High prevalence of elevated molybdenum levels in pediatric CKD patients. A cross-sectional and longitudinal study
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AIMS: Many of the secondary effects of high levels of molybdenum (Mo) overlap with symptoms commonly seen in pediatric patients with chronic kidney disease (CKD). We measured plasma Mo levels and examined the relationship between Mo levels and kidney function. MATERIALS AND METHODS: The study was carried out at the London Health Sciences Centre in London, Ontario, Canada with 36 children and adolescents 4 - 18 years of age with CKD. There were 1 - 6 trace element measurements (Mo and copper (Cu)) per patient. We studied the proportion of patients with abnormal trace element levels and the relationship between trace element levels and estimated glomerular filtration rate (eGFR), calculated using the Filler formula. Plasma Mo and Cu levels were measured using High Resolution Sector Field Inductively Coupled Mass Spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart program. RESULTS: Median eGFR was 51 mL/min/1.73m2 (35, 75). Median Mo level was 2.00 µg/L (1.40, 2.88). 20 patients had at least one set of Mo levels above the published reference interval in either unit, and the results of 46% of the tests were above the interval. There was a strong negative correlation between the Mo levels and the eGFR (Spearman's r = -0.627, p < 0.0001). CONCLUSIONS: Our study suggests that pediatric patients with CKD have elevated plasma levels of Mo, which may cause secondary effects commonly associated with CKD. The elevated Mo levels in our center's catchment area may cause an accumulation of this trace element in patients with impaired renal function.
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Minimum mycophenolic acid levels are associated with donor-specific antibody formation.

Although de novo DSA are associated with inferior graft survival, there are no effective strategies to prevent their formation. Underexposure to MPA (prodrug: MMF) also contributes to rejection rates early after transplantation, but the effect of this phenomenon on the formation of DSA long-term post-transplantation is unknown. Data are expressed as mean (standard deviation). All available data from 32 renal transplant recipients (age at transplantation 7.5 [4.5] yr) on tacrolimus and MPA immunosuppression with an average follow-up of 9.4 (s.d. 4.6) yr were analyzed. DSA were measured using the Luminex assay (>500 MFI was considered DSA-positive). Tacrolimus and MPA levels were measured with the Abbot Tacro II and EMIT assay, respectively. Among 1964 MPA and 3462 tacrolimus trough levels, the average MPA trough level was 3.2 (1.5) mg/L and the average tacrolimus level was 6.7 (2.8) ng/mL. At last follow-up, only 5/32 patients had undetectable DSA, with 5/32 having no class I antibodies and 6/32 having no class II antibodies. DSA formation was associated with a lower minimum MPA trough level (0.27 [0.23] vs. 0.47 [0.18] mg) and cystatin C eGFR (48 [21] vs. 70 [23] mL/min/1.73 m(2)) for class I DSA formers. The average eGFR of patients without class I DSA was 70 (23) mL/min/1.73 m(2), whereas the average eGFR of patients with class I DSA was 48 (21) mL/min/1.73 m(2) (p = 0.0071). MPA trough levels <1.3 mg/L long-term post-transplantation are associated with the formation of DSA. The association between the formation of DSA and minimum MPA exposure may support a strategy for preventing the formation of DSA.

Convenience Sampling of Children Presenting to Hospital-Based Outpatient Clinics to Estimate Childhood Obesity Levels in Local Surroundings.

Childhood obesity is a critical public health matter associated with numerous pediatric comorbidities. Local-level data are required to monitor obesity and to help administer prevention efforts when and where they are most needed. We hypothesized that samples of children visiting hospital clinics could provide representative local population estimates of childhood obesity using data from 2007 to 2013. Such data might provide more accurate, timely, and cost-effective obesity estimates than national surveys. Results revealed that our hospital-based sample could not serve as a population surrogate. Further research is needed to confirm this finding.

What is the intrapatient variability of mycophenolic acid trough levels?

TDM of MPA, the active compound of MMF, is rarely used despite its substantial intra- and interpatient variability. Little is known about the utility of long-term MPA TDM. Data are expressed as mean (one standard deviation). All available data from 27 renal transplant recipients (mean age at transplantation: 7.7 [5.0] yr) with an average follow-up of 9.3 (4.6) yr were analyzed. MPA levels were measured using the EMIT. GFR was measured using cystatin C and eGFR was calculated using the Filler formula. Intrapatient CV of the trough level was calculated as the ratio of the mean divided by one standard deviation. Mean cystatin C eGFR was 56.9 (24.4) mL/min/1.73 m(2) . There was a weak but significant correlation between the MPA trough level and the AUC (Spearman r = 0.6592, p < 0.0001). A total of 1964 MPA trough levels (73 [45]/patient) were measured, as compared to 3462 Tac trough levels (144 [71]/patient). The average MPA trough level was 3.01 (1.26) mg/L and the average trough Tac level was 7.3 (1.8) ng/mL. Intrapatient CV was statistically higher (p = 0.00093) for MPA at 0.68 (0.29) when compared to Tac with a CV of 0.46 (0.12). CV did not correlate with eGFR. Intrapatient MPA trough level CV is significantly higher than for Tac, while CV for both MPA and Tac was high. MPA trough level monitoring may be a feasible monitoring option to improve patient exposure and possibly outcomes.

