Calcineurin-inhibitor induced pain syndrome: a 4-case report on patients with kidney retransplantation

  • Fabio Rubén Acosta Hospital Provincial del Centenario, Rosario, Santa Fe
  • María Laura Benítez Hospital Provincial del Centenario, Rosario, Santa Fe
  • Juan Oddino Hospital Provincial del Centenario, Rosario, Santa Fe
  • Silvina Lema Hospital Provincial del Centenario, Rosario, Santa Fe
  • Juan Loureyro Hospital Provincial del Centenario, Rosario, Santa Fe
  • Julia Arnoldi Hospital Provincial del Centenario, Rosario, Santa Fe
  • Mariela Stur Hospital Provincial del Centenario, Rosario, Santa Fe
Keywords: tacrolimus, renal retransplant, pain syndrome, pain, diagnostic imaging, magnetic resonance, calcineurin

Abstract

Introduction: Kidney transplant is the first-line therapy for chronic kidney disease. Immunosuppressants such as calcineurin-inhibitors may be associated with side effects. Calcineurin-inhibitor induced pain syndrome (CIPS) is characterized by symmetrical, severe and disabling bone pain in the lower limbs and can be easily identified by magnetic resonance imaging due to its typical patterns. Four CIPS cases after kidney retransplantation are presented, confirmed by MRI and with immunosuppressive therapy consisting of tacrolimus. Methods: Four patients (3 females and 1 male) with cadaveric kidney retransplantation, performed between March 2014 and September 2015 showed intense pains in their lower limbs. Tacrolimus was the main immunosuppressive agent. MRI scans of the lower limbs were performed; tacrolimus treatment and dosage adjustment were indicated. Results: CIPS started 2 months after transplantation and 2 weeks after detection of tacrolimus toxic levels. Pain lasted around 2 weeks and it gradually became less severe. Symptoms were exclusively located in the lower limbs (knees, ankles and feet). Patients described the pain as sharp, throbbing, disabling, and becoming worse when standing. MRI confirmed the diagnosis, revealing a pattern of bone marrow edema in tibial plateau and tali. All cases were reversible with the indicated treatment. Conclusions: This study registers 4 cases of CIPS in patients who had undergone kidney retransplantation and had taken tacrolimus with good response. Diagnosis was reached by clinical suspicion, form and location of pain, and characteristic patterns in the MRI scans.

References

Bouteiller G, Lloveras JJ, Condouret J, Durroux R, Durand D. [Painful polyarticular syndrome probably induced by cyclosporin in three patients with a kidney transplant and one with a heart transplant]. Rev Rhum Mal Osteoartic. 1989;56(11):753-5.

Puig I Marí JM, Martinez-Miralles E, Perich X, Lloveras J, Mir M, Iñigo V, et al. Reflex sympathetic dystrophy syndrome of the lower limbs in a renal transplant patient treated with tacrolimus. Transplantation. 2000;70(1):210-1.

Grotz WH, Breitenfeldt MK, Braune SW, Allmann KH, Krause TM, Rump JA, et al. Calcineurininhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation. Transpl Int. 2001;14(1):16-23.

Melzack R, Katz J, Jeans ME. The role of compensation in chronic pain: analysis using a new method of scoring the McGill Pain Questionnaire. Pain. 1985;23(2):101-12.

Gauthier VJ, Barbosa LM. Bone pain in transplant recipients responsive to calcium channel blockers. Ann Intern Med. 1994;121(11):863-5.

Collini A, De Bartolomeis C, Barni R, Ruggieri G, Bernini M, Carmellini M. Calcineurin-inhibitor induced pain syndrome after organ transplantation. Kidney Int. 2006;70(7):1367-70.

Elder GJ. From marrow oedema to osteonecrosis: common paths in the development of post-transplant bone pain. Nephrology (Carlton). 2006;11(6):560-7.

Kida A, Ohashi K, Tanaka C, Kamata N, Akiyama H, Sakamaki H. Calcineurin-inhibitor pain syndrome following haematopoietic stem cell transplantation. Br J Haematol. 2004;126(3):288.

