Role of excess volume in the pathophysiology of hypertension in chronic kidney disease

Nina Vasavada, Rajiv Agarwal

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Background. The pathophysiology of hypertension in patients with chronic kidney disease (CKD) is largely attributed to positive sodium balance. It is unclear how loop diuretics affect fluid volume compartments, especially with respect to their antihypertensive effect. Methods. Subjects with CKD were administered a single therapeutically equivalent dose of an oral loop diuretic (furosemide or torsemide in randomized crossover design). We measured acute volume changes over 12 hours using biophysical and hormonal biomarkers and then 24-hour ambulatory blood pressure after daily diuretic therapy for 3 weeks. Results. Single-dose administration of loop diuretic decreased extracellular water (ECW) by 1.7 L [95% confidence interval (95% CI) 1.2, 2.2, P <0.001], total body water (TBW) by 1.2 L (95% CI 0.5, 1.9, P <0.001), and increased natural log (ln) plasma renin activity (PRA) from -1.2 ± 1.3 ng/mL/ hour to -0.5 ± 1.5 ng/mL/hour (P <0.001). Daily loop diuretic administration resulted in reduced ECW from 24.2 ± 6.4 L to 22.3 ± 5.2 L (P = 0.02) and TBW from 54.3 ± 12.7 L to 51.6 ± 11.9 L (P <0.001) in 1 week. After 3 weeks of diuretic therapy, whereas ECW reduction persisted at 22.8 ± 5.1 L (P = 0.05), TBW trended toward baseline level at 52.7 ± 11.8 L. A concomitant increase in ln PRA from -1.0 ± 1.3 ng/mL/hour to 0.4 ± 1.9 ng/mL/hour (P <0.001) and ln plasma aldosterone (PA) from 2.0 ± 0.8 ng/dL to 2.3 ± 0.8 ng/ dL (P <0.005) and fall in ln brain natriuretic peptide (BNP) from 4.3 ± 0.9 pg/mL to 3.7 ± 1.0 pg/mL (P <0.01) were seen at 1 week. Despite a trend toward restoration of TBW, changes in hormonal biomarkers were maintained at 3 weeks. Over these 3 weeks, furosemide reduced 24-hour ambulatory blood pressure from 147 ± 17/78 ± 11 mm Hg to 138 ± 21/74 ± 12 mm Hg (P = 0.021) and torsemide reduced it from 143 ± 18/75 ± 10 mm Hg to 133 ± 19/71 ± 10 mm Hg (P = 0.007). Conclusion. Patients with CKD have elevated extracellular fluid volume that can be corrected acutely with loop diuretics. Persistent diuretic use results in dynamic changes in ECW and other body fluid compartments that translate into chronic blood pressure reduction.

Original languageEnglish (US)
Pages (from-to)1772-1779
Number of pages8
JournalKidney International
Volume64
Issue number5
DOIs
StatePublished - Nov 2003
Externally publishedYes

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Sodium Potassium Chloride Symporter Inhibitors
Chronic Renal Insufficiency
torsemide
Body Water
Hypertension
Diuretics
Water
Furosemide
Blood Pressure
Renin
Body Fluid Compartments
Biomarkers
Confidence Intervals
Brain Natriuretic Peptide
Extracellular Fluid
Aldosterone
Cross-Over Studies
Antihypertensive Agents
Sodium
Therapeutics

Keywords

  • Brain natriuretic peptide
  • Chronic renal failure
  • Diuretics
  • Electrical impedance
  • Furosemide
  • Plasma aldosterone
  • Plasma renin activity
  • Randomized controlled trial
  • Torsemide

ASJC Scopus subject areas

  • Nephrology

Cite this

Role of excess volume in the pathophysiology of hypertension in chronic kidney disease. / Vasavada, Nina; Agarwal, Rajiv.

In: Kidney International, Vol. 64, No. 5, 11.2003, p. 1772-1779.

Research output: Contribution to journalArticle

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abstract = "Background. The pathophysiology of hypertension in patients with chronic kidney disease (CKD) is largely attributed to positive sodium balance. It is unclear how loop diuretics affect fluid volume compartments, especially with respect to their antihypertensive effect. Methods. Subjects with CKD were administered a single therapeutically equivalent dose of an oral loop diuretic (furosemide or torsemide in randomized crossover design). We measured acute volume changes over 12 hours using biophysical and hormonal biomarkers and then 24-hour ambulatory blood pressure after daily diuretic therapy for 3 weeks. Results. Single-dose administration of loop diuretic decreased extracellular water (ECW) by 1.7 L [95{\%} confidence interval (95{\%} CI) 1.2, 2.2, P <0.001], total body water (TBW) by 1.2 L (95{\%} CI 0.5, 1.9, P <0.001), and increased natural log (ln) plasma renin activity (PRA) from -1.2 ± 1.3 ng/mL/ hour to -0.5 ± 1.5 ng/mL/hour (P <0.001). Daily loop diuretic administration resulted in reduced ECW from 24.2 ± 6.4 L to 22.3 ± 5.2 L (P = 0.02) and TBW from 54.3 ± 12.7 L to 51.6 ± 11.9 L (P <0.001) in 1 week. After 3 weeks of diuretic therapy, whereas ECW reduction persisted at 22.8 ± 5.1 L (P = 0.05), TBW trended toward baseline level at 52.7 ± 11.8 L. A concomitant increase in ln PRA from -1.0 ± 1.3 ng/mL/hour to 0.4 ± 1.9 ng/mL/hour (P <0.001) and ln plasma aldosterone (PA) from 2.0 ± 0.8 ng/dL to 2.3 ± 0.8 ng/ dL (P <0.005) and fall in ln brain natriuretic peptide (BNP) from 4.3 ± 0.9 pg/mL to 3.7 ± 1.0 pg/mL (P <0.01) were seen at 1 week. Despite a trend toward restoration of TBW, changes in hormonal biomarkers were maintained at 3 weeks. Over these 3 weeks, furosemide reduced 24-hour ambulatory blood pressure from 147 ± 17/78 ± 11 mm Hg to 138 ± 21/74 ± 12 mm Hg (P = 0.021) and torsemide reduced it from 143 ± 18/75 ± 10 mm Hg to 133 ± 19/71 ± 10 mm Hg (P = 0.007). Conclusion. Patients with CKD have elevated extracellular fluid volume that can be corrected acutely with loop diuretics. Persistent diuretic use results in dynamic changes in ECW and other body fluid compartments that translate into chronic blood pressure reduction.",
keywords = "Brain natriuretic peptide, Chronic renal failure, Diuretics, Electrical impedance, Furosemide, Plasma aldosterone, Plasma renin activity, Randomized controlled trial, Torsemide",
author = "Nina Vasavada and Rajiv Agarwal",
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doi = "10.1046/j.1523-1755.2003.00273.x",
language = "English (US)",
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T1 - Role of excess volume in the pathophysiology of hypertension in chronic kidney disease

