Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease: The DIPAK 1 Randomized Clinical Trial

DIPAK-1 Investigators, Esther Meijer, Folkert W Visser, Rene M M van Aerts, Charles J Blijdorp, Niek F Casteleijn, Hedwig M A D'Agnolo, Shosha E I Dekker, Joost P H Drenth, Johan W de Fijter, Maatje D A van Gastel, Tom J Gevers, Marten A Lantinga, Monique Losekoot, A Lianne Messchendorp, Myrte K Neijenhuis, Michelle J Pena, Dorien J M Peters, Mahdi Salih, Darius SoonawalaEdwin M Spithoven, Jack F Wetzels, Robert Zietse, Ron T Gansevoort

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Abstract

Importance: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation in both kidneys and loss of renal function, eventually leading to a need for kidney replacement therapy. There are limited therapeutic management options.

Objective: To examine the effect of the somatostatin analogue lanreotide on the rate of kidney function loss in patients with later-stage ADPKD.

Design, Setting, and Participants: An open-label randomized clinical trial with blinded end point assessment that included 309 patients with ADPKD from July 2012 to March 2015 at 4 nephrology outpatient clinics in the Netherlands. Eligible patients were 18 to 60 years of age and had an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2. Follow-up of the 2.5-year trial ended in August 2017.

Interventions: Patients were randomized to receive either lanreotide (120 mg subcutaneously once every 4 weeks) in addition to standard care (n = 153) or standard care only (target blood pressure <140/90 mm Hg; n = 152).

Main Outcomes and Measures: Primary outcome was annual change in eGFR assessed as slope through eGFR values during the 2.5-year treatment phase. Secondary outcomes included change in eGFR before vs after treatment, incidence of worsening kidney function (start of dialysis or 30% decrease in eGFR), change in total kidney volume and change in quality of life (range: 1 [not bothered] to 5 [extremely bothered]).

Results: Among the 309 patients who were randomized (mean [SD] age, 48.4 [7.3] years; 53.4% women), 261 (85.6%) completed the trial. Annual rate of eGFR decline for the lanreotide vs the control group was -3.53 vs -3.46 mL/min/1.73 m2 per year (difference, -0.08; [95% CI, -0.71 to 0.56]; P = .81). There were no significant differences for incidence of worsening kidney function (hazard ratio, 0.87 [95% CI, 0.49 to 1.52]; P = .87), change in eGFR (-3.58 vs -3.45; difference, -0.13 mL/min/1.73 m2 per year [95% CI, -1.76 to 1.50]; P = .88), and change in quality of life (0.05 vs 0.07; difference, -0.03 units per year [95% CI, -0.13 to 0.08]; P = .67). The rate of growth in total kidney volume was lower in the lanreotide group than the control group (4.15% vs 5.56%; difference, -1.33% per year [95% CI, -2.41% to -0.24%]; P = .02). Adverse events in the lanreotide vs control group included injection site discomfort (32% vs 0.7%), injection site papule (5.9% vs 0%), loose stools (91% vs 6.6%), abdominal discomfort (79% vs 20%), and hepatic cyst infections (5.2% vs 0%).

Conclusions and Relevance: Among patients with later-stage autosomal dominant polycystic kidney disease, treatment with lanreotide compared with standard care did not slow the decline in kidney function over 2.5 years of follow-up. These findings do not support the use of lanreotide for treatment of later-stage autosomal dominant polycystic kidney disease.

Trial Registration: ClinicalTrials.gov Identifier: NCT01616927.

Original languageEnglish
Pages (from-to)2010-2019
Number of pages10
JournalJAMA
Volume320
Issue number19
Early online date2018
DOIs
Publication statusPublished - 20-Nov-2018
EventAnnual Kidney Week of the American-Society-of-Nephrology - San Diego, Canada
Duration: 25-Oct-2018 → …

Keywords

  • LONG-ACTING SOMATOSTATIN
  • LIVER-DISEASE
  • MOUSE KIDNEY
  • PASIREOTIDE
  • PROGRESSION
  • OCTREOTIDE
  • EXPRESSION
  • TOLVAPTAN
  • EFFICACY
  • VOLUME

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