Malat GE, Dupuis RE, Kassman B, Rhoads JM, Freeman K, Lichtman S, et al. Tacrolimus-induced pain syndrome in a pediatric orthotopic liver transplant patient. Pediatr Transplant. 2002;6(5):435-8.

Rahman AH, O'Brien C, Patchett SE. Leg bone pain syndrome in a patient with ulcerative colitis treated with cyclosporin. Ir J Med Sci. 2007;176(2):129-31.

Isaacs KL. Severe bone pain as an adverse effect of cyclosporin therapy for Crohn's disease. Inflamm Bowel Dis. 1998;4(2):95-7.

Lawson C, Fraser A, Veale D, Emery P. Cyclosporin treatment in psoriatic arthritis: a cause of severe leg pain. Ann Rheum Dis. 2003; 62(5):489.

Grotz W, Breitenfeldt K, Cybulla M. Immunosuppression and skeletal disorders. Transplant Proc. 2001;33(1-2):992-3.

Elder GJ. From marrow oedema to osteonecrosis: common paths in the development of post-transplant bone pain. Nephrology (Carlton). 2006;11(6):560-7.

Gurin L, Gohh R, Evangelista P. Pain syndrome with stress fractures in transplanted patients treated with calcineurin inhibitors. Clin Kidney J. 2012;5(1):13-6.

Textor SC, Taler SJ, Canzanello VJ, Schwartz L, Augustine JE. Posttransplantation hypertension related to calcineurin inhibitors. Liver Transpl. 2000;6(5):521-30.

Masaki T. Possible role of endothelin in endothelial regulation of vascular tone. Annu Rev Pharmacol Toxicol. 1995;35:235-55.

Smith JB, Araki H, Lefer AM. Thromboxane A2, prostacyclin and aspirin: effects on vascular tone and platelet aggregation. Circulation. 1980;62(6 Pt 2):V19-25.

Kou R, Greif D, Michel T. Dephosphorylation of endothelial nitric-oxide synthase by vascular endothelial growth factor. Implications for the vascular responses to cyclosporin A. J Biol Chem. 2002;277(33):29669-73.

Coates PT, Tie M, Russ GR, Mathew TH. Transient bone marrow edema in renal transplantation: a distinct post-transplantation syndrome with a characteristic MRI appearance. Am J Transplant. 2002;2(5):467-70.

Fujii N, Ikeda K, Koyama M, Aoyama K, Masunari T, Kondo E, et al. Calcineurin inhibitor-induced irreversible neuropathic pain after allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2006;83(5):459-61.

Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999-2000. Circulation. 2004;110(6):738-43.

Alis G, Alis M, Erturk T, Karayagiz AH, Berber I, Cakir U. Evaluation of Bone Disease in Kidney Transplant Recipients. Transplant Proc. 2017;49(3):509-511.

Hetzel GR, Malms J, May P, Heering P, Voiculescu A, Mödder U, et al. Post-transplant distal-limb bone-marrow oedema: MR imaging and therapeutic considerations. Nephrol Dial Transplant. 2000;15(11):1859-64.

Tillmann FP, Jäger M, Blondin D, Oels M, Rump LC, Grabensee B, et al. Post-transplant distal limb syndrome: clinical diagnosis and long-term out-come in 37 renal transplant recipients. Transpl Int. 2008;21(6):547-53.

Senzolo M, Ferronato C, Burra P. Neurologic complications after solid organ transplantation. Transpl Int. 2009;22(3):269-78.

Kozin F, Ryan LM, Carerra GF, Soin JS, Wortmann RL. The reflex sympathetic dystrophy syndrome (RSDS). III. Scintigraphic studies, further evidence for the therapeutic efficacy of systemic corticosteroids, and proposed diagnostic criteria. Am J Med. 1981;70(1):23-30.

Published
2017-10-03
How to Cite
1.
Acosta FR, Benítez ML, Oddino J, Lema S, Loureyro J, Arnoldi J, Stur M. Calcineurin-inhibitor induced pain syndrome: a 4-case report on patients with kidney retransplantation. Rev Nefrol Dial Traspl. [Internet]. 2017Oct.3 [cited 2024Dec.28];37(3):137-45. Available from: http://vps-1689312-x.dattaweb.com/index.php/rndt/article/view/183
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Original Article