title: Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study.
abstract: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature.
  
  
  
  The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18-60 years, estimated glomerular filtration rate 30-60 mL/min/1.73 m2) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians.
  
  
  
  We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48-55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m2[interquartile range: 41-58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship.
  
  
  
  These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk-benefit ratio. CLINICALTRIALS.
  
  
  
  NCT 01616927.
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: Marten A
authors.initials: MA
authors.lastname: Lantinga
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: Hedwig M A
authors.initials: HM
authors.lastname: D'Agnolo
authors.affiliation: Department of Nephrology, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Niek F
authors.initials: NF
authors.lastname: Casteleijn
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
authors.affiliation: Department of Nephrology, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Meijer
authors.affiliation: Department of Nephrology, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Annemarie L
authors.initials: AL
authors.lastname: Messchendorp
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Dorien J M
authors.initials: DJ
authors.lastname: Peters
authors.affiliation: Department of Nephrology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Salih
authors.affiliation: Department of Nephrology, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Spithoven
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Darius
authors.initials: D
authors.lastname: Soonawala
authors.affiliation: Department of Nephrology, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Visser
authors.affiliation: Department of Nephrology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.affiliation: Department of Nephrology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.affiliation: Department of Nephrology, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands. r.t.gansevoort@umcg.nl.
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
mesh_terms: D000293:Adolescent; D000328:Adult; D003560:Cysts / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008107:Liver Diseases / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000009:adverse effects; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000188:drug therapy*; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin