title: An association of losartan-hydrochlorothiazide, but not losartan-furosemide, completely arrests progressive injury in the remnant kidney.
abstract: We have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease.
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Simone Costa Alarcon
authors.initials: SC
authors.lastname: Arias
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Renata Alves
authors.initials: RA
authors.lastname: Souza
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Denise Maria Avancini Costa
authors.initials: DM
authors.lastname: Malheiros
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Camilla
authors.initials: C
authors.lastname: Fanelli
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Clarice Kazue
authors.initials: CK
authors.lastname: Fujihara
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil roberto.zatz@gmail.com.
authors.forename: Roberto
authors.initials: R
authors.lastname: Zatz
mesh_terms: D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004338:Drug Combinations; D005665:Furosemide / Q000494:pharmacology* / Q000627:therapeutic use; D006852:Hydrochlorothiazide / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*
chemical_list: D004338:Drug Combinations; C505809:hydrochlorothiazide, losartan drug combination; D006852:Hydrochlorothiazide; D005665:Furosemide; D019808:Losartan
keywords: 5/6 nephrectomy; chronic kidney disease; furosemide; thiazides