Nephrogenic Diabetes Insipidus in a Patient Taking Cidofovir
| Title: | Nephrogenic Diabetes Insipidus in a Patient Taking Cidofovir |
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| Authors: | Schliefer, Kirsten; Rockstroh, Jurgen K.; Spengler, Ulrich; Sauerbruch, Tilman |
| Publisher: | The Lancet |
| Date Published: | August 01, 1997 |
| Reference Number: | 177 |
Cidofovir is a nucleotide analogue with activity against cytomegalovirus (CMV) retinitis in HIV-infected patients, which may offer a therapeutic option in CMV infection resistant to ganciclovir and foscarnet.1 Nephrotoxicity with this drug leads to proteinuria in 40% and increased serum creatinine concentrations in 12% of patients.2 The manufacturers therefore recommend regular monitoring of serum creatinine concentrations and urinary protein excretion. Here, we present a case of nephrogenic diabetes insipidus as an adverse effect of this drug. It occurred without a notable preceding increase in serum creatinine or proteinuria.
A 28-year-old HIV-positive man from Brazzaville was treated in our hospital for active CMV retinitis, which had not responded to ganciclovir. Subsequent treatment with foscarnet had to be terminated after 18 days because of deterioration of anal ulcerations. After a 6-week safety interval, intermittent treatment was given (once weekly for 2 weeks and once every 2 weeks thereafter) with cidofovir 5 mg/kg body weight, with concomitant oral probenecid (4g) and intravenous saline hydration to reduce nephrotoxicity. During the first six treatment cycles the serum creatinine was stable and proteinuria was mild. After the seventh treatment cycle he suddenly developed polydipsia and polyuria (14 L per 24 h) (see figure). The diagnosis of nephrogenic diabetes insipidus was established on the basis of a pathological dehydration test,
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) with 5 mg/kg A drug-drug interaction seems unlikely as a potential cause, because the only additional medication was pneumocystis pneumonia prophylaxis with one single-strength table of co-trimoxazole (480 mg). Furthermore, although previous therapy with foscarnet increases the risk of nephrotoxicity during cidofovir therapy, nephrogenic diabetes insipidus as a complication by such sequential therapy has not been reported.
Vasopressin exerts its antidiuretic effects by increasing c-AMP concentrations and activating intracellular kinases. Cidofovir is metabolised by cellular, not viral, kinases to its active form cidofovir-diphosphate and other phosphorylated metabolites (monophosphate, phosphate choline adduct). Owing to its long half-life (87 h) cidofovir phosphate choline adduct can act as an intracellular storage reservoir.3 It may be hypothesised that metabolites of cidofovir may have caused an idiosyncratic interaction with vasopressin signalling by intracellular kinases. Convalescence may have been prolonged due to the intracellular storage reservoirs: 12 weeks after cidofovir withdrawal urine output fell to 1•5 L per 24 h and proteinuria disappeared.
We conclude that tubular damage by cidofovir can result in nephrogenic diabetes insipidus without premonitory laboratory abnormalities.
- Lea AP, Bryson HM. Cidofovir. Drugs 1996; 52: 225-30.
- Lazesari JP, Stagg JR, Kuppermann BD, et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1997; 126: 257-63.
- Ho HT, Woods KL, Bronson JJ, De Boeck, H, Martin JC, Hitchcock MJM. Intracellular metabolism of antiherpes agent (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine. Mol Pharmacol 1991; 41: 197-202.
K. Schliefer Department of General Internal Medicine University of Bonn, 53105 Bonn GERMANY |
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The authors' patient was being treated with Ganciclovir for his retina infection, but it wasn't working. He was switched to Cidofovir and after the seventh treatment cycle, he developed nephrogenic diabetes insipidus (NDI). Twelve weeks after he was taken off Cidofovir, the patient's symptoms of NDI disappeared.
This is the first time that NDI as a consequence of Cidofovir has been reported. The authors conclude that damage to the kidney tubules (the small tubes in the kidney through which filtered body fluid drains) by Cidofovir can result in NDI