Browsing by Author "Flynn, Joseph T."

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    Blood pressure in children with chronic kidney disease: Lessons learned from the Chronic Kidney Disease in Children Cohort Study
    (SpringerLink, 2020-07) Wilson, Amy C.; Flynn, Joseph T.; Pediatrics, School of Medicine
    Cardiovascular disease (CVD) is common amongst children and adolescents with chronic kidney disease (CKD) and end-stage kidney disease (ESRD). However, the early accrual of CVD risk factors in children with CKD has not been well studied. The Chronic Kidney Disease in Children (CKiD) Study, a multicenter, prospective cohort study of children with mild-to-moderate CKD at study entry counts among its primary aims investigation of the drivers of CVD risk in this population. As the most prevalent CVD risk factor in children with CKD, blood pressure (BP) has been a major focus of investigation for the CKiD Study Group. Over the first 15 years of the study, landmark publications have better defined the prevalence of hypertension, the frequency with which it is under-recognized and thus undertreated, and the consequences of elevated BP in this cohort. The purpose of this review is to summarize the contributions made by the CKiD Study in advancing knowledge of BP in this high-risk population, and to highlight areas in need of further study.
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    Blood Pressure Outcomes in NICU-Admitted Infants with Neonatal Hypertension: A Pediatric Nephrology Research Consortium Study
    (Elsevier, 2024) Xiao, Nianzhou; Starr, Michelle; Stolfi, Adrienne; Hamdani, Gilad; Hashmat, Shireen; Kiessling, Stefan G.; Sethna, Christina; Kallash, Mahmoud; Matloff, Robyn; Woroniecki, Robert; Sanderson, Keia; Yamaguchi, Ikuyo; Cha, Stephen D.; Semanik, Michael G.; Chanchlani, Rahul; Flynn, Joseph T.; Mitsnefes, Mark; Pediatrics, School of Medicine
    Objective: To describe the blood pressure outcomes of infants admitted to the neonatal intensive care unit (NICU) with idiopathic (nonsecondary) hypertension (HTN) who were discharged on antihypertensive therapy. Study design: Retrospective, multicenter study of 14 centers within the Pediatric Nephrology Research Consortium. We included all infants with a diagnosis of idiopathic HTN discharged from the NICU on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into (≤6 months, >6 months to 1 year, and >1 year). Comparisons between groups were made with χ2 tests, Fisher's exact tests, and ANOVA. Results: Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy >1 year after discharge. Conclusions: This multicenter study reports that most infants admitted to the NICU diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN, but should be confirmed prospectively.
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    KDOQI US Commentary on the 2017 ACC/AHA Hypertension Guideline
    (Elsevier, 2020-04-01) Kramer, Holly J.; Townsend, Raymond R.; Griffin, Karen; Flynn, Joseph T.; Weiner, Daniel E.; Rocco, Michael V.; Choi, Michael J.; Weir, Matthew R.; Chang, Tara I.; Agarwal, Rajiv; Beddhu, Srinivasan; Medicine, School of Medicine
    Hypertension is a modifiable risk factor for cardiovascular morbidity and mortality and reduction of elevated blood pressure (BP) remains an important intervention for slowing kidney disease progression. Over the past decade, the most appropriate BP target for initiation and titration of BP-lowering medications has been an area of intense research and debate within the clinical community. In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) in conjunction with several other professional societies released new hypertension guidelines based on data from a systematic review of clinical trials and observational data. While many of the recommendations in the ACC/AHA hypertension guideline are relevant to nephrology practice, BP targets and management strategies for patients receiving dialysis are not discussed. This Kidney Disease Outcomes Quality Initiative (KDOQI) commentary focuses largely on recommendations from the ACC/AHA hypertension guidelines that are pertinent to individuals at risk of chronic kidney disease or with non–dialysis-dependent chronic kidney disease. This KDOQI commentary also includes a brief discussion of the consensus statement regarding hypertension diagnosis and management for adults receiving maintenance dialysis published by the European Renal and Cardiovascular Medicine Working Group of the European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension. Overall, we support the vast majority of the ACC/AHA recommendations and highlight select areas in which best diagnosis and treatment options remain controversial.
