Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients.

BACKGROUND: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score. METHODS: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021. BKV status was classified at 6-months post-transplant as "BKV" or "no BKV" in landmark analysis. Primary outcome was T-cell mediated rejection (TCMR). Secondary outcomes included all-cause graft failure (ACGF), death-censored graft failure (DCGF), de novo donor specific antibody (dnDSA), and antibody-mediated rejection (ABMR). Predictors of outcomes were assessed in Cox proportional hazards models including BKV status and alloimmune risk defined by recipient age and molecular mismatch (RAMM) groups. RESULTS: At 6-months post-transplant, 72 patients had BKV and 388 had no BKV. TCMR occurred in 86 recipients, including 27.8% with BKV and 17% with no BKV (p = .05). TCMR risk was increased in recipients with BKV (HR 1.90, (95% CI 1.14, 3.17); p = .01) and high vs. low-risk RAMM group risk (HR 2.26 (95% CI 1.02, 4.98); p = .02) in multivariable analyses; but not HLA serological MM in sensitivity analysis. Recipients with BKV experienced increased dnDSA in univariable analysis, and there was no association with ABMR, DCGF, or ACGF. CONCLUSIONS: Recipients with BKV had increased risk of TCMR independent of induction immunosuppression and conventional alloimmune risk measures. Recipients with high-risk RAMM experienced increased TCMR risk. Future studies on optimizing immunosuppression for BKV should explore nuanced risk stratification and may consider novel measures of alloimmune risk.

Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study.

BACKGROUND: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes. METHODS: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines. RESULTS: Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62]). CONCLUSIONS: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury.

Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Methods: Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Results: Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65). Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.

Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

PURPOSE OF REVIEW: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients. SOURCES OF INFORMATION: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD. METHODS: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions. KEY FINDINGS: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool. LIMITATIONS: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.

JUSTIFICATION: (1) Commenter les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC); (2) appliquer les lignes directrices actualisées et fondées sur les données probantes en vue de leur mise en œuvre dans le système de soins de santé canadien; (3) commenter les soins prodigués aux enfants atteints d'insuffisance rénale chronique (IRC) et (4) définir les priorités de recherche des patients Canadiens. SOURCES: Les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC). MÉTHODOLOGIE: Les coprésidents du comité ont sélectionné les membres potentiels sur la base de leur connaissance du secteur de la santé rénale au Canada, tout en visant une bonne représentation de toutes les disciplines concernées, des centres universitaires et communautaires et des différentes régions géographiques. PRINCIPAUX COMMENTAIRES: Nous approuvons un grand nombre des recommandations du KDIGO. Cependant, compte tenu de la rareté des anomalies du calcium et du phosphate et de la faible probabilité d'anomalies graves de la PTH (hormone parathyroïde), nous déconseillons le dépistage et la surveillance des taux de calcium, de phosphate, de PTH et de phosphatase alcaline chez les adultes atteints d'IRC de stade G3. Nous suggérons de mesurer ces paramètres chez les adultes de stade G4 et nous le recommandons pour les patients de stade G5. Chez les enfants, nous appuyons la recommandation de commencer la surveillance des TMO-MRC dès le stade G2, mais nous suggérons de mesurer le calcium ionisé plutôt que les taux de calcium total ou de calcium corrigé en fonction de l'albumine. En ce qui concerne la vitamine D, nous déconseillons le dépistage de routine des carences chez les adultes atteints d'IRC de stade G3 à G5 et G1T à G5T; nous suggérons plutôt de suivre les recommandations visant la population générale pour un apport adéquat en vitamine D. Nous recommandons que la mesure et la prise en charge de la densité minérale osseuse (DMO) se fassent en suivant les recommandations pour la population générale chez les adultes atteints d'IRC de stade G3 et G3T, mais nous déconseillons les tests de DMO de routine chez les adultes de stades G4-G5 et G4T-G5T, de même que chez les enfants atteints d'IRC. En raison de données insuffisantes, nous déconseillons également la pratique systématique d'une biopsie osseuse chez les adultes atteints d'IRC ou d'IRC-TMO, ainsi que chez les enfants atteints d'IRC, bien que nous la considérions comme un important outil de recherche. LIMITES: Le comité s'est appuyé sur le résumé des preuves rédigé par le KDIGO. Le comité de la SCN n'a pas reproduit ou mis à jour les revues systématiques.

