spironolactone and Cardio-Renal Syndrome studies

Spironolactone: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
spironolactone : A steroid lactone that is 17alpha-pregn-4-ene-21,17-carbolactone substituted by an oxo group at position 3 and an alpha-acetylsulfanyl group at position 7.

Cardio-Renal Syndrome: Condition where a primary dysfunction of either heart or kidney results in failure of the other organ (e.g., HEART FAILURE with worsening RENAL INSUFFICIENCY).

Research Excerpts

Excerpt	Relevance	Reference
"The mechanisms underlying cardiorenal syndromes are complex and not fully understood; Fibrosis seems to be a primary driver of the diseases' pathophysiology."	5.51	Spironolactone inhibits endothelial-mesenchymal transition via the adenosine A2A receptor to reduce cardiorenal fibrosis in rats. ( Chen, L; Chen, X; Dong, T; Fan, X; Ge, W; Gong, Y; Hu, J; Zhou, H, 2019)
"The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion."	3.11	The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial. ( Chávez-Alonso, G; Chávez-Iñiguez, JS; De la Torre-Quiroga, A; de Quevedo, AA; Font-Yañez, JJ; García-García, G; Gómez-Fregoso, J; Ibarra-Estrada, M; Maggiani-Aguilera, P; Romero-González, G; Romero-Muñóz, A; Sánchez-Villaseca, S, 2022)
"The mechanisms underlying cardiorenal syndromes are complex and not fully understood; Fibrosis seems to be a primary driver of the diseases' pathophysiology."	1.51	Spironolactone inhibits endothelial-mesenchymal transition via the adenosine A2A receptor to reduce cardiorenal fibrosis in rats. ( Chen, L; Chen, X; Dong, T; Fan, X; Ge, W; Gong, Y; Hu, J; Zhou, H, 2019)

Research

Studies (6)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

An Elevation of at Least 0.3 mg/dl of Serum Creatinine From Day One of Intervention Compared With Serum Creatinine at 96hrs After Intervention Started

Change in 24 Hour Urine Output at 96 Hours After Intervention Started From 24 Hour Urine Output One Day Before Intervention Initiation)

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	5 (83.33)	24.3611
2020's	1 (16.67)	2.80

Authors	Studies
Chávez-Iñiguez, JS	1
Ibarra-Estrada, M	1
Sánchez-Villaseca, S	1
Romero-González, G	1
Font-Yañez, JJ	1
De la Torre-Quiroga, A	1
de Quevedo, AA	1
Romero-Muñóz, A	1
Maggiani-Aguilera, P	1
Chávez-Alonso, G	1
Gómez-Fregoso, J	1
García-García, G	1
Clarke, B	1
Verbrugge, FH	1
Martens, P	1
Ameloot, K	1
Haemels, V	1
Penders, J	1
Dupont, M	1
Tang, WHW	1
Droogné, W	1
Mullens, W	1
Chen, X	1
Ge, W	1
Dong, T	1
Hu, J	1
Chen, L	1
Fan, X	1
Gong, Y	1
Zhou, H	1
Kolkhof, P	1
Jaisser, F	1
Kim, SY	1
Filippatos, G	1
Nowack, C	1
Pitt, B	1
Homma, T	1
Sonoda, H	1
Manabe, K	1
Arai, K	1
Mizuno, M	1
Sada, T	1
Ikeda, M	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Effect on Kidney Function Recovery Guiding Decongestion With VExUS in Patients With Cardiorenal Syndrome 1[NCT05927285]		140 participants (Actual)	Interventional	2022-03-20	Completed
The Effect in Renal Function on Patients With Type 1 Cardiorenal Syndrome Treated With Two Strategies of Furosemide. A Randomized Controled Trial[NCT04393493]	Phase 2	80 participants (Actual)	Interventional	2017-07-01	Completed
Diamox/Aldactone to Increase the URinary Excretion of Sodium: an Investigational Study in Congestive Heart Failure[NCT01973335]	Phase 4	34 participants (Actual)	Interventional	2013-11-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	Participants (Count of Participants)
Stepped Furosemide	20
Diuretics Combined	24

Urine output was collected through an urinary catheter and measured and registered by a nurse. The sum of these registrations from 7 am from one day to 7 am of the next day was considered the 24 hour urinary output (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Bicarbonate Levels Measured at Day One of Intervention From Serum Bicarbonate Levels Measured at 96 Hrs After Intervention Started.

