Findings Offer Hope for Some
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Intensive BP Control Didn't Shine in Chronic Kidney Disease

Intensive blood pressure control didn't slow the progression of chronic kidney disease any better than standard blood pressure control in most patients, according to a report in the New England Journal of Medicine.

It appears that the more intensive approach may benefit only patients who have proteinuria with a protein-creatinine ratio greater than 0.22, a value that is compatible with the widely accepted threshold of 300 mg/day for absolute urinary protein excretion, said Dr. Lawrence J. Appel of Johns Hopkins University, Baltimore, and his associates in the AASK (African-American Study of Kidney Disease and Hypertension) Collaborative Research Group.

Until now, “few trials have tested the effects of intensive blood pressure control [compared with conventional control] on the progression of chronic kidney disease, and the findings from such trials have been inconsistent. Despite a lack of compelling evidence, numerous guidelines recommend a reduced blood pressure target in patients with [chronic kidney disease],” they wrote.

Previous studies have rarely followed patients beyond 5 years, even though it typically takes longer than that for end-stage renal disease (ESRD) to develop in patients with CKD, the researchers noted.

The AASK study compared outcomes between the two approaches to blood pressure control in 1,094 black adults with mild to moderate hypertensive chronic kidney disease (defined as diastolic BP greater than 95 mm Hg and a glomerular filtration rate of 20-65 mL/min) but without marked proteinuria.

Patients with diabetes were excluded from the clinical trial.

In the first phase of the AASK investigation, patients were randomly assigned to either intensive BP control with a target of 92 mm Hg or lower mean arterial pressure (that is, lower than the usual target of 130/80 mm Hg recommended for CKD patients) or to conventional BP control with a target of 102-107 mm Hg mean arterial pressure (which corresponds to the conventional BP target of 140/90 mm Hg).

Throughout this initial phase of the trial, which lasted approximately 4 years, mean blood pressure was significantly lower in the intensive-control group (130/78 mm Hg) than in the standard-control group (141/86 mm Hg).

However, there was no significant difference in the primary outcome of progression of kidney disease, development of ESRD, or death.

Likewise, there was no significant difference between the two approaches in secondary or clinical outcomes, the investigators noted.

In the second phase of the AASK investigation, patients who had not yet developed ESRD were invited to continue in a cohort portion of the trial, in which the BP target was 140/90 mm Hg.

In 2004, when national guidelines were changed, this target was amended to lower than 130/80 mm Hg.

After a cumulative follow-up of 8-12 years, there still was no significant difference in primary or secondary outcomes between those who were initially assigned to the intensive-control and the standard-control groups.

More intensive blood pressure control did not slow the rate of progression of CKD, Dr. Appel and his associates reported (N. Engl. J. Med. 2010;363:918-29).

However, the intensive-control approach did benefit one subgroup of patients with proteinuria: those who had a protein-creatinine ratio of more than 0.22 at baseline, the study investigators said.

These patients showed a significant reduction in the primary outcome of progression of kidney disease, development of ESRD, or death, as well as in secondary and clinical outcomes, the researchers added.

The reason for this discrepancy is not known.

“Overall, it is hard to develop a coherent, biologically plausible argument for a qualitative interaction between harm in patients without proteinuria and benefit in those with proteinuria,” the study authors said.

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This study lends hope to the concept that intensive treatment will improve renal outcomes in at least some patients with hypertension, chronic kidney disease, and microalbuminuria.

Data from other studies also support the conclusion that intensive BP control is beneficial in select patients.

The Modification of Diet in Renal Disease trial showed that intensive BP control, compared with standard control, benefited patients who had more than 1 g of proteinuria at baseline. The ESCAPE (Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of Chronic Renal Failure in Pediatric Patients) trial also demonstrated that intensive BP control with a fixed dose of an ACE inhibitor significantly slowed the progression of renal disease, with the largest effects seen in children who had substantial proteinuria, hypertension, and a reduced GFR at baseline.

In addition, intensive BP control was beneficial in a recent study of adults in Italy who had idiopathic glomerular diseases associated with hypertension and proteinuria.

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JULIE R. INGELFINGER, M.D., is chief of pediatric nephrology at Massachusetts General Hospital, Boston, and a deputy editor of the New England Journal of Medicine. These comments were summarized from her editorial accompanying the report (N. Engl. J. Med.
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This study lends hope to the concept that intensive treatment will improve renal outcomes in at least some patients with hypertension, chronic kidney disease, and microalbuminuria.

Data from other studies also support the conclusion that intensive BP control is beneficial in select patients.

