In patients with autosomal dominant polycystic kidney disease, the rate of increase in total kidney volume was not slowed by lisinopril and telmisartan, as compared with lisinopril and placebo, but was slowed with rigorous blood-pressure control.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by gradual cyst enlargement over a period of decades before the loss of kidney function. Hypertension occurs early and is associated with progression to end-stage renal disease (ESRD) and death from cardiovascular causes in patients with ADPKD. Immunohistologic studies and clinical studies support a central role of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of hypertension in patients with ADPKD. It is unclear whether more aggressive antihypertensive therapy or an increased use of RAAS inhibitors delays progression to ESRD in patients with ADPKD.
• Does rigorous blood pressure control confer benefits in young patients with early ADPKD?
In the study by Schrier et al., 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. Participants in the low-blood-pressure group had a 14.2% slower annual increase in total kidney volume, as compared with those in the standard-blood-pressure group (5.6% vs. 6.6%, P=0.006). Patients younger than 30 years of age with the largest kidneys were more likely to benefit from rigorous blood-pressure control than were patients of similar age with smaller kidneys. Men, but not women, also had evidence of a benefit from low blood pressure.
Figure 2. Changes in Total Kidney Volume and Estimated Glomerular Filtration Rate (eGFR) during Follow-up, and Subgroup Analyses, According to Blood-Pressure Group.
• Is there a benefit to dual blockade of the RAAS in patients with autosomal dominant polycystic kidney disease?
Lisinopril-telmisartan treatment did not show a benefit, as compared with lisinopril alone, with regard to the change in total kidney volume or estimated GFR. The total kidney volume increased at similar rates in the lisinopril-telmisartan group and the lisinopril-placebo group (6.0% per year and 6.2% per year, respectively; P=0.52). Urinary albumin excretion remained unchanged in the two treatment groups. A significant and similar decline from baseline in the left-ventricular-mass index occurred in the two groups. Renal blood flow decreased and renal vascular resistance increased similarly in the two groups.
Figure 3. Changes in Total Kidney Volume and eGFR during Follow-up, and Subgroup Analyses, According to Treatment Group.
Morning Report Questions
Q: Were there significant between-group differences with respect to adverse events?
A: The proportion of patients with one or more episodes of dizziness and light-headedness at the end of the study was greater in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P=0.002). The frequencies of death, serious cardiovascular or renal events, hyperkalemia, acute kidney injury, and cancer did not differ significantly between the two groups. The proportion of patients who had one or more serious adverse events and symptoms was similar in the two groups.
Table 2. Adverse Events in the 2-by-2 Factorial-Design Trial.
Q: What do the authors conclude about the lack of improvement in the slope of the estimated GFR in cases where treatment decreased the rate of increase in total kidney volume?
A: A beneficial effect on cyst burden (rate of total kidney-volume growth) was not associated with an improvement in the slope of the estimated GFR. Whether a time lag between the therapeutic effect on total kidney volume and stabilization of the estimated GFR occurs in patients with ADPKD is not yet known. Given the combination of the decline in the estimated GFR in the short-term phase and a potential temporal delay between the change in total kidney volume and the change in the estimated GFR, this study was not of sufficient size or duration to show a potential benefit of blood-pressure control on kidney function.