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Obese youth with sleep-disordered breathing are treated with positive airway pressure to improve sleep and cardiovascular status. While improvements in sleep parameters have been confirmed, a study by Katz et al. showed no major improvement in ambulatory blood pressure. The aim of this ancillary study was to analyze short-term blood pressure variability, following positive airway pressure treatment, as a more sensitive marker of cardiovascular health. We analyzed 24-h blood pressure variability data in 17 children, taken at baseline and after 12 months of treatment. These data were derived from an already published prospective, multicenter cohort study conducted in 27 youth (8-16 years) with obesity who were prescribed 1-year of positive airway pressure for moderate-severe sleep-disordered breathing. Significant decreases were found in 24 h systolic blood pressure (p = 0.040) and nighttime diastolic blood pressure (p = 0.041) average real variability, and diastolic blood pressure (p = 0.035) weighted standard deviation. Significant decreases were noted in nighttime diastolic blood pressure time rate variability (p = 0.007). Positive airway pressure treatment resulted in a significant decrease in blood pressure variability, suggesting a clinically significant improvement of sympathetic nerve activity in youth with obesity and sleep-disordered breathing. IMPACT: Cardiovascular variability, as measured by blood pressure variability, is improved in children following positive airway pressure treatment. Our novel findings of improved blood pressure time rate variability are the first described in the pediatric literature. Future studies aimed at analyzing target organ damage in this patient population will allow for a better understanding as to whether alterations in blood pressure variability translate to decreasing target organ damage in children, as seen in adults.

Arterial hypertension in renal transplant recipients warrants antihypertensive treatment. The preferable choice of antihypertensives that should be used in patients after kidney transplantation remains a matter of debate; however, calcium channel blockers (CCB) and angiotensin-converting enzyme inhibitors (ACEI) are currently the most commonly used antihypertensives. This educational review summarizes the current evidence about the effects of these two classes of medications in transplant recipients. Several studies have demonstrated that both classes of drugs can reduce blood pressure (BP) to similar extents. Meta-analyses of adult randomized controlled trials have shown that graft survival is improved in patients treated with ACEIs and CCBs, and that CCBs increase, yet ACEIs decrease, graft function. Proteinuria is usually decreased by ACEIs but remains unchanged with CCBs. In children, no randomized controlled study has ever been performed to compare BP or graft survival between CCBs and ACEIs. Post-transplant proteinuria could be reduced in children along with BP by ACEIs. The results of the most current meta-analyses recommend that due to their positive effects on graft function and survival, along with their lack of negative effects on serum potassium, CCBs could be the preferred first-line antihypertensive agent in renal transplant recipients. However, antihypertensive therapy should be individually tailored based on other factors, such as time after transplantation, presence of proteinuria/albuminuria, or hyperkalemia. Furthermore, due to the difficulty in controlling hypertension, combination therapy containing both CCBs and ACEIs could be a reasonable first-step therapy in treating children with severe post-transplantation hypertension.

Hemolytic uremic syndrome (HUS) is characterized bymicroangiopathic anemia, thrombocytopenia, and acute kidney injury [1]. In addition, severe HUS can be associated with irreversible renal and CNS complications, leading to chronic kidney disease and permanent neurological deficits [2]. The most common form of HUS is induced by a verocytotoxin/ Shiga toxin (Vtx/Stx)-producing bacteria [3]. Less commonly, HUS can be induced by bacterial (e.g., S. pneumoniae) [3] or viral (e.g., influenza) infections [4]. We report a patient with a severe clinical presentation of HUS following pneumonia (presumed S. pneumoniae infection). Making the correct diagnosis proved to be difficult as the patient presented with unusual findings, including a negative Coombs test and low C3 complement level on two occasions. These findings did not meet the usual diagnostic criteria of S. pneumoniae-induced HUS, which include a positive Coombs test and a normal complement C3 level. While HUS caused by defective complement alternative pathway (CAP) regulation, presents with low serum C3 complement in approximately 75 % of patients [5], patients with the infection-induced types of HUS do not exhibit complement dysregulation, and their C3 levels are normal [3, 6]. In patients with S. pneumoniae-induced HUS, the C3 levels are usually normal, and the Coombs test is positive, owing to antibodies binding to the exposed T-antigen on the surface of red blood cells [7, 8]. Thus, the combination of normal C3 complement levels with a positive Coombs test would confirm the diagnosis of S. pneumoniae-induced HUS [7, 8]. However, complement activation leading to a lower C3 complement can occur even in non-genetic forms of HUS [9], which can be considered an aggravating factor for the disease progression. Furthermore, the Coombs test can be positive in 25 to 90 % of cases [10, 11], indicating that a relatively large proportion of patients with pneumococcal HUS can have a negative Coombs test. This refers to the article that can be found at http://dx.doi.org/10.1007/ s00467-015-3101-y

Background Practice variation is common for nephrotic syndrome (NS) treatment. Methods A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS. Results Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4w eeks by 26 %, and 10 %p rescribed‘other’ .A lternateday GC was continued for 6 weeks by 63 % of respondents and for >6 and

In pediatric patients at risk of hyperkalemia there are limited treatment or preventive alternatives for this electrolyte imbalance. Oral or rectal sodium polystyrene sulfonate (SPS) has several potential adverse effects, and dietary potassium restriction may compromise nutrition. Pretreatment of infant formula with SPS has been previously studied with promising efficacy. The optimal dosing and contact time has not been fully elucidated for this practice, nor have brand and generic products been compared. The present study aimed to evaluate the effectiveness of varying amounts of brand and generic SPS for the removal of potassium from formula after 1 and 24 hours. SPS was added to infant formula in four different amounts measured in milliliters to reflect how a parent or caregiver would measure this product at home. After 1 and 24 hours samples were withdrawn and potassium and sodium levels were measured. Potassium decreased in all samples, with the greatest reduction after the addition of 10 mL of SPS. Sodium levels increased in all pretreated samples to a greater extent than the potassium reduction. Contact time of either 1 or 24 hours did not impact the amount of potassium removed or the increase in sodium concentration. There were also no differences found between generic and brand SPS products. The effectiveness of SPS for formula pretreatment appears to have a plateau effect beyond the addition of 20 mL (16.47 g of brand name product, 19.5 g of generic product). This study demonstrates an effective protocol for pretreatment of formula.

Summary: Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%). Introduction: Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome. Methods: Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis. Results: Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure. Conclusions: Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study. © 2011 International Osteoporosis Foundation and National Osteoporosis Foundation.

We assessed the effects of 12 months of non-pharmacological and pharmacological therapy on 24-h ambulatory blood pressure, regression of target organ damage (TOD) and metabolic abnormalities in 86 children (14.1 ± 2.4 years) with primary hypertension. Twenty-four hour systolic and diastolic blood pressure (BP) decreased (130 ± 8 vs 126 ± 8, 73 ± 7 vs 70 ± 7, p = 0.0001 and 0.004 respectively). Body mass index (BMI) did not change, but waist-to-hip (0.85 ± 0.07 vs 0.83 ± 0.05, p = 0.01) and waist-to-height ratio (WHtR; 0.49 ± 0.07 vs 0.48 ± 0.05, p = 0.008) decreased. Left ventricular mass index (LVMi; 38.5 ± 10.7 vs 35.2 ± 7.5 g/m2.7, p = 0.0001), prevalence of left ventricular hypertrophy (46.5% vs 31.4%; p = 0.0001), carotid intima-media thickness (cIMT; 0.44 ± 0.05 vs 0.42 ± 0.04 mm, p = 0.0001), wall cross sectional area (WCSA; 7.5 ± 1.3 vs 6.9 ± 1.2 mm2, p = 0.002), hsCRP (1.1 ± 1.0 vs 0.7 ± 0.7 mg/l, p = 0.002), and LDL-cholesterol (115 ± 33 vs 107 ± 26 mg/dl, p = 0.001) decreased. Patients who had lowered BP had a lower cIMT at the second examination (0.41 ± 0.04 vs 0.43 ± 0.04 mm, p = 0.04) and lower initial hsCRP values (0.9 ± 0.7 vs 1.5 ± 1.3 mg/l, p = 0.04) in comparison to non-responders. Regression analysis revealed that the main predictor of LVMi decrease was a decrease in abdominal fat expressed as a decrease in waist circumference (WC) (R 2 = 0.280, β = 0.558, p = 0.005), for WCSA-SDS a decrease in WC (R 2 = 0.332, β = 0.611, p = 0.009) and for a cIMT-SDS decrease the main predictor was a decrease in hsCRP concentrations (R 2 = 0.137, β = 0.412, p = 0.03). Standard antihypertensive treatment lowered BP and led to regression of TOD in hypertensive children. Lean body mass increase and decrease in abdominal obesity correlated with TOD regression.

