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Article ; Online: Approach to simple kidney cysts in children.

Dell, Katherine M / Hartung, Erum A

2024

Abstract: The finding of a simple kidney cyst in a child can pose a diagnostic and management challenge for pediatric nephrologists, urologists, and primary care providers. The reported prevalence varies from 0.22 to 1% in large ultrasonography-based series of ... ...

Abstract	The finding of a simple kidney cyst in a child can pose a diagnostic and management challenge for pediatric nephrologists, urologists, and primary care providers. The reported prevalence varies from 0.22 to 1% in large ultrasonography-based series of more than 10,000 children each. The true prevalence, however, may be higher or lower, as factors such as variations in referral patterns, indications for ultrasonography, or technical considerations could impact prevalence rates. For many patients, simple kidney cysts may be found incidentally when imaging is performed for another indication. Although simple cysts can occur in children, they may also represent the first sign of autosomal dominant polycystic kidney disease (ADPKD) or other less common cystic kidney diseases. Definitive guidelines regarding the evaluation and monitoring of children with simple kidney cysts have not been established. The desire on the part of the practitioner and/or parents to establish a definitive diagnosis should be balanced with the cost and inconvenience of repeated imaging and visits with specialists. The goals of this review are to (1) outline the definition, epidemiology, clinical presentation, and natural history of simple kidney cysts in childhood; (2) describe clinical features that could suggest a diagnosis other than a simple kidney cyst; and (3) present a suggested framework for evaluating and monitoring of children with one or more simple kidney cysts.
Language	English
Publishing date	2024-04-27
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-024-06386-6
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Article ; Online: Machine learning models to predict post-dialysis blood pressure in children and young adults on maintenance hemodialysis.

Bou-Matar, Raed / Dell, Katherine M / Bobrowski, Amy

Scientific reports

2023 Volume 13, Issue 1, Page(s) 19105

Abstract: Hypertension is associated with significant cardiovascular morbidity. Blood pressure (BP) control on maintenance hemodialysis (HD) is strongly impacted by volume status. The objective of this study was to assess whether machine learning (ML) is effective ...

Abstract	Hypertension is associated with significant cardiovascular morbidity. Blood pressure (BP) control on maintenance hemodialysis (HD) is strongly impacted by volume status. The objective of this study was to assess whether machine learning (ML) is effective in predicting post-HD BP in children and young adults on HD. We collected data on BP, IDWG, pulse, and weights for patients on maintenance HD (> 3 months). Input features included DW, pre-post weight difference, IDWG and pre-HD BP. Seven models were trained and tuned using open-source libraries. Model performance was evaluated using time-series cross-validation on a rolling basis (3-12 month training, 1-day testing). Various regression scores were compared between models. Data for 35 patients (14,375 HD sessions) were analyzed. Extreme gradient boosting (XGB) and vector autoregression with exogenous regressors (VARX) achieved better accuracy in predicting post-dialysis systolic BP than K-nearest neighbor, support vector regression (SVR) with radial basis function kernel and random forest (p < 0.001 for each). The differences in accuracy between XGB, VARX, SVR with linear kernel, random forest and linear regression were not significant. Using clinical parameters, ML models may be useful in predicting post-HD BP, which may help guide DW adjustment and optimizing BP control for maintenance HD patients.
MeSH term(s)	Humans ; Young Adult ; Child ; Blood Pressure/physiology ; Renal Dialysis ; Hypertension ; Linear Models ; Heart Rate ; Kidney Failure, Chronic/complications
Language	English
Publishing date	2023-11-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-46171-3
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Article ; Online: The role of cilia in the pathogenesis of cystic kidney disease.

Dell, Katherine M

Current opinion in pediatrics

2015 Volume 27, Issue 2, Page(s) 212–218

Abstract: Purpose of review: Primary (immotile) cilia are specialized organelles present on most cell types. Almost all of proteins associated with a broad spectrum of human cystic kidney diseases have been localized to the region in or around the cilia. Abnormal ...

