Philip Acott

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Papers by Philip Acott

Endocrine Biomarkers and Quality-of-Life Scores in a Healthy Cohort of Patients on Hemodialysis

Canadian Journal of Diabetes

Management of Pediatric Kidney Transplant Patients During the COVID-19 Pandemic: Guidance From the Canadian Society of Transplantation Pediatric Group

Canadian Journal of Kidney Health and Disease

Purpose of the program: To provide guidance on the management of pediatric kidney transplant pati... more Purpose of the program: To provide guidance on the management of pediatric kidney transplant patients during the COVID-19 pandemic. Sources of information: Program-specific documents, preexisting, and related to COVID-19; documents from provincial, national, and international kidney transplant societies/agencies and organ procurement agencies; national and international webinars, including webinars that we hosted for input and feedback; with additional information from formal and informal review of published academic literature. Methods: Challenges in the care of pediatric kidney transplant patients during the COVID-19 pandemic were highlighted within the Canadian Society of Transplantation (CST) Pediatric Group. It identified pediatric kidney transplant nephrologists (including a pediatric nephrologist ethicist) across the country and formed a workgroup. The initial guidance document was drafted and members of the workgroup reviewed and discussed all suggestions in detail via e-mai...

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123 Systemic hypertension in preterm infants - A population-based study

Paediatrics & Child Health

124 Long-term neurodevelopmental outcomes of preterm infants with systemic hypertension - A population-based study

Paediatrics & Child Health

Radiology and Pathology in a Child with Calcification and Simplified Gyration

Pediatric Neurology

Hypogonadotropic Hypogonadism in Males with Glycogen Storage Disease Type 1

Canadian Journal of Diabetes, 2016

Background: Glycogen storage disease type 1 is an autosomal recessive disorder with an incidence ... more Background: Glycogen storage disease type 1 is an autosomal recessive disorder with an incidence of 1 in 100,000. Long-term complications include chronic blood glucose lability, lactic academia, short stature, osteoporosis, delayed puberty, gout, progressive renal insufficiency, systemic or pulmonary hypertension, hepatic adenomas at risk for malignant transformation, anemia, vitamin D deficiency, hyperuricemic nephrocalcinosis, inflammatory bowel syndrome (type 1b), hypertriglyceridemia, and irregular menstrual cycles. We describe hypogonadotropic hypogonadism as a novel complication in glycogen storage disease (GSD) type 1. Case Studies and Methods: Four unrelated patients with GSD 1a (N ¼ 1) and 1b (N ¼ 3) were found to have hypogonadotropic hypogonadism diagnosed at different ages. Institutional Research Ethics Board approval was obtained as appropriate. Participant consent was obtained. A retrospective chart review was performed and clinical symptoms and results of investigations summarized as a case series. Results: All patients were confirmed biochemically to have low luteinizing hormone (LH) and follicular stimulating hormone (FSH), and correspondingly low total testosterone. Clinical symptoms of hypogonadism varied widely. Investigations for other causes of hypogonadotropic hypogonadism were unremarkable. In addition, all patients were found to have disproportionately low bone mineral density at the lumbar spine compared to the hip. Common to all patients was erratic metabolic control, including recurrent hypoglycemia and elevated lactate levels. Discussion: Recurrent elevations in cortisol in response to hypoglycemia may be the underlying pathology leading to suppression of gonadotropin-releasing hormone (GnRH) release. Incorporating clinical and/or biochemical screening of the hypothalamic-pituitary-gonadal axis may be important in the management of this disease. Testosterone therapy however needs to be carefully considered because of the risk of hepatic adenomas.

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Acadian variant of Fanconi syndrome is caused by mitochondrial respiratory chain complex I deficiency due to a non-coding mutation in complex I assembly factor NDUFAF6

Human molecular genetics, Sep 27, 2016

The Acadian variant of Fanconi Syndrome refers to a specific condition characterized by generaliz... more The Acadian variant of Fanconi Syndrome refers to a specific condition characterized by generalized proximal tubular dysfunction from birth, slowly progressive chronic kidney disease and pulmonary interstitial fibrosis. This condition occurs only in Acadians, a founder population in Nova Scotia, Canada. The genetic and molecular basis of this disease is unknown. We carried out whole exome and genome sequencing and found that nine affected individuals were homozygous for the ultra-rare non-coding variant chr8:96046914 T > C; rs575462405, whereas 13 healthy siblings were either heterozygotes or lacked the mutant allele. This variant is located in intron 2 of NDUFAF6 (NM_152416.3; c.298-768 T > C), 37 base pairs upstream from an alternative splicing variant in NDUFAF6 chr8:96046951 A > G; rs74395342 (c.298-731 A > G). NDUFAF6 encodes NADH:ubiquinone oxidoreductase complex assembly factor 6, also known as C8ORF38. We found that rs575462405-either alone or in combination with...

