Tags

Type your tag names separated by a space and hit enter

Diuretic uptitration with half dose combined ACEI + ARB better decreases proteinuria than combined ACEI + ARB uptitration.
Nephrol Dial Transplant. 2010 Jul; 25(7):2218-24.ND

Abstract

BACKGROUND

Residual proteinuria is a strong modifiable risk factor for renal failure progression. We previously showed that the antiproteinuric effect of combined half doses of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) is increased by raising diuretic dosage. Methods. We tested whether uptitration of loop diuretics on top of combined half doses of ACEI and ARB would better decrease proteinuria than uptitration to combined full doses of ACEI and ARB in a randomized, crossover, three periods of 6-week controlled study. Eighteen patients with stable proteinuria over 1 g/day with combined ramipril at 5 mg/day and valsartan at 80 mg/day in addition to conventional antihypertensive treatments were randomized to receive combined ramipril at 5 mg/day and valsartan at 80 mg/day, or combined ramipril at 10 mg/day and valsartan at 160 mg/day, or combined ramipril at 5 mg/day, valsartan at 80 mg/day and increased furosemide dosage in random order. The primary end point was the mean urinary protein/creatinine ratio in two 24-hour urine collections at the end of the three treatment periods. Secondary end points included mean 24-hour proteinuria, home systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP) and estimated glomerular filtration rate (eGFR) levels.

RESULTS

The geometric mean urinary protein/creatinine ratio was lower with combined ramipril at 5 mg/day, valsartan at 80 mg/day and increased furosemide dosage compared to combined ramipril at 5 mg/day and valsartan at 80 mg/day, but also to combined ramipril at 10 mg/day and valsartan at 160 mg/day. These differences remained significant after adjustment for SBP, DBP or MAP and 24-hour natriuresis but not after adjustment on eGFR. Diuretic dosage uptitration did not increase the number of home systolic blood pressure measurements below 100 mmHg, but led to a statistically significant increase in the number of symptomatic hypotension episodes.

CONCLUSIONS

A cautious uptitration of loop diuretic dosage in addition to combined half doses of ACEI and ARB better decrease proteinuria in patients with CKD and high residual proteinuria than uptitration to full dose of combined ACEI and ARB. This antiproteinuric effect of diuretics was partly explained by an eGFR decrease, suggesting the contribution of haemodynamic modifications, whose safety on the long term still need to be addressed.

Authors+Show Affiliations

Nephrology, Nice University Hospital, Nice Sophia-Antipolis University, Nice, France. esnault.v@chu-nice.frNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20106824

Citation

Esnault, Vincent L M., et al. "Diuretic Uptitration With Half Dose Combined ACEI + ARB Better Decreases Proteinuria Than Combined ACEI + ARB Uptitration." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 25, no. 7, 2010, pp. 2218-24.
Esnault VL, Ekhlas A, Nguyen JM, et al. Diuretic uptitration with half dose combined ACEI + ARB better decreases proteinuria than combined ACEI + ARB uptitration. Nephrol Dial Transplant. 2010;25(7):2218-24.
Esnault, V. L., Ekhlas, A., Nguyen, J. M., & Moranne, O. (2010). Diuretic uptitration with half dose combined ACEI + ARB better decreases proteinuria than combined ACEI + ARB uptitration. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 25(7), 2218-24. https://doi.org/10.1093/ndt/gfp776
Esnault VL, et al. Diuretic Uptitration With Half Dose Combined ACEI + ARB Better Decreases Proteinuria Than Combined ACEI + ARB Uptitration. Nephrol Dial Transplant. 2010;25(7):2218-24. PubMed PMID: 20106824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diuretic uptitration with half dose combined ACEI + ARB better decreases proteinuria than combined ACEI + ARB uptitration. AU - Esnault,Vincent L M, AU - Ekhlas,Amr, AU - Nguyen,Jean-Michel, AU - Moranne,Olivier, Y1 - 2010/01/26/ PY - 2010/1/29/entrez PY - 2010/1/29/pubmed PY - 2010/11/4/medline SP - 2218 EP - 24 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 25 IS - 7 N2 - BACKGROUND: Residual proteinuria is a strong modifiable risk factor for renal failure progression. We previously showed that the antiproteinuric effect of combined half doses of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) is increased by raising diuretic dosage. Methods. We tested whether uptitration of loop diuretics on top of combined half doses of ACEI and ARB would better decrease proteinuria than uptitration to combined full doses of ACEI and ARB in a randomized, crossover, three periods of 6-week controlled study. Eighteen patients with stable proteinuria over 1 g/day with combined ramipril at 5 mg/day and valsartan at 80 mg/day in addition to conventional antihypertensive treatments were randomized to receive combined ramipril at 5 mg/day and valsartan at 80 mg/day, or combined ramipril at 10 mg/day and valsartan at 160 mg/day, or combined ramipril at 5 mg/day, valsartan at 80 mg/day and increased furosemide dosage in random order. The primary end point was the mean urinary protein/creatinine ratio in two 24-hour urine collections at the end of the three treatment periods. Secondary end points included mean 24-hour proteinuria, home systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP) and estimated glomerular filtration rate (eGFR) levels. RESULTS: The geometric mean urinary protein/creatinine ratio was lower with combined ramipril at 5 mg/day, valsartan at 80 mg/day and increased furosemide dosage compared to combined ramipril at 5 mg/day and valsartan at 80 mg/day, but also to combined ramipril at 10 mg/day and valsartan at 160 mg/day. These differences remained significant after adjustment for SBP, DBP or MAP and 24-hour natriuresis but not after adjustment on eGFR. Diuretic dosage uptitration did not increase the number of home systolic blood pressure measurements below 100 mmHg, but led to a statistically significant increase in the number of symptomatic hypotension episodes. CONCLUSIONS: A cautious uptitration of loop diuretic dosage in addition to combined half doses of ACEI and ARB better decrease proteinuria in patients with CKD and high residual proteinuria than uptitration to full dose of combined ACEI and ARB. This antiproteinuric effect of diuretics was partly explained by an eGFR decrease, suggesting the contribution of haemodynamic modifications, whose safety on the long term still need to be addressed. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/20106824/Diuretic_uptitration_with_half_dose_combined_ACEI_+_ARB_better_decreases_proteinuria_than_combined_ACEI_+_ARB_uptitration_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfp776 DB - PRIME DP - Unbound Medicine ER -