Sección de Nefrología y1 Ginecología Hospital Alarcos Ciudad Real Spain Email: francisco.rivera{at}wanadoo.es
Sir,
A 21-year-old equadorian woman, previously healthy, was admitted to our hospital because of acute renal failure in her 30th week of pregnancy. Ten days before admission, she developed acute back pain with no urinary or intestinal symptoms. Without medical advice, she started treatment with oral magnesium dypirone (Nolotil®), 1.53 g/day for 10 days. Physical examination revealed a pale woman with generalized cutaneous rash and oedema. Supine blood pressure was 110/70 mmHg and abdominal palpation revealed that the size of the uterus corresponded to gestational week. Laboratory studies reported haemoglobin 8.9 g/dl, haematocrit 26%, creatinine 3.7 mg/dl, urea 117 mg/dl, white cell count 10 000 µl, with eosinophils 200 µl and platelet count 190 000 µl. Serum glucose 90 mg/dl, creatinine 3.7 mg/dl, urea 117 mg/dl, total proteins 5.6 g/l, bilirubin 3.2 mg/dl, AST 24 IU/l, ALT 9 IU/l, LDH 414 IU/l, CPK 11 IU/l and total alkaline phosphatase 311 IU/l. Antinuclear antibodies, c-ANCA, p-ANCA and anti-MBG were negative. Tests for serum antibodies to hepatitis C virus, hepatitis B surface antigen and anti-HIV were also negative. Serum levels of complement C3 and C4, serum immunoglobulins and TSH were normal. A renal ultrasound revealed normal sized and symmetric kidneys. Blood smear did not reveal schizocytes or eosinophilia. Urinary protein excretion was 0.8 g/24 h and the sediment revealed three red blood cells and leucocyturia. Obstetric ultrasound scan showed oligohydramnios with an amniotic fluid index of 2 (normal value 524.0 cm [1]). With parenteral fluids and discontinuation of magnesium dypirone the cutaneous rash disappeared, the amniotic fluid index was 6 and the blood analyses returned to normal. She delivered spontaneously without complications in the 42nd week.
We describe a case of acute renal failure and oligohydramnios induced by magnesium dypirone (metamizol, Nolotil®). Magnesium dypirone is a prostaglandin synthetase inhibitor widely used as analgesic or antipiretic drug. It is advised to be used with caution in pregnancy. Although other prostaglandin synthetase inhibitors have been associated with oligohydramnios [25], only in one case report has magnesium dypirone been involved where its use did not induce acute renal failure [6]. The mechanism of oligohydramnios with these drugs is unknown. It could be related to fetal oliguria due to the increase of arginine vasopressin in the fetal collecting duct induced by prostaglandin inhibition, as has been shown in animal models [7]. In our patient, the dose of self-administered magnesium dypirone was high, and probably part of the drug entered the fetal circulation transplacentally.
Magnesium dypirone can induce two different forms of acute renal failure: (i) reversible renal ischaemia secondary to inhibition of prostaglandin synthesis, appearing 37 days after initiation of therapy when drug levels inhibit prostaglandin synthesis [8]; and (ii) acute tubulointerstitial nephritis [9]. In our patient, the diagnosis of acute tubulointerstitial nephritis was made according to clinical and biochemical data as well as after a detailed history record, but both forms of renal disease associated with magnesium dypirone were probably present. Moreover, withdrawal of dypirone was associated with a dramatic improvement of renal function and the oligohydramnios, as has been described previously [6].
We conclude that magnesium dypirone may induce reversible acute renal failure and oligohydramnios in pregnancy. It should be used with caution, with monitoring of renal function and amniotic fluid volume.
Conflict of interest statement. None declared.
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