Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease

Abstract

BACKGROUND 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. METHODS 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 m2 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. RESULTS 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). CONCLUSIONS 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.

Stop chronic kidney disease progression: Time is approaching

“…According to KDIGO guidelines, BP should be kept at 130/80 mmHg or lower [91] . A much lower BP (less than 110/75 mmHg) is associated with slower rate of annual increase in kidney size and urine protein excretion rate in early cases of ADPKD as shown by a recent study, HALT-PKD [92] . The strict control of blood sugar has a positive impact on survival of pre-dialysis diabetic CKD patients.…”

“…The first phase 3 prospective doubleblinded clinical study of tolvaptan (vasopressin receptor antagonist, V2-receptor antagonist) demonstrated a significant slowing in the rate of increase in total kidney volume and the decline in kidney function over a 3-year period compared to placebo in patients with ADPKD [19] . These results beside the more recent trial on BP, HALT-PKD [92] , open a big hope to ADPKD patients, especially if their disease is checked in early stages.…”

New options in the treatment of autosomal dominant polycystic kidney disease

“…18 One arm of the study involved 558 patients with GFR values more than 60 mL/min who were randomized to either standard blood pressure group or low blood pressure group the two of each being randomized further to either lisinopril + telmisartan or lisinopril + placebo. 19 Patients in the low blood pressure group had slower increase in total kidney volume (38% vs. 44.2%) especially in younger men with larger kidneys. Patients in the low blood pressure group had greater GFR decline in the short term but similar degree of decline in GFR in long term; greater reduction in left ventricular mass and proteinuria.…”

Two autosomal dominant polycystic kidney (ADPKD) cases with advanced renal dysfunction, effectively treated with tolvaptan

“…A recent study showed that rigorous blood pressure control is associated with a slower increase in total kidney volume and no overall change in the estimated GFR as compared with standard blood pressure control [18]. Cyst expansion results in a decrease in renal blood flow (RBF) [19], and in these two cases, RBF was slightly decreased in comparison to GFR and filtration fractionation (FF) was slightly increased.…”