Saudi Journal of Kidney Diseases and Transplantation

ORIGINAL ARTICLE
Year
: 2011  |  Volume : 22  |  Issue : 1  |  Page : 75--78

Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension


Rozita Abolghasmi, Omolbanin Taziki 
 Nephrology Department, Shahid Beheshti University of Medical Science, Imam Hosein Hospital, Tehran, Iran

Correspondence Address:
Rozita Abolghasmi
Imam Hosein Hospital, Shaheed Madani Street, Tehran
Iran

Abstract

To determine the antihypertensive benefit of adding low dose sprinolactone to multi­drug regimens that included a diuretic, a calcium channel blocker and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in patients with moderately severe chronic kidney disease (CKD) [glomerular filtration rate (GFR) 25-50 mL/min] and resistant hyper­tension, we studied 41 patients randomly divided into two groups: group 1: patients who received placebo as spironolactone and group 2: patients who received spironolactone 25-50 mg/day. The patients were evaluated during follow-up at the 6th and 12th weeks. The mean decrease in systolic and diastolic blood pressure after 6 weeks of spironolactone was 33 ± 8 and 13 ± 2 mmHg, respectively, and it was maintained after 12 weeks of spironolactone wherein the values were 36 ± 10 and 12 ± 2 mmHg, respectively, while there was no change in the blood pressure in the control group. Hyperkalemia (serum potassium >5.5 meq/L) occurred in one subject in the spironolactone group. We conclude that low-dose spironolactone may provide a significant additive blood pressure reduction in CKD patients (stage 2 and 3) with resistant hypertension.



How to cite this article:
Abolghasmi R, Taziki O. Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension.Saudi J Kidney Dis Transpl 2011;22:75-78


How to cite this URL:
Abolghasmi R, Taziki O. Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2020 Aug 11 ];22:75-78
Available from: http://www.sjkdt.org/text.asp?2011/22/1/75/74355


Full Text

 Introduction



Resistant hypertension defined as a failure of use of three or more different classes of anti­hypertensive agents to control blood pressure (BP) to <140/90 mmHg remains a common clinical problem, especially in chronic kidney disease (CKD). Recent clinical trials suggest that 30% of hypertensive patients may be resistant to triple therapy combination. [1]

Angiotensin-converting enzyme (ACE) inhi­bitors are potent members of the armamen­tarium to treat hypertension in CKD patients. This class of drugs also reduces proteinuria and slows progression of CKD by reducing BP and decreasing intraglomerular pressure. [2],[3] Al­dosterone, the end product of the rennin-an­giotensin-aldosterone system (RAAS), has at­tracted renewed attention as an important me­diator of both cardiovascular and renal disease. [4],[5] Moreover, aldosterone blockade has been shown to greatly im-prove survival in patients with chronic heart failure. [6],[7]

The current study was designed to determine the anti-hypertensive benefit of low dose spi­ronolactone (25 mg/day) as an add-on therapy in patients with resistant hypertension.

 Patients and Methods



We studied 41 patients with moderately severe CKD [glomerular filtration rate (GFR) 25-50 mL/min] and resistant hypertension, randomly divided into two groups in a double-blind fa­shion, as follows: group 1: 22 patients who re­ceived placebo as spironolactone and group 2: 19 patients who received spironolactone 25-50 mg/day. The patients in both the groups were matched for age and sex and antihypertensive drug. All the patients signed written informed consents be-fore enrollment. Resistant hyper­tension was defined as uncontrolled hyperten­sion, as determined at two or more clinic vi­sits, in spite of the use of three or more anti­hypertensive medications at pharmacologically effective doses, including a diuretic, an ACE inhibitor, and calcium channel blocker. The patients were required to be on the same anti­hypertensive regimen for at least 4 weeks be­fore evaluation.

Spironolactone, amiloride or triamterene were discontinued in all the patients for at least 6 weeks before the start of the study. None of the study patients was on treatment with erythro­poietin. Other secondary causes of hyperten­sion such as reno-vascular, primary aldostero­nism, pheochromocytoma or Cushing syndrome had been excluded by laboratory analysis or radiological imaging as clinically indicated. All the study patients were encouraged to limit salt intake to less than 6 g/day.

Fasting plasma blood urea nitrogen (BUN), creatinine, sodium, and potassium levels were estimated. A 24-hour urinary collection for so­dium (UNA) and creatinine was obtained three times during the study period.

Blood tests were repeated at 6 and 12 weeks. Serum potassium, BUN, creatinine were checked at each follow-up visit and 2 weeks after ini­tiation of spironolactone therapy.

Blood pressure was measured by a physician according to the American Heart Association guidelines. If the systolic BP was not con­trolled, the spironolactone dose was increased from the initial 25 mg/day up to 50 mg/day.

 Statistical Analysis



Values were expressed as the mean ± stan­dard deviation (SD). Values between groups or time periods were compared by Student's "t" test or by one-way analysis of variance (ANO­VA). A P-value <0.05 was considered signi­ficant.

 Results



Baseline characteristics of the study patients are shown in [Table 1]. There were no diffe­rences in the characteristics between the study groups.

The comparison of the response to therapy and side effects are shown in [Table 2]. The mean decrease in systolic and diastolic BP after 6 weeks of spironolactone was 33 ± 8 and 13 ± 2 mmHg, respectively, and it was maintained after 12 weeks of spironolactone, i.e., the mean decrease was 36 ± 10 and 12 ± 2 mmHg, res­pectively, while there was no change in the BP in the control group. BP did not change in the control group after six and 12 weeks of therapy. Hyperkalemia (serum potassium > 5.5 mmol/L) occurred in one patient in the spironolactone group.{Table 1}{Table 2}

 Discussion



The results of this study demonstrate that low-dose spironolactone can induce substantial BP reduction when added to multi-drug regi­mens in CKD patients. Other studies showed that spironolactone could reduce BP in the non-CKD patients with resistant hypertension without hyperaldeosteronism . [8]

Extra-adrenal tissue may synthesize aldoste­rone. The vasculature, kidney and heart have been reported as sites of synthesis. [9],[10] Besides the well-documented effect of aldosterone to expand extra-cellular volume with the net re­sult of hypertension, direct vascular actions of aldosterone have been proposed. Systemic vas­cular resistance has been reported to change modestly in response to acute aldosterone in­fusion in normal humans. [11]

In the remnant kidney model of CKD, ACE inhibitors and angiotensin receptor blockers (ARB) attenuate renal injury. [12],[13] However, this protection, which is associated with sup­pression of aldosterone secretion, is abrogated by exogenous aldosterone infusion with return of hypertension, proteinuria and nephroscle­ rosis. [14]

Adding spironolactone 25 mg/day to an ARB in 22 patients with chronic glomerulonephritis resulted in further BP reduction and a 13% decrease in proteinuria. [15]

One study showed a strong correlation bet­ween aldosterone levels and degree of proteinuria, [16] and others supported this association. [15],[17]

Even though data thus far are encouraging to use aldosterone antagonists in reducing protei­nuria and BP, larger studies with long-term follow-up are still required.

In our study, hyperkalemia was observed in one patient. Another study showed a signifi­cant increase in serum potassium with eple­renone use regardless of renal function. [18]

We conclude that a low-dose spironolactone may provide a significant additive BP reduc­tion in CKD patients (stage 2 and 3) with re­sistant hypertension. Larger clinical studies are warranted to address more definitively the safety and efficacy of aldosterone antagonists in CKD patients.

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