Browsing by Author "Schwaderer, Andrew"

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    Acute Kidney Injury Associated With Urinary Stone Disease in Children and Young Adults Presenting to a Pediatric Emergency Department
    (Frontiers Media, 2020-11-30) Farris, Nicholas; Raina, Rupesh; Tibrewal, Abhishek; Brown, Miraides; Colvis, Maria; Schwaderer, Andrew; Kusumi, Kirsten; Pediatrics, School of Medicine
    Background: Acute kidney injury (AKI) due to urinary stone disease (USD) is rare in adults; AKI rates in children with USD may be higher, and emerging data links stones to chronic kidney disease (CKD) development in adults. Methods: This study is a retrospective analysis of USD patients at a single pediatric hospital system's emergency department (ED). Patients were initially identified by USD ICD codes; USD was then confirmed by imaging or physician documentation; patients had to have baseline creatinine (Cr) and Cr in the ED for comparison to be included. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO), Acute Kidney Injury Network (AKIN), and Pediatric Risk, Injury, Failure, Loss, End Stage (pRIFLE). Results: Of the 589 total visits, 264/589 (45%) had data to evaluate for AKI, 23% were AKI(+) and 77% were AKI(-). pRIFLE was most common (82%) and 18% were only positive by AKIN/KDIGO. AKI(+) were more likely to be younger (16.7 vs. 17.4 years, p = 0.046) and more likely to present with vomiting {odds ratio [OR] [95% confidence interval (CI)]: 2.4 [1.4-4.3], p = 0.002}; also, the proportion of AKI(+) was significantly higher in <18 vs. ≥18 years [26.9 vs. 15.5%, p = 0.032, OR (95% CI): 2.0 (1.1-3.9)]. Urinary tract infection (UTI) and obstruction rates were similar between groups. AKI(+) patients had a significant OR <1 suggesting less risk of receiving non-steroidal anti-inflammatory drugs (NSAIDs); however, 51% of them did receive NSAIDs during their ED encounter. AKI(+) patients were more likely to require admission to the hospital (53 vs. 32%, p = 0.001). Conclusion: We have demonstrated a novel association between USD-induced renal colic and AKI in a group of young adults and children. AKI(+) patients were younger and were more likely to present with vomiting. AKI(+) patients did not have higher rates of obstruction or UTI, and 51% of AKI(+) received NSAIDs.
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    Adolescents with urinary stones have elevated urine levels of inflammatory mediators
    (Springer, 2019-04-16) Kusumi, Kirsten; Ketz, John; Saxena, Vijay; Spencer, John David; Safadi, Fayez; Schwaderer, Andrew; Pediatrics, School of Medicine
    Background: Urinary stone are increasing in children, primarily during adolescence. Although urinary stones are often viewed in the context of intermittent stone events, increasing evidence indicates that stones are a metabolic process associated with chronic kidney disease and low bone mass. These aforementioned stone associated conditions may have pediatric origins. Objective: To compare urine inflammatory markers in otherwise healthy stone forming children versus matched controls. Methods: Urine samples were collected from 12 adolescents with urinary stones along with 15 controls. The levels of 30 urine cytokines were measured using a Mesoscale 30-Plex Human Cytokine panel and normalized to urine creatinine levels. Results: Macrophage inflammatory protein 1β and Interleukin 13 levels were significantly elevated in the urine of the stone forming adolescents compared to controls. Interleukin 17A was elevated in the urine of controls. Conclusions: This study indicates that urine levels of cytokines involved in chronic inflammation and fibrosis are elevated urinary stone formers as early as adolescence. Because stone formers are at risk for chronic kidney disease, Macrophage inflammatory protein 1β and Interleukin 13 represent investigative targets.
