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Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are characterized by bilateral cystic kidney disease leading to progressive kidney function decline. These diseases also have distinct liver manifestations. The range of clinical presentation and severity of both ADPKD and ARPKD is much wider than was once recognized. Pediatric and adult nephrologists are likely to care for individuals with both diseases in their lifetimes. This article will review genetic, clinical, and imaging predictors of kidney and liver disease progression in ADPKD and ARPKD and will briefly summarize pharmacologic therapies to prevent progression., Author(s): Eric G. Benz [sup.1] [sup.2] , Erum A. Hartung [sup.1] [sup.2] Author Affiliations: (1) grid.239552.a, 0000 0001 0680 8770, Division of Nephrology, Children's Hospital of Philadelphia, , 3401 Civic [...]

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 variable. The incidence of ARPKD is 1 in 20,000 live births, 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.”

Background Depression affects 7-35% of children with chronic kidney disease (CKD), and in adults with CKD, the presence of depression links to poorer medical outcomes, social functioning difficulties, and neurocognitive impairments. The relationship between depression and neurocognitive function in youth with CKD is unclear. We sought to identify factors associated with depression in youth with CKD and to determine whether depression affects neurocognitive performance. Methods We conducted cross-sectional analyses in 71 CKD and 64 control participants aged 8 to 25 years who completed depression inventories and neurocognitive assessments as part of the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with CKD Study. In the CKD group, multivariable logistic regression analysis determined associations between clinical and demographic factors and depression. In the full study cohort, multivariable linear regression analyses, including an interaction term between CKD status and depression evaluated the effect of depression on 11 neurocognitive outcome domains. Results Obesity significantly associated with depression in the CKD group (OR 10.25, P = 0.01). In adjusted analyses, depressed youth with CKD scored worse than non-depressed CKD participants by 0.6-1.0 standard deviations in 5 neurocognitive domains: attention, visual memory, visual-spatial, visual working memory, and problem solving. Conclusions CKD youth with obesity are more likely to be depressed, and those who are depressed exhibit worse neurocognitive performance. Depression may represent a therapeutic target to improve neurocognitive performance in youth with CKD., Author(s): Amy J. Kogon [sup.1] [sup.2] , Ji Young Kim [sup.3] , Nina Laney [sup.4] , Jerilynn Radcliffe [sup.2] [sup.5] , Stephen R. Hooper [sup.6] , Susan L. Furth [sup.1] [...]

Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. 'Hard' endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease., Author(s): Erum A. Hartung[sup.1] [sup.2] Author Affiliations: (1) Division of Nephrology, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, 19104, Philadelphia, PA, USA (2) Department of Pediatrics, Perelman School [...]

Background 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. The objectives of this study were (1) to determine whether ARPKD patients have greater neurocognitive deficits compared to that of children with other causes of CKD, and (2) to examine the relative prevalence of hypertension in ARPKD, a known risk factor for neurocognitive dysfunction. Methods We performed a cross-sectional, control-matched analysis of 22 ARPKD patients with mild-to-moderate CKD in the Chronic Kidney Disease in Children (CKiD) cohort study, compared with a control group of 44 children with other causes of CKD, matched based on glomerular filtration rate, age at study entry, and age at diagnosis. Results Children with ARPKD in this cohort had neurocognitive functioning comparable to children with other causes of CKD in domains of intellectual functioning, academic achievement, attention regulation, executive functioning, and behavior. Blood pressure parameters were similar between the two groups; however, ARPKD patients required a significantly greater number of antihypertensive medications to achieve similar BP levels. Conclusions ARPKD patients are potentially at risk for neurocognitive dysfunction due to early onset CKD and more severe hypertension. However, this study of children with mild-to-moderate CKD in the CKiD cohort did not demonstrate increased risk in children with ARPKD compared to children with other causes of CKD. Further studies are needed to determine if these findings are applicable to children with more severe manifestations of ARPKD. Keywords Autosomal recessive polycystic kidney disease * Behavior * Chronic kidney disease * Hypertension * Neurocognition * Neuropsychological, Introduction Autosomal recessive polycystic kidney disease (ARPKD, OMIM 263200) is an important genetic cause of progressive chronic kidney disease (CKD), and occurs in an estimated 1 in 20,000 live births [...]

TBX6 encodes transcription‐factor box 6, a transcription factor critical to paraxial mesoderm segmentation and somitogenesis during embryonic development. TBX6 haploinsufficiency is believed to drive the skeletal and kidney phenotypes associated with the 16p11.2 deletion syndrome. Heterozygous and biallelic variants in TBX6 are associated with vertebral and rib malformations (TBX6‐associated congenital scoliosis) and spondylocostal dysostosis, and heterozygous TBX6 variants are associated with increased risk of genitourinary tract malformations. Combined skeletal and kidney phenotypes in individuals harboring heterozygous or biallelic TBX6 variants are rare. Here, we present seven individuals with vertebral and rib malformations and structural kidney differences associated with heterozygous TBX6 gene deletion in trans with a hypomorphic TBX6 allele or biallelic TBX6 variants. Our case series highlights the association between TBX6 and both skeletal and kidney disease. [ABSTRACT FROM AUTHOR]

Growth failure has been almost inextricably linked with chronic kidney disease (CKD) and end-stage renal disease (ESRD) since initial reports of renal dwarfism dating back to the turn of the twentieth century. Growth failure in CKD has been associated with both increased morbidity and mortality. Growth failure in the setting of kidney disease is multifactorial and is related to poor nutritional status as well as comorbidities, such as anemia, bone and mineral disorders, and alterations in hormonal responses, as well as to aspects of treatment such as steroid exposure. In this issue of Pediatric Nephrology, Franke et al. report on the gains made in growth and maturation in pediatric patients with ESRD in recent decades, particularly in Germany. Through advances in the care of CKD and ESRD over recent decades, the prevalence of growth failure appears to be decreasing. These findings, along with a recent report demonstrating decreases in mortality in childhood ESRD in the United States Renal Data System (USRDS), suggest overall improvements in the outcomes of care, perhaps reflecting improvements in the quality of care for children with kidney disease worldwide. Keywords Growth * Chronic kidney disease * Dialysis * Transplantation * CKD-MBD, Historical perspective Growth failure has long been recognized in children with chronic kidney disease (CKD). Short stature in children with CKD was first described in 1897 [1], and publications dating [...]

Ciliopathy syndromes are a diverse spectrum of disease characterized by a combination of cystic kidney disease, hepatobiliary disease, retinopathy, skeletal dysplasia, developmental delay, and brain malformations. Though generally divided into distinct disease categories based on the pattern of system involvement, ciliopathy syndromes are known to display certain phenotypic overlap. We performed next‐generation sequencing panel testing, clinical exome sequencing, and research‐based exome sequencing reanalysis on patients with suspected ciliopathy syndromes with additional features. We identified biallelic pathogenic variants in BBS1 in a child with features of cranioectodermal dysplasia, and biallelic variants in BBS12 in a child with the clinical stigmata of Bardet‐Biedl syndrome, but also with anal atresia. We additionally identified biallelic pathogenic variants in WDR35 and DYNC2H1 in children with predominant liver disease and ductal plate malformation without skeletal dysplasia. Our study highlights the phenotypic and genetic diversity of ciliopathy syndromes, the importance of considering ciliopathy syndromes as a disease‐spectrum and screening for all associated complications in all patients, and describes exclusive extra‐skeletal manifestations in two classical skeletal dysplasia syndromes. [ABSTRACT FROM AUTHOR]