Efficacy of Combining Acetazolamide with Loop Diuretics Versus Using Double Dose Loop Diuretics for Decongestion in Patients with Chronic Kidney Disease: A Randomized Controlled Trial

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Efficacy of Combining Acetazolamide with Loop Diuretics Versus Using Double Dose Loop Diuretics for Decongestion in Patients with Chronic Kidney Disease: A Randomized Controlled Trial

https://doi.org/10.21203/rs.3.rs-4962398/v1

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Background

The combination of acetazolamide and loop diuretics in hospitalized heart failure patients has demonstrated positive results in improving diuresis and decongestion. However, the effectiveness of this combination in chronic kidney disease (CKD) patients with volume overload remains to be determined.

Methods

CKD patients with fluid overload, confirmed by bioimpedance spectroscopy, were randomized to receive either oral acetazolamide 250 mg/day plus furosemide or a doubled dose of furosemide. Volume status, changes in body fluid compartments (assessed by body composition monitoring), and urinary sodium were evaluated at baseline and 2 weeks. The primary outcomes were the proportion of patients with a bodyweight reduction of more than 2 kg or 5% and the mean change in body weight at 2 weeks.

Results

Fifty-two CKD patients with an estimated glomerular filtration rate of 38 mL/min/1.73 m² were included. Body weight reduction of more than 2 kg at week 2 occurred in 40.7% of the combination group compared to 12% of the doubled-dose group (risk ratio [RR] 3.39, 95% confidence interval [CI] 1.06–10.7). Body weight reduction of more than 5% at week 2 occurred in 25.9% of the combination group compared to 0% of the doubled-dose group (RR 2.25, 95% CI 1.62–3.12). The mean difference in body weight reduction between the combination and doubled-dose groups was − 1.37 kg (95% CI -2.50 to -0.24). No serious adverse events were reported in either group.

Conclusion

Adding acetazolamide to loop diuretics improves volume overload in CKD patients without significant or serious side effects.

Acetazolamide

Diuretic

Chronic kidney disease

Volume overload

The incidence and prevalence of heart failure and chronic kidney disease (CKD) are increasing, and both conditions are interconnected diseases. (1) Volume overload is also common in CKD patients, defined as overhydration > 1 L by body composition monitoring, and is a strong predictor of CKD progression. (2, 3) Greater fluid retention between two subsequent hemodialysis treatment sessions is associated with a higher risk of all-cause and cardiovascular death in hemodialysis.(4) Consequently, volume overload shows great promise as a potential modifiable risk factor.

From the analysis of the DOSE-AHF trial, a reduction in body weight of at least 2 kg was associated with improved clinical outcomes of rehospitalization or death.(5) Loop diuretics, the most efficacious class of diuretics, are the first-line treatment for decongestion.(6) However, a higher dose loop diuretic regimen modestly increases efficacy at the cost of higher rates of hypokalemia, metabolic alkalosis, and acute kidney injury.(7) Moreover, in a large observational study of patients with chronic heart failure, those prescribed higher doses of loop diuretics had a significantly higher rate of sudden cardiac death.(8)

Acetazolamide, a carbonic anhydrase inhibitor, is a diuretic that greatly enhances decongestion when combined with loop diuretics, without increasing rates of hypokalemia and acute kidney injury, and with a lower rate of metabolic alkalosis compared to standard treatment.(9) In a multicenter, randomized, placebo-controlled trial, the combination of acetazolamide and loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion.(10) Whether the addition of acetazolamide to loop-diuretic therapy for decongestion in CKD patients with volume overload is beneficial remains unclear. In our study, we examined whether adding acetazolamide to standardized oral loop-diuretic therapy would improve the incidence of successful decongestion among CKD patients with volume overload in the outpatient clinic setting.

We conducted a single-center, randomized, open-label, placebo-controlled, investigator-initiated, academic clinical trial. The trial protocol was approved by an ethics committee and the Institutional Review Board of the Royal Thai Army Medical Department (Approval number R020h/66) and the Thai Clinical Trials Registry Committee (Approval number TCTR20240329006). Our study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Guidelines for Good Clinical Practice. All patients provided written informed consent before any trial-specific procedures commenced.

CKD patients were screened at the nephrology clinic at Phramongkutklao Hospital. Patients with CKD stage 3–4, aged over 20 years, receiving a stable dose of furosemide for at least 2 weeks, and with volume overload > 1 L as determined by body composition analysis were eligible for participation. Exclusion criteria included a history of acetazolamide use within the past 12 weeks, allergy to sulfa drugs, systolic blood pressure less than 90 mmHg, organ transplant recipients, pregnancy, proteinuria > 3.5 g/d, hospitalization within the past 12 weeks, and electrolyte disturbances, including hypokalemia, hyperkalemia, metabolic acidosis, or metabolic alkalosis. The sample size was calculated based on the randomized controlled trial by Imiela et al., which showed mean fluid balance after acetazolamide and loop diuretics as − 666 ± 1,194 ml and 332 ± 705 ml in the control arm, respectively.(11) The sample size was set to 21 patients per group, with a p-value < 0.05 to detect statistical significance and a power of 90%. Considering a 25% possibility of loss to follow-up, the total sample size was increased to 53.

After screening, patients were randomly assigned in a 1:1 ratio using a block of 4 to receive either oral acetazolamide 250 mg once daily combined with the same baseline dose of loop diuretics or double the baseline dose of loop diuretics. Treatment was administered immediately after randomization for 2 weeks, as illustrated in Fig. 1.

Data collected before and after the study included relevant information on CKD, including diagnostic criteria and complications. Additionally, underlying diseases and comorbidities, as well as a history of medication including antihypertensive drugs and lipid-lowering agents, were recorded. Physical examination data, including height, weight, blood pressure, body mass index (BMI), and body fluid compartments from Body Composition Monitoring (BCM), a bioimpedance spectroscopy technique, were measured.⁽¹²⁾ Laboratory tests included fasting plasma glucose, serum electrolytes, serum albumin, hemoglobin, blood urea nitrogen, creatinine, and urine electrolytes. The researcher verified consistent intake by asking for the remaining tablets and monitored for side effects.

The primary endpoint was successful decongestion, defined as the absence of signs of volume overload as assessed by a nephrologist trained in completing the congestion score, with a body weight reduction of at least 2 kg or > 5% at week 2 within 2 weeks after randomization, without an indication for escalation of decongestive therapy. The secondary endpoints included changes in blood pressure, kidney function, electrolyte abnormalities, and adverse events.

Statistical analysis

Categorical variables were described as frequencies, and continuous variables were described as mean ± standard deviation (SD) if normally distributed. Differences between groups were assessed using independent samples t-tests or Mann–Whitney U tests and chi-squared tests for continuous and categorical variables, respectively, as appropriate. Differences within groups were assessed using paired t-tests. Results were reported as differences in mean change with 95% confidence intervals (95% CI). A two-sided p-value of 0.05 was used as the threshold for statistical significance in all analyses. Data analysis was performed using SPSS for Windows, Version 12 (SPSS, Chicago, IL, USA).

The study was conducted from July 2023 to December 2023. One hundred and nine patients were screened, and 53 patients were randomized. During the run-in period, one patient withdrew consent (Fig. 2). The mean age was 71.2 ± 11.9 years, and 73% of the participants were male. The mean estimated glomerular filtration rate was 37.93 ± 11.20 ml/min/1.73 m². The average dose of furosemide was 29.2 mg/day, and the average overhydration documented by bioimpedance spectroscopy was 2.7 ± 2.0 L. Underlying diseases included hypertensive nephropathy in 30.7% of patients and diabetic nephropathy in 67.3%. Medications that might have involved hemodynamic effects included renin-angiotensin-aldosterone inhibitors (57.5%), calcium channel blockers (63.5%), and beta-blockers (44.2%). Baseline demographic data, blood pressure, renal function, serum electrolytes, urinary sodium, and body fluid composition were well balanced between groups (Table 1).

Table 1

Baseline characteristics
Variables	Combination group (N = 27)	Double furosemide group (N = 25)
Male (%)	22 (81.5%)	17 (68%)
Age (years)	71 ± 14.2	71.4 ± 9.2
Body weight (kg)	68.9 ± 11.6	72.0 ± 9.8
Systolic blood pressure (mmHg)	134.7 ± 18.5	136.1 ± 21.9
Diastolic blood pressure (mmHg)	65.5 ± 14.3	67.7 ± 11.9
Causes of CKD (%)
- Diabetes	18 (66.7%)	17 (68%)
- Hypertension	9 (33.3%)	7 (28%)
History of heart failure (%)	9 (33.3%)	7 (28%)
Anti-hypertensive agents (N, %)
- ACEI/ARBs	15 (55.6%)	15 (60%)
- Calcium channel blockers	18 (66.7%)	15 (60%)
- Beta-blockers	11 (40.7%)	12 (48%)
Furosemide dose (mg/d)	34.8	24.3
eGFR (ml/min/1.73 m²)	37.67 ± 10.78	38.98 ± 11.71
Blood urea nitrogen (mg/dL)	25.58 ± 11.92	22.12 ± 9.07
Serum sodium (mmol/L)	139.44 ± 2.61	140.24 ± 3.18
Serum potassium (mmol/L)	4.22 ± 0.47	4.36 ± 0.54
Serum chloride (mmol/L)	103.1 ± 2.75	104.24 ± 2.86
Serum bicarbonate (mmol/L)	25.74 ± 2.69	25.44 ± 3.2
Serum NT-proBNP (pg/mL)	1357.82 ± 2159.3	2465.79 ± 6423.88
Urine sodium (mmol/L)	70.03 ± 39.75	69.59 ± 28.82
Urine albumin-creatinine ratio (mg/g)	453.9 ± 692.62	400.97 ± 625.39
Overhyrdation (L)	2.7 ± 1.5	2.7 ± 2.5
Extracelluar water (L)	17.1 ± 3.0	17.6 ± 2.8
Total body water (L)	31.5 ± 5.7	31.8 ± 4.7
All data are expressed as mean ± SD; BCM: body composition monitoring; eGFR: estimated glomerular filtration rate; ACEI: angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blockers; NT-proBNP: N-terminal pro B-type natriuretic peptide

Change in Body Weight or Fluid Overload During the Study

The change in body weight from baseline was − 1.64 ± 2.61 kg (P = 0.003) in the combination group and − 0.27 ± 1.05 kg (P = 0.181) in the double-dose group. At two weeks, the mean difference in body weight reduction between the combination group and the double-dose group was − 1.37 kg (95% CI -2.498 to -0.242, P = 0.0183) (Fig. 3). Additionally, body weight reduction of at least 2 kg at week 2 (40.7% vs. 12%, risk ratio (RR) 3.39, 95% CI 1.06–10.7) and body weight reduction > 5% at week 2 (25.9% vs. 0%, RR 2.25, 95% CI 1.62–3.12) was significantly greater in the combination group than in the double-dose group (Fig. 4). For body composition analysis, changes in overhydration, extracellular water, and total body water did not significantly differ between the two groups (Table 2).

Table 2

Changes of body fluid compartment and clinical parameters at 2 weeks
Variables	Combination group (N = 27)	Double furosemide group (N = 25)	P value
Body fluid compartment
Overhyrdation (L)	-0.69 (-1.34, -0.03)	-0.69 (-1.74, 0.36)	0.939
Extracelluar water (L)	-0.78 (-2.38, 0.81)	-0.39 (-1.87, 1.09)	0.269
Total body water (L)	-1.17 (-4.4, 2.06)	0.25 (-2.37, 2.88)	0.260
Clinical parameters
Systolic blood pressure (mmHg)	-6.85 (-16.17, 2.47)	-3.52 (-13.58, 6.54)	0.326
Diastolic blood pressure (mmHg)	-1.85 (-9.33, 5.63)	2.15 (-4.1, 8.4)	0.096
Serum NT-proBNP (pg/mL)	-438.21 (-1650.24, 773.83)	-450.01 (-4172.92, 3272.89)	0.454
Estimated GFR (ml/min/1.73 m²)	-5.05 (-10.77, 0.67)	-0.4 (-7.58, 6.78)	0.090
Blood urea nitrogen (mg/dL)	6.06 (-0.5, 12.62)	4.33 (-1.99, 10.66)	0.167
Serum creatinine (mg/dL)	0.2 (-0.1, 0.51)	0.09 (-0.3, 0.49)	0.355
Serum sodium (mmol/L)	-0.56 (-2.07, 0.95)	0.16 (-1.37, 1.69)	0.085
Serum potassium (mmol/L)	-0.13 (-0.38, 0.12)	-0.29 (-0.59, 0)	0.842
Serum chloride (mmol/L)	3.47 (1.4, 5.55)	-1.84 (-3.57, -0.11)	< 0.001
Serum bicarbonate (mmol/L)	-4.31 (-6.02, -2.6)*	1.4 (-0.19, 2.99)	< 0.001
Urine sodium (mmol/L)	1.74 (-23.17, 26.65)	-17.64 (-35.62, 0.34)	0.074
All data are expressed as mean with 95%CI

Change in Blood Pressure, Serum Electrolytes, and Kidney Function During the Study

At the 2-week period, changes in blood pressure, kidney function, serum sodium, serum potassium, and urine sodium did not significantly differ between the two groups (Table 2). In contrast, the change in serum bicarbonate from baseline was − 4.31 mmol/L (95% CI -6.02 to -2.6) in the combination group and − 1.4 mmol/L (95% CI -0.19 to 2.99) in the double-dose group, with a significant difference between the two groups (P < 0.001).

Adverse Events After Treatment

No serious adverse events, including serious hypotension and acute renal replacement therapy, were observed in either group during the study period. None of the patients were forced to drop out of the study due to adverse effects from treatment. Incidences of hyponatremia, hypokalemia, and severe metabolic acidosis were low, with no significant difference between the two groups. The incidence of acute kidney injury, defined as a serum creatinine increase of > 0.3 mg/dL from baseline, was 26.2% in the combination group and 24% in the double-dose group, with no significant difference between the two groups (P > 0.05) (Table 3).

Table 3

Adverse events
Variables	Combination group (N = 27)	Double furosemide group (N = 25)
Hyponatremia (< 135 mmol/L)	1 (3.8%)	0
Hypokalemia (< 3.5 mmol/L)	1 (3.8%)	1 (4%)
Severe metabolic acidosis (HCO3- < 16 mmol/L)	2 (7.6%)	0
Acute kidney injury (Serum creatinine > 0.3mg/dL from baseline)	7 (26.2%)	6 (24%)

The first open-label randomized controlled trial has demonstrated that adding acetazolamide to loop diuretics enhances diuretic efficacy. This enhancement is evidenced by significant body weight reduction compared to doubling the dose of loop diuretics in CKD patients with volume overload and chronic diuretic use in outpatient settings, without significant serious adverse events.

Acetazolamide, a carbonic anhydrase inhibitor, impedes the catalysis of the chemical reaction converting carbonic acid to carbon dioxide and water in the proximal convoluted tubules, which are responsible for approximately 65% of total tubular sodium reabsorption under normal circumstances—a proportion that may increase in CKD settings. Therefore, to achieve a potent natriuretic response, acetazolamide should be used together with a loop diuretic that works more distally.(13) A larger randomized controlled trial indicated that adding acetazolamide to standardized intravenous loop-diuretic therapy in patients with acute decompensated heart failure led to a higher incidence of successful decongestion.(10) A recent meta-analysis similarly demonstrated that acetazolamide, as an adjunctive diuretic, significantly improves global surrogate endpoints for decongestion therapy in patients with acute decompensated heart failure, although not all individual signs and symptoms of volume overload.(14) Our study involving CKD patients with overhydration of more than 1 L from BCM, which correlates well with the gold standard method (12, 15), showed that oral acetazolamide 250 mg once daily added to loop-diuretic therapy resulted in greater decongestion and significantly greater body weight reduction of at least 2 kg by week 2. This reduction in body weight correlated well with a composite outcome at 60 days of reduced rehospitalization rates, emergency department visits, or death.(5) Further studies with larger sample sizes are needed to elucidate the complex relationships among degree of decongestion, body weight reduction, and cardiovascular and renal outcomes in CKD patients. However, our study did not show statistically significant differences in body composition, especially overhydration data between groups. Two main hypotheses explain this observation: first, the extracellular water compartment comprises only 20% of the whole-body weight ⁽¹⁶⁾, and second, the changes observed were smaller, necessitating a larger sample size. Another reason could be that we calculated the sample size based on clinical data rather than BCM data.

