Lower blood pressure may preserve kidney function in some patients

"This is not a panacea. We have a lot more to figure out. But our evidence suggests that we have a way to at least delay or possibly even prevent end-stage kidney disease in some patients," says Lawrence J. Appel, M.D., M.P.H., a professor of medicine at the Johns Hopkins University School of Medicine and the study's leader.

End-stage kidney disease is the point at which patients need to be on dialysis or receive a kidney transplant in order to survive.

Still, not everyone in the study was helped by the aggressive blood pressure treatment. Those patients who had little or no protein in their urine -- that is, patients who were not as sick -- saw their kidney disease progress at roughly the same rate regardless of how low they tried to get their blood pressure. It was the sicker patients, that is, those with protein in their urine, who benefited most from the more intensive blood pressure therapy, with roughly a 25 percent reduction in end-stage kidney disease as compared with those who met the standard blood pressure goal. Roughly one-third of the participants had higher amounts of protein in their urine.

"This has always been a hot topic: Is a lower blood pressure goal better at preserving kidney function than the standard goal? The answer is a qualified yes, notably in people who have some protein in their urine," Appel says.

In the National Institutes of Health-sponsored African-American Study of Kidney Disease and Hypertension (AASK), 1,094 hypertensive African Americans with chronic kidney disease were randomized to one of two groups: standard blood pressure goal versus intensive (or lower) blood pressure goal. Both groups needed to get their blood pressure in check -- the first group's goal was a blood pressure of roughly 140/90 (the standard target of doctors when treating hypertensive patients), while the second group's goal was approximately 130/80. Researchers lowered blood pressure through a combination of commonly used drugs. The patients were followed between 8.8 and 12.2 years.

Chronic kidney disease is a major public health problem and one that is only growing, Appel says. In the United States, roughly one-third of cases of end-stage kidney disease -- in which the kidneys no longer function and patients require dialysis or a transplant -- are attributed to hypertension. The burden of kidney disease is especially high in African Americans. Though they constitute only 12 percent of the population, African Americans make up 32 percent of those with end-stage kidney disease. Appel says African Americans are four to 20 times more likely to reach end-stage kidney disease, though researchers remain unsure of the reasons why.

Physicians consider patients with blood pressure over 140/90 to be hypertensive, and they will often put those patients on blood pressure-lowering medication with the goal of getting them back below that hazardous threshold. In recent years, some doctors have suggested that their patients with kidney disease try to get their blood pressure lower than that to stave off the progression of kidney disease, though without much scientific evidence, Appel says.

Appel says his study suggests that physicians should check for protein in the urine before determining the blood pressure goal for African Americans with kidney disease. If the patient has protein in the urine, a lower blood pressure goal has the potential to slow the progression of kidney disease. But if the patient has little or no protein in the urine, Appel says, the study suggests that reaching the lower blood pressure goal is not worth the extra effort, and the standard goal is just as good. Getting hypertensive patients down to 130/80 takes more doctor visits and requires more medication -- on average, one more blood pressure prescription. However, once the lower blood pressure level is achieved, keeping the blood pressure there is not particularly difficult.

Even though the study found a benefit of aggressive blood pressure treatment in one group of hypertensive African Americans with kidney disease, a significant number of those patients still ended up with end-stage kidney disease or worse. While roughly 90 percent of those who were in the standard blood pressure group saw their disease progress, about 75 percent of those in the aggressive therapy arm of the trial still progressed to a poor outcome.

"That's still pretty high," Appel says. "The key is preventing early kidney damage in the first place."

More research is necessary, he says, to identify more factors that prevent early kidney damage, as well as factors that delay kidney disease progression among those who already have chronic kidney disease.

The study was conducted at 20 medical centers in the United States. Along with Appel, other Johns Hopkins faculty and staff involved in the research include Edgar Miller, M.D., Ph.D., Brad Astor, Ph.D., M.P.H., M.S.; Charalett Diggs, R.N.; Jeanne Charleston, R.N.; and Charles Harris.

The National Institutes of Health was the primary sponsor of the study. In addition, King Pharmaceuticals provided financial support and donated antihypertensive medications. Pfizer Inc., AstraZeneca Pharmaceuticals, Glaxo Smith Kline, Forest Laboratories, Pharmacia and Upjohn also donated medication.