DIFFERENCES IN HORMONAL AND RENAL VASCULAR-RESPONSES BETWEEN NORMOTENSIVE PATIENTS WITH AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE AND UNAFFECTED FAMILY MEMBERS

We tested the hypothesis that overactivity of the renal and systemic r enin-angiotensin system is important to the pathogenesis of hypertensi on in autosomal dominant polycystic kidney disease (ADPKD). Up to 21 n ormotensive subjects with ADPKD and creatinine clearance >70 ml/min/1. 73 m(2) were compared to 12 unaffected controls from the same families . Blood pressure, serum chemistry, sodium excretion, plasma renin and serum aldosterone and atrial natriuretic peptide (ANP) levels were mea sured at baseline, after acute sodium depletion, and after chronic hig her sodium intake with and without enalapril. Effective renal plasma f low was measured by paraaminohippurate clearance in the higher sodium state, before and during an intravenous infusion of angiotensin II at 3 ng/kg/min. This was to test whether, by analogy to non-modulating es sential hypertension, renal blood flow would fall to a lesser extent i n the ADPKD subjects. The groups were comparable at baseline apart fro m a higher supine mean arterial pressure in the ADPKD group (median 91 vs. 81 mm Hg, P = 0.002). There were no significant differences betwe en ADPKD and control subjects in blood pressure or hormonal response t o sodium depletion. During chronically higher sodium intake, serum ANP was significantly higher (median 130 vs. 81 ng/liter, P = 0.0006) and plasma renin tended to be higher (median 20.5 vs. 13.5, P = 0.08) in ADPKD than in control subjects. The ADPKD group had a higher renal vas cular resistance (median 7420 vs. 5915 dyn.sec.cm(-5), P = 0.009) befo re angiotensin, but tended to have a lower percentage rise in resistan ce during angiotensin (median 31.5 vs. 46, P = 0.14). The percent fall in effective renal plasma flow during angiotensin was lower in the AD PKD subjects (17 vs. 23, P = 0.04) and renal plasma flow fell by <120 ml/min/1.73 m(2) in 8 of 13 with ADPKD versus 2 of 10 controls (P = 0. 06). The relative insensitivity of the renal vasculature to exogenous angiotensin II in normotensive subjects with ADPKD is consistent with down-regulation of receptors due to tonically increased intrarenal ang iotensin levels. Given the higher blood pressure and ANP levels, the p lasma renin values were also inappropriately high in the ADPKD subject s. We conclude that increased intrarenal and possibly systemic renin-a ngiotensin system activity precedes and may contribute to the developm ent of hypertension in ADPKD.