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Use of Igf-I for the Treatment of Polycystic Kidney Disease and Related Indications

Use of IGF-I for the treatment of renal insufficiencies, steriod toxicity and related indications

Use of IGF-I for the treatment of kidney disorders

Use of polycyclic steroid compounds for the manufacture of a medicament for the treatment of cystic kidney diseases, vascular infarction, uremia and related conditions

Sirolimus Conversion in Pediatric Biopsy Proven Chronic Allograft Nephropathy Has No Sub-Clinical Rejection on 3 & 12 Month Follow- Up Biopsy

Transplantation, 2008

Chronic renal failure in the rat

Journal of Pharmacological Methods, 1987

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Norfloxacin interferes with cyclosporine disposition in pediatric patients undergoing renal transplantation*

Clinical Pharmacology & Therapeutics, 1995

Prophylactic treatment with norfloxacin was initiated in a group of pediatric patients undergoing... more Prophylactic treatment with norfloxacin was initiated in a group of pediatric patients undergoing renal transplantation who were receiving cyclosporine and were susceptible to recurrent urinary tract infections. At discharge from the hospital, the mean daily dose of cyclosporine needed to maintain trough cyclosporine blood levels of 150 to 400 ng/ml was 4.5 mg/kg/day for the patients who received norfloxacin compared with 7.4 mg/kg/day for patients who did not receive the antibiotic. This observation suggested that the clearance of cyclosporine was decreased by the concomitant use of norfloxacin. The effect of norfloxacin on specific drug-metabolizing cytochrome P450 isozymes in vitro was examined to determine if the metabolism and subsequent clearance of cyclosporine and possibly other drugs are altered through a metabolic interaction with norfloxacin. In human liver microsomes, the activity of cytochrome P4503A4, the isozyme that metabolizes cyclosporine in humans, was inhibited by norfloxacin. In rat liver microsomes, norfloxacin inhibited the activity of cytochrome P4503A2, the isozyme responsible for cyclosporine metabolism in this species, but did not alter the activity of the rat cytochrome P450 isozymes 1A, 2E1, and 4A1. The in vitro studies suggest that the lower cyclosporine dose required by pediatric patients who were given norfloxacin was caused by inhibition of the metabolism of cyclosporine.

Effects of chronic phthalate exposure on the kidney

Journal of toxicology and environmental health, 1988

Several investigators have reported the finding of polycystic kidney disease (PKD) at autopsy in ... more Several investigators have reported the finding of polycystic kidney disease (PKD) at autopsy in patients who had undergone long-term hemodialysis for renal failure due to causes other than PKD. We initiated studies to determine whether the drugs or chemicals to which patients on dialysis are exposed could be responsible for these cystic changes. Adult rats were tube fed chemical residues from an artificial kidney or phthalate esters [di(2-ethylhexyl) phthalate, DEHP], which are a main component of these plastic kidneys or a control solution. Rats receiving DEHP or residues showed a significantly higher incidence of focal cysts when compared to controls. Rats receiving DEHP developed a significant decrease in kidney function as demonstrated by creatinine clearance, and these animals had the highest tissue levels of measureable DEHP. We postulate that patients receiving long-term dialysis may acquire PKD secondary to their exposure to chemicals leached from artificial kidneys.

