplant immunosuppression is the mainstay of therapy after recurrence. Recently, new medications focused on complement regulation and avoidance of steroids have been shown to be effective in treating antineutrophil cytoplasmic antibody (ANCA) vasculitis with no studies in the pediatric population. METHODS: We report a 5-year-old patient with immediate recurrence of positive myeloperoxidase (MPO)-ANCA vasculitis after deceased donor kidney transplant and the novel use of eculizumab to salvage the graft. RESULTS: Eculizumab and transition to ravulizumab has been successful in improving graft function and maintenance of disease remission after immediate MPO-ANCA vasculitis recurrence posttransplant. CONCLUSIONS: Complement inhibitors may be used in addition to standard immunosuppression postkidney transplant in a pediatric patient with MPO-ANCA vasculitis recurrence without higher rates of infections.

Inhibition of histone deacetylase expands the renal progenitor cell population.

One of the first hallmarks of kidney regeneration is the reactivation of genes normally required during organogenesis. Identification of chemicals with the potential to enhance this reactivation could therapeutically promote kidney regeneration. Here, we found that 4-(phenylthio)butanoic acid (PTBA) expanded the expression domains of molecular markers of kidney organogenesis in zebrafish. PTBA exhibits structural and functional similarity to the histone deacetylase (HDAC) inhibitors 4-phenylbutanoic acid and trichostatin A; treatment with these HDAC inhibitors also expanded the renal progenitor cell population. Analyses in vitro and in vivo confirmed that PTBA functions as an inhibitor of HDAC activity. Furthermore, PTBA-mediated renal progenitor cell expansion required retinoic acid signaling. In summary, these results support a mechanistic link among renal progenitor cells, HDAC, and the retinoid pathway. Whether PTBA holds promise as a therapeutic agent to promote renal regeneration requires further study.

Characterization of an lhx1a transgenic reporter in zebrafish.

The LIM-domain containing transcription factor, Lhx1, is involved in the regulation of early gastrulation cell movements, kidney organogenesis and other processes in vertebrate model organisms. To follow the expression of this gene in live embryos, we created transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) under the control of lhx1a regulatory regions. Tg(lhx1a:EGFP)(pt303) recapitulates the expression of endogenous lhx1a beginning at early gastrula stages through 72 hours of development with only few exceptions. In addition, over-expression of the Nodal ligand, ndr1, results in the concomitant expansion of the transgene and endogenous lhx1a expression. Treatment of Tg(lhx1a:EGFP)(pt303) embryos with the small molecule SB-431542, an inhibitor of Nodal signaling, results in the loss of both transgene and endogenous lhx1a expression. These experiments suggest that Tg(lhx1a:EGFP)(pt303) is regulated in a manner similar to endogenous lhx1a. Therefore, this reporter can be utilized not only for monitoring lhx1a expression, but also for numerous applications, including chemical genetics screening.