Renal ischaemic injuries during the use of zolmitriptan for treatment of migraines in a transplanted patient under tacrolimus therapy

Abstract

A 26-year-old female patient underwent kidney transplantation from a 38-year-old deceased donor in 2001. Her renal disease was a focal segmental hyalinosis secondary to congenital vesico-ureteral reflux. She was started on triple immunosuppressive therapy [tacrolimus, mycophenolate mofetil (MPM) and prednisone]. Renal transplantation was complicated by delayed graft function and a renal biopsy was performed on the day 8, showing histological signs of tubular necrosis without acute rejection. Thereafter, evolution was excellent and corticosteroids were stopped after 1 year. Creatinine at 1 year was 100 mmol/l. She had arterial hypertension which was treated with four antihypertensive drugs just after renal transplantation; the treatment was progressively decreased and 18 months after transplantation, she required no further antihypertensive therapy. A routine renal biopsy was performed after steroid withdrawal in 2002, showing no evidence of rejection but a moderate interstitial fibrosis (10–20%). Tacrolimus and MPM were continued and trough levels of tacrolimus were aimed for 6–8 mg/l. All follow-up visits between 2002 and 2005 were unremarkable, except one respiratory infection which was treated with antibiotics for 7 days. Renal function was extremely stable with values averaging 100 mmol/l (83–114 mmol/l) of creatinine during these 3 years (Figure 1). She had no proteinuria (170mg/day). Tacrolimus trough level was kept between 6 and 8 mg/l with 1.5mg b.i.d. During this period, she was also taking an oral contraception (estradiol and progesterone), magnesium and paracetamol for common migraines. She did not smoke or drink alcohol. During the summer of 2005 her common migraines became exacerbated, no longer relieved by paracetamol. In September 2005, her general practitioner prescribed zolmitriptan 2.5mg to good effect. She used this medication 3–4 times a month. In October 2005 she had a slight increase of creatinine at 120 mmol/l, but no other changes which might have raised any concerns for her renal function; a control in January was stable at 115 mmol/l. Due to an increase in her headaches, she took zolmitriptan more frequently during the following 2 months, reporting an average consumption of 10 pills per week (Figure 1). She did not complain of abdominal pains. In March 2006, a control showed a creatinine value at 161 mmol/l associated with an increase in proteinuria (500mg/day) (Figure 1). There was no clinical explanation for this rise, but tacrolimus trough levels were at the upper limit of the target (8 mg/l) during the last 4 months under the same drug regimen (1.5mg b.i.d). A renal biopsy was performed. Several cortical ischaemic scars were observed with globally sclerotic glomeruli and arteriosclerosis (Figure 2A). The cortical region without scars included eight glomeruli, four of them globally sclerosed. Two glomeruli showed severe ischaemic injury with corrugation of the basement membranes (Figure 2B). In the two other glomeruli, lesions of focal and segmental sclerosis were observed. Some intratubular calcifications were detected. Arterioles appeared unremarkable. A 99m-Tc-DMSA renal scintigraphy was done, which did not reveal renal defects compatible with large scars. Zolmitriptan and tacrolimus were suspected to be involved in this acute decline in renal function. Zolmitriptan was stopped and tacrolimus dosage was slightly decreased, to 1mg in the morning and 0.5mg in the evening. Creatinine slowly decreased to 141 umol/l and a renal biopsy was performed again in June 2006. The histology showed the same cortical scars, and moderate arteriolar lesions Correspondence to: Pierre-Yves Martin, Service de Nephrologie, Departement de Medecine Interne, Hopitaux Universitaires de Geneve, 1211 Geneve 4, Switzerland. Email: pierre-yves.martin@hcuge.ch Nephrol Dial Transplant (2007) 22: 3341–3343