Renal injury in patients with rheumatoid arthritis treated with gold

Abstract

While severe nephrotoxicity is uncommon during Au therapy of rheumatoid arthritis (RA), the prevalence of mild nephrotoxicity has not been investigated. To study this, levels of leucine aminopeptidase (LAP) and N-acetyl-.beta.-glucosaminidase (NAG) (nmol/h per mg urinary creatinine), and B2-microglobulin (.beta.2M) (.mu.g/mg urinary creatinine) were measured in urine samples from 33 patients with RA receiving Au and 28 patients with various musculoskeletal diseases not receiving Au. Each patient had a normal urinalysis and blood urea N or serum creatinine. LAP was above 30 in 55% of RA patients and 7% of controls (P < 0.01). NAG was above 100 in 70% of RA patients and 14% of controls (P < 0.01). In 8 RA patients, NAG was over 200; LAP was over 100 in 4, but in none of the controls. .beta.2M was above 0.32 in 7 of 23 female RA patients and in none of 12 female controls (P = 0.012) and none of the male patients. Patients who excreted high levels of .beta.2M also excreted high levels of NAG and LAP. These data show that gold in therapeutic doses affects renal tubular cells, causing the release of NAG and LAP from lysosomes and brush borders of the cells. This may represent the mildest stage of nephrotoxicity. Elevated .beta.2M in the urine of some patients indicate a degree of nephrotoxicity sufficient to cause renal tubular dysfunction.