Pyrazinoic acid decreases peritoneal transfer rates

It was shown elsewhere that in a peritoneally dialyzed woman with pulmonary tuberculosis, oral treatment with rifampicin and pyrazinamide (11 and 25 mg/kg/day, respectively) caused a decrease in the peritoneal transport of sodium, potassium, urea, uric acid, protein, and ultrafiltration rate by 48% to 75% compared to the pretreatment values. Pyrazinoic acid (PA), a metabolite of pyrazinamide, may account for these changes, because rifampicin was also previously used in this patient without peritoneal function impairment. Thus in the present study the influence of PA on the human peritoneum is examined using the modified Ussing-type chamber. PA (1 mg/dL) was introduced into the medium on the interstitial side of the membrane. After the introduction of PA, uric acid transfer from the interstitial to the mesothelial side decreased by about 50%. There were no significant changes in the urea and albumin transfer rates. In conclusion, PA induces changes in uric acid transfer acting directly on mesothelial cells, whereas a decrease in the peritoneal transfer of other solutes may be caused by a decrease in convective transfer rates due to impaired ultrafiltration.