The combination of acetazolamide and loop diuretics did not increase the incidence of adverse events compared to dose-adjusted loop diuretics. However, short-term worsening of renal function occurred in approximately 25% of both groups, consistent with findings from previous studies.(9, 17, 18) Patients who achieved euvolemia by 2 weeks had their diuretics withdrawn, after which their renal function returned to baseline levels, indicating transient kidney injury or pseudo-worsening renal function—a term frequently mentioned in heart failure settings to describe insignificant rises in creatinine without long-term renal consequences.(19, 20) In terms of electrolyte abnormalities, both groups exhibited similar trends except for a significant difference in serum bicarbonate change, which was expected due to greater chloride loss from loop diuretics.(21) Metabolic alkalosis induced by loop diuretics is one mechanism contributing to diuretic resistance, which may explain why acetazolamide improves diuretic efficacy.(22) Combination therapy could be beneficial in CKD patients with loop diuretics and subclinical volume overload, especially in high-risk situations such as metabolic alkalosis.

There were several limitations in our study. The sample size was relatively small to detect significant differences in clinical outcomes, including body composition analysis. A larger-scale study might reveal more significant findings in body composition data. The rather short duration of our study does not confidently imply long-term decongestion status. Nearly all participants were Asian, as the trial was exclusively conducted in Thailand, which may limit the generalizability of our results to other racial or ethnic groups. Our study began before sodium-glucose transporter 2 inhibitors (SGLT2i)—a key medication beneficial for renal and cardiovascular outcomes in CKD patients—was generally approved regardless of diabetes status.(23, 24) Consequently, only 13% of our patients received SGLT2i, necessitating future studies to confirm the efficacy of acetazolamide in a population with chronic use of such drugs. Additionally, our patients had a history of CKD and had been receiving long-term outpatient furosemide treatment. Therefore, the results of our tested strategy may not be applicable to patients without prolonged diuretic treatment. Lastly, our study was open-label, potentially introducing bias, although most outcomes were objectively measured (such as body weight, body composition, and laboratory data) by data collectors unaware of treatment allocation.

Our study suggests that adding acetazolamide to standardized loop-diuretic therapy in advanced CKD patients with subclinical volume overload increases the likelihood of body weight reduction and successful decongestion, with no serious side effects observed.

Author Contribution

J.S., B.S., and O.S. wrote the main manuscript text. A.C. wrote and analyzed the statistics. All authors reviewed the manuscript.

Availability of data and materials:

Data supporting this study are available upon request.

ORCID of the author: https://orcid.org/0009-0000-2905-4561

Clinical trial registration: Registration code: TCTR20240329006 approved on 29 March 2024

Conflict of interest: The authors declare that they have no competing interests.

Ethics approval: The study was approved by the Ethics Committee of the Institute Review Board at the Royal Thai Army Medical Department and was conducted according to the Declaration of Helsinki.

Informed consent: Informed consent was obtained from all participants.

Availability of data and materials: Data supporting this study are available upon request.

