title: Infections in De Novo Kidney Transplant Recipients Treated With the RANKL Inhibitor Denosumab.
abstract: Infections are a major cause of morbidity and mortality in kidney allograft recipients. In this post hoc analysis of a randomized clinical trial which tested the effect of denosumab on bone mineral density, we assessed the impact of this drug on the incidence and severity of infections in the first year after kidney transplantation.
  
  
  
  In this clinical trial, we randomized 90 de novo kidney transplant recipients shortly after transplantation to either denosumab on top of standard treatment (calcium and vitamin D) (n = 46), or to standard treatment alone (n = 44). Among all adverse events, we analyzed all infections that occurred within the first year after transplantation, and compared their incidence and severity in both groups.
  
  
  
  Overall, we identified more infections (n = 146) in the denosumab group than in the control group (n = 99). The most common infections were urinary tract infection (cystitis) (34.9% vs 25.2%), cytomegalovirus viremia (17.8% vs 24.2%), flu-like syndrome (11.6% vs 14.1%), polyoma (BK) viremia (8.2% vs 11.1%), and herpes simplex infections (5.5% vs 4.0%). Episodes of urinary tract infection (cystitis) occurred more often in the denosumab than in the control group (51 vs 25 episodes in 24 vs 11 patients, P = 0.008), whereas episodes of transplant pyelonephritis or urosepsis were not more frequent (3 vs 5 episodes).
  
  
  
  This post hoc analysis reveals that treatment with denosumab to prevent bone loss in first-year kidney transplant recipients was associated with more frequent episodes of urinary tract infections, whereas other infections occurred with similar frequency in both treatment groups.
authors: 1 Division of Nephrology, University Hospital Zürich and University of Zürich, Switzerland. 2 Division of Rheumatology, University Hospital Zürich and University of Zürich, Switzerland. 3 Division of Visceral and Transplantation Surgery, University Hospital Zürich and University of Zürich, Switzerland. 4 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich and University of Zürich, Switzerland. 5 Graf Biostatistics, Winterthur, Switzerland.
authors: Marco
authors: M
authors: Bonani
authors: Diana
authors: D
authors: Frey
authors: Olivier
authors: O
authors: de Rougemont
authors: Nicolas J
authors: NJ
authors: Mueller
authors: Thomas F
authors: TF
authors: Mueller
authors: Nicole
authors: N
authors: Graf
authors: Rudolf P
authors: RP
authors: Wüthrich
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D000069448:Denosumab / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D011446:Prospective Studies; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index; D013557:Switzerland / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D014777:Virus Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D050071:Bone Density Conservation Agents; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab