The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study - PubMed (original) (raw)

Clinical Trial

The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study

R Rachmani et al. Diabet Med. 2004 May.

Retraction in

Abstract

Objective: The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension.

Patients and methods: Sixty female diabetic patients aged 45-70 years with blood pressure (BP) 140-180/90-110 mmHg, serum creatinine (sCr) < or = 160 micro mol/l, HbA(1c) < or = 10%, and albuminuria were treated by atenolol 12.5-75 mg/d and hydrochlorothiazide 6.25-25 mg/d. Titration-to-target helped to reach BP values < or = 135/85 mmHg in 46 patients after 12 weeks. These patients were randomized to spironolactone 100 mg/d or cilazapril 5 mg/d for 24 weeks. Then both groups received spironolactone 50 mg/d and cilazapril 2.5 mg/d for 24 weeks. BP was stabilized by tapering the dose of the initial agents. Urinary albumin/creatinine ratio (ACR), BP, K(+). sCr and HbA(1c) were assessed at baseline and at weeks 12, 16, 36 and 60.

Results: The average BP at week 12 was 128 +/- 4/81 +/- 3 mmHg and remained constant, in both groups, throughout the study. ACR declined on spironolactone from a median value (range) of 452 (124-1571) to 216 (64-875) mg/g (P = 0.001), and on cilazapril to 302 (90-975) mg/g (P = 0.001). The difference between spironolactone and cilazapril was significant (P = 0.002). Combined treatment resulted in a further modest decline in ACR. Serum creatinine was unaltered by spironolactone and rose slightly (121 to 126 micro mol/l, P = 0.02) on cilazapril.

Conclusion: At the doses tested, spironolactone was superior to cilazapril in reducing albuminuria. Combined administration was more effective than either drug alone. These effects were independent of BP values. Hyperkalaemia was the main side-effect.

PubMed Disclaimer

Cited by

Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021.
Banerjee D, Winocour P, Chowdhury TA, De P, Wahba M, Montero R, Fogarty D, Frankel AH, Karalliedde J, Mark PB, Patel DC, Pokrajac A, Sharif A, Zac-Varghese S, Bain S, Dasgupta I; Association of British Clinical Diabetologists and The Renal Association. Banerjee D, et al. BMC Nephrol. 2022 Jan 3;23(1):9. doi: 10.1186/s12882-021-02587-5. BMC Nephrol. 2022. PMID: 34979961 Free PMC article.
Glomerular Mesangial Cell pH Homeostasis Mediates Mineralocorticoid Receptor-Induced Cell Proliferation.
Gekle M, Mildenberger S. Gekle M, et al. Biomedicines. 2021 Aug 30;9(9):1117. doi: 10.3390/biomedicines9091117. Biomedicines. 2021. PMID: 34572303 Free PMC article.
A Pilot Trial on the Effect of Levothyroxine on Proteinuria in Patients With Advanced CKD.
Blackaller GN, Chávez-Iñiguez JS, Carreón-Bautista EE, González-Torres FJ, Villareal-Contreras M, Barrientos Avalos JR, Aguilera PM, Rosales FR, José Antonio TM, Gómez Fregoso JA, Michel Gonzalez JI, García-García G. Blackaller GN, et al. Kidney Int Rep. 2020 Dec 3;6(1):110-119. doi: 10.1016/j.ekir.2020.10.016. eCollection 2021 Jan. Kidney Int Rep. 2020. PMID: 33426390 Free PMC article.
Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease.
Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Chung EY, et al. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4. Cochrane Database Syst Rev. 2020. PMID: 33107592 Free PMC article.
Aldosterone and the mineralocorticoid receptor in renal injury: A potential therapeutic target in feline chronic kidney disease.
Spencer S, Wheeler-Jones C, Elliott J. Spencer S, et al. J Vet Pharmacol Ther. 2020 May;43(3):243-267. doi: 10.1111/jvp.12848. Epub 2020 Mar 3. J Vet Pharmacol Ther. 2020. PMID: 32128854 Free PMC article. Review.

The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study - PubMed (original) (raw)