Effect of pyrazinamide and probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis

Objective:We administered pyrazinamide (PZA) and probenecid (PB) - two well -known modulators of urate transport via the proximal tubules - to evaluate their impact on urate transport through the peritoneal membrane and to cla rify mechanisms affecting peritoneal transport. Setting: A continuous ambulatory peritoneal dialysis (CAPD) unit in 2nd Hos pital of IKA (Social Services Institute), Greece. Patients: In 20 stable CAPD patients, on the study day, a 4-hour, 2-L, 1.36 % glucose exchange was performed (control exchange). Pyrazinamide 3 g was g iven orally and another identical exchange was performed (study exchange). The same protocol was repeated with 2 g PB. Kt/V, peritoneal clearances of urea, creatinine, and urate for each exchange, and mass transfer area coeff icients (MTAC) for the three solutes and their dialysate-to-plasma concentr ation (D/P) ratios were used to estimate peritoneal transport. Results: Administration of PZA resulted in decreased clearances and MTAC va lues for the three solutes. The D/P ratio decreased significantly only for urate, indicating a more intense influence of PZA on urate. After PB admini stration, clearances of urea, creatinine, and urate were increased. MTAC an d DIP ratio increased significantly only for urate (p < 0.05), demonstratin g an action similar to that exerted on renal tubules. * Conclusions: These findings provide evidence that unrestricted diffusion is not the only transport mechanism in the case of urate, and demonstrate the existence of an active mechanism in peritoneal urate transport with a reab sorptive and, probably, a secretive component that resembles that of renal tubule urate transport. Attention should be given in the case of CAPD patie nts undergoing antituberculous (PZA) treatment: it might have a negative im pact on urea, creatinine, and urate peritoneal transport rates.