Low Incidence of BK Virus Nephropathy in Patients Treated with Mycophenolate Mofetil: A Cumulative Review of Reported Cases

Transplantation, 2008

Low Dose Heparin Infusion Reduces Vascular Thrombosis After Pediatric Renal Transplantation

Transplantation, 2008

Effect of chronic kidney disease on the expression of thiamin and folic acid transporters

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2011

Chronic kidney disease (CKD) is associated with significant cardiovascular, neurological and meta... more Chronic kidney disease (CKD) is associated with significant cardiovascular, neurological and metabolic complications. Thiamin and folate are essential for growth, development and normal cellular function, and their uptake is mediated by regulated transport systems. While plasma folate and thiamin levels are generally normal in patients with CKD, they commonly exhibit features resembling vitamin deficiency states. Earlier studies have documented impaired intestinal absorption of several B vitamins in experimental CKD. In this study, we explored the effect of CKD on expression of folate and thiamin transporters in the key organs and tissues. Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy or sham operation and observed for 12 weeks. Plasma folate and thiamin concentrations and gene expression of folate (RFC, PCFT) and thiamin transporters (THTR-1 and THTR-2) were determined in the liver, brain, heart and intestinal tissues using real-time PCR. Hepatic protein abundance ...

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Utilization of Vero Cells for Primary and Chronic BK Virus Infection

Transplantation Proceedings, 2006

BK virus (BKV) nephropathy has a poor prognosis for renal allograft survival with 30% to 60% risk... more BK virus (BKV) nephropathy has a poor prognosis for renal allograft survival with 30% to 60% risk of allograft loss over 1 year. In the past decade, BKV nephropathy has occurred in 1% to 10% of renal transplant patients, with higher rates observed in patients with increased immunosuppression exposure and renal allograft injury. Vero cells (Green monkey kidney cell origin) were optimized for BKV primary and chronic infection inclusive of culture requirements for 60-day growth and monolayer confluence. Quantification of BKV replication in the culture supernatant (SN) and cells was by real-time polymerase-chain reaction (PCR) using the Roche Lightcycler 2.0. Primary BKV infection of Vero cells is achieved by 2 hour incubation with 6.5 ϫ 10 5 BKV copies with subsequent washing of cells leading to steady-state cellular infection of 10 2 to 10 3 BKV copies. Primary infection is demonstrated within 7 to 10 days by a Ͼ10-fold increase of BKV copies in SN. Thereafter, a BKV viral load reduction in SN to a chronic/latent level (Ͻ10 2 BKV copies in SN) is observed by 14 days. Vero cells with chronic low-level BKV infection (10 2-10 3 BKV copies in cells) exhibited reactivation (Ͼ10 5 BKV copies in SN) in Ͼ72% of late culture wells after 40 days. Vero cells can accommodate primary and chronic BKV infection followed by viral reactivation in late culture. The performance characteristics of 3 different pathogenic BKV strains obtained from patients with BKV nephropathy had infectivity profiles that correlated well the relative clinical profile in this Vero cell culture system.

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Evaluation of Performance Factors Affecting Two Formulations of Cyclosporine in Pediatric Renal Transplant Patients

Transplantation Proceedings, 2006

Success of renal transplantation in children is largely due to improvements in immunosuppressant ... more Success of renal transplantation in children is largely due to improvements in immunosuppressant therapy since the introduction of calcineurin inhibitors. The aim of this study was to identify possible factors that result in formulation differences in the exposure of pediatric patients to cyclosporine (CsA). We examined the handling of the two major formulations of CsA in a group of pediatric renal transplant recipients. The pharmacokinetic profiles of both formulations were assessed, and the data stratified to assess the effects of age, gender, time posttransplant, and other concomitant drug therapy on the two CsA formulations. The microemulsified formulation (MEC) enhanced bioavailability compared to the older oil-based formulation (CYA), especially at C 2 , with more predictable and consistent absorption in children. This higher bioavailability allowed a 15% reduction of dosing to achieve equal drug exposure. The concentration achieved by MEC at C 2 demonstrated a much higher correlation with area under the concentration curve (AUC) than the concentration at C 0. In the case of CYA a strong correlation was obtained between AUC and the concentrations obtained at both C 0 and C 2. Calcium channel blockers increased AUC 0-8 for both CsA formulations. Norfloxacin and pravastatin cotreatment had no effect on either of the CsA formulations. In contrast, the bioavailability of CsA was increased in boys using MEC formulation but this gender-based difference was absent during the use of CYA. This suggests that caution is required for introduction of new formulations of drugs to pediatric patients to evaluate differential effects of age, gender, and concomitant drug therapy.

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Endocrine Biomarkers and Quality-of-Life Scores in a Healthy Cohort of Patients on Hemodialysis

Canadian Journal of Diabetes