• 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, DrenthJoost P HJPHDepartment of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands., 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, PetersDorien J MDJMDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands., Mahdi Salih, Darius Soonawala, Edwin M Spithoven, Jack F Wetzels, Robert Zietse, Ron T Gansevoort, and DIPAK-1 Investigators.
• Department of Nephrology, University Medical Center Groningen, University Hospital Groningen, Groningen, the Netherlands.
• JAMA. 2018 Nov 20; 320 (19): 201020192010-2019.

ImportanceAutosomal 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.ObjectiveTo examine the effect of the somatostatin analogue lanreotide on the rate of kidney function loss in patients with later-stage ADPKD.Design, Setting, And ParticipantsAn 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.InterventionsPatients 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 MeasuresPrimary 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]).ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT01616927.

29 keywords...

hide…