Intervention	ml (Mean)
Stepped Furosemide	125
Diuretics Combined	200

Calculated as serum bicarbonate levels at day one of intervention minus bicarbonate levels at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Brain Natriuretic Peptide Levels at Baseline From Serum Brain Natriuretic Peptide Levels at 96 Hours After Intervention Started

Intervention	mEq/L (Mean)
Stepped Furosemide	2.9
Diuretics Combined	3

Baseline levels were defined as the measurement at hospital admission. Calculated as serum brain natriuretic peptide levels at baseline minus serum brain natriuretic peptide levels at 96 hours after intervention started (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Calcium Levels Measured at Day One of Intervention From Serum Calcium Levels Measured at 96 Hrs After Intervention Started.

Intervention	ng/dl (Mean)
Stepped Furosemide	-1344
Diuretics Combined	-1378

Calculated as serum calcium levels at day one of intervention minus serum calcium levels at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Chloride Levels Measured at Day One of Intervention From Serum Chloride Levels Measured at 96 Hrs After Intervention Started.

Intervention	mg/dl (Mean)
Stepped Furosemide	0.15
Diuretics Combined	-0.05

Calculated as serum chloride levels at day one of intervention minus serum chloride levels at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Copeptin Levels at Day One of Intervention From Serum Copeptin Levels Measured at 96 Hrs After Intervention Started.

Intervention	mEq/L (Mean)
Stepped Furosemide	-0.6
Diuretics Combined	-0.4

Calculated as serum copeptin levels at day one minus serum copeptin levels measured at 96 hrs after intervention started (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Creatinine at Day One of Intervention From Serum Creatinine at 96 Hrs After Intervention Started

Intervention	ng/dl (Mean)
Stepped Furosemide	1.1
Diuretics Combined	-16

Calculated as serum creatinine at day one minus serum creatinine at 96 hrs after intervention started (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Lactate Levels Measured at Day One of Intervention From Serum Lactate Levels Measured at 96 Hrs After Intervention Started.

Intervention	mg/dl (Mean)
Stepped Furosemide	0.02
Diuretics Combined	0.2

Calculated as serum lactate levels at day one of intervention minus serum lactate levels at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Magnesium Levels Measured at Day One of Intervention From Serum Magnesium Levels Measured at 96 Hrs After Intervention Started.

Intervention	mmol/L (Mean)
Stepped Furosemide	0
Diuretics Combined	0.1

Calculated as serum magnesium levels at day one of intervention minus serum magnesium levels at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Partial Pressure of Carbon Dioxide Measured at Day One of Intervention From Serum Partial Pressure of Carbon Dioxide Measured at 96 Hrs After Intervention Started.

Intervention	mg/dl (Mean)
Stepped Furosemide	0.07
Diuretics Combined	-0.04

Calculated as serum partial pressure of carbon dioxide at day one of intervention minus serum partial pressure of carbon dioxide at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum pH Value Measured at Day One of Intervention From Serum pH Value Measured at 96 Hrs After Intervention Started.

Intervention	mmHg (Mean)
Stepped Furosemide	1
Diuretics Combined	3

Calculated as serum pH value at day one of intervention minus serum pH value at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Potassium Levels Measured at Day One of Intervention From Serum Potassium Levels Measured at 96 Hrs After Intervention Started.

Intervention	units (Mean)
Stepped Furosemide	0.03
Diuretics Combined	0.02

Calculated as serum potassium levels at day one of intervention minus serum potassium levels at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Sodium Levels Measured at Day One of Intervention From Serum Sodium Levels Measured at 96 Hrs After Intervention Started.

Intervention	mEq/L (Mean)
Stepped Furosemide	-0.2
Diuretics Combined	-0.4

Calculated as serum sodium levels at day one of intervention minus serum sodium levels at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

Change in Serum Urea Levels Measured at Day One of Intervention From Serum Urea Levels Measured at 96 Hrs After Intervention Started.

Intervention	mEq/L (Mean)
Stepped Furosemide	-1.2
Diuretics Combined	0.2

Calculated as serum urea levels at day one of intervention minus serum urea levels at 96 hrs after intervention started. (NCT04393493)
Timeframe: 96 hours after intervention started

In Hospital Mortality Defined as Number of Dead Patients From Day One of Intervention and Before Discharge

Intervention	mg/dl (Mean)
Stepped Furosemide	13
Diuretics Combined	18

(NCT04393493)
Timeframe: From day one of intervention up to discharge, an average of 1 week

Mortality During Follow up Defined as Number of Dead Patients After Discharge

Intervention	Participants (Count of Participants)
Stepped Furosemide	4
Diuretics Combined	4

(NCT04393493)
Timeframe: From day one after discharge up to an average of 161 days

Number of Days From the Beginning of the Intervention Until Patients Referred Dyspnea Improvement or a Reduction in Supplementary Oxygen Requirements Was Made.