Epidemiologic Characteristics of Acute Kidney Injury During Cisplatin Infusions in Children Treated for Cancer.

Importance: Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. Objective: To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. Design, Setting, and Participants: This prospective cohort study examined children (aged <18 years) recruited from May 23, 2013, to March 31, 2017, at 12 Canadian pediatric academic health centers who were receiving 1 or more cisplatin infusion. Children whose estimated or measured glomerular filtration rate (GFR) was less than 30 mL/min/1.73 m2 or who had received a kidney transplant were excluded. Data analysis was performed from January 3, 2018, to September 20, 2019. Exposures: Cisplatin infusions. Main Outcomes and Measures: The primary outcome was acute kidney injury during cisplatin infusion, defined using a Kidney Disease: Improving Global Outcomes serum creatinine criteria-based definition (stage 1 or higher). The secondary outcome was acute kidney injury defined by electrolyte criteria from the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1 or higher). Assessments occurred at early (first or second cycle) and late (last or second to last cycle) cisplatin infusions. Results: A total of 159 children (mean [SD] age at early cisplatin infusion, 7.2 [5.3] years; 80 [50%] male) participated. The most common diagnoses were central nervous system tumors (58 [36%]), neuroblastoma (43 [27%]), and osteosarcoma (33 [21%]). Acute kidney injury (by serum creatinine level increase) occurred in 48 of 159 patients (30%) at early cisplatin infusions and 23 of 143 patients (16%) at late cisplatin infusions. Acute kidney injury (by electrolyte abnormalities) occurred in 106 of 159 patients (67%) at early cisplatin infusion and 100 of 143 patients (70%) at late cisplatin infusions. Neuroblastoma diagnosis and higher precisplatin GFR were independently associated with acute kidney injury (serum creatinine level increase) at early cisplatin infusions (adjusted odds ratio [aOR] for neuroblastoma vs other, 3.25; 95% CI, 1.18-8.95; aOR for GFR, 1.01; 95% CI, 1.00-1.03) and late cisplatin infusions (aOR for neuroblastoma vs other, 6.85; 95% CI, 1.23-38.0; aOR for GFR, 1.01; 95% CI, 1.00-1.03). Higher cisplatin infusion dose was also independently associated with acute kidney injury (serum creatinine level increase) at later cisplatin infusions (aOR, 1.05; 95% CI, 1.01-1.10). Conclusions and Relevance: The findings suggest that acute kidney injury is common among children receiving cisplatin infusions and that rate and risk factors differ at earlier vs later infusions. These results may help with risk stratification with a goal of risk reduction.

The Canadian childhood nephrotic syndrome (CHILDNEPH) study: report on mid-study feasibility, recruitment and main measures.

BACKGROUND: To assess reasons for continuing practice variation in the management of childhood nephrotic syndrome despite expert reviews and guidelines, we are conducting a longitudinal cohort study in children with glucocorticoid sensitive nephrotic syndrome. Objectives of this mid-study report are to describe patient and physician recruitment characteristics, glucocorticoid prescriptions, use of second line agents, biopsy practices, and adherence to study protocol. METHODS: Children with new onset nephrotic syndrome and providers are being recruited from all 12 pediatric nephrology centres across Canada with > 2½ years follow-up. Data collection points of observation are over a minimum 36 months. Details of prescribed glucocorticoids and of all second line agents used during treatment are being collected. All relapses are being recorded with time to urinary remission of proteinuria. RESULTS: To date, 243 patients (57.1% male) from 12 centres were included. Median number of patients per centre was 29 (range 2-45), and median age of cohort was 7.3 (IQR 4.2) at enrollment. Forty-eight physicians were recruited, median 5 (range 2-8) per site. Median number of relapses per patient year of follow-up was 2.1 (IQR 4). Cumulative dose variability of glucocorticoids prescribed per episode of proteinuria and length of treatment was observed between participating centres. CONCLUSION: The Canadian pediatric nephrology community established a longitudinal childhood nephrotic syndrome cohort study that confirms ongoing practice variability. The study will help to evaluate its impact on patient outcomes, and facilitate clinical trial implementation in nephrotic syndrome.

