lisinopril and Polycystic-Kidney--Autosomal-Dominant

Hypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. Dual blockade of the RAAS may circumvent compensatory mechanisms that limit the efficacy of monotherapy with an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin II-receptor blocker (ARB).. In this double-blind, placebo-controlled trial, we randomly assigned 486 patients, 18 to 64 years of age, with ADPKD (estimated glomerular filtration rate [GFR], 25 to 60 ml per minute per 1.73 m(2) of body-surface area) to receive an ACE inhibitor (lisinopril) and placebo or lisinopril and an ARB (telmisartan), with the doses adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg. The composite primary outcome was the time to death, end-stage renal disease, or a 50% reduction from the baseline estimated GFR. Secondary outcomes included the rates of change in urinary aldosterone and albumin excretion, frequency of hospitalizations for any cause and for cardiovascular causes, incidence of pain, frequency of ADPKD-related symptoms, quality of life, and adverse study-medication effects. Patients were followed for 5 to 8 years.. There was no significant difference between the study groups in the incidence of the composite primary outcome (hazard ratio with lisinopril-telmisartan, 1.08; 95% confidence interval, 0.82 to 1.42). The two treatments controlled blood pressure and lowered urinary aldosterone excretion similarly. The rates of decline in the estimated GFR, urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, were also similar in the two groups.. Monotherapy with an ACE inhibitor was associated with blood-pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study B] ClinicalTrials.gov number, NCT01885559.).

Topics: Adolescent; Adult; Albuminuria; Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Pressure; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney Failure, Chronic; Lisinopril; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Renal Insufficiency, Chronic; Telmisartan; Young Adult

Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin-angiotensin-aldosterone system, and progression of kidney disease.. In this double-blind, placebo-controlled trial, we randomly assigned 558 hypertensive participants with ADPKD (15 to 49 years of age, with an estimated glomerular filtration rate [GFR] >60 ml per minute per 1.73 m(2) of body-surface area) to either a standard blood-pressure target (120/70 to 130/80 mm Hg) or a low blood-pressure target (95/60 to 110/75 mm Hg) and to either an angiotensin-converting-enzyme inhibitor (lisinopril) plus an angiotensin-receptor blocker (telmisartan) or lisinopril plus placebo. The primary outcome was the annual percentage change in the total kidney volume.. The annual percentage increase in total kidney volume was significantly lower in the low-blood-pressure group than in the standard-blood-pressure group (5.6% vs. 6.6%, P=0.006), without significant differences between the lisinopril-telmisartan group and the lisinopril-placebo group. The rate of change in estimated GFR was similar in the two medication groups, with a negative slope difference in the short term in the low-blood-pressure group as compared with the standard-blood-pressure group (P<0.001) and a marginally positive slope difference in the long term (P=0.05). The left-ventricular-mass index decreased more in the low-blood-pressure group than in the standard-blood-pressure group (-1.17 vs. -0.57 g per square meter per year, P<0.001); urinary albumin excretion was reduced by 3.77% with the low-pressure target and increased by 2.43% with the standard target (P<0.001). Dizziness and light-headedness were more common in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P=0.002).. In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard blood-pressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study A] ClinicalTrials.gov number, NCT00283686.).

Topics: Adolescent; Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Lisinopril; Male; Middle Aged; Organ Size; Polycystic Kidney, Autosomal Dominant; Telmisartan; Young Adult

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney condition and is associated with important renal and cardiovascular manifestations in childhood. Renal cystic disease can be documented in some cases as early as in utero. Early intervention is critical if the long-term complications of this condition, including end-stage renal disease, are to be ameliorated. Here we describe our ongoing randomized double-blind placebo-controlled phase III clinical trial to assess the effect of pravastatin treatment on renal and cardiovascular disease progression in 107 children and young adults age 8-22 years with ADPKD who are receiving the angiotensin converting enzyme inhibitor lisinopril. Baseline demographic and laboratory data are provided. Results of this study could markedly impact the standard of care for evaluation and treatment of ADPKD in this population.

Topics: Adolescent; Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Child; Disease Progression; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Hypertrophy, Left Ventricular; Kidney; Lisinopril; Male; Polycystic Kidney, Autosomal Dominant; Pravastatin; Renin-Angiotensin System; Young Adult

New research suggests that rigorous blood pressure control is beneficial in early autosomal dominant polycystic kidney disease (ADPKD). Although a positive effect on the rate of decline of estimated glomerular filtration rate remains to be demonstrated, this study is likely to change current treatment strategies for young patients with ADPKD.

Topics: Antihypertensive Agents; Benzimidazoles; Benzoates; Female; Humans; Hypertension; Kidney; Lisinopril; Male; Polycystic Kidney, Autosomal Dominant

Topics: Antihypertensive Agents; Benzimidazoles; Benzoates; Female; Humans; Hypertension; Kidney; Lisinopril; Male; Polycystic Kidney, Autosomal Dominant

Topics: Antihypertensive Agents; Benzimidazoles; Benzoates; Female; Humans; Hypertension; Kidney; Lisinopril; Male; Polycystic Kidney, Autosomal Dominant

Topics: Antihypertensive Agents; Benzimidazoles; Benzoates; Female; Humans; Hypertension; Kidney; Lisinopril; Male; Polycystic Kidney, Autosomal Dominant

Topics: Antihypertensive Agents; Benzimidazoles; Benzoates; Female; Humans; Hypertension; Kidney; Lisinopril; Male; Polycystic Kidney, Autosomal Dominant

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzimidazoles; Benzoates; Female; Humans; Hypertension; Kidney; Lisinopril; Male; Polycystic Kidney, Autosomal Dominant; Telmisartan

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Cyclic AMP; Enalapril; Hematuria; Humans; Lisinopril; Magnetic Resonance Imaging; Male; Polycystic Kidney, Autosomal Dominant; Vasopressins

Topics: Antihypertensive Agents; Dysgeusia; Female; Humans; Hypertension; Kidney Failure, Chronic; Lisinopril; Losartan; Middle Aged; Polycystic Kidney, Autosomal Dominant; Stomatitis, Aphthous

The pathogenesis of hypertension in autosomal-dominant polycystic kidney disease (ADPKD) is unclear, but increased activity of the renin-angiotension system may contribute. The renal and systemic hemodynamic response to lisinopril, an angiotension converting enzyme (ACE) inhibitor, in patients with ADPKD without renal failure was compared with the response in matched unaffected family members. Mean blood pressure and renal vascular resistance decreased in the affected group after lisinopril, with no significant change in the unaffected group. Glomerular filtration rate (GFR) was unchanged and therefore filtration fraction fell significantly. Changes in urinary excretion of 6-keto-PGF1 alpha and kallikrein suggested that increased renal synthesis of PGI2 or activation of the renal kallikrein-kinin system were not likely to be responsible for the hemodynamic effects. The acute decrease in renal vascular resistance without change in GFR suggests that ACE inhibition may have a particular value in the treatment of hypertension associated with ADPKD which should be assessed by further long-term studies.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Enalapril; Female; Glomerular Filtration Rate; Humans; Hypertension; Kallikreins; Lisinopril; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Renal Circulation; Renin; Vascular Resistance