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Article ; Online: Metabolomic profiling of pediatric post-tonsillectomy pain: A proof-of-concept study.

Mpody, Christian / Patel, Ambrish B / Smoyer, William E / Tobias, Joseph D / Nafiu, Olubukola O

2024

Abstract: Introduction: Tonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing ... ...

Abstract	Introduction: Tonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing tonsillectomy report moderate-to-severe pain upon recovering from anesthesia. The underlying molecular mechanisms of post-tonsillectomy pain are not well understood, limiting the development of targeted treatment strategies. Our study aimed to identify candidate serum metabolites associated with varying severity of post-tonsillectomy pain. Methods: Venous blood samples and pain scores were obtained from 34 children undergoing tonsillectomy ± adenoidectomy, and metabolomic analysis was performed. Supervised orthogonal projections to latent structures discriminant analysis were employed to identify differentially expressed metabolites between children with severe and mild pain, as well as between moderate and mild pain. Results: Pain scores differentiated children as mild (n = 6), moderate (n = 14), or severe (n = 14). Four metabolites (fatty acid 18:0(OH), thyroxine, phosphatidylcholine 38:5, and branched fatty acids C27H54O3) were identified as candidate biomarkers that differentiated severe vs. mild post-tonsillectomy pain, the combination of which yielded an AUC of 0.91. Similarly, four metabolites (sebacic acid, dicarboxylic acids C18H34O4, hydroxy fatty acids C18H34O3, and myristoleic acid) were identified as candidate biomarkers that differentiated moderate vs. mild post-tonsillectomy pain, with AUC values ranging from 0.85 to 0.95. Conclusion: This study identified novel candidate biomarker panels that effectively differentiated varying severity of post-tonsillectomy pain. Further research is needed to validate these data and to explore their clinical implications for personalized pain management in children undergoing painful surgeries.
Language	English
Publishing date	2024-03-11
Publishing country	France
Document type	Journal Article
ZDB-ID	1086049-6
ISSN	1460-9592 ; 1155-5645
ISSN (online)	1460-9592
ISSN	1155-5645
DOI	10.1111/pan.14876
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Zs.A 3306: Show issues

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Article ; Online: Glomerular B7-1 staining: toward precision medicine for treatment of recurrent focal segmental glomerulosclerosis.

Wang, Chia-Shi / Smoyer, William E / Cara-Fuentes, Gabriel

Pediatric nephrology (Berlin, Germany)

2022

Language	English
Publishing date	2022-06-20
Publishing country	Germany
Document type	Editorial
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-022-05650-x
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Zs.A 2196: Show issues

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Article ; Online: Long-term ACE inhibition in Alport syndrome: are the benefits worth the risks?

Rheault, Michelle N / Smoyer, William E

Kidney international

2020 Volume 97, Issue 6, Page(s) 1104–1106

Abstract: Gross et al. present results of the EARLY PRO-TECT trial, a randomized controlled trial of ramipril versus placebo in children with early-stage Alport syndrome. Although under-enrolled and not a positive trial in the traditional sense, EARLY PRO-TECT ... ...

Abstract	Gross et al. present results of the EARLY PRO-TECT trial, a randomized controlled trial of ramipril versus placebo in children with early-stage Alport syndrome. Although under-enrolled and not a positive trial in the traditional sense, EARLY PRO-TECT does provide strong supportive evidence for both long-term safety and a clinical benefit of early treatment with angiotensin-converting enzyme inhibitors in slowing the progression of both albuminuria and estimated glomerular filtration rate decline in children with Alport syndrome.
MeSH term(s)	Albuminuria ; Angiotensin-Converting Enzyme Inhibitors/adverse effects ; Child ; Glomerular Filtration Rate ; Humans ; Nephritis, Hereditary/drug therapy ; Ramipril/adverse effects
Chemical Substances	Angiotensin-Converting Enzyme Inhibitors ; Ramipril (L35JN3I7SJ)
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2020.01.030
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Zs.A 797: Show issues

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Article ; Online: Biomarkers in pediatric glomerulonephritis and nephrotic syndrome.

