Developing a Research Mentorship Program: The American Society of Pediatric Nephrology's Experience

Background: Most pediatric nephrologists work in academia. Mentor-mentee relationships provide support and guidance for successful research career. Mentorship program implementation is valuable in medical fields for providing research opportunities to young faculty. Methods: The American Society of Pediatric Nephrology (ASPN) established a research mentorship program to (a) assist with matching of appropriate mentor-mentee dyads and (b) establish metrics for desirable mentor-mentee outcomes with two independent components: (1) the grants review workshop, a short-term program providing mentor feedback on grant proposals, and (2) the longitudinal program, establishing long-term mentor-mentee relationships. Regular surveys of both mentors and mentees were reviewed to evaluate and refine the program. Results: Twelve mentees and 17 mentors participated in the grant review workshop and 19 mentees were matched to mentors in the longitudinal program. A review of NIH RePORTER data indicated that since 2014, 13 NIH grants have been awarded. Mentees in the longitudinal program reported that the program helped most with identifying an outside mentor, improving grant research content, and with general career development. Mentors perceived themselves to be most helpful in assisting with overall career plans. Email communications were preferred over phone or face-to-face communications. Mentees endorsed strong interest in staying in touch with their mentors and 100% of mentors expressed their willingness to serve in the future. Conclusion: This mentorship program was initiated and supported by a relatively small medical society and has shown early success in cultivating mentoring relationships for a future generation of clinician-scientists

Evaluation of Neurocognition in Youth with CKD Using a Novel Computerized Neurocognitive Battery

BACKGROUND AND OBJECTIVES: Neurocognitive problems in CKD are well documented; time-efficient methods are needed to assess neurocognition in this population. We performed the first study of the efficient 1-hour Penn Computerized Neurocognitive Battery (CNB) in children and young adults with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We administered the Penn CNB cross-sectionally to individuals aged 8-25 years with stage 2-5 CKD (n=92, enrolled from three academic nephrology practices from 2011 to 2014) and matched healthy controls (n=69). We analyzed results from 12 tests in four domains: executive control, episodic memory, complex cognition, and social cognition. All tests measure accuracy and speed; we converted raw scores to age-specific z-scores on the basis of Philadelphia Neurodevelopmental Cohort (n=1790) norms. We analyzed each test in a linear regression with accuracy and speed z-scores as dependent variables and with (1) CKD versus control or (2) eGFR as explanatory variables, adjusted for race, sex, and maternal education. RESULTS: Patients with CKD (mean±SD eGFR, 48±25 ml/min per 1.73 m(2); mean age, 16.3±3.9 years) and controls (mean eGFR, 98±20 ml/min per 1.73 m(2); mean age, 16.0±4.0 years) were similar demographically. CKD participants had lower accuracy than controls in tests of complex cognition, with moderate to large effect sizes: -0.53 (95% confidence interval [95% CI], -0.87 to -0.19) for verbal reasoning, -0.52 (95% CI, -0.83 to -0.22) for nonverbal reasoning, and -0.64 (95% CI, -0.99 to -0.29) for spatial processing. For attention, patients with CKD had lower accuracy (effect size, -0.35 [95% CI, -0.67 to -0.03]) but faster response times (effect size, 0.44 [95% CI, 0.04 to 0.83]) than controls, perhaps reflecting greater impulsivity. Lower eGFR was associated with lower accuracy for complex cognition, facial and visual memory, and emotion identification tests. CONCLUSIONS: CKD is associated with lower accuracy in tests of complex cognition, attention, memory, and emotion identification, which related to eGFR. These findings are consistent with traditional neurocognitive testing in previous studies

Consensus Expert Recommendations for the Diagnosis and Management of Autosomal Recessive Polycystic Kidney Disease: Report of an International Conference

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a severe, typically early onset form of cystic disease that primarily involves the kidneys and biliary tract. Phenotypic expression and age at presentation can be quite variable1. The incidence of ARPKD is 1 in 20,000 live births2, and its pleotropic manifestations are potentially life-threatening. Optimal care requires proper surveillance to limit morbidity and mortality, knowledgeable approaches to diagnosis and treatment, and informed strategies to optimize quality of life. Clinical management therefore is ideally directed by multidisciplinary care teams consisting of perinatologists, neonatologists, nephrologists, hepatologists, geneticists, and behavioral specialists to coordinate patient care from the perinatal period to adulthood. In May 2013, an international team of 25 multidisciplinary specialists from the US, Canada, Germany, and the United Kingdom convened in Washington, DC, to review the literature published from 1990 to 2013 and to develop recommendations for diagnosis, surveillance, and clinical management. Identification of the gene PKHD1, and the significant advances in perinatal care, imaging, medical management, and behavioral therapies over the past decade, provide the foundational elements to define diagnostic criteria and establish clinical management guidelines as the first steps towards standardizing the clinical care for ARPKD patients. The key issues discussed included recommendations regarding perinatal interventions, diagnostic criteria, genetic testing, management of renal and biliary-associated morbidities, and behavioral assessment. The meeting was funded by the National Institutes of Health and an educational grant from the Polycystic Kidney Disease Foundation. Here we summarize the discussions and provide an updated set of diagnostic, surveillance, and management recommendations for optimizing the pediatric care of patients with ARPKD. Specialist care of ARPKD-related complications including dialysis, transplantation, and management of severe portal hypertension will be addressed in a subsequent report. Given the paucity of information regarding targeted therapies in ARPKD, this topic was not addressed in this conference.

