Investigators from the Children’s Hospital of Michigan conducted a prospective study to determine if children 1 to 18 years old admitted with severe edema due to nephrotic syndrome and a fractional excretion of sodium (FeNa) >0.2% can be safely and effectively treated with diuretics alone. Severe edema was defined as evidence of 3+ or more pitting edema and ascites. Exclusion criteria included altered sensorium, decreased glomerular filtration rate, gross hematuria, fever, clinical peritonitis, current use of medications, and personal or family history of thrombosis.
All study patients were treated with sodium restriction (<2 mEq/kg/d), fluid restriction (two thirds of maintenance), and prednisone. An initial observational study demonstrated that a FeNa >0.2% identified a group of patients who, at admission, had significantly lower serum BUN and BUN/creatinine ratios, and higher serum and urine sodium concentrations. This group was defined as volume expanded (VE) while those subjects with a FeNa <0.2% were considered volume contracted (VC). During the interventional portion of the study, VE subjects were treated with twice-daily furosemide and twice-daily oral spironolactone while VC subjects were treated with twice-daily infusions of 25% albumin followed by intravenous furosemide. The interventional study included 20 patients (mean age 7.6±4.7 years), with nine in the VC group and 11 in the VE group
Prior to treatment, VC patients had significantly higher levels of antidiuretic hormone, plasma renin activity, and aldosterone as well as significantly higher serum BUN/creatinine ratios, lower urine sodium, and higher urine osmolality. The VE and VC groups had no significant differences in therapeutic outcome (percentage of weight lost) or duration of hospitalization. One patient in the VE group who initially received furosemide alone was switched to furosemide plus 25% albumin due to a rise in serum creatinine (>50% over baseline) and fall in serum sodium (141 to 133 mEq/L). Another patient in the VE group had a mild, transient rise in serum creatinine that resolved with discontinuation of furosemide.
The authors conclude that diuretics alone are safe and effective in children with severe edema due to nephrotic syndrome and VE, which can be identified by a FeNa >0.2%.
Dr Greenbaum has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
The management of edema in children with nephrotic syndrome is challenging and controversial.1 There are two theories of the mechanism of edema in nephrotic syndrome.2,3 The underfill hypothesis contends that hypoalbuminemia decreases plasma oncotic pressure, which leads to intravascular volume depletion, stimulating renal sodium and water retention. The overfill hypothesis postulates that excessive renal sodium retention leads to intravascular volume expansion and subsequent overflow of sodium and water into the interstitial space.
Use of a diuretic alone in children with nephrotic syndrome and intravascular volume...