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 m(2) 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 A higher resolution version of the Graphical abstract is available as Supplementary information.

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 METHODS 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. 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.

Abstract

BACKGROUND Intradialytic hypotension (IDH) occurs in 20% to 55% of haemodialysis sessions and is more frequent among patients on long-term haemodialysis. Symptomatic IDH is generally defined as a decrease in systolic blood pressure (BP) of at least 10 mm Hg or a systolic BP less than 100 mm Hg, with symptoms such as cramps, nausea, vomiting, and dizziness. IDH is managed acutely by volume expansion through the intravenous administration of fluids. OBJECTIVES To compare the benefits and harms of volume expansion with human albumin, alone or in combination with crystalloid or non-protein colloids, for treating IDH in haemodialysis patients. SEARCH STRATEGY The Cochrane Renal Group's Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 9) MEDLINE (1966 to Oct 2009), and EMBASE (1980 to Oct 2009) were searched. SELECTION CRITERIA Randomised controlled trials (RCTs), quasi-RCTs as well as randomised crossover studies were to be included. DATA COLLECTION AND ANALYSIS Two authors independently extracted data and assessed trial quality. Relative risk (RR) was to be used to analyse dichotomous variables and mean difference (MD) used to analyse continuous variables. MAIN RESULTS One double blind randomised crossover trial met the inclusion criteria and compared 5% albumin to normal saline in patients with a previous history of IDH. Results from 45 assessable participants did not lead to rejection of the null hypothesis of no difference between 5% albumin and normal saline in the primary outcome measure of percentage target ultrafiltration achieved, nor in 11/12 secondary outcomes. Additional (unblinded) saline was given less often when 5% albumin was used compared with saline (16% versus 36%, P = 0.04). However, the volume of additional fluid administered was similar in both groups. There were no significant differences in the nursing time required to treat IDH and the time to restore BP. AUTHORS' CONCLUSIONS No randomised or controlled trial was identified comparing albumin to crystalloids (other than normal saline) or non-protein colloids, or a combination of both, in the treatment of symptomatic hypotension during dialysis.One double blind crossover RCT in 45 assessable patients showed that 5% albumin is not superior to normal saline for the treatment of symptomatic hypotension in maintenance haemodialysis patients with a previous history of IDH. Given the cost and relative rarity of albumin use compared to saline, saline should be first line of therapy for treatment of IDH in stable dialysis patients.