Browsing by Author "Jovanovich, Anna"

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    Acute kidney injury is associated with subsequent infection in neonates after the Norwood procedure: a retrospective chart review
    (SpringerLink, 2018-07) SooHoo, Megan; Griffin, Benjamin; Jovanovich, Anna; Soranno, Danielle E.; Mack, Emily; Patel, Sonali S.; Faubel, Sarah; Gist, Katja M.; Pediatrics, School of Medicine
    Background: Acute kidney injury (AKI) and infection are common complications after pediatric cardiac surgery. No pediatric study has evaluated for an association between postoperative AKI and infection. The objective of this study was to determine if AKI in neonates after cardiopulmonary bypass was associated with the development of a postoperative infection. Methods: We performed a single center retrospective chart review from January 2009 to December 2015 of neonates (age ≤ 30 days) undergoing the Norwood procedure. AKI was defined by the modified neonatal Kidney Disease Improving Global outcomes serum creatinine criteria using (1) measured serum creatinine and (2) creatinine corrected for fluid balance on postoperative days 1-4. Infection, (culture positive or presumed), must have occurred after a diagnosis of AKI and within 60 days of surgery. Results: Ninety-five patients were included, of which postoperative infection occurred in 42 (44%). AKI occurred in 38 (40%) and 42 (44%) patients by measured serum creatinine and fluid overload corrected creatinine, respectively, and was most commonly diagnosed on postoperative day 2. The median time to infection from the time of surgery and AKI was 7 days (IQR 5-14 days) and 6 days (IQR 3-13 days), respectively. After adjusting for confounders, the odds of a postoperative infection were 3.64 times greater in patients with fluid corrected AKI (95% CI, 1.36-9.75; p = 0.01). Conclusions: Fluid corrected AKI was independently associated with the development of a postoperative infection. These findings support the notion that AKI is an immunosuppressed state that increases the risk of infection.
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    Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD
    (Wolters Kluwer, 2022) Nowak, Kristen L.; Farmer-Bailey, Heather; Wang, Wei; You, Zhiying; Steele, Cortney; Cadnapaphornchai, Melissa A.; Klawitter, Jelena; Patel, Nayana; George, Diana; Jovanovich, Anna; Soranno, Danielle E.; Gitomer, Berenice; Chonchol, Michel; Pediatrics, School of Medicine
    Background and objectives: Clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD), including evidence of vascular dysfunction, can begin in childhood. Curcumin is a polyphenol found in turmeric that reduces vascular dysfunction in rodent models and humans without ADPKD. It also slows kidney cystic progression in a murine model of ADPKD. We hypothesized that oral curcumin therapy would reduce vascular endothelial dysfunction and arterial stiffness in children/young adults with ADPKD. Design, setting, participants, & measurements: In a randomized, placebo-controlled, double-blind trial, 68 children/young adults 6-25 years of age with ADPKD and eGFR>80 ml/min per 1.73 m2 were randomized to either curcumin supplementation (25 mg/kg body weight per day) or placebo administered in powder form for 12 months. The coprimary outcomes were brachial artery flow-mediated dilation and aortic pulse-wave velocity. We also assessed change in circulating/urine biomarkers of oxidative stress/inflammation and kidney growth (height-adjusted total kidney volume) by magnetic resonance imaging. In a subgroup of participants ≥18 years, vascular oxidative stress was measured as the change in brachial artery flow-mediated dilation following an acute infusion of ascorbic acid. Results: Enrolled participants were 18±5 (mean ± SD) years, 54% were girls, baseline brachial artery flow-mediated dilation was 9.3±4.1% change, and baseline aortic pulse-wave velocity was 512±94 cm/s. Fifty-seven participants completed the trial. Neither coprimary end point changed with curcumin (estimated change [95% confidence interval] for brachial artery flow-mediated dilation [percentage change]: curcumin: 1.14; 95% confidence interval, -0.84 to 3.13; placebo: 0.33; 95% confidence interval, -1.34 to 2.00; estimated difference for change: 0.81; 95% confidence interval, -1.21 to 2.84; P=0.48; aortic pulse-wave velocity [centimeters per second]: curcumin: 0.6; 95% confidence interval, -25.7 to 26.9; placebo: 6.5; 95% confidence interval, -20.4 to 33.5; estimated difference for change: -5.9; 95% confidence interval, -35.8 to 24.0; P=0.67; intent to treat). There was no curcumin-specific reduction in vascular oxidative stress or changes in mechanistic biomarkers. Height-adjusted total kidney volume also did not change as compared with placebo. Conclusions: Curcumin supplementation does not improve vascular function or slow kidney growth in children/young adults with ADPKD.
