Preparative Regimen Dosing for Hematopoietic Stem Cell Transplantation in Patients with Chronic Kidney Disease: Analysis of the Literature and Recommendations

AbstractHematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that has traditionally been associated with high treatment-related mortality due to direct regimen toxicity and a high incidence of graft-versus-host disease. Historically, pre-existing renal insufficiency has been considered an exclusion criterion for transplantation. The advent of nonmyeloablative conditioning regimens as a less toxic modality for treatment has made HSCT more accessible to elderly patients and patients with comorbidities, such as renal impairment. However, there is no clear standard for how to dose preparative regimens for patients with chronic renal impairment who undergo HSCT. This article serves as a review of the current literature to provide dosing recommendations for commonly used preparative agents in the setting of chronic kidney disease, with the aim of providing optimal dosing for this patient population

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder