Among patients with established chronic kidney disease, the risk for progression to end-stage renal disease (ESRD) begins to rise with systolic blood pressure (SBP) above 140 mmHg and is highest among those with SBP greater than 150 mmHg. These findings, from the Kidney Early Evaluation Program (KEEP), were published in Archives of Internal Medicine (2012;172:41-47).
Although the results came from an observational study, they challenge currently recommended blood pressure targets, experts in the field suggested.
“Current guidelines recommend a blood pressure goal of less than 130/80,” said lead author Carmen A. Peralta, MD, MAS, Assistant Professor of Medicine in the Division of Nephrology at the University of California, San Francisco, in an interview. “They remain controversial because randomized, controlled trials comparing lower blood pressure goals with standard blood pressure goals have been largely null, except for persons with proteinuria.”
These lower blood pressure goals pose practical challenges, Dr. Peralta said.
“Prior work from our group and others showed that less than 45 percent of persons with CKD meet goals. In addition, in my own clinical practice, most persons require multiple medicines and attaining a blood pressure less than 130/80, which is the current recommendation, remains a difficult task.”
This new study adds support for a shift away from this low blood pressure target.
“In my opinion, the most important message for clinicians is that our efforts for blood pressure control and education as a community should and need to be targeted to persons whose blood pressure is highest risk—greater than 150,” Dr. Peralta said in an interview.
Lower Not Necessarily Better
The KEEP is a health-screening program of the National Kidney Foundation that aims to raise awareness of kidney disease among those at high risk for the condition, targeting adults who have hypertension, diabetes, or a family history of kidney disease. It is supported by Abbott, Amgen, Genentech, Genzyme, LifeScan, Nephroceuticals, Novartis, Pfizer, Siemens, and Suplena.
“The KEEP is the largest CKD screening program in the US,” Dr. Peralta said. “It has a very large sample size, and it includes high-risk persons from all over the US. KEEP is a resource to understand the kidney-related risks associated with blood pressure among persons in the community rather than a clinical trial setting.”
She and her team studied the associations of systolic blood pressure, diastolic blood pressure (DBP), and pulse pressure (PP) with risk of progression to ESRD in 16,129 KEEP participants who had an estimated glomerular filtration rate (eGFR) lower than 60 mL/min/1.73 m2.
Mean age was 69, mean systolic blood pressure was 139 mmHg, and mean diastolic blood pressure was 77 mmHg. Of the participants, 43% (n=6,936) had diabetes, and 93% (14,971) had hypertension.
In terms of self-identified race, about 25% of participants said they were non-Hispanic black, 6% reported they were Hispanic, 4% reported they were non-Hispanic Asian, and 5% reported other ethnicity.
The 4,486 individuals who had a systolic blood pressure of 150 mmHg or higher were older and more likely to have a public source of medical insurance, diabetes, albuminuria, and lower eGFR at baseline, with a mean eGFR of 46.8 mL/min/1.73 m2.
Over the median follow-up period of 2.87 years, 320 study participants progressed to ESRD. Higher systolic blood pressure was independently associated with a greater risk of ESRD among these patients with established chronic kidney disease.
After adjusting for age, sex, comorbidities, and sociodemographic factors, Dr. Peralta and colleagues found that only patients who had a systolic blood pressure of 150 mmHg or greater remained at a statistically significantly higher risk for ESRD compared with those who had an SBP lower than 130 mmHg, with a hazard ratio (HR) of 1.36. The adjusted hazard ratio in those with systolic blood pressure between 140 mmHg and 149 mmHg was 1.27.
Participants with a diastolic blood pressure of 90 mmHg or higher had a hazard ratio of 1.81 for progression to ESRD compared with those who had a DBP of 60 mmHg to 74 mmHg.
The study also found that higher pulse pressure was associated with higher risk of end-stage renal disease. Those with a pulse pressure of 80 mmHg or more had a hazard ratio of 1.44 for incident ESRD compared with those who had a pulse pressure less than 50 mmHg. However, that risk was attenuated after adjusting for systolic blood pressure.
About 33% of KEEP participants had systolic blood pressure of at least 150 mmHg or diastolic blood pressure of at least 90 mmHg. Most of these individuals had isolated systolic hypertension.
“Our finding that SBP of 140 mmHg or higher and DBP of 90 mmHg or higher, rather than the lower level of 130/80 mmHg, was associated with increased risk of incident ESRD has important implications,” Dr. Peralta said.
“We showed that, compared with SBP less than 130, persons with SBP 130 to 139 were not at higher ESRD risk,” she said. “We must note that we did not investigate cardiovascular [CV] risk, and the threshold for CV protection may differ.”
Still, Dr. Peralta believes that current blood pressure targets should be changed “based on all available evidence,” she said.
Dr. Peralta would also like to see education programs developed to identify and treat the large number of people with CKD whose blood pressure is very poorly controlled, and further studies conducted to replicate these findings from KEEP, she said.
‘The Lamppost in the Daytime’
Although these results came from an observational study, they may be in line with expected changes to the guidelines for blood pressure targets included in the Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8), experts in the field said.
“Given the lack of evidence of interventional studies demonstrating the benefits of lower blood pressure goals, we suspect that the JNC 8 is going to go with what the data shows, not with how you interpret the data or how you assume it might look,” noted Matthew R. Weir, MD, Professor of Medicine at the University of Maryland, in an interview.
The findings from the current study are “purely observational,” though, and one needs to be cautious in interpreting the results, Dr. Weir said.
“There is a great deal of unmeasured confounding in an observational study. You can't say for sure from these results if 140 is better than 130. What if they have a reduction in the risk for heart attack or stroke with a lower blood pressure goal?”
The data from the study are consistent with what the JNC 8 panel is currently considering for blood pressure treatment recommendations in patients with CKD, agreed Raymond R. Townsend, MD, Professor of Medicine at the University of Pennsylvania.
“I think this will help guideline-writing committees when they review the data on blood pressure goals in chronic kidney disease,” Dr. Townsend said in an interview.
“This is not a clinical trial testing a hypothesis that one blood pressure goal is superior to another blood pressure goal. This is like the lamppost in the daytime; it's supportive, but it's not the illuminating, definitive study.”
Still, the study shows that current paradigms for blood pressure management in CKD may be lacking in evidence, Dr. Townsend said.
“If you look at the consequences of blood pressure, at least in terms of end-stage renal disease, we currently worship at the altar of 130-over-80, but the KEEP data support the idea that, really, 140 is OK, and that it is at systolics of 150 or higher where you see the enhanced risk of progression to end-stage kidney disease or the development of the need for dialysis.”