atrial-natriuretic-factor and Polycystic-Kidney--Autosomal-Dominant

Hypertension is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD), often occurring early in the disease before the renal function starts to decrease. The pathogenesis of this early hypertension is controversial.. To review studies on the pathogenesis of early and late hypertension in ADPKD.. Studies on ADPKD and hypertension were retrieved from Medline from the last 20 years, with an emphasis on the last 10 years. These studies, together with selected published abstracts from recent hypertension and nephrology meetings, were reviewed critically.. Cyst growth, renal handling of sodium, activation of the renin-angiotensin-aldosterone system, volume expansion, an elevated plasma volume, and increased plasma atrial natriuretic peptide and plasma endothelin levels have all been found to be associated with hypertension in ADPKD. In some studies an inappropriate activity of the renin-angiotensin-aldosterone system that could be related to cyst growth and intrarenal ischemia was found. An increase in renal vascular resistance has been demonstrated and might be caused by intrarenal release of angiotensin II. Interestingly, the protective effect of angiotensin converting enzyme inhibitors on the renal function could not be demonstrated in ADPKD patients with a moderately decreased renal function. The importance, if any, of endothelial vasodilatory factors is not known. Sympathetic nervous activity seems to be increased in ADPKD, but the importance of this for the blood pressure level is not known.. The pathogenesis of hypertension in ADPKD is complex and likely to be dependent on the interaction of hemodynamic, endocrine and neurogenic factors.

Topics: Atrial Natriuretic Factor; Blood Pressure; Endothelium, Vascular; Hemodynamics; Humans; Hypertension; Kidney Tubules; Polycystic Kidney, Autosomal Dominant; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

Topics: Animals; Atrial Natriuretic Factor; Hemodynamics; Humans; Hypertension; Kidney Tubules; Polycystic Kidney, Autosomal Dominant; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

Renal handling of sodium and water is abnormal in chronic kidney diseases. To study the function and regulation of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in autosomal dominant polycystic kidney disease (ADPKD), we measured urinary excretion of AQP2 (u-AQP2), the β-subunit of ENaC (u-ENaC(β)), cAMP (u-cAMP), and prostaglandin E(2) (u-PGE(2)); free water clearance (C(H2O)); fractional sodium excretion (FE(Na)); and plasma vasopressin (p-AVP), renin (p-Renin), angiotensin II (p-ANG II), aldosterone (p-Aldo), and atrial and brain natriuretic peptide (p-ANP, p-BNP) in patients with ADPKD and healthy controls during 24-h urine collection and after hypertonic saline infusion during high sodium intake (HS; 300 mmol sodium/day) and low sodium intake (LS; 30 mmol sodium/day). No difference in u-AQP2, u-ENaC(β), u-cAMP, u-PGE(2), C(H2O), and vasoactive hormones was found between patients and controls at baseline, but during HS the patients had higher FE(Na). The saline caused higher increases in FE(Na) in patients than controls during LS, but the changes in u-ENaC(β), p-Aldo, p-ANP, p-BNP, p-Renin, and p-ANG II were similar. Higher increases in u-AQP2 and p-AVP were seen in patients during both diets. In conclusion, u-AQP2 and u-ENaC(β) were comparable in patients with ADPKD and controls at baseline. In ADPKD, the larger increase in u-AQP2 and p-AVP in response to saline could reflect an abnormal water absorption in the distal nephron. During LS, the larger increase in FE(Na) in response to saline could reflect a defective renal sodium retaining capacity in ADPKD, unrelated to changes in u-ENaC(β).

Topics: Adolescent; Adult; Aged; Aldosterone; Angiotensin II; Aquaporin 2; Atrial Natriuretic Factor; Chronic Disease; Cross-Over Studies; Cyclic AMP; Dinoprostone; Epithelial Sodium Channels; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Polycystic Kidney, Autosomal Dominant; Renin; Saline Solution, Hypertonic; Sodium; Vasopressins; Young Adult

We tested the hypothesis that overactivity of the renal and systemic renin-angiotensin system is important to the pathogenesis of hypertension in autosomal dominant polycystic kidney disease (ADPKD). Up to 21 normotensive subjects with ADPKD and creatinine clearance > 70 ml/min/1.73 m2 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 measured at baseline, after acute sodium depletion, and after chronic higher sodium intake with and without enalapril. Effective renal plasma flow 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 essential hypertension, renal blood flow would fall to a lesser extent in the ADPKD subjects. The groups were comparable at baseline apart from a higher supine mean arterial pressure in the ADPKD group (median 91 vs. 81 mm Hg, P = 0.002). There were no significant differences between ADPKD and control subjects in blood pressure or hormonal response to 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 vascular resistance (median 7420 vs. 5915 dyn.sec.cm-5, P = 0.009) before angiotensin, but tended to have a lower percentage rise in resistance during angiotensin (median 31.5 vs. 46, P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Enalapril; Female; Humans; Hypertension; Male; Middle Aged; Models, Biological; Polycystic Kidney, Autosomal Dominant; Renal Circulation; Renal Plasma Flow, Effective; Renin-Angiotensin System; Sodium, Dietary; Vascular Resistance

We studied young adults with autosomal dominant polycystic kidney disease (ADPKD) to determine the characteristics that precede renal impairment. Nineteen affected (A) and 20 unaffected (U) offspring from families with ADPKD showed no significant differences in basal glomerular filtration rate (A: mean 97, SD 19; U: 100, SD 23 ml/min/1.73 m2) or renal functional reserve, but effective renal plasma flow was significantly lower in affected offspring (A: 532, SD 86; U: 605, SD 118 ml/min/1.73 m2, P less than 0.01). Plasma renin activity [A: median 26 (95% CI: 15 to 37); U: 14 (11 to 27) microU/ml, P less than 0.05, one-tailed test] and aldosterone [A: 2.5 (2.0 to 3.0), U: 1.0 (1.5 to 2.0) micrograms/100 ml, P less than 0.04, one-tailed test] were increased in affected offspring despite the higher systolic blood pressure (A: mean 123, SD 5; U: 115, SD 3 mm Hg, P less than 0.02) and significant expansion of total exchangeable sodium (A: 40.8, SD 2.3; U: 38.0, SD 3.5 mmol/kg, P less than 0.01). The ouabain-sensitive component of red cell sodium efflux was less in affected offspring (A: 0.258; SD 0.040; U: 0.288, SD 0.042 hr-1, P less than 0.04) and in both groups was correlated inversely with total exchangeable sodium. Echocardiography revealed no difference in left ventricular mass index nor prevalence of mitral valve prolapse. Potential cyst growth factors such as the glucocorticoids and somatomedin C were similar in both affected and unaffected groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aldosterone; Atrial Natriuretic Factor; Dietary Proteins; Genes, Dominant; Glomerular Filtration Rate; Hemodynamics; Humans; Insulin-Like Growth Factor I; Kidney; Polycystic Kidney, Autosomal Dominant; Potassium; Renal Circulation; Renin; Sodium