Intervention	Participants (Count of Participants)
Stepped Furosemide	9
Diuretics Combined	12

"Dyspnea improvement was referred by the patient as the clinician asked them do you feel more or less difficult to breathe? or if the liters per minute or the fraction of inspired supplementary oxygen necessary maintain an oxygen saturation >90% were diminished" (NCT04393493)
Timeframe: Up to 4 days after intervention started

Number of Participants With Renal Function Recovery Defined as a Return to Individual Baseline Serum Creatinine Values

Intervention	days (Mean)
Stepped Furosemide	4
Diuretics Combined	4

Comparing patient's baseline serum creatinine (previous serum creatinine of 3 months ago and up to a year ago) with creatinine measurements every 24 hours during intervention (4 days) (NCT04393493)
Timeframe: Up to 96 hours after intervention started

Number of Patients That Achieved >30% Reduction in Brain Natriuretic Compared With Baseline Levels

Intervention	Participants (Count of Participants)
Stepped Furosemide	8
Diuretics Combined	5

Baseline levels were defined as the measurement at hospital admission (NCT04393493)
Timeframe: Up to 96 hours after intervention started

Number of Patients That Required Renal Replacement Therapy of Any Type During Intervention (4 Days).

Intervention	Participants (Count of Participants)
Stepped Furosemide	5
Diuretics Combined	7

The requirement of renal replacement therapy was assessed by the nephrology team in charge (NCT04393493)
Timeframe: Up to 96 hours after intervention started

Number of Patients Whose Interventions Were Stopped Because Clinical Improvement Was Achieved Before 96 Hours as Assessed by de Clinical Judgement of the Medical Team in Charge.

Intervention	Participants (Count of Participants)
Stepped Furosemide	7
Diuretics Combined	6

Clinical improvement was referred as remission of symptoms with achievement of 24 hour urine output equal or greater than 3000 milliliters (NCT04393493)
Timeframe: From the beginning of intervention and before 96 hours after that

Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements at 96 Hours After Intervention Started

Intervention	Participants (Count of Participants)
Stepped Furosemide	5
Diuretics Combined	7

"Dyspnea improvement was referred by the patient as the clinician asked them do you feel more or less difficult to breathe? or if the liters per minute or the fraction of inspired supplementary oxygen necessary to maintain an oxygen saturation >90% were diminished" (NCT04393493)
Timeframe: Up to 96 hours after intervention started

Number of Patients With Dyspnea Improvement as Referred by the Patient or Reduction in Supplementary Oxygen Requirements Before Day 3 of Intervention

Intervention	Participants (Count of Participants)
Stepped Furosemide	27
Diuretics Combined	27

Acetazolamide Arm: Natriuresis 24 h

Intervention	Participants (Count of Participants)
Stepped Furosemide	2
Diuretics Combined	7

For the acetazolamide arm of the study, the primary end-point is total natriuresis after 24 h (mmol). To assess this, urine is collected for 24 h after the first administration of diuretics according to the study protocol and natriuresis is calculated as the total amount of diuresis (L) multiplied by the urinary sodium concentration (mmol/L). Subsequently, patients receiving acetazolamide and low-dose loop diuretics (both the groups with and without upfront spironolactone together) are compared to patients not receiving acetazolamide but high-dose loop diuretics instead (both the groups with or without upfront spironolactone together) (NCT01973335)
Timeframe: 24h

NT-proBNP Change After 72 h

Intervention	mmol (Mean)
Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone	324
High-dose Loop Diuretics, Upfront Spironolactone	300
Acetazolamide/Low-dose Loop Diuretics, no Spironolactone	211
High-dose Loop Diuretics, no Spironolactone	190

Relative NT-proBNP change (%) after 72 h compared to baseline. (NCT01973335)
Timeframe: 72h

Number of Participants With Worsening Renal Function

Intervention	percentage change from baseline (Mean)
Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone	-20
High-dose Loop Diuretics, Upfront Spironolactone	-11
Acetazolamide/Low-dose Loop Diuretics, no Spironolactone	-3
High-dose Loop Diuretics, no Spironolactone	-6

Worsening renal function is defined as a rise in serum creatine >0.3 mg/dL or a >20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula compared to baseline at any time point before 72 h. Serum creatinine values are assessed at three consecutive mornings after study inclusion. (NCT01973335)
Timeframe: 72h

Peak Plasma Aldosterone Concentration After 72 h

Intervention	Participants (Count of Participants)
Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone	2
High-dose Loop Diuretics, Upfront Spironolactone	0
Acetazolamide/Low-dose Loop Diuretics, no Spironolactone	3
High-dose Loop Diuretics, no Spironolactone	0

