Renal toxicity of Oxaliplatin

Sir,

Oxaliplatin is an antitumoral agent derived from platinum (trans-1,2-diammino-cylo-hexane-platinum) with cytotoxic activity against a number of solid tumours, including colorectal cancer and metastatic ovarian carcinoma. Renal side-effects are unclear. We report the second case of acute renal failure following the use of oxaliplatin.

A 69-year-old woman was referred to our nephrology unit because of anuric acute renal failure. She had a history of ovarian adenocarcinoma treated in June 2001 by hysterectomy, ovariectomy and chemotherapy. Carboplatin and paclitaxel (six cycles) had been stopped in November 2001. In November 2002, oxaliplatin (85 mg/m2) and gemcitabine (1.5 g) were introduced. Three months before presentation, serum creatinine was 73 µmol/l (0.8 mg/dl).

On admission, after 10 cycles of oxaliplatin and gemcitabine, her blood pressure was 120–70 mmHg and she weighed 47.5 kg. Physical examination was normal. Serum creatinine was 1126 µmol/l and blood urea was 44.1 mmol/l. Haemoglobin was 9.8 g/dl and platelets were 64.000/mm3. Haptoglobin was 1.27 g/l. Renal sonography finding was normal. No monoclonal component could be detected in the blood. Circulating immune complexes, antinuclear antibody, rheumatoid arthritis haemaglutinin titre, antitubular basement membrane antibody and antineutrophil cystoplasmic antibody were negative. The patient required three haemodialysis sessions. On renal biopsy, severe tubular necrosis was observed with denudation of tubular basement membranes, cell fragments and red cells in the tubular lumen, and cellular dismorphy (Fig. 1). In the interstitium, only mild oedema was observed without cellular infiltration. Most of the glomeruli are ischaemic. Immunofluoresence study did not show specific deposits. Six weeks after admission, serum creatinine level was 1.09 mg/dl (120 µmol/l). Six months later, serum creatinine level was still 89 µmol/l (1.0 mg/dl).



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Fig. 1. Severe tubular necrosis and red cells in the tubular lumen.

 
In this case, oxaliplatin is very likely to have been responsible for acute renal failure. There was a close temporal relationship between the onset of renal failure and oxaliplatin administration. Renal biopsy showed severe tubular lesion necrosis, which corresponds to the spectrum of adverse effects reported on primary cultures of rabbit proximal tubular cells [4] and also in the first case report [1]. Besides oxaliplatin, the patient had been taking gemcitabine — drugs implicated in thrombotic microangiopathy [3], a diagnosis that was ruled out by the renal biopsy.

This case report points out that the spectrum of oxaliplatin side effects also includes reversible acute renal failure with tubular necrosis. Factors predisposing to nephrotoxicity are unknown; they would include concomitant administration of a nephrotoxic drug, but the patient had previously received oxaliplatin with gemcitabine without any renal damage. Gemcitabine was always given before oxaliplatin. An animal study [5] suggested that the administration of gemcitabine prior to cisplatin aggravates cisplatin-induced nephrotoxicity. Pinotti [1] also suggests that the renal damage could have been caused by a cumulative dose of oxaliplatin (in our case 1210 mg).

Internists, oncologists and nephrologists must be aware of this possible complication and we recommend monitoring of renal function in these patients.

Conflict of interest statement. None declared.

Jacques Labaye1, Damien Sarret1, Christan Duvic1, Michel Hérody1, Francis Didelot1, Georges Nédélec1 and Laure-Hélène Noël2

1 Armed Forces Hospital of Val de Grâce Paris France2 INSERM U507 Hôpital Necker (AP-HP) Paris France Email: jah.labaye{at}wanadoo.fr

References

  1. Pinotti G, Martinelli B. A case of acute tubular necrosis due to oxaliplatin. Ann Oncol 2002; 13: 1951–1952[Free Full Text]
  2. Aapro MS, Martin C, Hatty S. Gemcitabine—a safety review. Anticancer Drugs 1998; 9: 191–201[ISI][Medline]
  3. Gietema JA, Groen HJM, Meijer S, Smit EF. Effects of gemcitabine on renal function in patients with non-small cell lung cancer. Eur J Cancer 1998; 34: 199–202[CrossRef][ISI][Medline]
  4. Legallicier B, Leclere C, Monteil C, Morin JP, Fillastre JP. Action toxique de deux agents antitumoraux dérivés du platine, le cisplatine et l’oxaloplatine sur des cultures primaires de cellules tubulaires proximales de rein de lapin. Pathologie Biologie 1993; 41: 873–880[ISI][Medline]
  5. Saad SY, Najjar TA, Noreddin AM, Al-Rikabi AC. Effects of gemcitabine on cisplatin-induced nephrotoxicity in rats: schedule-dependent study. Pharmacol Res 2001; 43: 193–198[CrossRef][ISI][Medline]




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