Blood Pressure Above 140/80 Worsens Proteinuric Diabetic Kidney Disease

SAN DIEGO – Among patients with proteinuric diabetic kidney disease, a mean systolic blood pressure greater than 140 mm Hg and a mean diastolic blood pressure greater than 80 mm Hg were associated with worse renal outcomes, a large national analysis showed.

“Proteinuric diabetic kidney disease frequently progresses to end-stage renal disease,” lead study author Dr. David J. Leehey said at a meeting sponsored by the American Society of Nephrology. “Control of blood pressure delays progression, but the optimal blood pressure to improve outcomes remains unclear.”

In a recent report from the Eighth Joint National Committee, panel members recommended a blood pressure of less than 140/90 mm Hg both for patients with diabetes and patients with chronic kidney disease (JAMA. 2014 Feb 5;311[5]:507-20).

“There are few data with regard to target blood pressure in proteinuric diabetic kidney disease, however, leaving physicians uncertain about how aggressively to lower blood pressure in such patients,” said Dr. Leehey, a nephrologist at the Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill.

In an effort to assess the relationship between blood pressure and renal outcomes in proteinuric diabetic kidney disease, the researchers evaluated blood pressure data from all 1,448 patients who were randomized to the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, which evaluated the combination of losartan with lisinopril, compared with losartan alone (N Engl J Med. 2013 Nov 14;369[20]:1892-1903). Randomization occurred between July 2008 and September 2012, but the trial was halted in October of 2012 due to safety reasons (acute kidney injury and hyperkalemic episodes).

For the current analysis, Dr. Leehey and his associates evaluated the associations of mean on-treatment blood pressure with the primary endpoint (defined as a decline in estimated glomerular filtration rate [eGFR], end-stage renal disease [ESRD], or death), the renal endpoint (defined as a decline in eGFR or cystatin C), the rate of eGFR decline, and mortality.

Trough sitting blood pressure measurements were obtained at every visit during the screening, titration, randomization, and treatment phases of VA NEPHRON-D. Mean blood pressure was defined as the average of all on-treatment blood pressures from the randomization visit to the last blood pressure measurement taken.

Dr. Leehey reported that there were 284 primary endpoints: 132 in the combination group and 152 in the monotherapy group. The mean blood pressure was based on a mean of 7.7 readings per participant.

Both mean systolic and mean diastolic blood pressure were strongly associated with the primary endpoint (P less than .001), univariate analysis revealed. The hazard of developing the primary endpoint increased as the mean systolic blood pressure rose from less than 120 mm Hg to greater than 150 mm Hg (P = .018), multivariate analysis showed.

A significant increase in hazard ratio was seen when mean systolic blood pressure was greater than 140 mm Hg (HR, 1.51). The researchers also observed a significant effect of mean diastolic blood pressure on the hazard of developing the primary endpoint (P = .005), with an increase in hazard ratio when mean diastolic blood pressure was greater than 80 mm Hg (HR, 1.54).

“Associations between BP and both renal endpoint and rate of eGFR decline were similar to those with the primary endpoint,” Dr. Leehey said. “There was a U-shaped relationship between rate of eGFR decline and mean diastolic blood pressure, with the lowest rate of eGFR decline seen when diastolic blood pressure was in the 70-79 mm Hg range. No effect of BP with mortality was observed, possibly because of the limited number of mortality events.”

The study was funded by support from the Veterans Administration. Dr. Leehey reported having no financial disclosures.

SAN DIEGO – Among patients with proteinuric diabetic kidney disease, a mean systolic blood pressure greater than 140 mm Hg and a mean diastolic blood pressure greater than 80 mm Hg were associated with worse renal outcomes, a large national analysis showed.

“Proteinuric diabetic kidney disease frequently progresses to end-stage renal disease,” lead study author Dr. David J. Leehey said at a meeting sponsored by the American Society of Nephrology. “Control of blood pressure delays progression, but the optimal blood pressure to improve outcomes remains unclear.”

In a recent report from the Eighth Joint National Committee, panel members recommended a blood pressure of less than 140/90 mm Hg both for patients with diabetes and patients with chronic kidney disease (JAMA. 2014 Feb 5;311[5]:507-20).

“There are few data with regard to target blood pressure in proteinuric diabetic kidney disease, however, leaving physicians uncertain about how aggressively to lower blood pressure in such patients,” said Dr. Leehey, a nephrologist at the Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill.

In an effort to assess the relationship between blood pressure and renal outcomes in proteinuric diabetic kidney disease, the researchers evaluated blood pressure data from all 1,448 patients who were randomized to the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, which evaluated the combination of losartan with lisinopril, compared with losartan alone (N Engl J Med. 2013 Nov 14;369[20]:1892-1903). Randomization occurred between July 2008 and September 2012, but the trial was halted in October of 2012 due to safety reasons (acute kidney injury and hyperkalemic episodes).

For the current analysis, Dr. Leehey and his associates evaluated the associations of mean on-treatment blood pressure with the primary endpoint (defined as a decline in estimated glomerular filtration rate [eGFR], end-stage renal disease [ESRD], or death), the renal endpoint (defined as a decline in eGFR or cystatin C), the rate of eGFR decline, and mortality.

