Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome

Carpenter, Shannon L.; Goldman, Jennifer L.; Sherman, Ashley; Selewski, David T.; Kallash, Mahmoud; Tran, Cheryl L.; Seamon, Meredith; Katsoufis, Chryso; Ashoor, Isa; Hernandez, Joel D.; Supe-Markovina, Katarina; D’Alessandri-Silva, Cynthia; DeJesus-Gonzalez, Nilka; Vasylyeva, Tetyana L.; Formeck, Cassandra L.; Woll, Christopher; Gbadegesin, Rasheed; Geier, Pavel; Devarajan, Prasad; Smoyer, William E.; Kerlin, Bryce A.; Rheault, Michelle N.

doi:10.1007/s00467-018-4072-6

Cited by 35 publications

(26 citation statements)

References 28 publications

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“…Infection (60%), CVC (40%), and ICU admission (20%) were also seen in most patients. Our study showed a higher percentage (83.33%) of nephrotic patients with VTE, considering a recent cohort study of 370 children with nephrotic syndrome admitted to 17 pediatric hospitals across North America from 2010 to 2012, where only 11 (3%) of patients developed VTE [28].…”

Section: Plos Onesupporting

confidence: 46%

“…The nonselective proteinuria results in hemostatic abnormalities mainly due to loss of anticoagulant and fibrinolytic proteins (such as antithrombin III, plasminogen, protein S, and plasmin) and increase of prothrombotic substances (factor V, VIII, alpha-2 macroglobulin, thromboxane A2, and fibrinogen) produced by the liver to balance the loss of anticoagulant elements contributing to a procoaguable state [ 27 ]. Other reported risk factors for venous thromboembolism (VTE) in this population include infection, CVCs, diuretics, and intravascular volume depletion [ 28 ]. In our study, 5 of 6 (83.33%) patients with nephrotic syndrome developed VTE.…”

Section: Resultsmentioning

confidence: 99%

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Risk factors for the development of hospital-acquired pediatric venous thromboembolism—Dealing with potentially causal and confounding risk factors using a directed acyclic graph (DAG) analysis

et al. 2020

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Introduction Hospital-acquired venous thromboembolism (HA-VTE) in children comprises multiple risk factors that should not be evaluated separately due to collinearity and multiple cause and effect relationships. This is one of the first case-control study of pediatric HA-VTE risk factors using a Directed Acyclic Graph (DAG) analysis. Material and methods Retrospective, case-control study with 22 cases of objectively confirmed HA-VTE and 76 controls matched by age, sex, unit of admission, and period of hospitalization. Descriptive statistics were used to define distributions of continuous variables, frequencies, and proportions of categorical variables, comparing cases and controls. Due to many potential risk factors of HA-VTE, a directed acyclic graph (DAG) model was created to identify confounding, reduce bias, and increase precision on the analysis. The final model consisted of a DAG-informed conditional logistic regression. Results In the initial conventional univariable model, the following variables were selected as potential risk factors for HA-VTE: length of stay (LOS, days), immobility, ICU admission in the last 30 days, LOS in ICU, infection, central venous catheter (CVC), number of CVCs placed, L-asparaginase, heart failure, liver failure, and nephrotic syndrome. The final model using the set of variables selected by DAG analysis revealed LOS (OR = 1.106, 95%CI = 1.021–1.198, p = 0.013), L-asparaginase (OR = 26.463, 95%CI = 1.609–435.342, p = 0.022), and nephrotic syndrome (OR = 29.127, 95%CI = 1.044–812.508, p = 0.004) as independent risk factors for HA-VTE. Conclusion The DAG-based approach was useful to clarify the influence of confounders and multiple causalities of HA-VTE. Interestingly, CVC placement—a known thrombotic risk factor highlighted in several studies—was considered a confounder, while LOS, L-asparaginase use and nephrotic syndrome were confirmed as risk factors to HA-VTE. Large confidence intervals are related to the sample size; however, the results were significant.

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Section: Plos Onesupporting

confidence: 46%

Section: Resultsmentioning

confidence: 99%

Risk factors for the development of hospital-acquired pediatric venous thromboembolism—Dealing with potentially causal and confounding risk factors using a directed acyclic graph (DAG) analysis

et al. 2020

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“…A 3% incidence of thromboembolic events has been reported in children with NS (summarized in [158][159][160]. Risk factors include disease-related hypercoagulability, underlying thrombophilic predisposition, infections [161], and treatment, e.g., central venous lines.…”

Section: Evidence and Rationalementioning

confidence: 99%

IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome

et al. 2020

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Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.

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“…Using these criteria, the majority of our patients were found exhibit a considerable risk of developing premature vascular disease. Hyperlipidemia is also involved in the pathogenesis of various acute complications in NS [23,24].…”

Section: Discussionmentioning

confidence: 99%

Markedly Increased Small Dense Low-Density Lipoprotein During Acute Phase in Childhood and Adolescent Nephrotic Syndrome

Sugimoto¹,

Miyazaki²,

Enya³

et al. 2020

Preprint

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Background: Hyperlipidemia is an important characteristic feature of idiopathic nephrotic syndrome (NS) in children. This study was conducted to examine the lipid profiles, including small dense low-density lipoprotein (sdLDL-C), in childhood-onset NS.Methods: This retrospective study enrolled patients diagnosed with initial-onset NS in childhood and adolescence. Study parameters included lipid profiles. The “alternative LDL window” comprises the number and sizes of LDL particles estimated according to non-HDL-C and TG levels.Results: A total of 39 patients were enrolled who exhibited markedly increased lipid abnormalities, including TC, TG, LDL-C, and non-HDL-C levels (TC, 409.7 TC, TG, and sizes of LDL particles estimated as non-HDL-C, 332.3). Of the 39 patients, 32 (82%) were categorized in the area of hyper-TG/-non-HDL levels, which is considered as sdLDL. A positive correlation was found between non-HDL-C and TC (r = 0.96, P < 0.001), TG (r = 0.38, P = 0.018), LDL-C (r = 0.84, P < 0.001), TC/HDL (r = 0.53, P < 0.001), and atherogenic index of plasma (r = 0.42, P = 0.008).Conclusions: Our study demonstrated markedly increased lipid profiles during the acute phase of NS. Evaluation of lipid profiles using the “alternative LDL window” may help understand the state of hyperlipidemia in NS.

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Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome

Abstract: Hospitalized children with NS have high rates of infection. Presence of VTE was associated with infection. Both were associated with longer hospitalizations and ICU stays.

Cited by 35 publications

References 28 publications

Risk factors for the development of hospital-acquired pediatric venous thromboembolism—Dealing with potentially causal and confounding risk factors using a directed acyclic graph (DAG) analysis

Risk factors for the development of hospital-acquired pediatric venous thromboembolism—Dealing with potentially causal and confounding risk factors using a directed acyclic graph (DAG) analysis

IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome

Markedly Increased Small Dense Low-Density Lipoprotein During Acute Phase in Childhood and Adolescent Nephrotic Syndrome

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