Division of Nephrology

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https://ir.vanderbilt.edu/handle/1803/9580
With leading researchers, clinicians, and instructors working in state-of-the-art facilities our contributions are significant and validated through the many publications, honors, and grant funding received as we help to advance cures for kidney disease through scientific discoveries, cutting-edge treatments, and renal transplants.

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    Erenumab in chronic migraine with medication overuse Subgroup analysis of a randomized trial
    (2019-05-14) Brandes, Jan Lewis
    Objective To determine the effect of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody, in patients with chronic migraine and medication overuse. Methods In this double-blind, placebo-controlled study, 667 adults with chronic migraine were randomized (3: 2: 2) to placebo or erenumab (70 or 140 mg), stratified by region and medication overuse status. Data from patients with baseline medication overuse at baseline were used to assess changes in monthly migraine days, acute migraine-specific medication treatment days, and proportion of patients achieving >= 50% reduction from baseline in monthly migraine days. Results Of 667 patients randomized, 41% (n = 274) met medication overuse criteria. In the medication overuse subgroup, erenumab 70 or 140 mg groups had greater reductions than the placebo group at month 3 in monthly migraine days (mean [95% confidence interval]-6.6 [-8.0 to -5.3] and-6.6 [-8.0 to -5.3] vs-3.5 [-4.6 to -2.4]) and acute migraine-specific medication treatment days (-5.4 [-6.5 to-4.4] and-4.9 [-6.0 to-3.8] vs-2.1 [-3.0 to -1.2]). In the placebo and 70 and 140 mg groups, = 50% reductions in monthly migraine days were achieved by 18%, 36% (odds ratio [95% confidence interval] 2.67 [1.36-5.22]) and 35% (odds ratio 2.51 [1.28-4.94]). These clinical responses paralleled improvements in patient-reported outcomes with a consistent benefit of erenumab across multiple measures of impact, disability, and healthrelated quality of life. The observed treatment effects were similar in the non-medication overuse subgroup. Conclusions Erenumab reduced migraine frequency and acute migraine-specific medication treatment days in patients with chronic migraine and medication overuse, improving disability and quality of life.
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    Loss of Function of Colgant1 Disrupts Collagen Post-translationa Modification and Causes Musculoskeletal Defects
    (DISEASE MODELS & MECHANISMS, 2019-06) Geister, Krista A.; Lopez-Jimenez, Alberto Jose; Houghtaling, Scott; Ho, Tzu-Hua; Vanacore, Roberto; Beier, David R.
    In a screen for organogenesis defects in N-ethyl-N-nitrosourea (ENU)-induced mutant mice, we discovered a line carrying a mutation in Colgaft1 [collagen beta(1-O)galactosyltransferase type 1], which is required for proper galactosylation of hydroxylysine residues in a number of collagens. Colgaft1 mutant embryos have not been previously characterized; here, we show that they exhibit skeletal and muscular defects. Analysis of mutant-derived embryonic fibroblasts reveals that COLGALT1 acts on collagen IV and VI, and, while collagen VI appears stable and its secretion is not affected, collagen IV accumulates inside of cells and within the extracellular matrix, possibly due to instability and increased degradation. We also generated mutant zebrafish that do not express the duplicated orthologs of mammalian Colgaft1. The double-homozygote mutants have muscle defects; they are viable through the larvae stage but do not survive to 10 days post-fertilization. We hypothesize that the Colgaft1 mutant could serve as a model of a human connective tissue disorder and/or congenital muscular dystrophy or myopathy.