Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Comparison between the effects of hydrochlorothiazide and indapamide on the kidney in hypertensive patients inadequately controlled with losartan

Abstract

The aim of the study is to compare the effects of hydrochlorothiazide and indapamide on the kidney in patients with hypertension inadequately controlled with losartan. A total of 140 patients who met the criteria and inadequately controlled with losartan 50 mg per day for 2 weeks were randomized in two groups and administered either hydrochlorothiazide 12.5 mg per day (n=70) or indapamide (sustained release) 1.5 mg per day (n=70) in combination with losartan 50 mg per day. Office blood pressure (BP) were collected at baseline and upon each follow-up visit. Creatinine, urine albumin–creatinine ratio (ACR), urine neutrophil gelatinase-associated lipocalin (NGAL) and renal resistive index (RRI) were also collected at baseline and at the 24-week follow-up. None of the baseline characteristics was statistically significantly different between the two groups. After excluding those patients with office BP uncontrolled, 46 patients in the hydrochlorothiazide group (45.7% males, 58.8±10.8 years) and 44 patients in the indapamide group (38.4% males, 61.5±10.9 years) were analysed. There were insignificant changes in creatinine and significant decreases in ACR, NGAL and RRI compared to baseline levels in the two groups. The decrease in ACR (3.8 (0, 28.7) vs 4.2 (0.4, 64.8) mg g−1, P=0.485) was not significantly different between the two groups, while the decrease in NGAL (16.07±7.07 vs 28.77±7.64 ng ml−1, P<0.001) and RRI (0.04±0.02 vs 0.07±0.04, P<0.001) was more significant in the indapamide group than in the hydrochlorothiazide group. In conclusion, indapamide is superior to hydrochlorothiazide to improve renal tubular injury and renal haemodynamics in combination with losartan in hypertensive patients with controlled BP.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M et al. ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34: 2159–2219.

    Article  Google Scholar 

  2. Roush GC, Ernst ME, Kostis JB, Tandon S, Sica DA . Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension 2015; 65: 1041–1046.

    Article  CAS  Google Scholar 

  3. Vinereanu D, Dulgheru R, Magda S, Dragoi Galrinho R, Florescu M, Cinteza M et al. The effect of indapamide versus hydrochlorothiazide on ventricular and arterial function in patients with hypertension and diabetes: results of a randomized trial. Am Heart J 2014; 168: 446–456.

    Article  CAS  Google Scholar 

  4. Redon J, Pascual JM . Development of microalbuminuria in essential hypertension. Curr Hypertens Rep 2006; 8: 171–177.

    Article  CAS  Google Scholar 

  5. Pascual JM, Rodilla E, Costa JA, Garcia-Escrich M, Gonzalez C, Redon J . Prognostic value of microalbuminuria during antihypertensive treatment in essential hypertension. Hypertension 2014; 64: 1228–1234.

    Article  CAS  Google Scholar 

  6. Fassett RG, Venuthurupalli SK, Gobe GC, Coombes JS, Cooper MA, Hoy WE . Biomarkers in chronic kidney disease: a review. Kidney Int 2011; 80: 806–821.

    Article  CAS  Google Scholar 

  7. Nielsen SE, Schjoedt KJ, Astrup AS, Tarnow L, Lajer M, Hansen PR et al. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril. Diabet Med 2010; 27: 1144–1150.

    Article  CAS  Google Scholar 

  8. Bhavsar NA, Köttgen A, Coresh J, Astor BC . Neutrophil gelatinaseassociated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) as predictors of incident CKD stage 3: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis 2012; 60: 233–240.

    Article  CAS  Google Scholar 

  9. Radermacher J, Ellis S, Haller H . Renal resistance index and progression of renal disease. Hypertension 2002; 39: 699–703.

    Article  CAS  Google Scholar 

  10. Ikee R, Kobayashi S, Hemmi N, Imakiire T, Kikuchi Y, Moriya H et al. Correlation between the resistive index by Doppler ultrasound and kidney function and histology. Am J Kidney Dis 2005; 46: 603–609.

    Article  Google Scholar 

  11. Václavík J, Sedlák R, Plachy M, Navrátil K, Plásek J, Jarkovsky J et al. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension 2011; 57: 1069–1075.

    Article  Google Scholar 

  12. Singer E, Elger A, Elitok S, Kettritz R, Nickolas TL, Barasch J et al. Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney Int 2011; 80: 405–414.

    Article  CAS  Google Scholar 

  13. Circelli M, Nicolini G, Egan CG, Cremonesi G . Efficacy and safety of delapril/indapamide compared to different ACE-inhibitor/hydrochlorothiazide combinations: a meta-analysis. Int J Gen Med 2012; 5: 725–734.

    Article  CAS  Google Scholar 

  14. Krum H, Skiba M, Gilbert RE . Comparative metabolic effects of hydrochlorothiazide and indapamide in hypertensive diabetic patients receiving ACE inhibitor therapy. Diabet Med 2003; 20: 708–712.

    Article  CAS  Google Scholar 

  15. Erley CM, Risler T . Microalbuminuria in primary hypertension: Is it a marker of glomerular damage? Nephrol Dial Transplant 1995; 9: 1713–1715.