Cara-Fuentes, Gabriel / Smoyer, William E

Pediatric nephrology (Berlin, Germany)

2021 Volume 36, Issue 9, Page(s) 2659–2673

Abstract: Glomerular diseases are often chronic or recurring and thus associated with a tremendous physical, psychological, and economic burden. Their etiologies are often unknown, and their pathogeneses are frequently poorly understood. The diagnoses and ... ...

Abstract	Glomerular diseases are often chronic or recurring and thus associated with a tremendous physical, psychological, and economic burden. Their etiologies are often unknown, and their pathogeneses are frequently poorly understood. The diagnoses and management of these diseases are therefore based on clinical features, traditional laboratory markers, and, often, kidney pathology. However, the clinical presentation can be highly variable, the kidney pathology may not establish a definitive diagnosis, and the therapeutic responses and resulting clinical outcomes are often unpredictable. To try to address these challenges, significant research efforts have been made over the last decade to identify potential biomarkers that can help clinicians optimize the diagnosis and prognosis at clinical presentation, as well as help predict long-term outcomes. Unfortunately, these efforts have to date only identified a single biomarker for glomerular disease that has been fully validated and developed for widespread clinical use (anti-PLA2R antibodies to diagnose membranous nephropathy). In this manuscript, we review the definitions and development of biomarkers, as well as the current knowledge on both historical and novel candidate biomarkers of glomerular disease, with an emphasis on those associated with idiopathic nephrotic syndrome.
MeSH term(s)	Antibodies/blood ; Biomarkers/blood ; Child ; Glomerulonephritis, Membranous/diagnosis ; Humans ; Nephrotic Syndrome/diagnosis ; Receptors, Phospholipase A2/immunology
Chemical Substances	Antibodies ; Biomarkers ; Receptors, Phospholipase A2
Language	English
Publishing date	2021-01-03
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/s00467-020-04867-y
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Article ; Online: Results of the PROPINE randomized controlled trial: determining the ever-elusive target, the optimal plan for relapses of nephrotic syndrome in children.

Mahan, John D / Kallash, Mahmoud / Smoyer, William E

Kidney international

2021 Volume 99, Issue 2, Page(s) 311–313

Abstract: Best treatments for initial presentation and relapses in children with nephrotic syndrome (NS) are still to be defined. The PROPINE study, published in this issue of Kidney International, demonstrates for relapse of childhood NS, the non-inferiority of a ...

Abstract	Best treatments for initial presentation and relapses in children with nephrotic syndrome (NS) are still to be defined. The PROPINE study, published in this issue of Kidney International, demonstrates for relapse of childhood NS, the non-inferiority of a short taper (over 36 days) after remission with steroids. This study reinforces the need for more well-designed studies and the incorporation of predictive biomarkers, genetic studies, and other details to personalize treatment for each child with idiopathic NS.
MeSH term(s)	Child ; Epinephrine/analogs & derivatives ; Humans ; Nephrotic Syndrome/diagnosis ; Nephrotic Syndrome/drug therapy ; Prednisone ; Recurrence
Chemical Substances	dipivefrin (8Q1PVL543G) ; Prednisone (VB0R961HZT) ; Epinephrine (YKH834O4BH)
Language	English
Publishing date	2021-01-28
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2020.10.034
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Article ; Online: Saving more young lives in Africa.

Cullis, Brett / Lalya, Francis / Smoyer, William E

Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis

2020 Volume 40, Issue 5, Page(s) 438–440

MeSH term(s)	Acute Kidney Injury ; Africa ; Child ; Health Resources ; Humans ; Peritoneal Dialysis
Language	English
Publishing date	2020-06-18
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	645010-6
ISSN	1718-4304 ; 0896-8608
ISSN (online)	1718-4304
ISSN	0896-8608
DOI	10.1177/0896860820931662
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Article ; Online: Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome.