The Modification of Diet in Renal Disease trial showed that intensive BP control, compared with standard control, benefited patients who had more than 1 g of proteinuria at baseline. The ESCAPE (Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of Chronic Renal Failure in Pediatric Patients) trial also demonstrated that intensive BP control with a fixed dose of an ACE inhibitor significantly slowed the progression of renal disease, with the largest effects seen in children who had substantial proteinuria, hypertension, and a reduced GFR at baseline.

In addition, intensive BP control was beneficial in a recent study of adults in Italy who had idiopathic glomerular diseases associated with hypertension and proteinuria.

Body

This study lends hope to the concept that intensive treatment will improve renal outcomes in at least some patients with hypertension, chronic kidney disease, and microalbuminuria.

Data from other studies also support the conclusion that intensive BP control is beneficial in select patients.

The Modification of Diet in Renal Disease trial showed that intensive BP control, compared with standard control, benefited patients who had more than 1 g of proteinuria at baseline. The ESCAPE (Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of Chronic Renal Failure in Pediatric Patients) trial also demonstrated that intensive BP control with a fixed dose of an ACE inhibitor significantly slowed the progression of renal disease, with the largest effects seen in children who had substantial proteinuria, hypertension, and a reduced GFR at baseline.

In addition, intensive BP control was beneficial in a recent study of adults in Italy who had idiopathic glomerular diseases associated with hypertension and proteinuria.

Name
JULIE R. INGELFINGER, M.D., is chief of pediatric nephrology at Massachusetts General Hospital, Boston, and a deputy editor of the New England Journal of Medicine. These comments were summarized from her editorial accompanying the report (N. Engl. J. Med.
Name
JULIE R. INGELFINGER, M.D., is chief of pediatric nephrology at Massachusetts General Hospital, Boston, and a deputy editor of the New England Journal of Medicine. These comments were summarized from her editorial accompanying the report (N. Engl. J. Med.
Title
Findings Offer Hope for Some
Findings Offer Hope for Some

Intensive blood pressure control didn't slow the progression of chronic kidney disease any better than standard blood pressure control in most patients, according to a report in the New England Journal of Medicine.

It appears that the more intensive approach may benefit only patients who have proteinuria with a protein-creatinine ratio greater than 0.22, a value that is compatible with the widely accepted threshold of 300 mg/day for absolute urinary protein excretion, said Dr. Lawrence J. Appel of Johns Hopkins University, Baltimore, and his associates in the AASK (African-American Study of Kidney Disease and Hypertension) Collaborative Research Group.

Until now, “few trials have tested the effects of intensive blood pressure control [compared with conventional control] on the progression of chronic kidney disease, and the findings from such trials have been inconsistent. Despite a lack of compelling evidence, numerous guidelines recommend a reduced blood pressure target in patients with [chronic kidney disease],” they wrote.

Previous studies have rarely followed patients beyond 5 years, even though it typically takes longer than that for end-stage renal disease (ESRD) to develop in patients with CKD, the researchers noted.

The AASK study compared outcomes between the two approaches to blood pressure control in 1,094 black adults with mild to moderate hypertensive chronic kidney disease (defined as diastolic BP greater than 95 mm Hg and a glomerular filtration rate of 20-65 mL/min) but without marked proteinuria.

Patients with diabetes were excluded from the clinical trial.

In the first phase of the AASK investigation, patients were randomly assigned to either intensive BP control with a target of 92 mm Hg or lower mean arterial pressure (that is, lower than the usual target of 130/80 mm Hg recommended for CKD patients) or to conventional BP control with a target of 102-107 mm Hg mean arterial pressure (which corresponds to the conventional BP target of 140/90 mm Hg).

Throughout this initial phase of the trial, which lasted approximately 4 years, mean blood pressure was significantly lower in the intensive-control group (130/78 mm Hg) than in the standard-control group (141/86 mm Hg).

However, there was no significant difference in the primary outcome of progression of kidney disease, development of ESRD, or death.

Likewise, there was no significant difference between the two approaches in secondary or clinical outcomes, the investigators noted.

In the second phase of the AASK investigation, patients who had not yet developed ESRD were invited to continue in a cohort portion of the trial, in which the BP target was 140/90 mm Hg.

In 2004, when national guidelines were changed, this target was amended to lower than 130/80 mm Hg.

After a cumulative follow-up of 8-12 years, there still was no significant difference in primary or secondary outcomes between those who were initially assigned to the intensive-control and the standard-control groups.

More intensive blood pressure control did not slow the rate of progression of CKD, Dr. Appel and his associates reported (N. Engl. J. Med. 2010;363:918-29).

However, the intensive-control approach did benefit one subgroup of patients with proteinuria: those who had a protein-creatinine ratio of more than 0.22 at baseline, the study investigators said.

These patients showed a significant reduction in the primary outcome of progression of kidney disease, development of ESRD, or death, as well as in secondary and clinical outcomes, the researchers added.

