Espironolactona en diálisis

María Juliana Valenzuela-Rangel

Residente de Medicina Interna

Universidad de La Sabana
 ORIGINAL PAPER

Effects of Spironolactone on Dialysis Patients With Refractory

Hypertension: A Randomized Controlled Study
Xiaoying Ni, BS;1,* Jisheng Zhang, BS;2,* Ping Zhang, PhD;3,* Fuquan Wu, BS;2 Min Xia, BS;2 Guanghui Ying, BS;2
3
Jianghua Chen, PhD

From the Department of Nephrology, People’s Hospital of Yinzhou, College of Medicine, Ningbo University;1 Department of Nephrology, Beilun
Branch of the First Affiliated Hospital;2 and Department of Nephrology, The First Affiliated Hospital, College of Medicine, Zhejiang University,
Hangzhou, China3

The purpose of this study was to evaluate the effects of hypertension. Average placebo-corrected morning BP was
Evaluar los efectos de la espironolactona en pacientes
spironolactone on dialysis patients with refractory hyperten- en diálisis con hipertensión refractaria y posibles
reduced by 16.7/7.6 mm Hg. Mean 24-hour ambulatory BP
efectos
sion andadversos
possible adverse effects. This was a 12-week was reduced by 10.9/5.8 mm Hg. In contrast, serum
prospective, randomized, double-blind trial of 82 patients aldosterone levels in the spironolactone group slightly
•randomly
Prospectivo,
assignedaleatorizado, doble ciego,
to 12-week treatment with 12
25 semanas,
mg/d 82 pacientes.
increased

and serum potassium levels insignificantly

•spironolactone
Tratamientoorde 12 semanas
placebo as add-oncon espironolactona
therapy. Visits were 25 increased.
mg / día This
Vs. study
placebo como terapia
has demonstrated that spironolactone
scheduled at the start of treatment and after 12 weeks.
complementaria (50 mg) safely and effectively reduces BP in patients with
Measurements of 24-hour ambulatory blood pressure (BP) refractory hypertension undergoing dialysis. J Clin Hyper-
monitoring and morning BP were performed. After tens (Greenwich). 2014;16:658–663. ª 2014 Wiley Periodi-
12 weeks, spironolactone significantly improved refractory cals, Inc.
La HTA más frecuente en personas con ERC terminal
Suele ser, especialmente en HD, resistente a la terapia y refractaria a intervenciones médicas.

Resistente: PA no controlada en dosis óptimas de ≥3 agentes antihipertensivos

Causas secundarias: SAHOS, hiperaldosteronismo, enf. renovascular: COEXISTEN

Espironolactona
En sospecha de hiperaldosteronismo
Síndrome neurótico
Falla cardíaca
Cirrosis

En diálisis, ¿efectos secundarios?

 Mean body weight, kg 67.5!10.8 66.8!12.2
Effect of Spironolactone in Dialysis Patients With Refractory Hypertension | Ni et al.
Mean urine volume, %
Resultados <100 mL/24 h 77.5 80.6
>100 mL/24 h 22.5 29.4
received
Mean 25 mg/d,
morning BP, and
mm 70%
Hg (28 of 40) received 50 mg/
TABLE I. Sociodemographic and Clinical Data of
d. At 12 weeks after introduction of spironolactone, 4
Study Groups Systolic BP 153.5!12.5 151.5!16.5
patients required discontinuation because of adverse
Spironolactone Placebo Diastolic
effects, suchBPas gynecomastia, nausea, and92.5!14.5
hyperkalemia 89.5!12.0
Characteristics (n=40) (n=36) as opposed
Mean to 2 in the BP,
24-h ambulatory placebo group.
Age, y 55.7!12.3 54.9!14.2 The
mm potassium
Hg level rose in the spironolactone group,
Male sex, % 60.0 58.3 but not significantly different from the placebo group
Systolic BP 147.0!12.5 145.5!9.5
Primary kidney disease, % during the 12 weeks (P>.05). Serum potassium levels
Nephritis 60 61.1 Diastolicto
increased BP>5 mmol/L in 3 patients. Adverse
90.5!11.5events 90.0!13.5
Hypertensive nephropathy 5 5.5 including mastauxy and
Mean hemoglobin, g/L nausea were observed with the 12.2!4.9
12.3!5.7
Diabetic nephrology 15a 19.4 use of spironolactone.
Mean serum potassium, Adverse events led4.1!1.5
to discontin- 3.9!0.9
Polycystic kidney disease 5a 8.3 uation of medication in patients receiving spironolac-
mmol/L
Other 15 5.7 tone (2 due to hyperkalemia [5.66 vs 5.92 mmol/L], 1
Hypertension medications, No. 5.1!1.7 4.8!0.9 Mean
due serum sodium,and
to gynecomastia, mmol/L 137.3!1.7
1 due to nausea). 139.2!2.5
Type of antihypertensive medications, No. (%) Thereserum
Mean was no difference
intact in hs-CRP215.6!89.4
parathyroid or brain natri- 217.0!97.6
Calcium channel blockers 40 (100) 36 (100) uretic peptidepg/mL
before and after dialysis or between the
hormone,
b-Blockers 26 (65) 24 (66.7) spironolactone and placebo groups. The aldosterone
a-Blockers 12 (30) 10 (27.8) High-sensitivity C-reactive 7.8!2.6 8.3!0.9
level slightly increased in response to treatment with
Vasodilators 30 (75) 28 (77.8) protein, mg/L(23.8!10.9–24.5!11.0 pg/mL), but not
spironolactone
ACE inhibitors/ARBs 22 (55) 19 (52.8)
significantly
Mean time (P>.05).
on dialysis, mo 56.5!10.2 54.9!14.7
Central-acting agents 36 (90) 33 (91.7)
Modality of dialysis, HD, % 65.0 61.1 Comorbidity index 5.7!0.6 5.3!1.9
Smoking, % 12.5 11.1
DISCUSSION
KT/V 1.55!0.37 1.49!0.16
Smoker 30 30.6
Refractory hypertension is a common clinical problem
Mean body weight, kg 67.5!10.8 66.8!12.2
with an increasing
Abbreviations: prevalence rate that, enzyme;
ACE, angiotensin-converting if not suffi-
ARB, angioten-
Mean urine volume, % ciently
sin treated,
receptor causes
blocker; BP,ablood
high pressure;
risk for cardiovascular
HD, hemodialysis. The
<100 mL/24 h 77.5 80.6 morbidity and mortality. The prevalence of refractory
differences in proportions were tested using Pearson chi-square
14 test
>100 mL/24 h 22.5 29.4 hypertension is estimated to be up to 5% to 10%.
 Effect of Spironolactone in Dialysis Patients With Refractory Hypertension | Ni et al.