A cross-sectional study measuring vanadium and chromium levels in paediatric patients with CKD.

OBJECTIVES: Although many secondary effects of high levels of vanadium (V) and chromium (Cr) overlap with symptoms seen in paediatric patients with chronic kidney disease (CKD), their plasma V and Cr levels are understudied. DESIGN: Ancillary cross-sectional study to a prospective, longitudinal, randomised controlled trial. SETTING: Children's Hospital of Western Ontario, London Health Sciences Centre, London, Ontario, Canada. PARTICIPANTS: 36 children and adolescents 4-18 years of age with CKD. INTERVENTIONS: 1-6 trace element measurements per patient. Cystatin C (CysC) estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma V and Cr levels were measured using high-resolution sector field inductively coupled mass spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart programme. Water Cr and V data were obtained from the Ontario Water (Stream) Quality Monitoring Network. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: plasma Cr and V. SECONDARY OUTCOMES: age, season, CysC, CysC eGFR, and Cr and V levels in environmental water. RESULTS: The median (IQR) eGFR was 51 mL/min/1.73 m2 (35, 75). The median V level was 0.12 µg/L (0.09, 0.18), which was significantly greater than the 97.5th percentile of the reference interval of 0.088 µg/L; 32 patients had at least one set of V levels above the published reference interval. The median Cr level was 0.43 µg/L (0.36, 0.54), which was also significantly greater than the established reference interval; 34 had at least one set of Cr levels above the published reference interval. V and Cr levels were moderately correlated. Only some patients had high environmental exposure. CONCLUSIONS: Our study suggests that paediatric patients with CKD have elevated plasma levels of V and Cr. This may be the result of both environmental exposure and a low eGFR. It may be necessary to monitor V and Cr levels in patients with an eGFR <30 mL/min/1.73 m2. TRIAL REGISTRATION NUMBER: NCT02126293; HC#172241.

Seizures Related to Hypomagnesemia: A Case Series and Review of the Literature.

OBJECTIVE: Childhood seizures have various nonneurological etiologies. The patient's magnesium levels should be measured when evaluating afebrile seizures. The purpose of the current case series is to describe a systematic approach for diagnosing hypomagnesemia using 3 recent patient cases. METHODS: This case series describes 3 patients with unprovoked hypomagnesemia-associated seizures. The authors describe the differential diagnosis, pathophysiology, and the workup of hypomagnesemia-associated seizures. RESULTS: Hypomagnesemia contributed to the cause of the seizures in all 3 cases. Various causes of hypomagnesemia were investigated, including genetic etiologies. All 3 patients were maintained at a magnesium level >0.65 mmol/L, which improved or eliminated the seizures. SIGNIFICANCE: Magnesium levels should always be measured when trying to determine the etiology of seizures. Hypomagnesemia and afebrile seizures should be treated with the goal of maintaining a magnesium concentration >0.65 mmol/L. Although rare, genetic causes of hypomagnesemia should be considered, once common causes of hypomagnesemia are ruled out.

Beta-trace protein as a marker of GFR--history, indications, and future research.

OBJECTIVES: Recent findings suggest that beta-trace protein (BTP), a small molecular weight protein, is at least equal if not superior to serum creatinine as a marker of glomerular filtration rate (GFR), particularly since it is independent from height, gender, age, and muscle mass. The authors sought to summarize knowledge on BTP and its use as a marker of GFR using the most recent literature available. DESIGN AND METHODS: The authors compiled key articles and all relevant recent literature on this topic. Physical and chemical features of the molecule are described, as well as factors that may affect its expression. The use of BTP in estimating GFR as a whole and in specific patient groups, including pregnant women, neonates and infants, children and adolescents, and patients who have undergone renal transplantation is discussed. The use of BTP as a marker for cardiovascular risk factors is also briefly addressed. RESULTS: Although its performance in the general population is marginally inferior to cystatin C, studies have suggested that it may be superior in accurately estimating GFR in select patient groups such as pregnant women and neonates. CONCLUSIONS: This novel marker shows promise, but further research is required to clarify findings from available data.