The reason for this discrepancy is not known.

“Overall, it is hard to develop a coherent, biologically plausible argument for a qualitative interaction between harm in patients without proteinuria and benefit in those with proteinuria,” the study authors said.

Intensive blood pressure control didn't slow the progression of chronic kidney disease any better than standard blood pressure control in most patients, according to a report in the New England Journal of Medicine.

It appears that the more intensive approach may benefit only patients who have proteinuria with a protein-creatinine ratio greater than 0.22, a value that is compatible with the widely accepted threshold of 300 mg/day for absolute urinary protein excretion, said Dr. Lawrence J. Appel of Johns Hopkins University, Baltimore, and his associates in the AASK (African-American Study of Kidney Disease and Hypertension) Collaborative Research Group.

Until now, “few trials have tested the effects of intensive blood pressure control [compared with conventional control] on the progression of chronic kidney disease, and the findings from such trials have been inconsistent. Despite a lack of compelling evidence, numerous guidelines recommend a reduced blood pressure target in patients with [chronic kidney disease],” they wrote.

Previous studies have rarely followed patients beyond 5 years, even though it typically takes longer than that for end-stage renal disease (ESRD) to develop in patients with CKD, the researchers noted.

The AASK study compared outcomes between the two approaches to blood pressure control in 1,094 black adults with mild to moderate hypertensive chronic kidney disease (defined as diastolic BP greater than 95 mm Hg and a glomerular filtration rate of 20-65 mL/min) but without marked proteinuria.

Patients with diabetes were excluded from the clinical trial.

In the first phase of the AASK investigation, patients were randomly assigned to either intensive BP control with a target of 92 mm Hg or lower mean arterial pressure (that is, lower than the usual target of 130/80 mm Hg recommended for CKD patients) or to conventional BP control with a target of 102-107 mm Hg mean arterial pressure (which corresponds to the conventional BP target of 140/90 mm Hg).

Throughout this initial phase of the trial, which lasted approximately 4 years, mean blood pressure was significantly lower in the intensive-control group (130/78 mm Hg) than in the standard-control group (141/86 mm Hg).

However, there was no significant difference in the primary outcome of progression of kidney disease, development of ESRD, or death.

Likewise, there was no significant difference between the two approaches in secondary or clinical outcomes, the investigators noted.

In the second phase of the AASK investigation, patients who had not yet developed ESRD were invited to continue in a cohort portion of the trial, in which the BP target was 140/90 mm Hg.

In 2004, when national guidelines were changed, this target was amended to lower than 130/80 mm Hg.

After a cumulative follow-up of 8-12 years, there still was no significant difference in primary or secondary outcomes between those who were initially assigned to the intensive-control and the standard-control groups.

More intensive blood pressure control did not slow the rate of progression of CKD, Dr. Appel and his associates reported (N. Engl. J. Med. 2010;363:918-29).

However, the intensive-control approach did benefit one subgroup of patients with proteinuria: those who had a protein-creatinine ratio of more than 0.22 at baseline, the study investigators said.

These patients showed a significant reduction in the primary outcome of progression of kidney disease, development of ESRD, or death, as well as in secondary and clinical outcomes, the researchers added.

The reason for this discrepancy is not known.

“Overall, it is hard to develop a coherent, biologically plausible argument for a qualitative interaction between harm in patients without proteinuria and benefit in those with proteinuria,” the study authors said.

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Intensive BP Control Didn't Shine in Chronic Kidney Disease
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Major Finding: Compared with standard BP control, intensive BP

control failed to slow the progression of CKD, prevent the development

of end-stage renal disease, or prevent death in most patients who had

mild to moderate chronic kidney disease. Intensive BP control was

beneficial only in the subgroup of patients who had proteinuria with a

protein-creatinine ratio greater than 0.22 at baseline.

Data

Source: AASK, a clinical trial with an initial 4-year randomized

phase comparing intensive BP control with standard BP control in 1,094

black adults, as well as an observational cohort phase with a further

4-8 years of extended follow-up.

Disclosures: This study

was funded by the National Institute of Diabetes and Digestive and

Kidney Diseases, the Office of Research in Minority Health, and the

National Institutes of Health. King Pharmaceuticals provided financial

support and donated antihypertensive medications to each clinical

center. AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia,

Pfizer, and Upjohn also donated antihypertensive drugs. None of these

companies had any role in the design of the study, the accrual or

analysis of data, or the preparation of the manuscript. Some of the

investigators reported being in consultant and/or advisory board roles

or receiving funds from numerous companies including Daiichi-Sankyo,

Novartis, Amgen, King Pharmaceuticals, Abbott, Boehringer-Ingelheim,

Litholink, Eli Lilly, Takeda, Merck, and Watson.

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