Case Report

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A 43-year-old white woman with persistent acute renal failure 2 months after liver transplantation developed acute hyponatremia during treatment of thrombocytopenia with IVIG (4.5% to 5.5% human immune globulin in 9% to 11% maltose; Gamimune N, Cutter Biological, Elkhart, Indiana). Before therapy her serum sodium concentration was stable at 131 mmol/L. One gram/kg of IVIG (80 g, 1600 mL) was administered over 12 hours on 2 successive days. After the second infusion her serum sodium level was 118 mmol/L. After 4 hours of hemodialysis, the serum sodium level was 133 mmol/L. Hyponatremia recurred during each of four successive infusions of IVIG.

Methods

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Serum sodium, potassium, chloride, bicarbonate, glucose, and blood urea nitrogen concentrations were measured before, during, and 4 to 10 hours after completion of IVIG infusions by an Ektachem 700XRC autoanalyzer (Eastman Kodak; Rochester, New York), using direct potentiometry for the sodium assay. Simultaneous plasma osmolality was determined by freezing-point depression (Advanced Instruments, Inc.; Medham Heights, Massachusetts).

The osmolal gap (Osm) was calculated as the difference between the measured serum osmolality (S_Osm) and the osmolality calculated from serum sodium (S_Na), glucose (S_Glu), and blood urea nitrogen (S_Urea) concentrations:

Osm = S_{Osm –}[(2 x S_Na) + S_Glu + S_Urea]

Effective serum osmolality (serum tonicity, S_Ton) was calculated as

S_Ton = S_{Osm – SUrea}

The serum maltose concentration was measured as the increment in serum glucose concentration, assayed by glucose oxidase, after treatment with maltase (Sigma Biological; St. Louis, Missouri) for 45 minutes at 37 °C. Recovery of maltose in control assays was 98%. Data are presented as mean ±SD. Statistical comparisons used paired t-test and least squares regression.

Results

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The serum sodium concentration progressively declined from 129 ± 1.8 mmol/L before IVIG treatment to 122 ± 2.5 mmol/L during the last 4 hours of IVIG infusion (P < 0.01). The serum sodium concentration increased to (130 ± 3.2 mmol/L) within 10 hours after infusion (Figure 1). Despite progressive hyponatremia, the serum tonicity increased by 5.5 ± 3.5 mmol/kg. Serum maltose levels increased from 1.8 ± 1.7 mmol/L before IVIG to 7.5 ± 1.8 mmol/L (P < 0.02) at end of IVIG infusion. The osmolal gap increased by 13.5 ± 0.2 mmol/kg during the IVIG infusions. Serum glucose levels did not change (P > 0.10). The relations between the serum sodium concentration and the concentration of serum maltose and the osmolal gap are plotted in Figure 2. Linear regression showed a decrease in the serum sodium level of 0.59 mmol/L for each millimolar increase in the serum maltose level (R = 0.51) and a decrease of 0.31 mmol/L for each mmol/kg increase in the osmolal gap (R = 0.55).

View larger version (14K): [in this window] [in a new window]   Figure 1. Serum sodium, osmolal gap, and serum maltose concentrations during intravenous immune globulin infusions. Serum sodium (top panel), osmolal gap (middle panel), and serum maltose (bottom panel) concentrations before (pre-IVIG), during the final 4 hours of (end-IVIG), and 6 to 12 hours after the completion of (post-IVIG) infusions of intravenous immune globulin (IVIG) in 10% maltose in a patient with acute renal failure. Data are expressed as mean ±SD. (Serum sodium: Pre-IVIG versus end-IVIG, P < 0.01; end-IVIG versus post-IVIG, P < 0.05. Osmolal gap: pre-IVIG versus end-IVIG, P = 0.066; end-IVIG versus post-IVIG, P < 0.05. Serum maltose: pre-IVIG versus end-IVIG, P < 0.02; end-IVIG versus post-IVIG, P < 0.05).

View larger version (14K): [in this window] [in a new window]   Figure 2. Serum sodium concentrations in relation to serum maltose concentrations and the osmolal gap. Linear regression of the serum sodium concentration in relation to serum maltose concentrations (Panel A) and the osmolal gap (Panel B), before, during, and after repeated infusions of intravenous immune globulin in 10% maltose in a patient with acute renal failure.

Discussion

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We have described a patient who developed recurrent hyponatremia after repeated infusions of IVIG in 10% maltose. Although each infusion of IVIG was accompanied by a 1600-mL water load, this was insufficient to account for the decrease in serum sodium level. Furthermore, serum tonicity increased rather than decreased, as would be seen with water intoxication.

Maltose, a disaccharide composed of two glucose moieties, is hydrolyzed to glucose in the gastrointestinal tract after oral ingestion. When maltose is administered intravenously, it is predominately metabolized by maltase in the renal proximal tubule [7, 8] and is excreted in the urine [7, 9]. In patients with normal renal function who received maltose infusions at rates comparable to those in our patient, accumulation of maltose in blood is minimal [6, 9]; the fate of maltose in patients with renal failure has not been elucidated. In our patient, substantial quantities of maltose remained in the extracellular compartment at the conclusion of the IVIG infusion. We suspect that unidentified metabolic products of maltose metabolism also accumulated because the measured increase in maltose during each IVIG infusion was only one half the corresponding increment in the osmolal gap and a progressive increase in the osmolal gap occurred with each successive IVIG infusion.

The effect of the accumulation of maltose and its metabolic byproducts on the serum sodium concentration is similar to the effect of hyperglycemia. The change in the serum sodium concentration was 0.31 mmol/L for each mmol/kg increase in the osmolal gap, corresponding to the 0.29 to 0.36 mmol/L decrease in serum sodium associated with hyperglycemia [2, 10]. Thus, we postulate that our patient's hyponatremia resulted from the accumulation of maltose and other osmotically active metabolites in the extracellular fluid after IVIG infusion.