Renal damage during treatment with antirheumatic drugs.

Beta-N-acetyl glucosaminidase (NAG) is a lyosomal enzyme found in high concentrations in the epithelial cells of renal tubules. It is excreted in the urine of normal people, but much larger quantities are excreted by patients with renal disease,' those taking nephrotoxic drugs,' and those starting treatment with aspirin.3 Measuring NAG excretion may be a convenient way of assessing early damage to renal tubules: the output rises sharply within a few days of the onset of the insult. The present study used NAG excretion to explore the possibility that non-steroidal anti-inflammatory drugs other than aspirin might also damage renal tubules. Enzyme excretion was also monitored in patients with rheumatoid arthritis receiving long-term treatment with D-penicillamine or levamisole. Normal subjects, or patients with osteoarthritis but no renal disease or hypertension, were included in the first study. Aliquots of urine were obtained before giving the drugs, and again at intervals during the course of treatment. The drugs studied were aspirin, diflunisal, indomethacin, ibuprofen, naproxen, and azopropazone in their usual therapeutic doses. Aspirin and diflunisal were tested in both high-and low-dose regimens. In a second study, patients with rheumatoid arthritis starting treatment with D-penicillamine or levamisole were observed for intervals up to six months. Measurements of disease activity were observed over the same period. Specimens were stored at 4°C before analysis by the fluorimetric method of Tucker et al.4 The results are shown in the table. No significant increase in NAG excretion was seen with the lower dose of aspirin or diflunisal, but concentrations were appreciably increased with higher dosage, this effect being sustained at six weeks. In tests on patients taking the other non-steroidal anti-inflammatory drugs, no increase in urinary excretion of NAG was observed. When patients with rheumatoid arthritis were treated with either D-penicillamine or levamisole a significant fall in NAG excretion was observed by the 12th week, and maintained at 26 weeks. This decrease seemed to correlate with improvement in clinical estimates of disease activity. No increase in NAG excretion was observed in eight other patients receiving D-penicillamine who developed proteinuria. Comment Aspirin has a dramatic acute effect on the excretion of renal tubular cells and enzymes, but its long-term effects on the kidney are small, and probably of little clinical importance.4 Nevertheless, it has been suggested that other, newer analgesic anti-inflammatory drugs might also be nephrotoxic, highlighting the need for a sensitive test of early renal changes. NAG excretion is …