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Original Investigation
November 20, 2018

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

Author Affiliations
  • 1Department of Nephrology, University Medical Center Groningen, University Hospital Groningen, Groningen, the Netherlands
  • 2Department of Internal Medicine, Hospital Group Twente, Almelo, the Netherlands
  • 3Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands
  • 4Department of Internal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
  • 5Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
  • 6Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
  • 7Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University, Hospital Groningen, Groningen, the Netherlands
  • 8Department of Internal Medicine, Haga Teaching Hospital, The Hague, the Netherlands.
  • 9Department of Nephrology, Radboud University Medical Center, Nijmegen, the Netherlands
JAMA. 2018;320(19):2010-2019. doi:10.1001/jama.2018.15870
Key Points

Question  Can the somatostatin analogue lanreotide slow the rate of decline in kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD)?

Findings  In this randomized clinical trial that included 305 patients with later-stage ADPKD, treatment with lanreotide, 120 mg subcutaneously once every 4 weeks, compared with standard care resulted in a decline of estimated glomerular filtration rate of 3.53 vs 3.46 mL/min/1.73 m2 per year over 2.5 years, a difference that was not statistically significant.

Meaning  Lanreotide was not effective in slowing the decline in kidney function in patients with later-stage ADPKD.

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

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