Agrawal, Shipra / Brier, Michael E / Kerlin, Bryce A / Smoyer, William E

Kidney international reports

2021 Volume 6, Issue 3, Page(s) 785–795

Abstract: Introduction: Glucocorticoids (GCs) are the primary treatment for nephrotic syndrome (NS), although ∼10% to 20% of children develop steroid-resistant NS (SRNS). Unfortunately, there are no validated biomarkers able to predict SRNS at initial disease ... ...

Abstract	Introduction: Glucocorticoids (GCs) are the primary treatment for nephrotic syndrome (NS), although ∼10% to 20% of children develop steroid-resistant NS (SRNS). Unfortunately, there are no validated biomarkers able to predict SRNS at initial disease presentation. We hypothesized that a plasma cytokine panel could predict SRNS at disease presentation, and identify potential pathways regulating SRNS pathogenesis. Methods: Paired plasma samples were collected from 26 children with steroid-sensitive NS (SSNS) and 14 with SRNS at NS presentation and after ∼7 weeks of GC therapy, when SSNS versus SRNS was clinically determined. Plasma cytokine profiling was performed with a panel of 27 cytokines. Results: We identified 13 cytokines significantly different in Pretreatment SSNS versus SRNS samples. Statistical modeling identified a cytokine panel (interleukin [IL]-7, IL-9, monocyte chemoattractant protein-1 [MCP-1]) able to discriminate between SSNS and SRNS at disease presentation (receiver operating characteristic [ROC] value = 0.846; sensitivity = 0.643; specificity = 0.846). Furthermore, GC treatment resulted in significant decreases in plasma interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-7, IL-13, and IL-5 in both SSNS and SRNS patients. Conclusions: These studies suggest that initial GC treatment of NS reduces the plasma cytokines secreted by both CD4
Language	English
Publishing date	2021-01-06
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2020.12.027
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Article ; Online: Psychosocial supports within pediatric nephrology practices: A pediatric nephrology research consortium survey.

Dawson, Anne E / Wilson, Camille S / Smoyer, William E / Pottanat, Neha / Wilson, Amy C / Mahan, John D / LaMotte, Julia E

PloS one

2023 Volume 18, Issue 5, Page(s) e0285126

Abstract: Background: The landscape of available psychosocial services within pediatric nephrology care is poorly characterized. However, the effects of kidney disease on emotional health and health-related quality of life are well documented, as is the impact of ...

Abstract	Background: The landscape of available psychosocial services within pediatric nephrology care is poorly characterized. However, the effects of kidney disease on emotional health and health-related quality of life are well documented, as is the impact of social determinants of health on kidney disease outcomes. The objectives of this study were to assess pediatric nephrologists' perceptions of available psychosocial services and to elucidate inequities in access to psychosocial care. Methods: A web-based survey was distributed to members of the Pediatric Nephrology Research Consortium (PNRC). Quantitative analyses were performed. Results: We received responses from 49 of the 90 PNRC centers. With regards to dedicated services, social work was most commonly available (45.5-100%), followed by pediatric psychology (0-57.1%) and neuropsychology (0-14.3%), with no centers having embedded psychiatry. Availability of psychosocial providers was positively associated with nephrology division size, such that as center size increased, access to various psychosocial providers increased. Notably, the majority of respondents indicated that perceived need for psychosocial support exceeds that which is currently available, even at centers with higher levels of current support. Conclusions: Within the US, there is wide variability in the availability of psychosocial services within pediatric nephrology centers despite a well-documented necessity for the provision of holistic care. Much work remains to better understand the variation in funding for psychosocial services and in utilization of psychosocial professionals in the pediatric nephrology clinic, and to inform key best practices for addressing the psychosocial needs of patients with kidney disease.
MeSH term(s)	Child ; Humans ; Nephrology ; Psychosocial Support Systems ; Quality of Life ; Pediatricians ; Ambulatory Care Facilities
Language	English
Publishing date	2023-05-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0285126
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Article ; Online: Role of albumin and its modifications in glomerular injury.

Agrawal, Shipra / Smoyer, William E

Pflugers Archiv : European journal of physiology

2017 Volume 469, Issue 7-8, Page(s) 975–982

Abstract: Albuminuria is both a characteristic hallmark and a known risk factor for progressive glomerular disease. Although the molecular basis for a potential causative role for albuminuria in progressive chronic kidney disease remains poorly understood, there ... ...

