Quantification of gadolinium in fresh skin and serum samples from patients with nephrogenic systemic fibrosis.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a rare, potentially fatal fibrosing disorder associated with renal insufficiency and gadolinium (Gd)-based contrast exposure. The cause remains unknown. To date, all efforts to investigate skin Gd concentrations in patients with NSF have been performed on paraffin-embedded samples, and Gd deposition has not been correlated with disease activity by a statistically significant analysis. OBJECTIVE: We sought to: (1) quantify Gd concentration in fresh tissue skin biopsy specimens; (2) quantify and compare synchronous Gd concentration of affected skin and unaffected skin in patients with NSF (n = 13) with a control group (n = 13); and (3) quantify serum Gd. METHODS: We used inductively coupled plasma mass spectrometry. RESULTS: In patients with NSF, the mean ratio of paired Gd concentrations of affected skin to unaffected skin was 23.1, ranging from 1.2 to 88.9. Mean serum Gd concentrations in patients with NSF were 4.8 ng/mL, which is more than 10 times the level in control patients. A statistically significant correlation existed between serum and affected skin Gd concentrations (r(2) = .74, P < .0001). LIMITATIONS: Because of the feasibility of this study, the main limitation was the small sample size (n = 13 affected and 13 control). CONCLUSIONS: Determination of Gd concentrations in fresh skin samples and serum using inductively coupled plasma mass spectrometry demonstrates significant differences in the amounts of Gd in involved versus nonlesional skin of patients with NSF. This supports the role of differential free Gd deposition from Gd-based contrast in the pathogenesis of NSF.

Reliable, Rapid, and Robust Speciation of Arsenic in Urine by IC-ICP-MS.

BACKGROUND: Arsenic is a naturally occurring element with varying species and levels of toxicity. Inorganic arsenic (e.g., arsenite (AsIII) and arsenate (AsV)) are toxic, while its metabolites (e.g., monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) are less toxic). Symptoms of exposure can include headaches, confusion, diarrhea, and drowsiness. As these symptoms overlap with many other conditions, arsenic exposure can often be overlooked as a cause. Arsenic toxicity may be treated with chelation and/or electrolyte replacement therapy. However, treatment is not without risks and is unnecessary for exposure to organic (nontoxic) forms of arsenic. This makes screening and differentiation of arsenic important for clinical testing. METHOD: An IC-ICP-MS method was developed using a Dionex 5000 with ion exchange chromatography for separation and iCAP Q for detection. Nontoxic species are arsenobetaine and arsenocholine, and toxic species are AsIII, DMA, MMA, and AsV. RESULTS: Precision, linearity, and specificity studies produced acceptable results. For accuracy, proficiency testing and method comparison samples were analyzed and produced acceptable results. Carryover studies demonstrated single species carryover from the diluter at levels of 500 µg/L, which can be avoided by analysis rules in the standard operating procedure. Limit of detection studies yielded a lower limit of quantitation of 1 µg/L per species. CONCLUSIONS: Here, we present a rapid and reliable method for quantifying and differentiating toxic and nontoxic forms of arsenic to allow for swift and appropriate management of patients with exposure.

Fecal electrolyte testing for evaluation of unexplained diarrhea: Validation of body fluid test accuracy in the absence of a reference method.

BACKGROUND: Validation of tests performed on body fluids other than blood or urine can be challenging due to the lack of a reference method to confirm accuracy. The aim of this study was to evaluate alternate assessments of accuracy that laboratories can rely on to validate body fluid tests in the absence of a reference method using the example of sodium (Na(+)), potassium (K(+)), and magnesium (Mg(2+)) testing in stool fluid. METHODS: Validations of fecal Na(+), K(+), and Mg(2+) were performed on the Roche cobas 6000 c501 (Roche Diagnostics) using residual stool specimens submitted for clinical testing. Spiked recovery, mixing studies, and serial dilutions were performed and % recovery of each analyte was calculated to assess accuracy. Results were confirmed by comparison to a reference method (ICP-OES, PerkinElmer). RESULTS: Mean recoveries for fecal electrolytes were Na(+) upon spiking=92%, mixing=104%, and dilution=105%; K(+) upon spiking=94%, mixing=96%, and dilution=100%; and Mg(2+) upon spiking=93%, mixing=98%, and dilution=100%. When autoanalyzer results were compared to reference ICP-OES results, Na(+) had a slope=0.94, intercept=4.1, and R(2)=0.99; K(+) had a slope=0.99, intercept=0.7, and R(2)=0.99; and Mg(2+) had a slope=0.91, intercept=-4.6, and R(2)=0.91. Calculated osmotic gap using both methods were highly correlated with slope=0.95, intercept=4.5, and R(2)=0.97. Acid pretreatment increased magnesium recovery from a subset of clinical specimens. CONCLUSIONS: A combination of mixing, spiking, and dilution recovery experiments are an acceptable surrogate for assessing accuracy in body fluid validations in the absence of a reference method.

Chelation of gadolinium with deferoxamine in a patient with nephrogenic systemic fibrosis.

A 65-year-old female with biopsy-confirmed nephrogenic systemic fibrosis (NSF) received a kidney transplantation. Despite good kidney function, her symptoms continued to progress. Deferoxamine was administered intramuscularly at 500 mg/day and later 1000 mg/day after 1 week with no adverse effects. Urine excretion of gadolinium increased from 6.0 µg/day to 11.6 µg/day and subsequently to 13.0 µg/day with 500 mg/day and 1000 mg/day of deferoxamine, respectively. Serum levels, however, remain unchanged from 1.7 ng/ml to 1.4 ng/ml. Although chelation therapy may have a role in the treatment of NSF, deferoxamine is too weak and a stronger chelator is needed.