Noramidopyrine (Metamizol) and acute interstitial nephritis.

Abstract

amount ingested: 30 g). On admission his serum creatiIntroduction nine and blood urea nitrogen (BUN) were 4.5 mg/dl and 39 mg/dl respectively. Urinalysis revealed 30 mg/dl Noramidopyrine (Metamizol ) is a non-narcotic, protein, 3+ positive for blood (dipstick), and 5–10 analgesic and antipiretic pyrazolone derivative which red blood cells and 3–5 white blood cells per highbelongs to the non-steroidal anti-inflammatory class power field in the sediment. During the second hospital of drugs (NSAID) [1]. This drug is used, even if day he developed oliguria (200 ml/day); his serum subject to limitations, in Germany, Spain and Italy, creatinine and BUN were 9.2 mg/dl and 52 mg/dl and in many South American Countries. It is prohibrespectively. ited in other countries because of its capacity to induce On the third day after admission the patient was agranulocytosis and aplastic anaemia. In addition to referred to our unit. Blood pressure and pulse were its effects on bone marrow, noramidopyrine may also 130/80 mmHg and 68 beats/min respectively; tempercause cutaneous reactions, allergic idiosyncratic reacature was 36.5°C. There were no skin eruptions or tions such as bronchospasm, anaphylactic shock, toxic lymphadenopathy. Auscultation and percussion of the epidermal necrolysis [2], and severe hypotension [3]. chest were within normal limits. Serum creatinine In addition to acute renal failure (ARF) secondary to and BUN were increased to 12.7 mg/dl and 70 mg/dl loss of counterregulatory prostaglandins during plasma respectively. Serum Na was 138 mEq/l, K 4.4 mEq/l, volume contraction, acute interstitial nephritis is a Ca 7.9 mg/dl and P 5 mg/dl. Arterial pH was 7.348, well-recognized side-effect of NSAIDs [4]. However, pCO2 37.2 mmHg and [HCO3 ] 20.1 mmo/l. Haemwhile both the clinical and pathological changes occuratological evaluation revealed an haematocrit of 32%; ring in acute interstitial nephritis induced by NSAIDs haemoglobin at 11.3 g/dl and a leukocyte count of are well recognized, reports on the renal toxicity of 7800/mm3 with a small increase in the eosinophil count noramidopyrine are scant and the renal effects of this (580 cells/mm3). Blood cultures and a urine culture drug have not been thoroughly evaluated. revealed no growth. Serological studies were unrevealWe report on a case of acute renal failure due to ing. C3, C4, IgG, IgA, IgM, ANCA, ANA tests, and acute interstitial nephritis (AIN) following the ingescryoglobulins were within normal limits or undetecttion of a self-prescribed mega-dose of noramidopyrine able. Total IgE was 397 mg/dl (normal 12–240). Bence in an otherwise healthy man. Jones proteinuria was absent. Urinalysis revealed proteinuria (1 g/l ) and a moderate number of white blood Case cells, with no eosinophiluria and occasional red blood cells, hyaline-granular casts and no glucosuria. A further renal sonogram showed an increase in kidney size An otherwise healthy 45-year-old man was admitted (approximately 13 cm in length each). to another hospital with complaints of lumbar pain A percutaneous renal biopsy was performed 2 days and oliguria. The man was an entrepreneur in good after hospitalization (Figures 1 and 2). The specimen physical fitness and had routinely received yearly physrevealed 15 glomeruli, all appearing normal. There was ical examinations. About 1 year before, his serum severe diffuse mononuclear and moderate eosinophil creatinine was 1.1 mg/dl with a normal urinalysis. interstitial infiltration, with focal invasion and disrupFive days before his admission he had developed tion of the epithelium of proximal and distal tubules. malaise, fever (39°C) and headache. To relieve his The vessels were normal. Immunofluorescence examsymptoms he had taken noramidopyrine (three 20 ml ination showed no glomerular or tubular immunobottles, 0.5 g/ml ) over two consecutive days (total globulin or complement deposits. A diagnosis of acute interstitial nephritis was made. Correspondence and offprint requests to: Giacomo Garibotto MD, The patient was treated with pulse methylpredDipartimento di Medicina Interna, Divisione di Nefrologia, Viale Benedetto XV, 6, I-16132 Genova, Italy. nisolone (500 mg daily for 3 days) followed by oral