How to improve duration and efficiency of the antiproteinuric response to Ramipril: RamiPROT—a prospective cohort study
- 285 Downloads
The antiproteinuric pharmacokinetics of Ramipril in response to different doses and modalities of administration has been poorly investigated so far.
Prospective, open-label and not placebo controlled study.
Setting and participants
40 Caucasian adult patients having GFR ≥ 50 mL/min, proteinuria 1–3 g/day; SBP/DBP ≤ 150/90 mmHg were recruited between June 2014 and November 2014.
Factor and outcome
Impact on 24 h proteinuria and fractioned proteinuria of Ramipril given at different dosages (2.5 mg/day or Ramipril 5 mg/day or Ramipril 10 mg/day) and with different daily administration modalities (single or two divided doses) for cycles of 10 days.
At the end of each cycle, 24 h and fractioned proteinuria on three timed urinary collections (morning, afternoon and night) were measured.
Compared to baseline, Ramipril significantly reduced 24 h proteinuria at each dose and modality of administration. In particular, the greatest effects were evident with the higher and divided dose of the drug. The analysis of the fractioned proteinuria showed that the greatest reduction was obtained in the night urinary collection by administering Ramipril 10 mg/day in two divided doses.
Small sample size.
Ramipril reduces proteinuria at any of the tested doses. Although the using of high and divided doses seems to maximize the antiproteinuric effect of the drug, possibly due to a better pharmacological coverage of the nocturnal period.
KeywordsACE-inhibitors CKD Pharmacokinetics Pharmacodynamics Proteinuria
Compliance with ethical standards
Conflict of interest
All authors have none conflict of interest to declare.
All procedures performed on humans were in accordance with the ethical standards of the local Medical Ethics Committee (approval number: 2011/42) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE et al (2003) Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med 139(4):244–252. doi: 10.7326/0003-4819-139-4-200308190-00006 CrossRefPubMedGoogle Scholar
- 3.Ruggenenti P, Perna A, Mosconi L, Pisoni R, Remuzzi G (1998) Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Kidney Int 53(5):1209–1216. doi: 10.1046/j.1523-1755.1998.00874.x CrossRefPubMedGoogle Scholar
- 5.Simeoni M, Nicotera R, Colao M, Citraro ML, Pelagi E, Cerantonio A et al (2015) Direct inhibition of plasmatic renin activity with aliskiren: a promising but under-investigated therapeutic option for non-diabetic glomerulonephritis. Int Urolol Nephrol. doi: 10.1007/s11255-015-1128-4
- 9.Eijkelkamp WB, Zhang Z, Remuzzi G, Parving HH, Cooper ME, Keane WF et al (2007) Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial. J Am Soc Nephrol 18(5):1540–1546. doi: 10.1681/ASN.2006050445 CrossRefPubMedGoogle Scholar
- 12.Simeoni M, Cianfrone P, Comi N, Gentile I, Fabiano FF, Piraina V et al (2015) Is it feasible to improve the duration and the efficiency of Ramipril anti-proteinuric response? G Ital Nefrol 32(1)Google Scholar
- 16.Simeoni M, Cerantonio A, Pastore I, Liguori R, Greco M, Foti D et al (2015) The correct renal function evaluation in patients with thyroid dysfunction. J Endocrinol Invest. doi: 10.1007/s40618-015-0402-8
- 17.Goncalves AR, Fujihara CK, Mattar AL et al (2004) Renal expression of COX-2, ANG II, and AT1 receptor in remnant kidney: strong renoprotection by therapy with losartan and a nonsteroidal anti-inflammatory. Am J Physiol Renal Physiol 286(5):F945–F954. doi: 10.1152/ajprenal.00238 CrossRefPubMedGoogle Scholar
- 18.Benigni A, Tomasoni S, Gagliardini E et al (1046) 2001 Blocking angiotensin II synthesis/activity preserves glomerular nephrin in rats with severe nephrosis. J Am Soc Nephrol 12(5):941–948Google Scholar