House AA, Wanner C, Sarnak MJ, Piña IL, McIntyre CW, Komenda P, et al. Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019;95(6):1304-17.
Hung SC, Lai YS, Kuo KL, Tarng DC. Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies. J Am Heart Assoc. 2015;4(5).
Hung SC, Kuo KL, Peng CH, Wu CH, Lien YC, Wang YC, et al. Volume overload correlates with cardiovascular risk factors in patients with chronic kidney disease. Kidney Int. 2014;85(3):703–9.
Kalantar-Zadeh K, Regidor DL, Kovesdy CP, Van Wyck D, Bunnapradist S, Horwich TB, et al. Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis. Circulation. 2009;119(5):671–9.
Kociol RD, McNulty SE, Hernandez AF, Lee KL, Redfield MM, Tracy RP, et al. Markers of decongestion, dyspnea relief, and clinical outcomes among patients hospitalized with acute heart failure. Circ Heart Fail. 2013;6(2):240–5.
McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–726.
Kazory A. Combination Diuretic Therapy to Counter Renal Sodium Avidity in Acute Heart Failure: Trials and Tribulations. Clin J Am Soc Nephrol. 2023;18(10):1372–81.
Eshaghian S, Horwich TB, Fonarow GC. Relation of loop diuretic dose to mortality in advanced heart failure. Am J Cardiol. 2006;97(12):1759–64.
Sabina M, Barakat Z, Feliciano A, Lamb A, Alsamman MM. Unlocking the Potential of Acetazolamide: A Literature Review of an Adjunctive Approach in Heart Failure Management. J Clin Med. 2024;13(1).
Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, et al. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022;387(13):1185–95.
Imiela T, Budaj A. Acetazolamide as Add-on Diuretic Therapy in Exacerbations of Chronic Heart Failure: a Pilot Study. Clin Drug Investig. 2017;37(12):1175–81.
Moissl UM, Wabel P, Chamney PW, Bosaeus I, Levin NW, Bosy-Westphal A, et al. Body fluid volume determination via body composition spectroscopy in health and disease. Physiol Meas. 2006;27(9):921–33.
Guo L, Fu B, Liu Y, Hao N, Ji Y, Yang H. Diuretic resistance in patients with kidney disease: Challenges and opportunities. Biomed Pharmacother. 2023;157:114058.
Siddiqi AK, Maniya MT, Alam MT, Ambrosy AP, Fudim M, Greene SJ, et al. Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs. 2024;24(2):273–84.
Accardi AJ, Matsubara BS, Gaw RL, Daleiden-Burns A, Heywood JT. Clinical Utility of Fluid Volume Assessment in Heart Failure Patients Using Bioimpedance Spectroscopy. Front Cardiovasc Med. 2021;8:636718.
Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, et al. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022;387(13):1185–95.
Kosiorek A, Urban S, Detyna J, Biegus J, Hurkacz M, Zymliński R. Diuretic, natriuretic, and chloride-regaining effects of oral acetazolamide as an add-on therapy for acute heart failure with volume overload: a single-center, prospective, randomized study. Pol Arch Intern Med. 2023;133(12).
Yamada T, Ueyama H, Chopra N, Yamaji T, Azushima K, Kobayashi R, et al. Systematic Review of the Association Between Worsening Renal Function and Mortality in Patients With Acute Decompensated Heart Failure. Kidney Int Rep. 2020;5(9):1486–94.
Martins JL, Santos L, Faustino A, Viana J, Santos J. Worsening or 'pseudo-worsening' renal function? The prognostic value of hemoconcentration in patients admitted with acute heart failure. Rev Port Cardiol (Engl Ed). 2018;37(7):595–602.
Kataoka H. Acetazolamide as a potent chloride-regaining diuretic: short- and long-term effects, and its pharmacologic role under the 'chloride theory' for heart failure pathophysiology. Heart Vessels. 2019;34(12):1952–60.
Loon NR, Wilcox CS. Mild metabolic alkalosis impairs the natriuretic response to bumetanide in normal human subjects. Clin Sci (Lond). 1998;94(3):287–92.
Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117–27.
Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436–46.

No competing interests reported.

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Efficacy of Combining Acetazolamide with Loop Diuretics Versus Using Double Dose Loop Diuretics for Decongestion in Patients with Chronic Kidney Disease: A Randomized Controlled Trial

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Background

Methods

Statistical analysis

Results

Change in Body Weight or Fluid Overload During the Study

Change in Blood Pressure, Serum Electrolytes, and Kidney Function During the Study

Adverse Events After Treatment

Discussion

Conclusion

Declarations

Author Contribution

Availability of data and materials:

References

Additional Declarations

Status:

Version 1