Neurocognition in children with autosomal recessive polycystic kidney disease in the CKiD cohort study

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disorder characterized by enlarged, cystic kidneys with progressive chronic kidney disease (CKD), systemic hypertension, and congenital hepatic fibrosis. Children with ARPKD can have early onset CKD and severe hypertension, both of which are known to have adverse neurocognitive effects. Objectives of this study were to (1) determine whether ARPKD patients have greater neurocognitive deficits compared to that of children with other causes of CKD, and (2) examine the relative prevalence of hypertension in ARPKD, a known risk factor for neurocognitive dysfunction

Design and methods of the NiCK study: neurocognitive assessment and magnetic resonance imaging analysis of children and young adults with chronic kidney disease

Abstract Background Chronic kidney disease is strongly linked to neurocognitive deficits in adults and children, but the pathophysiologic processes leading to these deficits remain poorly understood. The NiCK study (Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease) seeks to address critical gaps in our understanding of the biological basis for neurologic abnormalities in chronic kidney disease. In this report, we describe the objectives, design, and methods of the NiCK study. Design/methods The NiCK Study is a cross-sectional cohort study in which neurocognitive and neuroimaging phenotyping is performed in children and young adults, aged 8 to 25 years, with chronic kidney disease compared to healthy controls. Assessments include (1) comprehensive neurocognitive testing (using traditional and computerized methods); (2) detailed clinical phenotyping; and (3) multimodal magnetic resonance imaging (MRI) to assess brain structure (using T1-weighted MRI, T2-weighted MRI, and diffusion tensor imaging), functional connectivity (using functional MRI), and blood flow (using arterial spin labeled MRI). Primary analyses will examine group differences in neurocognitive testing and neuroimaging between subjects with chronic kidney disease and healthy controls. Mechanisms responsible for neurocognitive dysfunction resulting from kidney disease will be explored by examining associations between neurocognitive testing and regional changes in brain structure, functional connectivity, or blood flow. In addition, the neurologic impact of kidney disease comorbidities such as anemia and hypertension will be explored. We highlight aspects of our analytical approach that illustrate the challenges and opportunities posed by data of this scope. Discussion The NiCK study provides a unique opportunity to address key questions about the biological basis of neurocognitive deficits in chronic kidney disease. Understanding these mechanisms could have great public health impact by guiding screening strategies, delivery of health information, and targeted treatment strategies for chronic kidney disease and its related comorbidities

Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects

Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of chronic kidney disease in children. The care of ARPKD patients has traditionally been the realm of pediatric nephrologists; however, the disease has multisystem effects, and a comprehensive care strategy often requires a multidisciplinary team. Most notably, ARPKD patients have congenital hepatic fibrosis, which can lead to portal hypertension, requiring close follow-up by pediatric gastroenterologists. In severely affected infants, the diagnosis is often first suspected by obstetricians detecting enlarged, echogenic kidneys and oligohydramnios on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Surgical considerations can include the possibility of nephrectomy to relieve mass effect, placement of dialysis access, and kidney and/or liver transplantation. Families of patients with ARPKD also face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. They may therefore interface with genetic counselors, geneticists, and reproductive endocrinologists. Children with ARPKD may also be at risk for neurocognitive dysfunction and may require neuropsychological referral. The care of patients and families affected by ARPKD is therefore a multidisciplinary effort, and the general pediatrician can play a central role in this complex web of care. In this review, we outline the spectrum of clinical manifestations of ARPKD and review genetics of the disease, clinical and genetic diagnosis, perinatal management, management of organ-specific complications, and future directions for disease monitoring and potential therapies

Growth in children with autosomal recessive polycystic kidney disease in the CKiD cohort study

Background: Previous studies have suggested that some children with autosomal recessive polycystic kidney disease (ARPKD) have growth impairment out of proportion to their degree of chronic kidney disease (CKD). The objective of this study was to systematically compare growth parameters in children with ARPKD to those with other congenital causes of CKD in the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Methods: Height standard deviation scores (z-scores), proportion of children with severe short stature (z-score <-1.88), rates of growth hormone use, and annual change in height z-score were analyzed in children with ARPKD (n=22) compared to two matched control groups: children with aplastic/hypoplastic/dysplastic (A/H/D) kidneys (n=44) and obstructive uropathy (OU) (n=44). Differences in baseline characteristics were tested by Wilcoxon rank sum test or Fisher’s exact test. Matched differences in annual change in height z-score were tested by Wilcoxon signed rank test.Results: Median height z-score in children with ARPKD was -1.1 [interquartile range -1.5, -0.2]; 14% of the ARPKD group had height z-score <-1.88, and 18% were using growth hormone. There were no significant differences in median height z-score, proportion with height z-score <-1.88, growth hormone use, or annual change in height z-score between the ARPKD and control groups. Conclusions: Children with ARPKD and mild-to-moderate CKD in the CKiD cohort have a high prevalence of growth abnormalities, but these are similar to children with other congenital causes of CKD. This study does not support a disease-specific effect of ARPKD on growth, at least in the subset of children with mild-to-moderate CKD