Abstract: PUB119
Inclusion Body Myositis in a Patient with Previous Tolvaptan-Associated Liver Injury
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Author
- Baker, Richard Henry, University of Maryland Medical System, Baltimore, Maryland, United States
Introduction
Tolvaptan is a vasopressin antagonist that is used to slow progression of autosomal dominant polycystic kidney disease (ADPKD) via reduction of V2-induced cyclic AMP activity. Tolvaptan-associated liver injury (TALI), a use-limiting adverse effect, is thought to be due to toxicity, bile acid accumulation, and adaptive immune activation. T cells responsive to tolvaptan metabolites have been identified in patients with TALI.
Inclusion body myositis (IBM) is an inflammatory myopathy often characterized by quadriceps and finger flexor weakness, CD8+ T cell invasion of the endomysium, and distinct autophagic vacuoles on muscle biopsy. While not clearly linked to any environmental triggers, IBM is associated with HIV and hepatitis C virus.
While tolvaptan has been associated with rhabdomyolysis, it has not been linked to inflammatory myositis or autoimmune conditions.
Case Description
A 57-year-old male with history of ADPKD, polycystic liver disease with hepatomegaly, chronic kidney disease (CKD) G3aA2, polycystic liver disease, hypertension, gout, achalasia, and Raynaud’s phenomenon presented with weakness and difficulty climbing the stairs. Two years prior, he stopped a fifteen-year regimen of tolvaptan due to liver injury. Muscle biopsy revealed inflammatory myopathy with rimmed vacuoles consistent with IBM. The patient developed progressive hand, shoulder, and leg weakness partially responsive to steroids. One year later, renal evaluation showed CKD worsening to stage G3bA2.
Discussion
The role of T cell activation in TALI and IBM suggests potential causal connection. While direct activity from TALI T cells is unlikely, inflammatory T cells implicated in TALI could indirectly promote IBM development, much like chronic viremia. Alternatively, the development of IBM and TALI in this patient may suggest a susceptibility to inflammatory activity observed in both conditions.
Though coincidence is possible, the occurrence of both conditions in a single patient may suggest either a tolvaptan-associated IBM or a common risk factor for otherwise unrelated conditions. Further exploration of links between tolvaptan, TALI, and inflammatory conditions is warranted.