At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma aldosterone levels. The highest value will constitute the peak plasma aldosterone concentration (ng/L). (NCT01973335)
Timeframe: 72h

Peak Plasma Renin Activity After 72 h

Intervention	ng/L (Median)
Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone	196
High-dose Loop Diuretics, Upfront Spironolactone	234
Acetazolamide/Low-dose Loop Diuretics, no Spironolactone	302
High-dose Loop Diuretics, no Spironolactone	204

At three consecutive mornings after study inclusion, blood samples will be taken to assess plasma renin activity. The highest value will constitute the peak plasma renin activity (ng/mL/h). (NCT01973335)
Timeframe: 72h

Persistent Renal Impairment

Intervention	µg/L/h (Median)
Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone	3.8
High-dose Loop Diuretics, Upfront Spironolactone	5.0
Acetazolamide/Low-dose Loop Diuretics, no Spironolactone	12.0
High-dose Loop Diuretics, no Spironolactone	2.5

Persistent renal impairment is defined as a persistently elevated serum creatine >0.3mg/dL or >20% decrease in estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, above the baseline value of the patient and will be assessed on a scheduled follow-up appointment 4 weeks after hospital discharge. (NCT01973335)
Timeframe: 4 weeks after hospital discharge

Spironolactone Arm: Incidence of Hypo- (Serum Potassium <3.5 mmol/L) or Hyperkalemia (Serum Potassium >5.0 mmol/L)

Intervention	Participants (Count of Participants)
Acetazolamide/Low-dose Loop Diuretics, Upfront Spironolactone	3
High-dose Loop Diuretics, Upfront Spironolactone	1
Acetazolamide/Low-dose Loop Diuretics, no Spironolactone	0
High-dose Loop Diuretics, no Spironolactone	1

For the spironolactone arm of the study, the primary end-point is the incidence of either hypo- (serum potassium <3.5 mmol/L) or hyperkalemia (serum potassium >5.0 mmol/L) at any of 3 morning blood samples at consecutive days after randomization. Patients receiving upfront spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy) are compared with them receiving no spironolactone (both the group receiving acetazolamide+low dose loop diuretics and the group receiving high-dose loop diuretic therapy). (NCT01973335)
Timeframe: 72h

Article	Year
The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial. BMC nephrology, 2022, 01-03, Volume: 23, Issue:1 Topics: Adult; Cardio-Renal Syndrome; Chlorthalidone; Diuretics; Double-Blind Method; Drug Administration Sc	2022
The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial. BMC nephrology, 2022, 01-03, Volume: 23, Issue:1 Topics: Adult; Cardio-Renal Syndrome; Chlorthalidone; Diuretics; Double-Blind Method; Drug Administration Sc	2022
The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial. BMC nephrology, 2022, 01-03, Volume: 23, Issue:1 Topics: Adult; Cardio-Renal Syndrome; Chlorthalidone; Diuretics; Double-Blind Method; Drug Administration Sc	2022
The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial. BMC nephrology, 2022, 01-03, Volume: 23, Issue:1 Topics: Adult; Cardio-Renal Syndrome; Chlorthalidone; Diuretics; Double-Blind Method; Drug Administration Sc	2022
Spironolactone to increase natriuresis in congestive heart failure with cardiorenal syndrome. Acta cardiologica, 2019, Volume: 74, Issue:2 Topics: Administration, Oral; Aged; Aged, 80 and over; Cardio-Renal Syndrome; Dose-Response Relationship, Dr	2019

Article	Year
Cardiorenal Interactions, Diuretic Resistance, and Acute Heart Failure: Renal Response vs Renal Function. The Canadian journal of cardiology, 2019, Volume: 35, Issue:9 Topics: Cardio-Renal Syndrome; Diuretics; Heart Failure; Humans; Risk Factors; Spironolactone	2019
Spironolactone inhibits endothelial-mesenchymal transition via the adenosine A2A receptor to reduce cardiorenal fibrosis in rats. Life sciences, 2019, May-01, Volume: 224 Topics: Animals; Cardio-Renal Syndrome; Cells, Cultured; Epithelial-Mesenchymal Transition; Fibrosis; Human	2019
Activation of renal angiotensin type 1 receptor contributes to the pathogenesis of progressive renal injury in a rat model of chronic cardiorenal syndrome. American journal of physiology. Renal physiology, 2012, Mar-15, Volume: 302, Issue:6 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Cardio-Renal Syndrome; Gene Expression; Imidazoles	2012

spironolactone and Cardio-Renal Syndrome