    Google Scholar 

  16. Leoncini G, Viazzi F, Vercelli M, Deferrari G, Pontremoli R . Metabolic syndrome and microalbuminuria predict renal outcome in non-diabetic patients with primary hypertension: the MAGIC study. J Hum Hypertens 2012; 26: 149–156.

    Article  CAS  Google Scholar 

  17. Fujisaki K, Tsuruya K, Nakano T, Taniguchi M, Higashi H, Katafuchi R et al. Impact of combined losartan/hydrochlorothiazide on proteinuria in patients with chronic kidney disease and hypertension. Hypertens Res 2014; 37: 993–998.

    Article  CAS  Google Scholar 

  18. Mogensen CE, Viberti G, Halimi S, Ritz E, Ruilope L, Jermendy G et al. Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER. Hypertension 2003; 41: 1063–1071.

    Article  CAS  Google Scholar 

  19. Bakris GL, Toto RD, McCullough PA, Rocha R, Purkayastha D, Davis P . Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study. Kidney Int 2008; 73: 1303–1309.

    Article  CAS  Google Scholar 

  20. Cowland JB, Sorensen OE, Sehested M, Borregaard N . Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1b, but not by TNF-a. J Immunol 2003; 171: 6630–6639.

    Article  CAS  Google Scholar 

  21. Leoncini G, Mussap M, Viazzi F, Fravega M, Degrandi R, Bezante GP et al. Combined use of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and albumin as markers of early cardiac damage in primary hypertension. Clin Chim Acta 2011; 412: 1951–1956.

    Article  CAS  Google Scholar 

  22. Hvidberg V, Jacobsen C, Strong RK, Cowland JB, Moestrup SK, Borregaard N . The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett 2005; 579: 773–777.

    Article  CAS  Google Scholar 

  23. Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P et al. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2007; 18: 407–413.

    Article  CAS  Google Scholar 

  24. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol 2009; 4: 337–344.

    Article  CAS  Google Scholar 

  25. Mai M, Geiger H, Hilgers KF, Veelken R, Mann JF, Dämmrich J et al. Early interstitial changes in hypertensioninduced renal injury. Hypertension 1993; 22: 754–765.

    Article  CAS  Google Scholar 

  26. Tylicki L, Manitius J, Łysiak-Szydłowska W, Rutkowski B . Tubular injury: the first symptom of hypertensive kidney involvement? Med Sci Monit 2003; 9: 135–141.

    Google Scholar 

  27. Kasahara M, Mori K, Satoh N, Kuwabara T, Yokoi H, Shimatsu A et al. Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients. Nephrol Dial Transplant 2009; 24: 2608–2609.

    Article  CAS  Google Scholar 

  28. Nosadini R, Velussi M, Brocco E, Abaterusso C, Carraro A, Piarulli F et al. Increased renal arterial resistance predicts the course of renal function in type 2 diabetes with microalbuminuria. Diabetes 2006; 55: 234–239.

    Article  CAS  Google Scholar 

  29. Okura T, Kurata M, Irita J, Enomoto D, Jotoku M, Nagao T et al. Renal resistance index is a marker of future renal dysfunction in patients with essential hypertension. J Nephrol 2010; 23: 175–180.

    PubMed  Google Scholar 

  30. Caruso D, D'Avino M, Acampora C, Romano L, Bevilacqua N, Caruso G et al. Effects of losartan and chlorthalidone on blood pressure and renal vascular resistance index in non-diabetic patients with essential hypertension and normal renal function. J Cardiovasc Pharmacol 2004; 44: 520–524.

    Article  CAS  Google Scholar 

  31. Tamargo J, Segura J, Ruilope LM . Diuretics in the treatment of hypertension. Part 1: thiazide and thiazide-like diuretics. Expert Opin Pharmacother 2014; 15: 527–547.

    Article  CAS  Google Scholar 

  32. Hayashi K, Wakino S, Sugano N, Ozawa Y, Homma K, Saruta T . Ca2+ channel subtypes and pharmacology in the kidney. Circ Res 2007; 100: 342–353.

    Article  CAS  Google Scholar 

  33. Roush GC, Kaur R, Ernst ME . Diuretics: a review and update. J Cardiovasc Pharmacol Ther 2014; 19: 5–13.

    Article  CAS  Google Scholar 

  34. Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JJ, Phillips BB, Zimmerman MB et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension 2006; 47: 352–358.

    Article  CAS  Google Scholar 

  35. Hansson L, Hedner T, Dahlöf B . Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective Randomized Open Blinded End-Point. Blood Press 1992; 1: 113–119.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all patients who took part in the studies and the staff in the Laboratory Medicine Department and Endocrine Laboratory of West China Hospital, Sichuan University. This study was funded by the project of the Science and Technology Department in Sichuan Province (2011SZ0207).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to X Chen.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, S., Li, J., Zhou, X. et al. Comparison between the effects of hydrochlorothiazide and indapamide on the kidney in hypertensive patients inadequately controlled with losartan. J Hum Hypertens 31, 848–854 (2017). https://doi.org/10.1038/jhh.2017.51

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2017.51

This article is cited by

Search

Quick links