Caffeine augments proteinuria in puromycin-aminonucleoside nephrotic rats

Several studies indicate that increased intrarenal adenosine concentrations may attenuate puromycin-aminonucleoside (PAN)-induced nephropathy in rats. The purpose of this study was to investigate the chronic effects of caffei ne, a nonselective adenosine receptor antagonist, on renal function and str ucture in PAN-induced nephropathy. Animals were randomized to receive drink ing water or 0.1% caffeine solution. PAN was administered in two doses to a subset from each group at 1 week (100 mg/kg, sc.; Purom-1) and 15 wks (80 mg/kg, sc.; Purom-2) after initiating caffeine treatment (PAN and GAFF-PAN groups). The remaining animals served as time controls (CON and GAFF groups ). Renal excretory function was followed for 23 wks. Caffeine consumption s ignificantly augmented PAN-induced proteinuria after both PAN injections (P urom-1 and Purom-2, p < 0.05 and p < 0.001 respectively; GAFF-PAN vs. PAN). In addition, caffeine potentiated the transient reduction in creatinine cl earance (CrCl) induced by PAN. Caffeine consumption for 23 wks significantl y reduced CrCl in conscious nephrotic animals (4.76 +/- 0.98 vs. 8.51 +/- 1 .55 L/kg/day, GAFF-PAN vs. PAN). Seven days after both PAN injections, incr eased plasma renin activity was detected in animals that were consuming caf feine as compared with corresponding control groups (CAFF and CAFF + PAN vs CON and PAN, respectively). Eight weeks after the second injection of PAN, acute measures of renal hemodynamic and excretory function were compared i n anesthetized animals and renal samples were analyzed for histological cha nges; In PAN-rats, caffeine treatment for 23 weeks significantly reduced in ulin clearance (0.28 +/- 0.09 vs. 0.57 +/- 0.12 mL/min/gr kidney, GAFF-PAN vs PAN. p < 0.05). tended to increase renal vascular resistance (59.0 +/- 9 .5 vs. 42.9 +/- 5.5 mmHg/mL/min/gr kidney, GAFF-PAN vs. PAN, p < 0.06), pot entiated the development of more severe tubulointerstitial damage (tubular atrophy, presence of proteinaceous material, tubular dilatation. interstiti al inflammation, interstitial fibrosis), and tended to increase glomerulosc lerosis. In conclusion, this study indicates that caffeine adversely affect s renal function in PAN-nephrotic rats, and that this effect may be due, in part, to increased activity of the renin angiotensin system.