Trough sitting blood pressure measurements were obtained at every visit during the screening, titration, randomization, and treatment phases of VA NEPHRON-D. Mean blood pressure was defined as the average of all on-treatment blood pressures from the randomization visit to the last blood pressure measurement taken.

Dr. Leehey reported that there were 284 primary endpoints: 132 in the combination group and 152 in the monotherapy group. The mean blood pressure was based on a mean of 7.7 readings per participant.

Both mean systolic and mean diastolic blood pressure were strongly associated with the primary endpoint (P less than .001), univariate analysis revealed. The hazard of developing the primary endpoint increased as the mean systolic blood pressure rose from less than 120 mm Hg to greater than 150 mm Hg (P = .018), multivariate analysis showed.

A significant increase in hazard ratio was seen when mean systolic blood pressure was greater than 140 mm Hg (HR, 1.51). The researchers also observed a significant effect of mean diastolic blood pressure on the hazard of developing the primary endpoint (P = .005), with an increase in hazard ratio when mean diastolic blood pressure was greater than 80 mm Hg (HR, 1.54).

“Associations between BP and both renal endpoint and rate of eGFR decline were similar to those with the primary endpoint,” Dr. Leehey said. “There was a U-shaped relationship between rate of eGFR decline and mean diastolic blood pressure, with the lowest rate of eGFR decline seen when diastolic blood pressure was in the 70-79 mm Hg range. No effect of BP with mortality was observed, possibly because of the limited number of mortality events.”

The study was funded by support from the Veterans Administration. Dr. Leehey reported having no financial disclosures.

SAN DIEGO – Among patients with proteinuric diabetic kidney disease, a mean systolic blood pressure greater than 140 mm Hg and a mean diastolic blood pressure greater than 80 mm Hg were associated with worse renal outcomes, a large national analysis showed.

“Proteinuric diabetic kidney disease frequently progresses to end-stage renal disease,” lead study author Dr. David J. Leehey said at a meeting sponsored by the American Society of Nephrology. “Control of blood pressure delays progression, but the optimal blood pressure to improve outcomes remains unclear.”

In a recent report from the Eighth Joint National Committee, panel members recommended a blood pressure of less than 140/90 mm Hg both for patients with diabetes and patients with chronic kidney disease (JAMA. 2014 Feb 5;311[5]:507-20).

“There are few data with regard to target blood pressure in proteinuric diabetic kidney disease, however, leaving physicians uncertain about how aggressively to lower blood pressure in such patients,” said Dr. Leehey, a nephrologist at the Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill.

In an effort to assess the relationship between blood pressure and renal outcomes in proteinuric diabetic kidney disease, the researchers evaluated blood pressure data from all 1,448 patients who were randomized to the Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial, which evaluated the combination of losartan with lisinopril, compared with losartan alone (N Engl J Med. 2013 Nov 14;369[20]:1892-1903). Randomization occurred between July 2008 and September 2012, but the trial was halted in October of 2012 due to safety reasons (acute kidney injury and hyperkalemic episodes).

For the current analysis, Dr. Leehey and his associates evaluated the associations of mean on-treatment blood pressure with the primary endpoint (defined as a decline in estimated glomerular filtration rate [eGFR], end-stage renal disease [ESRD], or death), the renal endpoint (defined as a decline in eGFR or cystatin C), the rate of eGFR decline, and mortality.

Trough sitting blood pressure measurements were obtained at every visit during the screening, titration, randomization, and treatment phases of VA NEPHRON-D. Mean blood pressure was defined as the average of all on-treatment blood pressures from the randomization visit to the last blood pressure measurement taken.

Dr. Leehey reported that there were 284 primary endpoints: 132 in the combination group and 152 in the monotherapy group. The mean blood pressure was based on a mean of 7.7 readings per participant.

Both mean systolic and mean diastolic blood pressure were strongly associated with the primary endpoint (P less than .001), univariate analysis revealed. The hazard of developing the primary endpoint increased as the mean systolic blood pressure rose from less than 120 mm Hg to greater than 150 mm Hg (P = .018), multivariate analysis showed.

A significant increase in hazard ratio was seen when mean systolic blood pressure was greater than 140 mm Hg (HR, 1.51). The researchers also observed a significant effect of mean diastolic blood pressure on the hazard of developing the primary endpoint (P = .005), with an increase in hazard ratio when mean diastolic blood pressure was greater than 80 mm Hg (HR, 1.54).

“Associations between BP and both renal endpoint and rate of eGFR decline were similar to those with the primary endpoint,” Dr. Leehey said. “There was a U-shaped relationship between rate of eGFR decline and mean diastolic blood pressure, with the lowest rate of eGFR decline seen when diastolic blood pressure was in the 70-79 mm Hg range. No effect of BP with mortality was observed, possibly because of the limited number of mortality events.”

The study was funded by support from the Veterans Administration. Dr. Leehey reported having no financial disclosures.