Human albumin infusion for treating oedema in people with nephrotic syndrome

What is the issue?

Nephrotic syndrome is a kidney disorder that causes the body to excrete high quantities of protein in urine. The loss of protein causes the body to retain fluid that would normally be excreted in the urine and swelling (oedema) typically starting at the ankles and sometimes involving the hands and face.

Oedema is often treated by a diuretic (a medication that stimulates the kidney to increase the excretion of salt and water). However, in nephrotic syndrome diuretics alone often don't work. Human albumin has been used to replace the protein lost. This might result in the oedema fluid being drawn back into the blood circulation so it can be excreted by the kidneys. It might be given alone or in combination with a diuretic. We wanted to find out whether albumin could treat oedema in people with nephrotic syndrome.

What did we do?

We searched for randomised controlled trials (RCTs) or quasi-RCTs comparing (1) albumin with a placebo or no treatment, (2) albumin with a diuretic, (3) albumin combined with a diuretic compared with a diuretic alone, or (4) albumin with other treatments. We excluded cross-over studies but would have included data for the first period before the cross-over if available. The last search was done in June 2019.

What did we find?

The review found one small RCT (26 patients) comparing human albumin plus the diuretic furosemide with placebo suitable for inclusion. We found nine studies on people with nephrotic syndrome that tested these comparisons but these were 'cross-over' studies which we judged not suitable. To find out whether there was any improvement after albumin, the study measured weight loss and serum sodium. The adverse effect measured was blood pressure. Although the authors reported increased weight loss we were not able to confirm this due to inconsistency between the data reported in the table and the text. There was no change in serum sodium or blood pressure. We judged these outcomes all to be of very low certainty. Death, quality of life, and kidney function were not reported.

Conclusions
Because there was only one small study found we cannot tell whether albumin is effective in people with nephrotic syndrome and we do not know from the studies we looked at whether it is safe. There is no evidence in adults. We judged the evidence to be very low certainty. Therefore RCTs are needed.

Authors' conclusions: 

We identified only one small study that was relevant to our review, therefore we are unable to draw any conclusions regarding the use of human albumin with or without diuretics in nephrotic syndrome. More RCTs are needed.

Read the full abstract...
Background: 

Oedema is a common clinical symptom in people with nephrotic syndrome and human albumin has been widely used in the treatment of oedema by increasing vascular volume and this inducing diuresis. It may be used with or without diuretics such as furosemide. However, the quantitative contribution of human albumin in treating oedema is not fully understood. If human albumin were found to be effective and safe in the treatment of oedema, it could help clinicians to develop therapeutic strategies to improve the management of diuretic resistance associated with nephrotic syndrome.

Objectives: 

This review aimed to examine the benefits and harms of human albumin infusion for treating oedema associated with nephrotic syndrome.

Search strategy: 

We searched the Cochrane Kidney and Transplant Register of Studies up to 23 June 2019 through contact with the Information Specialists using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: 

We included randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of human albumin infusion compared with placebo or no intervention, human albumin with diuretics compared with diuretic alone, human albumin compared with diuretics and other treatments, clinical outcomes, death, quality of life, kidney function and adverse effects in people with nephrotic syndrome. We excluded cross-over studies but data for the first period was to be included if available.

Data collection and analysis: 

Standard methods of the Cochrane Collaboration were used. Two authors independently assessed eligibility, risk of bias, study quality and extracted data. We calculated mean difference (MD) for continuous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE.

Main results: 

One study met our inclusion criteria (26 children with minimal change nephrotic syndrome) and 11 were excluded (nine cross-over studies, one where albumin was not used for nephrotic syndrome and one where authors did not state whether the children had oedema). Risk of bias for the included study was unclear for selection bias, high for performance and detection bias, low for attrition bias, and high for selective reporting. The included study compared albumin plus furosemide with an equal volume of dextrose. Of our prespecified outcomes, the authors reported clinical improvement as weight change, serum sodium and adverse outcomes (blood pressure). The authors reported a greater weight loss in the albumin treated group initially but no difference overall at 10 days. However, the data in the text and the figures were inconsistent so we could not confirm the authors statements (very low certainty evidence). It is uncertain whether albumin infusion improves serum sodium when compared with an equal volume of dextrose (MD 2.00 mEq/L, 95% CI -0.09 to 4.09), systolic blood pressure (MD 2.00 mmHg, 95% CI -3.52 to 7.52) or diastolic blood pressure (MD 2.00 mmHg, 95%CI -4.29 to 8.29). Death, quality of life, and kidney function were not reported.

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