The Effect of Spironolactone on Calcineurininhibitor Induced Nephrotoxicity.
1Department of Nephrology, Odense University Hospital, Odense, Denmark
2Department of Biostatistics, University of Southern Denmark, Odense, Denmark
3Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
4Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.
Meeting: 2016 American Transplant Congress
Abstract number: A250
Keywords: Calcineurin, Fibrosis, Graft survival, Kidney transplantation
Session Information
Date: Saturday, June 11, 2016
Session Name: Poster Session A: Long Term Outcomes in Kidney Transplantation
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Halls C&D
Purpose: Evidence points towards activation of the mineralocorticoid receptor (MR) to be involved in CNI nephrotoxicity. The SPIREN trial was designed to test the hypothesis that treatment with the MR-antagonist spironolactone attenuates renal injury in kidney transplant patients measured by changes in mGFR, proteinuria and renal fibrosis.
Methods: Interim analysis from a 3-year placebo-controlled, double-blinded, randomized clinical trial including 41 renal transplant recipients (n=20 in group A/n=21 in group B) of a planned total of 170. Plasma creatinine was used as a surrogate marker of kidney function to ensure a sufficient number of measurements for each individual and levels were compared between groups to evaluate the development of renal function during the first two years of participation.
We wished to evaluate the development of creatinine levels after titrating the spironolactone dosage to 50 mg per day. Hence values from the 6th visit (at a median of 6.4 months after entry into the study) to 24 months were evaluated.
Proteinuria was evaluated by 24-hour urine samples obtained yearly. Only patients with three values of proteinuria were included in the analysis (n=33).
Data was analyzed using a linear mixed model to compare the slopes between groups.
Results: We found no significant difference in the development of plasma creatinine levels between placebo vs. spironolactone groups. The slope for group A was 0.12 [micro]mol/L/month (-0.33;0.58) and for group B was -0.19 [micro]mol/L/month (-0.70;0.31) (p=0.36).
There was no significant difference in levels of proteinuria between the two groups.
Conclusion: Spironolactone treatment for 18 months does not affect kidney function in kidney transplant patients as evaluated by plasma creatinine.
The impact of spironolactone on the development of fibrosis will be evaluated by light microscopy of kidney biopsies as part of the interim analysis. The impact of spironolactone on long-term kidney graft survival remains to be analyzed at trial completion.
CITATION INFORMATION: Mortensen L, Thiesson H, Bistrup C, Nielsen F, Halekoh U, Jensen B, Marcussen N. The Effect of Spironolactone on Calcineurininhibitor Induced Nephrotoxicity. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Mortensen L, Thiesson H, Bistrup C, Nielsen F, Halekoh U, Jensen B, Marcussen N. The Effect of Spironolactone on Calcineurininhibitor Induced Nephrotoxicity. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/the-effect-of-spironolactone-on-calcineurininhibitor-induced-nephrotoxicity/. Accessed October 30, 2020.« Back to 2016 American Transplant Congress