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BASIC RESEARCH
Studying Chromatin Identifies Candidate CKD Genes
Establishing causality for CKD-associated variants that are distal to protein coding regions remains challenging. Because many of these susceptibility loci overlap with DNA regulatory elements, Brandt et al. studied chromatin interactions to identify target genes that could be transcriptionally affected by these variants. In primary renal cells, their approach identified 304 target genes that may be transcriptionally dysregulated by DNA regulatory elements that colocalize with CKD-associated single nucleotide polymorphisms. This method may facilitate the identification of causal roles for many variants in CKD and other complex diseases. See Brandt et al., pages 462–476.
Collecting Duct MicroRNA Function
MicroRNAs (miRNAs) have emerged as potential therapeutic targets for genetic kidney diseases, but the physiologic role of miRNAs in postnatal renal tubules remains unknown. Using three different mouse models, Hajarnis et al. found that miRNA suppression in collecting ducts induces partial epithelial-to-mesenchymal transition, leading to progressive tubulointerstitial fibrosis and renal failure. These findings suggest that miRNAs regulate collecting duct homeostasis, which in turn has a key role in the initiation and progression of tubulointerstitial fibrosis. See Hajarnis et al., pages 518–531.
Adenosine Regulates Proton Secretion by Medullary Intercalated Cells
In several cell types, adenosine induces apical membrane accumulation of the vacuolar H+-ATPase (V-ATPase) proton pump. However, the effect of adenosine on V-ATPase in renal intercalated cells, which regulate acid-base homeostasis, is unknown. Here, Battistone et al. show that luminal adenosine signals through apical adenosine receptors in these cells, leading to stimulation of the cAMP/protein kinase A pathway and V-ATPase-dependent proton secretion. These findings reveal a novel mechanism through which intercalated cells respond to luminal purinergic agonists and may help explain the effects of adenosine-targeted therapeutics on kidney function. See Battistone et al., pages 545–556.
CLINICAL RESEARCH
Bortezomib and Kidney Allograft Rejection
Uncontrolled studies suggest that bortezomib may be effective against late donor-specific antibody (DSA)-mediated rejection. In this issue, Eskandary et al. report results from a randomized, placebo-controlled trial undertaken to assess the effects of bortezomib in 44 DSA-positive kidney transplant recipients. Bortezomib did not significantly affect DSA levels, rejection phenotypes, graft survival, or kidney, but did associate with hematologic and gastrointestinal toxicity. These data highlight the importance of evaluating treatments for graft failure in randomized, controlled trials. See Eskandary et al., pages 591–605.
Clinical Decision Support System for AKI
Does implementation of a clinical decision support system (CDSS) to automate the detection of AKI in the hospital setting improve outcomes? To address this question, Al-Jaghbeer et al. conducted a multicenter analysis of 528,108 patients without ESRD before admission. Use of a CDSS for AKI led to decreased hospital length of stay, mortality, and dialysis rates in patients with AKI. Outcomes for patients without AKI were not affected. Considering the incidence of AKI, these results suggest that implementation of a CDSS for AKI could save >17,000 lives and $1.2 billion annually in the United States. See Al-Jaghbeer et al., pages 654–660.
Polyomavirus Nephropathy Classification Scheme
The effects of morphologic polyomavirus nephropathy (PVN) variants on renal allograft function are unclear. Nickeleit et al. conducted a retrospective, multicenter study of 192 patients with definitive PVN, correlating morphologic findings from index biopsies with clinical findings. On the basis of interstitial fibrosis and intrarenal polyomavirus loads, the authors defined three morphologic classes of PVN. Patients in class 1 have early PVN with favorable outcomes, and those in classes 2 and 3 have more advanced disease, with graft failure rates of up to 50% in class 3. If validated in a mixed population, this classification scheme should provide important prognostic information. See Nickeleit et al., pages 680–693
- Copyright © 2018 by the American Society of Nephrology
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