Abstract	Purpose of review: Primary (immotile) cilia are specialized organelles present on most cell types. Almost all of proteins associated with a broad spectrum of human cystic kidney diseases have been localized to the region in or around the cilia. Abnormal cilia structure and function have both been reported in animal models and human cystic kidneys. The goal of this review is to discuss current understanding of the mechanisms by which abnormal genes/proteins and cilia interact to potentially influence renal cystogenesis. Recent findings: Novel direct recording of cilia calcium levels/channel activity suggests that cilia form a calcium-mediated signaling microenvironment separate from the cytoplasm, which could provide a mechanism for cilia-specific downstream signaling. Genetic-based studies confirm that cilia are not required for cystogenesis, but modulate cystic kidney disease severity through a novel, undefined mechanism. Mechanisms by which both cilia-associated and noncilia-associated proteins can alter cilia structure/function have also been identified. Summary: Considerable progress has been made in defining the mechanisms by which abnormal genes and proteins affect cilia structure and function. However, the exact mechanisms by which these interactions cause renal cyst formation and progression of cystic kidney disease are still unknown.
MeSH term(s)	Calcium Signaling/physiology ; Cell Proliferation ; Cilia/physiology ; Humans ; Kidney/pathology ; Kidney Diseases, Cystic/pathology ; Kidney Diseases, Cystic/physiopathology ; Signal Transduction/physiology ; Up-Regulation
Language	English
Publishing date	2015-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1049374-8
ISSN	1531-698X ; 1040-8703
ISSN (online)	1531-698X
ISSN	1040-8703
DOI	10.1097/MOP.0000000000000187
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Article ; Online: The link between executive function, socio-emotional functioning and health-related quality of life in children and adolescents with mild to moderate chronic kidney disease.

Alhamed, Arwa A / Toly, Valerie B / Hooper, Stephen R / Dell, Katherine M

Child: care, health and development

2021 Volume 48, Issue 3, Page(s) 455–464

Abstract: Background: Children and adolescents with mild to moderate chronic kidney disease (CKD) are at high risk for mild but persistent impairment in executive functions, which have been associated with low health-related quality of life (HRQOL) among children ...

Abstract	Background: Children and adolescents with mild to moderate chronic kidney disease (CKD) are at high risk for mild but persistent impairment in executive functions, which have been associated with low health-related quality of life (HRQOL) among children and adolescents with chronic health conditions. However, no similar link has been established among children and adolescents with mild to moderate CKD. Given the essential role executive functions play in the development of adequate cognitive, emotional and social skills, it is essential to gain a clearer understating of the magnitude and attributes of executive functions and its link to HRQOL in order to inform appropriate medical and educational interventions for this patient population. Objective: The aim of this study is to examine the relationship between executive functions, socio-emotional functioning and HRQOL in children and adolescents with mild to moderate CKD. Methods: A cross-sectional design was used for this secondary data analysis of 199 children and adolescents (ages 6-17) with mild to moderate CKD from the United States and Canada who receive care at hospitals associated with the Chronic Kidney Disease in Children Study (CKiD). Results: The presence of impairment in executive functions and socio-emotional functioning (internalizing problems) significantly predicted lower HRQOL after controlling for key covariates (i.e., maternal education, anaemia and hypertension). Further, internalizing problems partially mediated the relationship between executive functions and HRQOL such that impairment in executive functions predicted lower HRQOL directly and indirectly by contributing to higher internalizing problems, which further contributed to low HRQOL. Conclusion: This study underscores the importance of executive functions and socio-emotional functioning in the manifestation of HRQOL. Given that HRQOL is potentially compromised for many children and adolescents with mild to moderate CKD, it will be important for both clinicians and researchers to examine a range of factors, including executive functions and socio-emotional functioning, in order to optimize HRQOL.
MeSH term(s)	Adolescent ; Child ; Cross-Sectional Studies ; Emotions ; Executive Function ; Humans ; Quality of Life/psychology ; Renal Insufficiency, Chronic/psychology
Language	English
Publishing date	2021-12-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	223039-2
ISSN	1365-2214 ; 0305-1862
ISSN (online)	1365-2214
ISSN	0305-1862
DOI	10.1111/cch.12946
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Article ; Online: Kidney disease progression in pediatric and adult posterior urethral valves (PUV) patients.