Adults with ambulatory hypertension or white coat hypertension (WCH) display abnormal cardiovascular rhythms. We studied cardiovascular rhythms by Fourier analysis of 24-h ambulatory blood pressure (BP) measurement profiles in 129 hypertensive children, 54 children with WCH, and 146 age-, height-, and gender-matched healthy subjects. The day/night mean arterial pressure ratio was lower in hypertensive and patients with WCH compared with controls (1.13 versus 1.16 versus 1.21, respectively; p < 0.0001). Eighty-five percent of controls were dippers compared with 74% of WCH (n.s.) and 64% of patients with ambulatory hypertension (p < 0.0001). The prevalence of 24-h rhythms was similar among the groups, but prevalence of 12-h BP rhythms was increased in hypertensive (67%) and WCH (72%) compared with controls (51%, p < 0.0001). The amplitudes of the 24-, 8-, and 6-h BP rhythms were reduced in hypertensive and WCH compared with controls (p < 0.05). Hypertensive and patients with WCH displayed delayed 24-, 12-, 8-, 6-h acrophases in comparison with controls (p < 0.05). In conclusion, hypertensive children exhibit abnormal cardiovascular rhythmicity compared with controls, especially a higher prevalence of nondipping compared with normotensive children. Abnormalities in patients with WCH are intermediate between healthy children and patients with ambulatory hypertension.

We report on a rare case of hypoxanthine guanine phosphoribosyl transferase (HGPRT) deficiency that presented in the newborn period with acute renal failure (ARF). The clinical diagnosis was made on the basis of non-oliguric ARF and evidence of crystal nephropathy on renal biopsy. HGPRT deficiency was eventually confirmed by enzymatic and genetic testing, showing a novel point mutation, 293 A>G. Immediate treatment consisted of peritoneal dialysis with, initially, lactate- then bicarbonate-buffered 1.36% glucose solution together with oral administration of allopurinol. Follow-up after more than 4 years continued to show hyper-echogenic kidneys with almost normal renal glomerular function. There continues to be no neurobehavioural abnormalities.

In a cross-sectional study, we compared the prevalence of anemia based on age- and gender-specific reference intervals for hemoglobin (Hgb) and hematocrit (Hct) with the Kidney Disease Outcomes Quality Initiative (KDOQI) anemia definition (Hgb < 110 g/L) in 351 children with chronic kidney disease (CKD) stages I–V. Cystatin C-based GFRs were 122 ± 36 mL/min/1.73 m2 in patients with stage I CKD (n = 196), 76 ± 8 mL/min/1.73 m2 for stage II (n = 104), 45 ± 9 mL/min/1.73 m2 for stage III (n = 36), and 22 ± 5 mL/min/1.73 m2 in patients with stage IV+V CKD (n = 15). Fifty-nine patients received iron therapy and 32 patients were treated with Darbepoetin. For Hgb, a total of 90 patients fit the age and gender derived criteria, compared to only 54 patients identified by the KDOQI guidelines (p = 0.0010). Similarly, for Hct, a total of 78 patients fit the age and gender derived criteria, which was a significantly higher proportion than the 56 identified by the KDOQI guidelines (r = 0.22, p = 0.0435). There was a significant correlation between the GFR and both the Hgb Z-score (p = 0.0068) and the Hct Z-score (p = 0.0128). There was poor agreement between conventional and KDOQI definitions of anemia in children with CKD.

Peritoneal dialysis (PD) continues to be an important modality of treatment for children with end-stage renal disease. The Canadian Association of Pediatric Nephrologists recognized the need nationally to review the literature on the delivery of PD in children to provide optimal standardized care. This resulted in the development of the Canadian Clinical Practice Guidelines for pediatric PD. Clinical practice guidelines are a useful adjunct to clinical care. The present review includes recommendations for catheter placement and types, requirement for prophylactic omentectomy, initiation and adequacy of dialysis, PD prescription, and solute clearance. It provides physicians with updated evidence-based recommendations that include consideration towards practicality with the major goal of improved and standardized patient care.

