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Furosemide and albumin for the treatment of nephrotic edema: a systematic review

  • Systematic Review/Meta-analysis
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Edema is one of the cardinal clinical features of nephrotic syndrome (NS). It may vary from mild periorbital edema to severe generalized edema (anasarca). In patients where edema does not improve with prednisone therapy, the most common supportive medications are diuretics and albumin. However, due to the complex pathophysiology of edema formation in NS patients resulting in intravascular normovolemia or hypovolemia, optimal therapy for edema is still debated. We conducted a systematic review with the objective of evaluating the change in urine volume and urine sodium excretion after treatment with furosemide only versus furosemide with albumin in edematous patients with NS.

Objectives

(1) To evaluate efficacy of furosemide alone versus furosemide with albumin in the treatment of nephrotic edema in adults and children. (2) To compare the harms and benefits of different doses of furosemide for treating nephrotic edema.

Search methods

The search included all randomized or quasi-randomized controlled trials in English and French using MEDLINE, Embase, and CENTRAL Trials Registry of the Cochrane Collaboration using the Ovid interface. ClinicalTrials.gov and the International Clinical Trials Registry Platform were also searched.

Selection criteria

We included all RCTs and randomized cross-over studies in which furosemide and furosemide plus albumin are used in the treatment of children or adults with nephrotic edema. We excluded patients with hypoalbuminemia of non-renal origin and severe chronic kidney disease (CKD) with a glomerular filtration rate below 30 ml/min/1.74 m2 and patients with congenital NS.

Data collection and analysis

All abstracts were independently assessed by at least two authors to determine which studies met the inclusion criteria. Information on study design, methodology, and outcome data (urine volume, urine sodium excretion, adverse effects) from each identified study was entered into a separate data sheet. The differences in outcomes between the types of therapy were expressed as standardized mean difference (SMD) with 95% confidence intervals (CI).

Results

The search yielded 525 records, and after screening, five studies were included in the systematic review and four of those studies in the meta-analysis. One study had high risk of bias and the remaining three studies were deemed to have some concerns. Urine excretion was greater after treatment with furosemide and albumin versus furosemide (SMD 0.85, 95% CI = 0.33 to 1.38). Results for sodium excretion were inconclusive (SMD 0.37, 95%CI =  − 0.28 to 1.02).

Authors’ conclusions

The current evidence is not sufficient to make definitive conclusions about the role of albumin in treating nephrotic edema. High-quality randomized studies with adequate samples sizes are needed. Including an assessment of intravascular volume status may be helpful.

Trial registration

Prospero: CRD4201808979. https://www.crd.york.ac.uk/PROSPERO

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

N/A.

Abbreviations

NS:

Nephrotic syndrome

RAS:

Renin-aldosterone system

IV:

Intravenous

ADH:

Antidiuretic hormone

RCT:

Randomized controlled trials

GFR:

Glomerular filtration rate

SMD:

Standardized mean difference

CI:

Confidence intervals

AKI:

Acute kidney injury

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Acknowledgements

We thank Katie O’Hearn, Msc, (Children’s Hospital of Eastern Ontario Research Institute) for methodological assistance and Margaret Sampson, MLIS, PhD, AHIP, (Children’s Hospital of Eastern Ontario) for developing the electronic search strategies.

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Authors and Affiliations

  1. Department of Pediatrics, Stollery Children’s Hospital, University of Alberta, 8440 112 St NW, Edmonton, AB, T6G2B7, Canada

    Erin Hedin

  2. Department of Pediatrics, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada

    Erin Hedin & Pavel Geier

  3. CHEO Research Institute, University of Ottawa, Ottawa, ON, Canada

    Vid Bijelić & Nick Barrowman

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Contributions

Dr. Erin Hedin helped design the study, carried out the systematic review, drafted the initial manuscript, and reviewed and revised the manuscript. Vid Bijelić and Dr. Nick Barrowman carried out the data analysis and reviewed and revised the manuscript. Dr. Pavel Geier conceptualized and designed the study, carried out the systematic review, helped draft the initial manuscript, and critically reviewed the manuscript for intellectual content.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Erin Hedin.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Methods S1: Electronic search strategies.

Supplementary Material S2: Risk of bias assessment of included studies.

Supplementary Figure S3: Risk of bias assessment of included studies.

Supplementary Figure S4: Risk of bias assessment of included studies.(PDF 255 KB)

Supplementary file2 (PPTX 254 KB)

Supplementary file3 (DOC 64 KB)

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Hedin, E., Bijelić, V., Barrowman, N. et al. Furosemide and albumin for the treatment of nephrotic edema: a systematic review. Pediatr Nephrol 37, 1747–1757 (2022). https://doi.org/10.1007/s00467-021-05358-4

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  • DOI: https://doi.org/10.1007/s00467-021-05358-4

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