Huang, Victoria W / Behairy, Mohga / Abelson, Benjamin / Crane, Alice / Liu, Wei / Wang, Lu / Dell, Katherine M / Rhee, Audrey

Pediatric nephrology (Berlin, Germany)

2023 Volume 39, Issue 3, Page(s) 829–835

Abstract: Background: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, ... ...

Abstract	Background: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. Methods: We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20 ml/min/1.73 m Results: Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m Conclusion: PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies.
MeSH term(s)	Male ; Adult ; Child ; Humans ; Infant ; Renal Dialysis/adverse effects ; Disease Progression ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/etiology ; Urethral Obstruction/surgery ; Urethral Obstruction/complications ; Retrospective Studies ; Glomerular Filtration Rate ; Proteinuria/etiology ; Kidney ; Acute Kidney Injury/complications
Language	English
Publishing date	2023-09-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-023-06128-0
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Article: Long-Term Outcomes in Children with Steroid-Resistant Nephrotic Syndrome Treated with Calcineurin Inhibitors.

Beins, Nathan T / Dell, Katherine M

Frontiers in pediatrics

2015 Volume 3, Page(s) 104

Abstract: Background: Steroid-resistant nephrotic syndrome (SRNS) is an important cause of chronic kidney disease (CKD) in children that often progresses to end-stage renal disease (ESRD). Calcineurin inhibitors (CNIs) have been shown to be effective in inducing ... ...

Abstract	Background: Steroid-resistant nephrotic syndrome (SRNS) is an important cause of chronic kidney disease (CKD) in children that often progresses to end-stage renal disease (ESRD). Calcineurin inhibitors (CNIs) have been shown to be effective in inducing short-term remission in some patients with SRNS. However, there are little data examining their long-term impact on ESRD progression rates. Methods: We performed a retrospective chart review of all patients treated for SRNS with CNIs at our institution from 1995 to 2013. Data collected including demographics, initial response to medical therapy, number of relapses, progression to ESRD, and treatment complications. Results: A total of 16 patients met inclusion criteria with a mean follow-up of 6.6 years (range 0.6-17.6 years). Histopathological diagnoses were focal segmental glomerulosclerosis (8), mesangial proliferative glomerulonephritis (4), IgM nephropathy (3), and minimal change disease (1). Three patients (18.8%) were unresponsive to CNIs while the remaining 13 (81.2%) achieved remission with CNI therapy. Six patients (37.5%) progressed to ESRD during the study period, three of whom did so after initially responding to CNI therapy. Renal survival rates were 87, 71, and 57% at 2, 5, and 10 years, respectively. Non-Caucasian ethnicity was associated with progression to ESRD. Finally, a higher number of acute kidney injury (AKI) episodes were associated with a lower final estimated glomerular filtration rate. Discussion: Despite the majority of SRNS patients initially responding to CNI therapy, a significant percentage still progressed to ESRD despite achieving short-term remission. Recurrent episodes of AKI may be associated with progression of CKD in patients with SRNS.
Language	English
Publishing date	2015-11-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2015.00104
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Article ; Online: Quantitative magnetic resonance imaging assessments of autosomal recessive polycystic kidney disease progression and response to therapy in an animal model.

Erokwu, Bernadette O / Anderson, Christian E / Flask, Chris A / Dell, Katherine M

Pediatric research

2018 Volume 83, Issue 5, Page(s) 1067–1074

Abstract: BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is associated with significant mortality and morbidity, and currently, there are no disease-specific treatments available for ARPKD patients. One major limitation in establishing new ... ...

