A Comprehensive Mixed-Method Approach to Characterize the Source of Diurnal Tacrolimus Exposure Variability in Children: Systematic Review, Meta-analysis, and Application to an Existing Data Set.

Tacrolimus is widely reported to display diurnal variation in pharmacokinetic parameters with twice-daily dosing. However, the contribution of chronopharmacokinetics versus food intake is unclear, with even less evidence in the pediatric population. The objectives of this study were to summarize the existing literature by meta-analysis and evaluate the impact of food composition on 24-hour pharmacokinetics in pediatric kidney transplant recipients.

COVID-19 in pediatric kidney transplantation: a follow-up report of the Improving Renal Outcomes Collaborative.

Background: We report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC).

Methods: Patient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test.

Results: From September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients.

Timing of procedural interventions in childhood renovascular hypertension.

Background: Renovascular hypertension (RVHTN) is a rare, often complex condition due to multiple etiologies including congenital stenoses, vasculitides, and fibromuscular dysplasia. Among children with RVHTN who require multiple and escalating medications to control blood pressure, the optimal timing of a procedural intervention involves a balance of numerous factors.

Case-diagnosis/treatment: In this presentation of a 1-month-old girl with RVHTN, the treating medical team had to consider multiple factors in the initial management and timing of interventions to treat her underlying cause of RVHTN, including concerns for kidney health, degree of hypertension, age and size of the patient, and potential methods of procedural intervention.

The Improving Renal Outcomes Collaborative: Blood Pressure Measurement in Transplant Recipients.

Background And Objectives: Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients.

Surgical management of pediatric renin-mediated hypertension secondary to renal artery occlusive disease and abdominal aortic coarctation.

Background: Renovascular hypertension (RVH) associated with renal artery and abdominal aortic narrowings is the third most common cause of pediatric hypertension. Untreated children may experience major cardiopulmonary complications, stroke, renal failure, and death. The impetus of this study was to describe the increasingly complex surgical practice for such patients with an emphasis on anatomic phenotype and contemporary outcomes after surgical management as a means of identifying those factors responsible for persistent or recurrent hypertension necessitating reoperation.

Remedial operations for failed endovascular therapy of 32 renal artery stenoses in 24 children.

Background: Percutaneous transluminal angioplasty (PTA) for the treatment of pediatric renovascular hypertension (RVH) in contemporary practice is accompanied with ill-defined complications. This study examines the mode of pediatric renal PTA failures and the results of their surgical management.

Methods: Twenty-four children underwent remedial operations at the University of Michigan from 1996 to 2014 for failures of renal PTA.

Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population.

Purpose: Acute kidney injury (AKI) occurs commonly in critically ill children and has been associated with increased mortality of up to 50 %. The Kidney Disease: Improving Global Outcomes (KDIGO) AKI working group has proposed a standardized definition of AKI. Utilizing routinely available clinical data, we evaluated the KDIGO AKI criteria and the relationship of AKI with relevant outcomes in a single center tertiary pediatric intensive care (PICU) and cardiac intensive care unit (CICU) population.

Incidence of nonconfounded post-computed tomography acute kidney injury in hospitalized patients with stable renal function receiving intravenous iodinated contrast material.

Objective: The purpose of our investigation was to determine the frequency of proximate acute and chronic confounding risk factors for acute kidney injury (AKI) in a cohort of adult hospitalized patients with stable renal function who developed AKI following an intravenous (IV) contrast-enhanced computed tomography (CT) examination.

Materials And Methods: Institutional review board approval was obtained for this retrospective, Health Insurance Portability and Accountability Act-compliant investigation. Overall, 100 adult inpatients (50 males [mean age = 61 years, range: 24-94 years] and 50 females [mean age = 60 years, range: 20-95 years]) with stable pre-CT renal function who developed post-CT AKI using the Acute Kidney Injury Network (AKIN) laboratory criteria following an IV contrast-enhanced CT examination comprised the study population.

Gaining the Patient Reported Outcomes Measurement Information System (PROMIS) perspective in chronic kidney disease: a Midwest Pediatric Nephrology Consortium study.

Background And Objectives: Chronic kidney disease is a persistent chronic health condition commonly seen in pediatric nephrology programs. Our study aims to evaluate the sensitivity of the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric instrument to indicators of disease severity and activity in pediatric chronic kidney disease.

Methods: This cross sectional study included 233 children 8-17 years old, with chronic kidney disease from 16 participating institutions in North America.

Renal sonography with Doppler for detecting suspected pediatric renin-mediated hypertension - is it adequate?

Background: Renal Doppler US is used to evaluate suspected vascular causes of hypertension in children, despite mostly unknown diagnostic performance characteristics.

Objective: To evaluate renal Doppler US for detecting vascular causes of hypertension in children with high clinical suspicion of aortic or renal artery narrowing.

Materials And Methods: We identified pediatric renal Doppler US examinations performed for hypertension between January 1995 and June 2010 at our institution.

Gaining the PROMIS perspective from children with nephrotic syndrome: a Midwest pediatric nephrology consortium study.

Background And Objectives: Nephrotic syndrome (NS) represents a common disease in pediatric nephrology typified by a relapsing and remitting course and characterized by the presence of edema that can significantly affect the health-related quality of life in children and adolescents. The PROMIS pediatric measures were constructed to be publically available, efficient, precise, and valid across a variety of diseases to assess patient reports of symptoms and quality of life. This study was designed to evaluate the ability of children and adolescents with NS to complete the PROMIS assessment via computer and to initiate validity assessments of the short forms and full item banks in pediatric NS.

Fluid overload and fluid removal in pediatric patients on extracorporeal membrane oxygenation requiring continuous renal replacement therapy.

Objective: In pediatric patients, fluid overload at continuous renal replacement therapy initiation is associated with increased mortality. The aim of this study was to characterize the association between fluid overload at continuous renal replacement therapy initiation, fluid removal during continuous renal replacement therapy, the kinetics of fluid removal and mortality in a large pediatric population receiving continuous renal replacement therapy while on extracorporeal membrane oxygenation.

Design: Retrospective chart review.

Weight-based determination of fluid overload status and mortality in pediatric intensive care unit patients requiring continuous renal replacement therapy.

Purpose: In pediatric intensive care unit (PICU) patients, fluid overload (FO) at initiation of continuous renal replacement therapy (CRRT) has been reported to be an independent risk factor for mortality. Previous studies have calculated FO based on daily fluid balance during ICU admission, which is labor intensive and error prone. We hypothesized that a weight-based definition of FO at CRRT initiation would correlate with the fluid balance method and prove predictive of outcome.

Recruitment of podocytes from glomerular parietal epithelial cells.

Loss of a critical number of podocytes from the glomerular tuft leads to glomerulosclerosis. Even in health, some podocytes are lost into the urine. Because podocytes themselves cannot regenerate, we postulated that glomerular parietal epithelial cells (PECs), which proliferate throughout life and adjoin podocytes, may migrate to the glomerular tuft and differentiate into podocytes.

Immune response to rabies vaccination in pediatric transplant patients.

Children have become engaged in a wider variety of activities as the success of solid organ transplantation has improved. These activities can result in exposure to infectious agents for which there are no data documenting the efficacy of standard treatment in children on immunosuppressive therapy. This is a retrospective review of five OLT patients and three RT patients who were potentially exposed to rabies during camp.

Pediatric renovascular hypertension: 132 primary and 30 secondary operations in 97 children.

Purpose: This study was undertaken to characterize the contemporary surgical treatment of pediatric renovascular hypertension.

Methods: A retrospective analysis was conducted of the clinical data of 97 consecutive pediatric patients (39 girls, 58 boys), aged from 3 months to 17 years, who underwent operation at the University of Michigan from 1963 to 2006. All but one patient had refractory hypertension not responsive to contemporary medical therapy.

Renal replacement therapy in the treatment of confirmed or suspected inborn errors of metabolism.

Objective: Analysis of mortality and risk factors for mortality in the use of renal replacement therapy to correct metabolic disturbances associated with confirmed or suspected inborn errors of metabolism.

Study Design: A retrospective review of an institutional review board-approved pediatric acute renal failure data base at the University of Michigan. Eighteen patients underwent 21 renal replacement therapy treatments for metabolic disturbances caused by urea cycle defects (n = 14), organic acidemias (n = 5), idiopathic hyperammonemia (n = 1), and Reye syndrome (n = 1).

Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression.

Podocalyxin is a CD34-related cell surface molecule with anti-adhesive qualities. We probed a tissue microarray (n = 272) linked to long-term outcome data and found that podocalyxin was highly overexpressed in a distinct subset of invasive breast carcinomas (n = 15; 6%). Univariate disease-specific (P < 0.

Enhanced podocalyxin expression alters the structure of podocyte basal surface.

Glomerular basement membrane (GBM) and podocalyxin are essential for podocyte morphology. We provide evidence of functional interconnections between basement membrane components (collagen IV and laminin), the expression of podocalyxin and the morphology of human glomerular epithelial cells (podocytes). We demonstrated that GBM and laminin, but not collagen IV, up-regulated the expression of podocalyxin.

Clearance of amino acids by hemodialysis in argininosuccinate synthetase deficiency.

We determined the dialytic clearance of amino acids involved in ammoniagenesis and nitrogen excretion in a neonate with argininosuccinate synthetase deficiency who underwent acute hemodialysis. Plasma ammonia and plasma and dialysate amino acid concentrations were obtained at baseline, 30-minute intervals during hemodialysis, and 30 minutes after the completion of hemodialysis. Plasma ammonia concentrations declined by 56% during the 90-minute hemodialysis treatment, whereas arginine, citrulline, glutamine, and glycine concentrations decreased by 65%, 55%, 40%, and 34%, respectively.

Use of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome.

Cyclosporin (Cs-A) is an effective treatment for difficult cases of nephrotic syndrome (NS), but its use can be complicated by renal toxicity and a high incidence of relapses after withdrawal. We reviewed the charts of 10 Cs-A-dependent patients and 4 patients with steroid-dependent nephrotic syndrome (SDNS) not previously treated with Cs-A therapy. All patients had persistent NS, even after prior treatment with oral cyclophosphamide.

Human embryonal carcinoma tumor antigen, Gp200/GCTM-2, is podocalyxin.

We previously characterized a peanut agglutinin-binding tumor antigen, gp200, a surface membrane glycoprotein expressed on human embryonal carcinoma, a malignant stem cell of testicular tumors. Gp200 is remarkably similar to another embryonal carcinoma antigen, GCTM-2, a cell differentiation marker that is also detected in blood of testis cancer patients, yet neither molecular identity is known. We now report the identity of gp200 as podocalyxin.

PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2.

The transmembrane sialoglycoprotein podocalyxin is thought to be essential in the fine interdigitating foot process structure of the podocyte. The intracellular COOH-terminal amino acids Asp-Thr-His-Leu (DTHL) of podocalyxin comprise a putative ligand for a type I PSD95-Dlg-zona occludens-1 (PDZ) domain. A 20-amino acid synthetic peptide containing this motif was used to screen a cDNA library, and clones of rabbit Na(+)/H(+) exchange regulatory factor-2 (NHERF-2) were obtained.