Schrier et al. evaluated high blood pressure concerns in early autosomal dominant polycystic kidney disease (ADPKD) (Schrier, 2014). The authors wanted to evaluate the efficacy and safety of combined treatment with two pharmaceuticals versus the use of one pharmaceutical. Lisinopril, an angiotensin converting enzyme inhibitor and telmisartan, an angiotensin receptor blocker was used versus just lisinopril by itself. They hypothesized and tested the impact of dual blockade of the RAAS on total kidney volume growth and estimated GFR (Schrier et al., 2014).
Using a previously published trial design of clients from seven clinical locations, data was collected between February 2006 to June 2009; with the last study visit conducted on June 2014 (Schrier et al., 2014). The basic methodology and design consisted of a sample size of 1,156 screened participants with informed consent; 558 participants went through the randomization process where they were randomly assigned either lisinopril and a placebo or lisinopril and telmisartan; this was done using a one to one ratio, along with standard versus low blood pressure goals for patients between the ages of 15 and 49 with ADPKD already diagnosed (Schrier et al., 2014). Blood pressure rates were between 120/70 up to 130/80 mmHg on the high end; and the low blood pressure targets were between 95/60 and 110/75; The participants had glomerular filtration rates, GFR, of greater than 60 millimeters per minute per 1.73 m2 of the total body surface (Schrier et al., 2014). The authors’ primary outcome metric was the percentage change in the total kidney volume over time; the rate of change in the estimated GFR was the first and secondary outcome, along with various other secondary outcomes measures.
The authors’ results consisted of 423 patients completing the trial based on the established protocol; the rest of the participants dropped out for various reasons including medication discontinuation, part-time participation, and no follow-up (Schrier et al., 20140). The two medication group had substantially lower mean standard deviations of treatment adherence, than the single drug and placebo group; there were no significant differences in baseline blood pressure metrics between the groups; there was, however, a difference in what measures were reported from home blood pressure monitoring for both groups (Schrier et al., 2014). Both groups had reduced urinary aldosterone excretion levels from the baseline levels until the study was completed (Schrier et al., 2014). The low blood pressure group had 14.2 percent less yearly increase in total kidney volume versus the standard blood pressure group; the total kidney volumes increased for both groups from baseline to 60 months, 38 percent represented the low blood pressure group and 44.2 percent represented the standard group (Schrier et al., 2014). The total kidney volume increased in like levels for both groups, and the estimated GFR did not change (Schrier et al., 2014).
Schrier et al. concluded that the dual medication did not deliver any benefits versus the single drug use of lisinopril that impacted total kidney volume changes, as well as GFR estimation (Schrier et al., 2014). Reduced urinary albumin excretion and increased total kidney volumes are associated with a faster pace towards end stage renal disease (Schrier et al., 2014). Younger patients with larger kidneys appeared to benefit at higher levels of rigorous blood pressure monitoring than the same age patients with smaller kidneys (Schrier et al., 2014). Men showed greater benefits of low blood pressure measures than women; GFR measures were impacted by the lack of documented creatinine measures when the study was completed, and the study drugs had been discontinued (Shrier et al., 2014). They further concluded that the rate of total kidney volume changes and increases, as well as the estimated GFR slope were not impacted by the dual blockade of the RAAS (Shrier et al., 2014). The authors’ conclusion appeared to be reasonable, but due to the lack of complete documentation about creatinine, the impact of the various variables and the slope change impacts appear to need additional information to agree or disagree with the authors.
- Schrier, R., Abebe, K., Perrone, R., Torres, V., Braun, W., & Steinman, T. et al. (2014). Blood Pressure in Early Autosomal Dominant Polycystic Kidney Disease. New England Journal Of Medicine, 371(24), 2255-2266. http://dx.doi.org/10.1056/nejmoa1402685