Abstract	BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is associated with significant mortality and morbidity, and currently, there are no disease-specific treatments available for ARPKD patients. One major limitation in establishing new therapies for ARPKD is a lack of sensitive measures of kidney disease progression. Magnetic resonance imaging (MRI) can provide multiple quantitative assessments of the disease.MethodsWe applied quantitative image analysis of high-resolution (noncontrast) T2-weighted MRI techniques to study cystic kidney disease progression and response to therapy in the PCK rat model of ARPKD.ResultsSerial imaging over a 2-month period demonstrated that renal cystic burden (RCB, %)=[total cyst volume (TCV)/total kidney volume (TKV) × 100], TCV, and, to a lesser extent, TKV detected cystic kidney disease progression, as well as the therapeutic effect of octreotide, a clinically available medication shown previously to slow both kidney and liver disease progression in this model. All three MRI measures correlated significantly with histologic measures of renal cystic area, although the correlation of RCB and TCV was stronger than that of TKV.ConclusionThese preclinical MRI results provide a basis for applying these quantitative MRI techniques in clinical studies, to stage and measure progression in human ARPKD kidney disease.
MeSH term(s)	Animals ; Cysts/metabolism ; Disease Models, Animal ; Disease Progression ; Image Processing, Computer-Assisted/methods ; Liver Diseases/pathology ; Magnetic Resonance Imaging ; Male ; Octreotide/pharmacology ; Polycystic Kidney, Autosomal Recessive/diagnostic imaging ; Polycystic Kidney, Autosomal Recessive/pathology ; Rats ; Rats, Sprague-Dawley ; Software
Chemical Substances	Octreotide (RWM8CCW8GP)
Language	English
Publishing date	2018-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/pr.2018.24
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Longitudinal analysis of blood pressure and lipids in childhood nephrotic syndrome.

Pediatric nephrology (Berlin, Germany)

2024

Abstract: Background: In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children ... ...

Abstract	Background: In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response. Methods: A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia. Results: Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time. Conclusions: Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.
Language	English
Publishing date	2024-02-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-024-06301-z
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Article ; Online: Growth in children with nephrotic syndrome: a post hoc analysis of the NEPTUNE study.

Pediatric nephrology (Berlin, Germany)

2024

Abstract: Background: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression.: Methods: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study ... ...

Abstract	Background: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. Methods: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. Results: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (β - 7.5 × 10 Conclusion: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.
Language	English
Publishing date	2024-04-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-024-06375-9
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Article ; Online: Gluten-Free Diet in Childhood Difficult-to-Treat Nephrotic Syndrome: A Pilot Feasibility Study.

Srivastava, Tarak / Dell, Katherine M / Lemley, Kevin V / Gipson, Debbie S / Kaskel, Frederick J / Meyers, Kevin Edward / Faul, Christian / Goldhaber, Ayelet / Pehrson, LauraJane / Trachtman, Howard

Glomerular diseases

2022 Volume 2, Issue 4, Page(s) 176–183

Abstract: Introduction: Minimal change disease in childhood can follow a frequently relapsing or steroid-dependent course in up to 40% of cases. Second-line immunosuppressive medications that are used to manage these patients are associated with significant ... ...

Abstract	Introduction: Minimal change disease in childhood can follow a frequently relapsing or steroid-dependent course in up to 40% of cases. Second-line immunosuppressive medications that are used to manage these patients are associated with significant adverse effects. There is a need for safer alternative treatments for difficult-to-treat nephrotic syndrome. Therefore, we conducted an open-label feasibility study to assess the safety and efficacy of a gluten-free diet as treatment for pediatric patients with difficult-to-treat nephrotic syndrome. As a second aim, we sought to determine if the plasma zonulin concentration can identify those who are more likely to respond to this intervention. Methods: Seventeen patients were placed on a gluten-free diet for 6 months. A positive response was defined as a 50% reduction in the relapse rate compared to the preceding 6 months or the ability to discontinue 1 immunosuppressive drug. Results: Five (29%) participants had a positive response to the dietary intervention. The gluten-free diet was well tolerated with no clinical or laboratory adverse events. Plasma zonulin concentration was elevated in patients who failed to benefit from the gluten-free diet. Discussion/conclusion: A gluten-free diet may be a useful adjunctive intervention for patients with difficult-to-treat nephrotic syndrome that can be implemented prior to resorting to second-line immunosuppressive therapy. Development of the plasma zonulin level as a biomarker to predict efficacy would facilitate rational use of a gluten-free diet in the management of nephrotic syndrome.
Language	English
Publishing date	2022-06-22
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-3633
ISSN (online)	2673-3633
DOI	10.1159/000525587
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