This study describes the pharmacokinetics of mycophenolate mofetil (MMF) in 15 pediatric patients with vasculitis and connective tissue disease involving the kidney. Patients included 10 with systemic lupus erythematosus (SLE), 1 with antiphospholipid antibody syndrome, 2 with Wegener granulomatosis, and 1 each with Goodpasture syndrome, Henoch-Schönlein-associated nephritis, and 1 with severe tubulointerstitial nephritis and uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF, which was administered for a median of 491 days. Mean starting dose of MMF was 974+/-282 mg/m(2 )in two divided doses. Pharmacokinetic monitoring of the active compound of MMF, mycophenolic acid (MPA), was performed using an EMIT assay. The mean MPA AUC after a median of 39 days was 61.8+/-31.0 micro gxh/ml, median time to maximum concentration was 60 min, and mean maximum concentration was 18.5+/-8.4 micro g/ml. At last follow-up, mean MMF dose was 900+/-341 mg/m(2) per day, and mean trough MPA concentration was 3.1+/-1.1 (range 0.6-4.6) micro g/ml. Therapy was effective in inducing remission in 4 of 9 patients with active disease. Only 1 of the 5 other patients relapsed. All 6 patients with controlled disease maintained remission. There were few side effects: one episode each of diarrhea and leukocytopenia and two viral infections. We conclude that MMF at 900 mg/m(2) per day appears to be effective in these patients.

Dual energy X-ray absorptiometry (DEXA) is a non-invasive accurate method which estimates bone mineral content and density (BMD), as well as fat (FM) and lean (LM) body mass. This method was used in control children in order to establish normal values for BMD of lumbar spine and whole body composition ¿logistic curves, general equation E = k+K/[1+ alpha exp(- beta A)]¿. In children with chronic renal failure (CRF), LM correlated with the urinary excretion of creatinine (r = 0.97, P = 0.0001) independently from glomerular filtration rate. However, the assessment of LM by DEXA must take into account the hydration level, since there is a positive correlation between fluid loss and reduction in LM in children on hemodialysis (r = 0.98, P = 0.0001). After renal transplantation, a significant loss of BMD (median -9.2%) was observed at 6 months which returned to 95% of pretransplant values by the end of the 1st year. Maximal changes in LM and FM occurred during the first 3 months (-7.8% and +7.2%, respectively) and may be due to steroids; these should be influenced by physical activity since FM correlated inversely with maximal oxygen consumption (r = 0.69, P = 0.0001). Recombinant growth hormone treatment could also increase LM and decrease FM, as shown in 9 patients. DEXA appears therefore to be a reliable method for evaluating therapeutic interventions affecting nutritional status in children with CRF.

Residual renal function was studied in 28 haemodialysis (HD) and 31 peritoneal dialysis (PD) patients aged 1-20 years observed over 6-43 (median 19) months. After the start of dialysis urine volume (UV) decreased to 57%, 46% and 26% of initial mean values in HD patients after 6, 12 and 24 months, respectively. In PD patients the corresponding figures were 57%, 69% and 62%. Mean UV calculated from all individual mean UV measurements observed was higher in PD than HD patients (954 vs. 537 ml/m2 per 24 h, P < 0.01). A better conservation of diuresis in PD patients was also suggested by a significantly longer persistence of a UV greater than 500 ml/m2 per 24 h compared with HD patients. Cox proportional hazard analysis identified dialysis modality and pre-dialysis UV of less than 1,000 ml/m2 per 24 h as the only significant risk factors for UV survival. However, the decline of UV per time was similar in both modes of treatment. No significant changes of glomerular filtration rate were observed during both HD and PD treatment.