Design and Methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study: A Prospective Observational Cohort Study.

BACKGROUND: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited. OBJECTIVE: To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension). DESIGN: This is a 3-year observational prospective cohort study. SETTING: The study includes 12 Canadian pediatric oncology centers. PATIENTS: The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin. Exclusion criteria: Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 or a pre-existing renal transplantation at baseline. MEASUREMENTS: Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected. METHODS: Outcomes: AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR <90 mL/min/1.73m2 or albumin-to-creatinine ratio≥3mg/mmol. Hypertension is defined as per guidelines. Procedure: Patients are recruited before their first or second cisplatin cycle. Participants are evaluated during 2 cisplatin infusion episodes (AKI biomarker validation) and at 3, 12, and 36 months post-cisplatin treatment (late outcomes). LIMITATIONS: The study has a relatively moderate sample size and short follow-up duration. There is potential for variability in data collection since multiple sites are involved. CONCLUSIONS: ABLE will provide a national platform to study biomarkers of late cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow-up needs.

MISE EN CONTEXTE: Les survivants d'un cancer infantile éprouvent des effets indésirables dus à leurs traitements, ce qui leurs engendrent des problèmes de santé à vie. L'équipe The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) vise à valider des biomarqueurs d'effets indésirables causés par les traitements contre le cancer et identifier les enfants à risque de développer des complications associées aux problèmes de coagulation, à la maladie du greffon contre l'hôte, la perte auditive et l'insuffisance rénale. La chimiothérapie cisplatine cause des dommages aux reins à court et à long terme. Relativement peu de données existent sur les biomarqueurs d'insuffisance rénale aigüe (IRA) et sur les problèmes rénaux à long terme chez les enfants traités avec le cisplatine. OBJECTIFS: Décrire les méthodologies de l'étude pancanadienne néphrotoxique ABLE qui vise à évaluer si les biomarqueurs urinaires (neutrophil gelatinase-associated lipocalin [NGAL] et kidney injury molecule-1[KIM-1]) peuvent diagnostiquer l'IRA, et s'ils peuvent prédire le risque de développer l'insuffisance rénale chronique (IRC) et l'hypertension artérielle à long terme. CADRE ET TYPE D'ÉTUDE: Étude prospective observationnelle de 3 ans dans 12 centres d'oncologie pédiatrique canadiens. PARTICIPANTS: cible de 150 patients âgés <18 ans recevant du cisplatine. Critères d'exclusion: Débit de filtration glomérulaire estimé (DFGe)<30 mL/min/1.73m2 ou avoir reçu une transplantation rénale. MESURES: Créatinine sérique, NGAL/KIM-1 sont mesurés pendant les infusions de cisplatine (échantillonnage avant l'infusion, après, et avant la sortie de l'hôpital). Visites de suivi: DFGe, microalbuminurie et tension artérielle sont mesurés; les résultats sont recueillis. MÉTHODOLOGIE: Critères d'évaluation: L'IRA est définie selon les critères de créatinine sérique de la classification Kidney Disease: Improving Global Outcomes (KDIGO). L'IRC est définie comme ayant un DFGe<90 mL/min/1.73m2 ou un ratio d'albumine/créatinine ≥3mg/mmol. L'hypertension est définie selon les lignes directrices. Procédure: Le recrutement: à lieu au premier ou deuxième cycle de cisplatine. Les patients sont évalués pendant deux infusions de cisplatine (validation des biomarqueurs d'IRA) et 3, 12 et 36 mois après le cisplatine (évaluation des problèmes rénaux à long terme). LIMITES DE L'ÉTUDE: La taille de l'échantillon est relativement modérée et la durée du suivi est moyennement courte. Il pourrait potentiellement avoir de la variabilité dans la collecte de données car plusieurs sites d'études sont impliqués. CONCLUSIONS: ABLE génèrera une plateforme nationale pour étudier les biomarqueurs de complications à long terme des traitements contre le cancer. L'étude néphrotoxique ABLE est une étude novatrice des biomarqueurs de l'IRA chez les enfants traités avec le cisplatine qui contribuera grandement à identifier les problèmes rénaux à long terme causés par le cisplatine et la nécessité de suivis cliniques.

Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation.

BACKGROUND: The contribution of copy-number variation (CNV) to disease has been highlighted with the widespread adoption of array-based comparative genomic hybridisation (aCGH) and microarray technology. Contiguous gene deletions involving ANKRD11 in 16q24.3 are associated with autism spectrum disorder (ASD) and intellectual disability (ID), while 16q24.1 deletions affecting FOXF1 are associated with congenital renal malformations, alveolar capillary dysplasia, and various other abnormalities. The disease associations of deletions in the intervening region, 16q24.2, have only been defined to a limited extent. AIM: To determine whether deletions affecting 16q24.2 are correlated with congenital anomalies. METHODS: 35 individuals, each having a deletion in 16q24.2, were characterised clinically and by aCGH and/or SNP-genotyping microarray. RESULTS: Several of the 35 16q24.2 deletions identified here closely abut or overlap the coding regions of FOXF1 and ANKRD11, two genes that have been previously associated with the disease. 25 patients were reported to have ASD/ID, and three were found to have bilateral hydronephrosis. 14 of the deletions associated with ASD/ID overlap the coding regions of FBXO31 and MAP1LC3B. These same genes and two others, C16orf95 and ZCCHC14, are also included in the area of minimal overlap of the three deletions associated with hydronephrosis. CONCLUSIONS: Our data highlight 16q24.2 as a region of interest for ASD, ID and congenital renal malformations. These conditions are associated, albeit without complete penetrance, with deletions affecting C16orf95, ZCCHC14, MAP1LC3B and FBXO31. The function of each gene in development and disease warrants further investigation.

Assessment of ondansetron-associated hypokalemia in pediatric oncology patients.

Objectives. Ondansetron is a 5-hydroxytryptamine (5-HT(3), serotonin) receptor antagonist used as antiemetic prophylaxis preceding chemotherapy administration. Hypokalemia is a rare complication of ondansetron, which may be underreported due to confounding emesis and chemotherapy-induced tubulopathy. We performed a prospective cohort study to determine if ondansetron caused significant hypokalemia independently as a result of renal potassium wasting. Methods. Twelve patients were recruited, with ten completing the study. Blood and urine samples were collected before and after ondansetron administration in patients admitted for intravenous (IV) hydration and chemotherapy. Dietary histories and IV records were analyzed to calculate sodium and potassium balances. Results. We observed an expected drop in urine osmolality, an increase in urine sodium, but no statistically significant change in sodium or potassium balance before and after ondansetron. Conclusion. Ondansetron does not cause significant potassium wasting in appropriately hydrated and nutritionally replete patients. Careful monitoring of serum potassium is recommended in patients with chronic nutritional or volume status deficiencies receiving this medication.

Quality of life in children with vesicoureteral reflux.

Vesicoureteral reflux (VUR) is commonly diagnosed in children presenting with urinary tract infections. Antibiotic prophylaxis and ureteric surgery are standard treatments for these children. Our aim was to investigate whether health-related quality of life (HRQOL) was altered in children treated for VUR. Children aged 1-5 years with grade III or higher VUR were identified through electronic records at the Stollery Children's Hospital. Parents of these children were mailed the TNO-AZL Netherlands Organisation for Applied Scientific Research Academic Medical Centre Quality of Life (TAPQOL) questionnaire. QOL scores for this group were compared with normative controls from the instrument's creators using the Mann-Whitney U test. Thirty-two of the 96 (33%) mailed surveys were returned. Eight children had surgery, and 19 were treated with antibiotic prophylaxis. When comparing the VUR group with the control group, we found that anxiety and social functioning scores were significantly better in patients with VUR (p < 0.01). The VUR group had worse scores in problem behavior, stomach complaints ,and communication (p < 0.01). This study reveals that children with VUR have a reasonable QOL when compared with controls. However, the diagnosis of VUR and its management does have an impact on gastrointestinal complaints, behavior, and communication, which may occur as a result of chronic medical intervention.