Resultados
TABLE II. Change in Primary and Secondary Variables After Intervention According to Study Group
Spironolactone (n=40) Placebo (n=36)

Primary variables
Mean morning SBP, mm Hg
Baseline 153.5!12.5 151.5!16.5
12 weeks 133.5!10.5 148.5!14.0
Mean change from baseline vs placebo (95% CI) "17.0 ("18 to "16) –
P value <.05 –
Mean morning DBP, mm Hg
Baseline 92.5!14.5 89.5!12.0
12 weeks 83.5!9.0 88.5!14.5
Mean change from baseline vs placebo (95% CI) "8 ("10 to "6.1) –
P value <.05 –
Mean 24-h ambulatory SBP, mm Hg
Baseline 147.0!12.5 145.5!9.5
12 weeks 135.5!9.0 146.0!11.5
Mean change from baseline vs placebo (95% CI) "12.5 ("13.8 to "11.2) –
P value <.05 –
Mean 24-h ambulatory DBP, mm Hg
Baseline 90.5!11.5 90.0!13.5
12 weeks 83.0!7.5 88.5!10.5
Mean change from baseline vs placebo (95% CI) "7.0 ("8.6 to "5.4) –
P value <.05 –
Secondary variables
 Baseline 90.5!11.5 90.0!13.5

Resultados12 weeks
Mean change from baseline vs placebo (95% CI)
83.0!7.5
"7.0 ("8.6 to "5.4)
88.5!10.5
–
P value <.05 –
Secondary variables
Mean body weight, kg
Baseline 67.5!10.8 66.8!12.2
12 weeks 67.8!14.2 66.9!9.8
Mean change from baseline vs placebo (95% CI) 0.2 ("1.1 to 1.5) –
P value >.05 –
Urine volume, mL/24 h
Baseline 336.8!209.4 344.5!178.5
12 weeks 321.5!197.3 353.9!183.2
Mean change from baseline vs placebo (95% CI) "24.7 ("28.9 to 20.5)
P value >.05
Mean serum potassium, mmol/L
Baseline 4.1!1.5 3.9!0.9
12 weeks 4.4!0.7 4.1!1.4
Mean change from baseline vs placebo (95% CI) 0.1 ("0.2 to 0.4) –
P value >.05 –
Mean plasma aldosterone, pg/mL
Baseline 23.8!10.9 23.4!10.2
12 weeks 24.5!11.0 23.5!9.8
Mean change from baseline vs placebo (95% CI) 0.6 (0.5–0.7) –
P value >.05 –
Mean high-sensitivity C-reactive protein, mg/L
Baseline 7.8!2.6 8.3!0.9
12 weeks 8.1!3.6 8.5!1.7
Mean change from baseline vs placebo (95% CI) 0.1 ("0.3 to 0.5) –
P value >.05 –
Resultados

La PA promedio por la mañana y la PA ambulatoria media se redujeron significativamente y la

hipertensión en la mayoría de los pacientes dentro de los 3 meses posteriores al inicio de la
espironolactona se controló adecuadamente

No aumentó el nivel sérico de potasio, lo que confirman las observaciones previas.

