Probenecid-induced membranous nephropathy

Résumé fourni par la source

Sir, Nephrotic syndrome (NS) associated with probenecid therapy for gout has been previously reported [1–4]. Minimal or no abnormalities were seen on renal tissue examination. We report the first case of membranous nephropathy (MN) induced by probenecid therapy. A 79-year-old white man was admitted for pitting oedema. His past history was remarkable for familial gout. He had been treated for the previous year with probenecid (500 mg twice daily), because of allopurinol intolerance. Serum acid uric level decreased from 10.92 mg/l to 5.88 mg/l. He denied taking any other drugs and was not exposed to industrial chemicals. One month previously, routine examination revealed blood pressure 120/70 mmHg, negative urinalysis and serum creatinine level 1.1 mg/dl, but an increase in serum uric acid to 8.4 mg/l. Probenecid daily dose was increased to 1500 mg. Two weeks later, his weight had further increased, and gross pitting oedema was noted. Urinalysis revealed a ++++ test for protein and a negative test for red blood cell. Other laboratory studies included a 24 h protein excretion of 5.5g and serum albumin 2.2g/dl. Renal biopsy was done with the diagnosis of MN (Figure 1). There was no evidence of any disease (negative check-up for thoracoabdominal CT scan, cystoscopy, colonoscopy and immunological tests) or drug therapy usually associated with MN, and no other evidence of an allergic response to probenecid. Drug was discontinued and within 6 weeks, the urine was free of protein and the patient was oedema-free. (A) Light microscopy showed non-specific changes, the capillary loops somewhat rigid and minimally thickened (B) silver straining confirmed patchy thickening of the glomeruli basement membrane, with some spikes but no double contours were seen (C) Immonofluoresence demonstrated strong membranes fine granular IgG deposition. NS associated with probenecid therapy for gout has been described previously in five patients [1–4]. Ferris et al. [1] described the case of a man who within 4 months of starting treatment with probenecid developed NS, which disappeared when the drug was stopped. NS reappeared and recovered on two occasions, when probenecid was re-introduced and withdrawn, successively. Renal biopsy was not performed. Sokol et al. [2] described a similar patient who developed NS 3 months after starting probenecid. Recovery followed withdrawal, and the same sequence was repeated when probenecid was re-introduced. Renal biopsy showed no abnormality apart from precipitated protein in Bowman's spaces and in the convoluted tubules. Scott and O’Brien [3] reported two patients who developed oedema and proteinuria 8 and 15 months after starting treatment with probenecid. In one patient, rapid recovery from a full NS followed withdrawal of probenecid. Renal biopsy showed a few foci of tubular atrophy and fibrosis without crystal spaces. The second patient continued to take the drug and died in renal failure. Post-mortem examination revealed widespread dilatation of cortical tubule and crystals were found in collecting tubules and in the interstitium. No glomerular abnormalities were seen in any of these patients. Finally, Hertz et al. [4] described the case of a man who within 5 months of starting treatment with probenecid developed NS, which disappeared 3 weeks after the drug was stopped. Minimal change nephropathy was suspected on electron microscopy, showing a coalescence of foot processes over normal glomerular basement membranes. In our patient, NS developed 1 year after probenecid therapy started, but 2 weeks after increasing the daily dose. As in four of the five previously reported cases, the nephrosis disappeared soon after administration of the drug was stopped. In our patient case, the nephrotic syndrome remission might be explained by the natural evolution of MN. However, the fact that proteinuria appeared 15 days following the introduction of treatment, and disappeared 6 weeks after stopping, leads us to believe that a cause–effect relationship between the drug and the clinical profile exists. We deemed it unethical to re-introduce the molecule to test for imputability. Drug-induced MN included gold salts, d-penicillamine and high-dose captopril [5]. Probenecid should be added to this list. However, the drug has been in widespread use for over half a century and renal complications remain very rare. Conflict of interest statement. None declared.

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