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    Asymptomatic Bacteriuria versus Symptom Underreporting in Older Emergency Department Patients with Suspected Urinary Tract Infection
    (Wiley, 2020-11) Caterino, Jeffrey M.; Stephens, Julie A.; Camargo, Carlos A., Jr.; Wexler, Randell; Hebert, Courtney; Southerland, Lauren T.; Hunold, Katherine M.; Hains, David S.; Bischof, Jason J.; Wei, Lai; Wolfe, Alan J.; Schwaderer, Andrew; Pediatrics, School of Medicine
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    Initial collection of an inadequate 24-hour urine sample in children does not predict subsequent inadequate collections
    (Elsevier, 2018) Chan, Katherine H.; Moser, Elizabeth A.; Whittam, Benjamin M.; Misseri, Rosalia; Cain, Mark P.; Krambeck, Amy; Schwaderer, Andrew; Urology, School of Medicine
    Introduction Approximately half of adult stone formers submit specimens that are either under or over collections as determined by 24-h creatinine/kg. Previously identified predictors of inadequate collection in adults include female sex, older age, higher body mass index (BMI), vitamin D supplementation, and weekday collection. Objective The objective of this study is to determine risk factors for inadequate 24-h urinary specimen collection in the pediatric population. Study design A retrospective analysis of all children (<18 years of age) with renal and/or ureteral calculi evaluated at the study tertiary care pediatric center from 2005 to 2015 was performed. Those who had at least one 24-h urinary metabolic profile after a clinical visit for kidney and/or ureteral stones were included; children with bladder stones were excluded. Adequate collections had a urine creatinine of 10–15 mg/kg/24 h. A bivariate analysis of potential factors associated with inadequate collection of the initial urinary metabolic profile, including child demographics, parental socio-economic factors, history of stone surgery, and weekday vs. weekend urine collection, was performed. A mixed-effects logistic regression, controlling for correlation of specimens from the same patient, was also performed to determine whether an initial inadequate collection predicted a subsequent inadequate collection. Results Of 367 patients, 80 had an adequate collection (21.9%): median age, 13 years (interquartile range, 8–16); 61.1% female; 93.5% white; 19.5% obese; and 13.0% overweight. No parental or child factors were associated with inadequate collection (Summary Table). Of inadequate collections, more than 80% were over collections. In the 175 patients with more than one 24-h urinary specimen collection, the effect of an initial inadequate collection on subsequent inadequate collections was not significant after controlling for the correlation of samples from the same patient (p = 0.8). Discussion Any parental or child factors associated with the collection of inadequate 24-h urine specimens in children were not found. An initial inadequate collection does not predict subsequent inadequate collections. It was surprising that >80% of the inadequate collections were over collections rather than under collections. Possible explanations are that children collected urine samples for longer than the 24-h period or that stone-forming children produce more creatinine per 24-h period than healthy children due to hyperfiltration. Conclusion Inadequate collections are very common, and the risk factors for them are unclear. A repeat collection would be suggested if the first is inadequate. Further studies must be planned to explore barriers to accurate specimen collection using qualitative research methodology.
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    MAP3K7 is an innate immune regulatory gene with increased expression in human and murine kidney intercalated cells following uropathogenic Escherichia coli exposure
    (Wiley, 2022) Saxena, Vijay; Arregui, Samuel; Kamocka, Malgorzata Maria; Hains, David S.; Schwaderer, Andrew; Pediatrics, School of Medicine
    Understanding the mechanisms responsible for the kidney's defense against ascending uropathogen is critical to devise novel treatment strategies against increasingly antibiotic resistant uropathogen. Growing body of evidence indicate Intercalated cells of the kidney as the key innate immune epithelial cells against uropathogen. The aim of this study was to find orthologous and differentially expressed bacterial defense genes in human versus murine intercalated cells. We simultaneously analyzed 84 antibacterial genes in intercalated cells enriched from mouse and human kidney samples. Intercalated cell “reporter mice” were exposed to saline versus uropathogenic Escherichia coli (UPEC) transurethrally for 1 h in vivo, and intercalated cells were flow sorted. Human kidney intercalated cells were enriched from kidney biopsy using magnetic‐activated cell sorting and exposed to UPEC in vitro for 1 h. RT2 antibacterial PCR array was performed. Mitogen‐activated protein kinase kinase kinase 7 (MAP3K7) messenger RNA (mRNA) expression increased in intercalated cells of both humans and mice following UPEC exposure. Intercalated cell MAP3K7 protein expression was defined by immunofluorescence and confocal imaging analysis, was consistent with the increased MAP3K7 mRNA expression profiles defined by PCR. The presence of the orthologous innate immune gene MAP3K7/TAK1 suggests that it may be a key regulator of the intercalated cell antibacterial response and demands further investigation of its role in urinary tract infection pathogenesis.
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    Pediatric kidney transplant recipients with and without underlying structural kidney disease have a comparable risk of hospitalization associated with urinary tract infections
    (Frontiers Media, 2022-09-02) Spiwak, Elizabeth; Nailescu, Corina; Schwaderer, Andrew; Pediatrics, School of Medicine
    Introduction: Urinary tract infections (UTIs) are a common and potentially serious kidney transplant complication. Pediatric kidney transplants are potentially at increased risk for UTIs when structural kidney disease is the underlying end-stage kidney disease (ESKD) etiology. The objective of this manuscript is to determine if children with structural kidney disorders are more prone to UTIs post kidney transplant. Materials and methods: Hospitalizations for pediatric kidney transplant recipients were retrospectively reviewed over a 4-year period for UTIs in the diagnostic codes. The patient's age, sex, graft age, underlying diagnosis for cause of ESKD, symptoms at presentation, urinalysis results, and urine culture results were recorded. UTI rates, febrile UTI rates, and UTI rates in the 1st year post-transplant were compared between children with ESKD due to structural vs. non-structural kidney disease. Results: Overall, 62 of 145 pediatric patients with kidney transplants accounted for 182 hospitalizations for kidney transplant complications over the 4-year study period. UTIs were components of 34% of the hospitalizations. Overall, UTI rates, febrile UTI rates, and UTI rates for the 1st year post kidney transplant were comparable for children with vs. without structural ESKD etiologies. Conclusion: Urinary tract infections are frequent components of hospitalizations for pediatric kidney transplant recipients. Children with and without structural kidney disease as an ESKD etiology have similar UTI rates indicating that UTI susceptibility is primarily due to the transplant process and/or medication regimens. UTIs represent a potentially modifiable risk factor for pediatric kidney transplant complications.