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    The Preserving Kidney Function in Children With CKD (PRESERVE) Study: Rationale, Design, and Methods
    (Elsevier, 2023-09-14) Denburg, Michelle R.; Razzaghi, Hanieh; Goodwin Davies, Amy J.; Dharnidharka, Vikas; Dixon, Bradley P.; Flynn, Joseph T.; Glenn, Dorey; Gluck, Caroline A.; Harshman, Lyndsay; Jovanovska, Aneta; Pefkaros Katsoufis, Chryso; Kratchman, Amy L.; Levondosky, Mark; Levondosky, Rebecca; McDonald, Jill; Mitsnefes, Mark; Modi, Zubin J.; Musante, Jordan; Neu, Alicia M.; Pan, Cynthia G.; Patel, Hiren P.; Patterson, Larry T.; Schuchard, Julia; Verghese, Priya S.; Wilson, Amy C.; Wong, Cynthia; Forrest, Christopher B.; Pediatrics, School of Medicine
    Rationale & objective: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. Study design: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). Setting & participants: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to <90 mL/min/1.73 m2 separated by ≥90 days without an intervening value ≥90 mL/min/1.73 m2 and no prior dialysis or kidney transplant. Exposures: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class. Outcomes: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of <15 mL/min/1.73 m2, long-term dialysis or kidney transplant. Secondary outcomes include change in eGFR, adverse events, and PROs. Analytical approach: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics. Limitations: Causal inference limited by observational analyses. Conclusions: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients. Plain-language summary: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for >19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management.
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    Using Electronic Health Record Data to Rapidly Identify Children with Glomerular Disease for Clinical Research
    (American Society of Nephrology, 2019-12) Denburg, Michelle R.; Razzaghi, Hanieh; Bailey, L. Charles; Soranno, Danielle E.; Pollack, Ari H.; Dharnidharka, Vikas R.; Mitsnefes, Mark M.; Smoyer, William E.; Somers, Michael J. G.; Zaritsky, Joshua J.; Flynn, Joseph T.; Claes, Donna J.; Dixon, Bradley P.; Benton, Maryjane; Mariani, Laura H.; Forrest, Christopher B.; Furth, Susan L.; Pediatrics, School of Medicine
    Background: The rarity of pediatric glomerular disease makes it difficult to identify sufficient numbers of participants for clinical trials. This leaves limited data to guide improvements in care for these patients. Methods: The authors developed and tested an electronic health record (EHR) algorithm to identify children with glomerular disease. We used EHR data from 231 patients with glomerular disorders at a single center to develop a computerized algorithm comprising diagnosis, kidney biopsy, and transplant procedure codes. The algorithm was tested using PEDSnet, a national network of eight children's hospitals with data on >6.5 million children. Patients with three or more nephrologist encounters (n=55,560) not meeting the computable phenotype definition of glomerular disease were defined as nonglomerular cases. A reviewer blinded to case status used a standardized form to review random samples of cases (n=800) and nonglomerular cases (n=798). Results: The final algorithm consisted of two or more diagnosis codes from a qualifying list or one diagnosis code and a pretransplant biopsy. Performance characteristics among the population with three or more nephrology encounters were sensitivity, 96% (95% CI, 94% to 97%); specificity, 93% (95% CI, 91% to 94%); positive predictive value (PPV), 89% (95% CI, 86% to 91%); negative predictive value, 97% (95% CI, 96% to 98%); and area under the receiver operating characteristics curve, 94% (95% CI, 93% to 95%). Requiring that the sum of nephrotic syndrome diagnosis codes exceed that of glomerulonephritis codes identified children with nephrotic syndrome or biopsy-based minimal change nephropathy, FSGS, or membranous nephropathy, with 94% sensitivity and 92% PPV. The algorithm identified 6657 children with glomerular disease across PEDSnet, ≥50% of whom were seen within 18 months. Conclusions: The authors developed an EHR-based algorithm and demonstrated that it had excellent classification accuracy across PEDSnet. This tool may enable faster identification of cohorts of pediatric patients with glomerular disease for observational or prospective studies.