A previously healthy 9-month-old boy presented to the hospital with a 10-day history of decreased energy, feeding difficulties, maculopapular rash, vomiting, and fever. He had been diagnosed with pneumonia and started on oral amoxicillin 2 days before hospital admission. On physical examination, he had a rectal temperature of 38.5 °C, a pulse of 134 beats per minute, and a blood pressure of 118/69 mmHg. He had mild intercostal retractions with abdominal breathing and decreased air entry at the left base. He had mild periorbital edema and a maculopapular rash on the trunk and upper extremities. He was started on intravenous (IV) fluids because of clinical signs of dehydration (estimated body weight loss of 5–10 %). A chest X-ray confirmed a left lower lobe pneumonia with moderate effusion, his antibiotics were changed to IV cefuroxime and vancomycin, and he was admitted to the hospital. Overnight he developed non-bloody diarrhea. While his urine output was within normal limits, his initial renal function analysis revealed a slightly elevated serum creatinine (SCr) of 48 μmol/L and a blood urea of 12.1 mmol/L, likely due to dehydration. The white cell and platelet counts were normal at 4.83 × 10 and 302 × 10/L, respectively; hemoglobin was decreased to 105 g/L. Urinalysis was negative for protein, blood, and nitrites. A repeat blood test performed 24 h later showed a rise in SCr to 60 μmol/L and in blood urea to 17.6 mmol/L. Subsequently, his hemoglobin dropped to 73 g/L and his platelets dropped to

Longitudinal bone mineral changes after renal transplantation were studied in 14 children aged 8 +/- 4 years. Combination immunosuppressive therapy was given to all patients (prednisone, azathioprine, cyclosporine). Bone mineral density (BMD) measurements of the first through fourth lumbar vertebrae by dual-energy X-ray absorptiometry were performed within 1 year preceding renal transplantation and 6, 12, and 24 months afterward (M0, M6, M12, and M24, respectively). The results of BMD obtained in grams of hydroxyapatite per square centimeter of spine projected area were subsequently transformed to standard deviation scores for a normal pediatric population. In addition, we used a mathematical spine volume correction to give the results in grams per cubic centimeter. All patients had a well-functioning renal graft at M6, M12, and M24 and a normal serum creatinine level. Significant decreases in BMD, standard deviation score, and spine volume-corrected BMD were observed 6 months after renal transplantation (p0.05, p0.01, and p0.01 respectively); the median loss of BMD and spine volume-corrected BMD was 9.2% and 15.6% at M6, respectively, and the median serum parathyroid hormone level dropped from 125 to 34 pg/ml. Between M6 and M12, BMD increased significantly up to 95% (median) of pretransplantation values and reached 97.2% (median) at M24. Similar but less marked improvement was observed in spine volume-corrected BMD results, reaching 87.7% and 87.4% at M12 and M24, respectively. A negative correlation was found between the cumulative prednisone dose and BMD in grams per square centimeter at M6 (r2 = 0.603; p = 0.006), M12 (r2 = 0.532; p = 0.015), and M24 (r2 = 0.40; p = 0.014). There was no correlation between cumulative prednisone dose and spine volume-corrected BMD or standard deviation score. Mean 6-month cyclosporine levels did not correlate with any measure of BMD. We conclude that after renal transplantation children have a significant decrease of BMD during the first 6 months after the operation, despite normal graft function and growth improvement.

Successful renal transplantation is supposed to correct the majority of bone mineral metabolism disturbances induced by chronic renal failure. We examined bone mineral density (BMD) in 14 children (8 girls, 6 boys) aged 8 ± 4 years at the time of renal transplantation (Tx). Dual energy X-ray densitometry of lumbar vertebrae (L1-L4) was performed within one year preceding Tx (T0), 6, 12 and 24 months after Tx (T6, T12 and T24 respectively). The results of BMD obtained in g of hydroxyapatite per cm2 of spine projected area were subsequently transformed to Z scores (Z) for normal pediatric population. All patients had a well functioning renal graft at T6, T12 and T24, median serum creatinine levels were 54, 63 and 84 μmol/l, respectively. BMD ± SD decreased from initial level of 0.65 ± 0.18 at T0 to 0.59 ± 0.16 at T6 (p < 0.05). BMD ± SD measured at T12 (0.61 ± 0.15) and T24 (0.67 ± 0.16) was not significantly different from T0. Similar significant (p < 0.01) decrease of BMD expressed in median Z was observed between T0 (0.19) and T6 (−1.04), remained significantly (p < 0.01) lower at T12 (−0.93) and increased to −0.52 at T24 (p < 0.05 vs T0). In conclusion, children after kidney transplantation experienced a significant decrease of bone mineral density during the first 6 months after operation despite normal graft function. Progressive improvement of BMD was noted 12 and 24 months after Tx.