AU - Vasavada, Nina

AU - Agarwal, Rajiv

PY - 2003/11

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N2 - Background. The pathophysiology of hypertension in patients with chronic kidney disease (CKD) is largely attributed to positive sodium balance. It is unclear how loop diuretics affect fluid volume compartments, especially with respect to their antihypertensive effect. Methods. Subjects with CKD were administered a single therapeutically equivalent dose of an oral loop diuretic (furosemide or torsemide in randomized crossover design). We measured acute volume changes over 12 hours using biophysical and hormonal biomarkers and then 24-hour ambulatory blood pressure after daily diuretic therapy for 3 weeks. Results. Single-dose administration of loop diuretic decreased extracellular water (ECW) by 1.7 L [95% confidence interval (95% CI) 1.2, 2.2, P <0.001], total body water (TBW) by 1.2 L (95% CI 0.5, 1.9, P <0.001), and increased natural log (ln) plasma renin activity (PRA) from -1.2 ± 1.3 ng/mL/ hour to -0.5 ± 1.5 ng/mL/hour (P <0.001). Daily loop diuretic administration resulted in reduced ECW from 24.2 ± 6.4 L to 22.3 ± 5.2 L (P = 0.02) and TBW from 54.3 ± 12.7 L to 51.6 ± 11.9 L (P <0.001) in 1 week. After 3 weeks of diuretic therapy, whereas ECW reduction persisted at 22.8 ± 5.1 L (P = 0.05), TBW trended toward baseline level at 52.7 ± 11.8 L. A concomitant increase in ln PRA from -1.0 ± 1.3 ng/mL/hour to 0.4 ± 1.9 ng/mL/hour (P <0.001) and ln plasma aldosterone (PA) from 2.0 ± 0.8 ng/dL to 2.3 ± 0.8 ng/ dL (P <0.005) and fall in ln brain natriuretic peptide (BNP) from 4.3 ± 0.9 pg/mL to 3.7 ± 1.0 pg/mL (P <0.01) were seen at 1 week. Despite a trend toward restoration of TBW, changes in hormonal biomarkers were maintained at 3 weeks. Over these 3 weeks, furosemide reduced 24-hour ambulatory blood pressure from 147 ± 17/78 ± 11 mm Hg to 138 ± 21/74 ± 12 mm Hg (P = 0.021) and torsemide reduced it from 143 ± 18/75 ± 10 mm Hg to 133 ± 19/71 ± 10 mm Hg (P = 0.007). Conclusion. Patients with CKD have elevated extracellular fluid volume that can be corrected acutely with loop diuretics. Persistent diuretic use results in dynamic changes in ECW and other body fluid compartments that translate into chronic blood pressure reduction.

AB - Background. The pathophysiology of hypertension in patients with chronic kidney disease (CKD) is largely attributed to positive sodium balance. It is unclear how loop diuretics affect fluid volume compartments, especially with respect to their antihypertensive effect. Methods. Subjects with CKD were administered a single therapeutically equivalent dose of an oral loop diuretic (furosemide or torsemide in randomized crossover design). We measured acute volume changes over 12 hours using biophysical and hormonal biomarkers and then 24-hour ambulatory blood pressure after daily diuretic therapy for 3 weeks. Results. Single-dose administration of loop diuretic decreased extracellular water (ECW) by 1.7 L [95% confidence interval (95% CI) 1.2, 2.2, P <0.001], total body water (TBW) by 1.2 L (95% CI 0.5, 1.9, P <0.001), and increased natural log (ln) plasma renin activity (PRA) from -1.2 ± 1.3 ng/mL/ hour to -0.5 ± 1.5 ng/mL/hour (P <0.001). Daily loop diuretic administration resulted in reduced ECW from 24.2 ± 6.4 L to 22.3 ± 5.2 L (P = 0.02) and TBW from 54.3 ± 12.7 L to 51.6 ± 11.9 L (P <0.001) in 1 week. After 3 weeks of diuretic therapy, whereas ECW reduction persisted at 22.8 ± 5.1 L (P = 0.05), TBW trended toward baseline level at 52.7 ± 11.8 L. A concomitant increase in ln PRA from -1.0 ± 1.3 ng/mL/hour to 0.4 ± 1.9 ng/mL/hour (P <0.001) and ln plasma aldosterone (PA) from 2.0 ± 0.8 ng/dL to 2.3 ± 0.8 ng/ dL (P <0.005) and fall in ln brain natriuretic peptide (BNP) from 4.3 ± 0.9 pg/mL to 3.7 ± 1.0 pg/mL (P <0.01) were seen at 1 week. Despite a trend toward restoration of TBW, changes in hormonal biomarkers were maintained at 3 weeks. Over these 3 weeks, furosemide reduced 24-hour ambulatory blood pressure from 147 ± 17/78 ± 11 mm Hg to 138 ± 21/74 ± 12 mm Hg (P = 0.021) and torsemide reduced it from 143 ± 18/75 ± 10 mm Hg to 133 ± 19/71 ± 10 mm Hg (P = 0.007). Conclusion. Patients with CKD have elevated extracellular fluid volume that can be corrected acutely with loop diuretics. Persistent diuretic use results in dynamic changes in ECW and other body fluid compartments that translate into chronic blood pressure reduction.

KW - Brain natriuretic peptide

KW - Chronic renal failure

KW - Diuretics

KW - Electrical impedance

KW - Furosemide

KW - Plasma aldosterone

KW - Plasma renin activity

KW - Randomized controlled trial

KW - Torsemide

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