Introduction: Previous animal studies of ADPKD suggest sirolimus reduces kidney volume, cyst size and density, and restores overall kidney function as measured by BUN and serum creatinine. Based on these findings, we evaluated if use of sirolimus prevented volumetric expansion and cyst growth in ADPKD patients native kidneys and liver following renal transplantation.
Methods: Nine ADPKD post-kidney transplant patients who were converted from calcineurin-based immunosuppression to sirolimus (5-15 ng/mL) were enrolled into the study. Serial MRI/CT/US imaging was conducted upon enrollment and at 6, 12 and 24 months to measure change in total volume, dominant cyst volume and percent cyst volume in the patients kidneys and liver. Data interpreted with multivariate repeated measure ANOVA.
Results: Combined averages of left and right native kidney volumes decreased significantly (2441.61 mL to 2143.81 mL, p<.05) with no significant difference in change over time between the two kidneys (p>.05). The combined averages of the left and right native kidney dominant cyst volumes decreased significantly (67.61 mL to 63.02 mL, p<.05) with no significant difference in change over time between the two kidneys (p>.05). The combined averages of the left and right native kidney percent cyst volume did not change significantly (94.78% to 94.53%, p>05) with no significant difference in change over time between the two kidneys (p>.05). The total liver volume did not change significantly (3131.89 mL to 3112.25 mL, p>.05). The dominant liver cyst volume did not change significantly (67.99 mL to 55.31 mL, p>.05), nor did percent liver cyst volume (30% to 26%, p>.05).
Conclusions: Use of sirolimus significantly reduced kidney volume and dominant cyst volume, while not having an effect on the percent cyst volume. Liver total volume, dominant liver cyst volume and percent cyst volume did not change significantly over time. A recent study shows a 5.8% increase per year in kidney volume in untreated pre-ESRD ADPKD patients. These data showing reduction in the renal volume and stabilization of the liver volume suggests that conversion of patients with ADPKD to an mTOR inhibitor may prevent post-transplant complications associated with compression caused by expanding cysts. Thus, conversion to an mTOR inhibitor may be worthwhile to prevent comorbidities associated with further enlargement of native kidneys and liver following renal transplantation.
Rees, M.: Grant/Research Support, Pfizer. Twining, L.: Grant/Research Support, Pfizer. Ratnam, S.: Grant/Research Support, Pfizer.
To cite this abstract in AMA style:Mandabach J, Rees M, Elsamaloty H, Gowharji L, Twining L, Khuder S, Ratnam S. Evaluation of Cystic Growth in ADPKD Renal Transplant Recipients Following Conversion to an mTOR Inhibitor [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/evaluation-of-cystic-growth-in-adpkd-renal-transplant-recipients-following-conversion-to-an-mtor-inhibitor/. Accessed March 31, 2020.
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