Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease

Maria Irazabal Mira, Vicente Torres, Marie C Hogan, James Glockner, Bernard Francis King, Troy G. Ofstie, Holly B. Krasa, John Ouyang, Frank S. Czerwiec

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Tolvaptan and related V 2-specific vasopressin receptor antagonists have been shown to delay disease progression in animal models of polycystic kidney disease. Slight elevations in serum creatinine, rapidly reversible after drug cessation, have been found in clinical trials involving tolvaptan. Here, we sought to clarify the potential renal mechanisms to see whether the antagonist effects were dependent on underlying renal function in 20 patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) before and after 1 week of daily split-dose treatment. Tolvaptan induced aquaresis (excretion of solute-free water) and a significant reduction in glomerular filtration rate (GFR). The serum uric acid increased because of a decreased uric acid clearance, and the serum potassium fell, but there was no significant change in renal blood flow as measured by para-aminohippurate clearance or magnetic resonance imaging (MRI). No correlation was found between baseline GFR, measured by iothalmate clearance, and percent change in GFR induced by tolvaptan. Blinded post hoc analysis of renal MRIs showed that tolvaptan significantly reduced total kidney volume by 3.1% and individual cyst volume by 1.6%. Preliminary analysis of this small cohort suggested that these effects were more noticeable in patients with preserved renal function and with larger cysts. No correlation was found between changes of total kidney volume and body weight or estimated body water. Thus, functional and structural effects of tolvaptan on patients with ADPKD are likely due to inhibition of V 2-driven adenosine cyclic 3′,5′-monophosphate generation and its aquaretic, hemodynamic, and anti-secretory actions.

Original languageEnglish (US)
Pages (from-to)295-301
Number of pages7
JournalKidney International
Volume80
Issue number3
DOIs
StatePublished - Aug 1 2011

Fingerprint

Autosomal Dominant Polycystic Kidney
Kidney
Glomerular Filtration Rate
Uric Acid
Cysts
Serum
Cohort Effect
Polycystic Kidney Diseases
Body Water
Renal Circulation
Adenosine
Disease Progression
tolvaptan
Creatinine
Potassium
Animal Models
Hemodynamics
Body Weight
Magnetic Resonance Imaging
Clinical Trials

Keywords

  • ADPKD
  • kidney volume
  • polycystic kidney disease
  • renal function
  • vasopressin

ASJC Scopus subject areas

  • Nephrology

Cite this

Short-term effects of tolvaptan on renal function and volume in patients with autosomal dominant polycystic kidney disease. / Irazabal Mira, Maria; Torres, Vicente; Hogan, Marie C; Glockner, James; King, Bernard Francis; Ofstie, Troy G.; Krasa, Holly B.; Ouyang, John; Czerwiec, Frank S.

In: Kidney International, Vol. 80, No. 3, 01.08.2011, p. 295-301.

Research output: Contribution to journalArticle

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