JAC Advance Access originally published online on May 11, 2007
Journal of Antimicrobial Chemotherapy 2007 60(1):193-194; doi:10.1093/jac/dkm143
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Correspondence |
Simultaneous development of Fanconi syndrome and acute renal failure associated with cidofovir
1 Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, FL, USA 2 Department of Medicine, Orlando Regional Medical Center, Orlando, FL, USA
* Corresponding author. Tel: +1-352-392-4007; Fax: +1-352-392-3581; E-mail: amir.kazory{at}medicine.ufl.edu
Keywords: nephrotoxicity , nucleoside analogues , side effects
Cidofovir is a nucleoside analogue with potent activity against a number of viruses including BK virus and cytomegalovirus. It is commonly used for the treatment of viral diseases in the context of immunosuppression. Acute renal failure (ARF) secondary to necrosis of the proximal tubular cells is the major side effect of cidofovir.1
A 34-year-old male with chronic myeloblastic leukaemia received an umbilical cord transplant. Immunosuppression consisted of tacrolimus and prednisone. Post-transplant course was complicated by BK virus-related haemorrhagic cystitis, adenovirus viraemia and cytomegalovirus infection, for which cidofovir (1 mg/kg, three times a week, intravenously) was started. He was hydrated with normal saline, and also received 2 g of oral probenecid prior to cidofovir infusion and 2 g 2 and 8 h afterwards. Renal function was normal with a serum creatinine level of 0.7 mg/dL (NL: 0.8–1.2) and normal urine analysis except for haematuria. Three weeks later, he developed acute renal failure with a serum creatinine rising to 1.4 mg/dL necessitating cessation of cidofovir. The renal dysfunction stabilized then at that level. Ten days later, the serum adenovirus load rose and cidofovir infusions were restarted. The renal function deteriorated rapidly again with a serum creatinine level rising to 3.1 mg/dL. Urine output was normal at ~2 L/day. Further laboratory studies revealed a serum BUN of 20 mg/dL (NL: 6–20), sodium of 140 mg/dL (NL: 136–145), bicarbonate of 10 mmol/L (NL: 22–30), chloride of 121 mmol/L (NL: 98–107), magnesium of 1.3 mg/dL (NL: 1.5–2.8), phosphorus of 2.4 mg/dL (NL: 2.7–4.5) and glucose of 78 mg/dL (NL: 65–99). Concomitantly, urine analysis revealed an abundant amount of glucose (>1000 mg/dL), phosphorus (18.7 mg/dL) and magnesium (143 mg/dL) in the urine along with a pH of 8.0 and mild proteinuria (100 mg/dL). Cidofovir was discontinued and electrolytes were replaced. This was followed by progressive amelioration of kidney function (creatinine 1.5 mg/dL) while urine leakage of electrolytes continued necessitating replacement over the next 2 months.
ARF secondary to proximal tubular toxicity is the most commonly known adverse effect of cidofovir.1 Intracellular accumulation due to increased entry through the human organic anion transporter 1 is the main mechanism of toxicity.2 This patient is the third reported case of Fanconi syndrome associated with administration of cidofovir.3,4 Based on these observations, it is plausible that cidofovir-induced proximal tubular cytotoxicity is not limited to cellular degeneration and necrosis manifesting as ARF; it can also lead to loss of normal function of viable cells leading to urinary leakage of electrolytes. While cidofovir-associated ARF is dose-dependent and reversible in the vast majority of the patients, there are reports of end-stage renal failure secondary to use of this medication.4 In our case, cessation of cidofovir was followed by stabilization of kidney dysfunction while Fanconi syndrome persisted. Of note, renal adverse effects occurred while the dose of cidofovir was within the recommended range (<5 mg/kg/week).
Based on this observation coupled with previous reports, we suggest that proximal tubular function be also assessed in patients receiving cidofovir. This can be done by frequent measurements of serum creatinine and urea level, as well as sodium, potassium, bicarbonate, magnesium, phosphorus and calcium. Urine analysis and urine electrolytes (including sodium, potassium, magnesium and phosphorus) can also be helpful if Fanconi syndrome is suspected. Cessation of cidofovir as well as replacement of electrolytes would be warranted if tubular toxicity develops.
No specific financial support was obtained for preparation of this article.
The authors have no potential conflicts of interest to declare with respect to this paper.
References
1 Polis MA, Spooner KM, Baird BF, et al. Anticytomegaloviral activity and safety of cidofovir in patients with human immunodeficiency virus infection and cytomegalovirus viruria. Antimicrob Agents Chemother (1995) 39:882–6.[Abstract]
2
Ho ES, Lin DC, Mendel DB, et al. Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J Am Soc Nephrol (2000) 11:383–93.
3 Vittecoq D, Dumitrescu L, Beaufils H, et al. Fanconi syndrome associated with cidofovir therapy. Antimicrob Agents Chemother (1997) 41:1846.[Web of Science][Medline]
4
Meier P, Dautheville-Guibal S, Ronco PM, et al. Cidofovir-induced end-stage renal failure. Nephrol Dial Transplant (2002) 17:148–9.
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