Abstract	Albuminuria is both a characteristic hallmark and a known risk factor for progressive glomerular disease. Although the molecular basis for a potential causative role for albuminuria in progressive chronic kidney disease remains poorly understood, there have been several recent advances in our understanding of the role of albumin, and its molecular modifications, in the development and progression of glomerular disease. This review discusses recent findings related to the ability of albumin and its associated factors to directly induce podocyte and glomerular injury. Additional recent studies confirming the ability and mechanisms by which podocytes endocytose albumin are also discussed. Lastly, we present several known molecular modifications in the albumin molecule itself, as well as substances bound to it, which may be important and potentially clinically relevant mediators of albumin-induced glomerular injury. These recent findings may create entirely new opportunities to develop novel future therapies directed at albumin that could potentially help reduce podocyte and renal tubular injury and slow the progression of chronic glomerular disease.
Language	English
Publishing date	2017-08
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-017-2029-4
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Uc I Zs.35: Show issues

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Article ; Online: Exploring the Role of Antithrombin in Nephrotic Syndrome-Associated Hypercoagulopathy: A Multi-Cohort Study and Meta-Analysis.

Abdelghani, Eman / Waller, Amanda P / Wolfgang, Katelyn J / Stanek, Joseph R / Parikh, Samir V / Rovin, Brad H / Smoyer, William E / Kerlin, Bryce A

Clinical journal of the American Society of Nephrology : CJASN

2023 Volume 18, Issue 2, Page(s) 234–244

Abstract: Background: Nephrotic syndrome is associated with an acquired hypercoagulopathy that is thought to drive its predisposition for venous thromboembolism. Previous studies have suggested that urinary antithrombin (AT) loss leading to acquired AT deficiency ...

Abstract	Background: Nephrotic syndrome is associated with an acquired hypercoagulopathy that is thought to drive its predisposition for venous thromboembolism. Previous studies have suggested that urinary antithrombin (AT) loss leading to acquired AT deficiency is the primary mechanism underlying this hypercoagulopathy, but this hypothesis has not been directly tested. The objectives of this study were to test the influence of AT levels on hypercoagulopathy in nephrotic syndrome patient samples and perform meta-analyses to evaluate the likelihood of AT deficiency in patients with nephrotic syndrome. Methods: Samples from three independent nephrotic syndrome cohorts were analyzed. AT antigen and activity assays were performed using ELISA and amidolytic assays, respectively. Plasma thrombin generation, albumin, and urine protein-to-creatinine ratios were determined using established methods. Meta-analyses were performed by combining these new data with previously published data. Results: AT levels were not consistently related to either plasma albumin or proteinuria. AT was quantitatively related to hypercoagulopathy in adult nephrotic syndrome, whereas AT activity was inconsistently associated with hypercoagulopathy in childhood nephrotic syndrome. Notably, hypercoagulopathy did not differ between patients with normal AT levels and those with levels below the threshold used to define clinical AT deficiency (<70%). Moreover, ex vivo AT supplementation did not significantly alter hypercoagulopathy in AT-deficient plasma samples. The meta-analyses demonstrated that AT deficiency was not a uniform feature of nephrotic syndrome and was more common in children than adults. Conclusions: These data suggest that AT deficiency plays only a limited role in the mechanisms underlying the acquired hypercoagulopathy of nephrotic syndrome. Moreover, AT deficiency was not present in all patients with nephrotic syndrome and was more likely in children than adults despite the higher risk for venous thromboembolism in adults than children.
MeSH term(s)	Adult ; Child ; Humans ; Nephrotic Syndrome/complications ; Antithrombins ; Venous Thromboembolism/complications ; Cohort Studies ; Antithrombin III/urine
Chemical Substances	Antithrombins ; Antithrombin III (9000-94-6)
Language	English
Publishing date	2023-02-08
Publishing country	United States
Document type	Meta-Analysis ; Journal Article
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.0000000000000047
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