Pseudohyperphosphatemia associated with high-dose liposomal and lipid complex amphotericin B when tested with Synchron LX 20 (Beckman/Coulter) phosphorous assay.

Although case reports of hyperphosphatemia have been previously described in patients receiving liposomal amphotericin B, this has not been reported in patients receiving the lipid complex formulation. We report a case of hyperphosphatemia that persisted despite switching from liposomal to lipid complex amphotericin B in a child with invasive zygomycosis. This case suggests that in the context of acute renal dysfunction, hyperphosphatemia may also be observed with lipid complex amphotericin B. This case highlights the importance of differentiating between pseudohyperphosphatemia and hyperphosphatemia to prevent complications.

Renal interstitial fibrosis in children treated with FK506 for nephrotic syndrome.

BACKGROUND: Steroid-dependent, steroid-resistant or frequently relapsing nephrotic syndrome carries a poor prognosis, including progression to renal failure. There are a number of studies confirming the efficacy of FK506 in steroid-resistant or steroid-dependent nephrotic syndrome. Although the use of this medication is becoming more common, we know very little about the potential nephrotoxicity when used in nephrotic syndrome. METHOD: We retrospectively reviewed the characteristics and biopsy findings of 11 children with steroid-dependent or frequently relapsing nephrotic syndrome treated with FK506. Two sequential biopsies were evaluated for the change in interstitial fibrosis, measured by a quantitative stereological method, and the change in arteriolar hyaline thickening, tubular atrophy and interstitial fibrosis, graded according to Banff criteria. RESULTS: There was an increase in interstitial fibrosis (P = 0.005), with a median absolute change in the per cent volume density between initial and follow-up biopsies of 1.8% [interquartile range (IQR) 3.9%]. Median percentage change in volume density of interstitial fibrosis, relative to volume density of interstitial fibrosis prior to initiating FK506, was 93% (IQR 138%). Banff scores for interstitial fibrosis and tubular atrophy also increased following tacrolimus therapy (P = 0.04 for both). Average FK506 trough level over the treatment period was significantly associated with change in fibrosis (Spearman's rho = 0.67 and P = 0.02). CONCLUSIONS: This is some of the first histological data concerning tacrolimus nephrotoxicity in childhood nephrotic syndrome. Although the role of the natural progression of the underlying disease in the observed change is not definitively clear, the changes seen are in keeping with the known nephrotoxic effects of FK506 demonstrated in renal transplant. This increase is small when presented as a median change. However, there were a number of children who had a larger change in fibrosis. The factors predictive of interstitial fibrosis while on FK506 are not well defined; the findings from this study suggest that FK506 level may be a factor. Given the observations and limitations of the few published studies, there is an obvious need for further study in a large multicenter prospective trial.

Ondansetron-associated hypokalemia in a 2-year-old with pre-B-cell ALL.

Ondansetron is a commonly used medication in the treatment of nausea and vomiting arising from many etiologies, including chemotherapy. Although it is a highly safe drug, ondansetron use has been associated, rarely, with hypokalemia. However, it is unknown whether hypokalemia is due to the medication itself or to an underlying potassium disturbance caused by prior metabolic derangements, including vomiting. We relate a patient who presents with hypokalemia of unknown etiology, with evidence suggesting a possible relationship to ondansetron. We also present a proposed mechanism for this phenomenon.

Acute myelogenous leukemia and glycogen storage disease 1b.

Glycogen storage disease 1b (GSD 1b) is caused by a deficiency of glucose-6-phosphate translocase and the intracellular accumulation of glycogen. The disease presents with failure to thrive, hepatomegaly, hypoglycemia, lactic acidosis, as well as neutropenia causing increased susceptibility to pyogenic infections. We present a case of a young woman with GSD 1b who developed acute myelogenous leukemia while on long-term granulocyte colony-stimulating factor therapy. The presence of two rare diseases in a single patient raises suspicion that GSD 1b and acute myelogenous leukemia are linked. Surveillance for acute myelogenous leukemia should become part of the long-term follow-up for GSD 1b.