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    Curcumin therapy to treat vascular dysfunction in children and young adults with autosomal dominant polycystic kidney disease: Design and baseline characteristics of participants
    (Elsevier, 2020-08-12) Nowak, Kristen L.; Farmer-Bailey, Heather; Cadnapaphornchai, Melissa A.; You, Zhiying; George, Diana; Wang, Wei; Jovanovich, Anna; Soranno, Danielle E.; Gitomer, Berenice; Chonchol, Michel; Pediatrics, School of Medicine
    Although often considered to be a disease of adults, complications of autosomal dominant polycystic kidney disease (ADPKD) begin in childhood. While the hallmark of ADPKD is the development and continued growth of multiple renal cysts that ultimately result in loss of kidney function, cardiovascular complications are the leading cause of death among affected patients. Vascular dysfunction (endothelial dysfunction and large elastic artery stiffness) is evident very early in the course of the disease and appears to involve increased oxidative stress and inflammation. Treatment options to prevent cardiovascular disease in adults with ADPKD are limited, thus childhood may represent a key therapeutic window. Curcumin is a safe, naturally occurring polyphenol found in the Indian spice turmeric. This spice has a unique ability to activate transcription of key antioxidants, suppress inflammation, and reduce proliferation. Here we describe our ongoing randomized, placebo-controlled, double-blind clinical trial to assess the effect of curcumin therapy on vascular function and kidney growth in 68 children and young adults age 6–25 years with ADPKD. Baseline demographic, vascular, and kidney volume data are provided. This study has the potential to establish a novel, safe, and facile therapy for the treatment of arterial dysfunction, and possibly renal cystic disease, in an understudied population of children and young adults with ADPKD.
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    Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice
    (Elsevier, 2019-03) Fox, Benjamin M.; Gil, Hyo-Wook; Kirkbride-Romeo, Lara; Bagchi, Rushita A.; Wennersten, Sara A.; Haefner, Korey R.; Skrypnyk, Nataliya I.; Brown, Carolyn N.; Soranno, Danielle E.; Gist, Katja M.; Griffin, Benjamin R.; Jovanovich, Anna; Reisz, Julie A.; Wither, Matthew J.; D'Alessandro, Angelo; Edelstein, Charles L.; Clendenen, Nathan; McKinsey, Timothy A.; Altmann, Christopher; Pediatrics, School of Medicine
    Acute kidney injury (AKI) is a systemic disease associated with widespread effects on distant organs, including the heart. Normal cardiac function is dependent on constant ATP generation, and the preferred method of energy production is via oxidative phosphorylation. Following direct ischemic cardiac injury, the cardiac metabolome is characterized by inadequate oxidative phosphorylation, increased oxidative stress, and increased alternate energy utilization. We assessed the impact of ischemic AKI on the metabolomics profile in the heart. Ischemic AKI was induced by 22 minutes of renal pedicle clamping, and 124 metabolites were measured in the heart at 4 hours, 24 hours, and 7 days post-procedure. 41% of measured metabolites were affected, with the most prominent changes observed 24 hours post-AKI. The post-AKI cardiac metabolome was characterized by amino acid depletion, increased oxidative stress, and evidence of alternative energy production, including a shift to anaerobic forms of energy production. These metabolomic effects were associated with significant cardiac ATP depletion and with echocardiographic evidence of diastolic dysfunction. In the kidney, metabolomics analysis revealed shifts suggestive of energy depletion and oxidative stress, which were reflected systemically in the plasma. This is the first study to examine the cardiac metabolome after AKI, and demonstrates that effects of ischemic AKI on the heart are akin to the effects of direct ischemic cardiac injury.