La espironolactona fue más segura en pacientes en diálisis que en pacientes sin diálisis, ya
que los riñones representan solo una pequeña parte del metabolismo del potasio, y la mayor
parte del potasio se excreta por diálisis.
Original Investigation

The Safety and Efficacy of Mineralocorticoid Receptor

Antagonists in Patients Who Require Dialysis: A Systematic
Review and Meta-analysis
1 1 2 3
Kevin Quach, MSc, Lyubov Lvtvyn, MSc, Colin Baigent, FRCP, Joe Bueti, MD,
4,5 6,7 2
Amit X. Garg, MD, PhD, Carmel Hawley, MBBS, MMedSci, Richard Haynes, DM,
8 ,9 10
Braden Manns, MD, MSc, Vlado Perkovic, MD, PhD,
11 12
Christian G. Rabbat, MD, MSc, Ron Wald, MDCM, MPH, and
1,11,13
Michael Walsh, MD, PhD

Background: Patients who require dialysis are at high risk for cardiovascular mortality, which may be
improved by mineralocorticoid receptor antagonists (MRAs).
Study Design: Systematic review and meta-analysis of randomized controlled trials.
Setting & Population: Adults undergoing long-term hemodialysis or peritoneal dialysis with or without heart
failure.
Selection Criteria for Studies: Randomized controlled trials evaluating an MRA in dialysis and reported at
 Effect of Spironolactone on Blood Pressure and the
Renin-Angiotensin-Aldosterone System in Oligo-Anuric
Hemodialysis Patients
Evan Gross, MD, Marcos Rothstein, MD, Susan Dombek, RN, and Henrikas Irmantas Juknis, MD

● Background: Through its actions on nonepithelial tissues, including brain, blood vessels, and heart, aldosterone
may mediate hypertension, cardiac hypertrophy, and fibrosis. Whether aldosterone has a direct pathogenic role in
the development of cardiovascular complications in patients with end-stage renal disease is unknown. Oligo-anuric
dialysis patients provide a clinical setting to study the effects of the mineralocorticoid receptor blocker spironolac-
tone that are independent of the diuretic properties of the drug. We performed a randomized, double-blinded,
placebo-controlled, crossover study to assess the effect of spironolactone on blood pressure and the renin-
angiotensin-aldosterone system in oligo-anuric hemodialysis patients. Methods: Eight hemodialysis patients were
administered either spironolactone, 50 mg, or placebo orally twice daily for 2 weeks, followed by a 3-week washout
period, after which patients crossed over in their treatment arms for 2 more weeks. Results: Administration of
spironolactone for 2 weeks decreased predialysis systolic blood pressure from 142.0 ! 19.6 to 131.4 ! 18.2 mm Hg
(P < 0.05). Compared with placebo, a 2-week course of spironolactone had no effect on predialysis and postdialysis
 International Journal of Cardiology

journal homepage: www.elsevier.com/locate/ijcard

Spironolactone is associated with reduced risk of new-onset atrial

fibrillation in patients receiving renal replacement therapy
a c,d b b b b
Yi-Wei Chung , Yao-Hsu Yang , Cho-Kai Wu , Chih-Chieh Yu , Jyh-Ming Jimmy Juang , Yi-Chih Wang ,
Chia-Ti Tsai , Lian-Yu Lin ⁎, Ling-Ping Lai , Juey-Jen Hwang , Fu-Tien Chiang ,
b b, b b b,e
e b
Pau-Chung Chen , Jiunn-Lee Lin
a
Division of Cardiology, Department of Internal Medicine, Chi Mei hospital, Taiwan
b
Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
c
Department for Traditional Chinese Medicine, Chang Gung Memorial Hospital Chia-Yi, Taiwan
d
Institute of Occupational Medicine and Industrial Hygiene, National Taiwan, University College of Public Health, Taipei, Taiwan
e
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

a r t i c l e i n f o a b s t r a c t

Article history: Objectives: Whether the spironolactone treatment remains effective for the prevention of atrial fibrillation (AF) in
Received 2 April 2015 dialysis patients is unclear.
Received in revised form 27 May 2015 Methods: We used a database from the Registry for Catastrophic Illness from the National Health Research
Accepted 29 May 2015 Institute. All dialysis patients aged 18 or older without history of AF before ESRD were incorporated. A total of
Available online xxxx
113,191 dialysis patients were enrolled in the study. The median follow-up time was 4.17 years. We collected
information on prescribed drug dosage, number of days of treatment and the total number of pills dispensed
Keywords:
Spironolactone
from the outpatient pharmacy prescription database. All individuals in the study cohort with the first occurrence
Journal of the American College of Cardiology Vol. 63, No. 6, 2014
! 2014 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00
Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2013.09.056

Spironolactone Reduces Cardiovascular

and Cerebrovascular Morbidity and
Mortality in Hemodialysis Patients
Yoshihiro Matsumoto, MD,* Yasuo Mori, MD,y Shinji Kageyama, MD,z Kazuo Arihara, MD,x
Toshikazu Sugiyama, MD,jj Hiromichi Ohmura, MD,{ Toru Yakushigawa, MD,y
Hatsumi Sugiyama, MD,jj Yasushi Shimada, MD,* Youichi Nojima, MD,* Nobuo Shio, MDz
Shizuoka, Japan

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