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Kidney Week

Abstract: SA-PO485

Effect of Somatostatin Analogues on the Vasopressin Pathway in Patients with ADPKD

Session Information

  • ADPKD: Clinical Studies
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • Messchendorp, A. Lianne, UMCG, Groningen, GRONINGEN, Netherlands
  • Kramers, Bart J., UMCG, Groningen, GRONINGEN, Netherlands
  • Stade, Katrin, Brahms GmbH, Hennigsdorf, Germany
  • Meijer, Esther, UMCG, Groningen, GRONINGEN, Netherlands
  • Gansevoort, Ron T., UMCG, Groningen, GRONINGEN, Netherlands

Group or Team Name

  • DIPAK consortium
Background

The vasopressin V2 receptor antagonist tolvaptan slows the rates of total kidney volume growth and GFR decline in ADPKD, but its effect is limited and aquaretic side effects hamper wide spread clinical use. Therefore somatostatin analogues are of interest, which also interfere with cyst formation. Interestingly, several studies have suggested that somatostatin is involved in renal water handling, indicating that there may be an interaction between the somatostatin and vasopressin pathways. We therefore investigated if the somatostatin analogue lanreotide has an effect on vasopressin levels and aquaresis in patients with ADPKD.

Methods

Patients were included who participated in the DIPAK-1 study, a randomized, open-label controlled clinical trial to test the efficacy and safety of the somatostatin analogue lanreotide in later stage ADPKD. Patients were invited for a baseline visit, and randomized to receive either lanreotide or standard care in a 1:1 ratio. Blood and 24 hour urine samples were collected at baseline and after 12 weeks. Free water clearance (FWC) was calculated as 24 hour urine volume-((Urine osmolality*24 hour urine volume)/plasma osmolality) and fractional free water clearance (FFWC) as (FWC/eGFR)*100%.

Results

Overall, 305 ADPKD patients were included, 53% female, 48±7 years of age, with an eGFR of 50±11 ml/min/1.73m2. At baseline, there were no differences in plasma copeptin levels (a surrogate for vasopressin), 24 hour urine volume, FWC and FFWC between patients randomized to lanreotide (n=153) or standard care (n=152). From baseline to week 12, we observed no differences in change in plasma copeptin, 24 hour volume, FWC and FFWC between patients receiving lanreotide or standard care (-0.93±13.5 vs. -0.07±5.58 pmol/L, p=0.48; -0.02±0.6 vs. 0.07±0.7 L/24hr, p=0.25; 0.09±0.6 vs. 0.2±0.8 L/24hr, p=0.39 and 0.2±1.3 vs. 0.3±1.7 %, p=0.79 respectively).

Conclusion

The somatostatin analogue lanreotide does not affect vasopressin levels or aquaresis in patients with ADPKD. Our data therefore do not support an effect of somatostatin on the vasopressin pathway. An effect of lanreotide on vasopressin V2 receptor antagonist induced renoprotection and polyuria is therefore not to be expected.

Funding

  • Commercial Support