Browsing by Subject "Creatinine"

Now showing 1 - 9 of 9
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    Acute kidney injury in Ugandan children with severe malaria is associated with long-term behavioral problems
    (Public Library of Science, 2019-12-17) Hickson, Meredith R.; Conroy, Andrea L.; Bangirana, Paul; Opoka, Robert O.; Idro, Richard; Ssenkusu, John M.; John, Chandy C.; Pediatrics, School of Medicine
    Background Acute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown. Methods We conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity. Results AKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children <6 years of age. Conclusions AKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.
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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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    Atlas-based GABA-mapping with 3D MEGA-MRSI: Cross-correlation to single voxel MRS
    (Wiley, 2021) Ma, Ruoyun E.; Murdoch, James B.; Bogner, Wolfgang; Andronesi, Ovidiu; Dydak, Ulrike; Radiology and Imaging Sciences, School of Medicine
    The purpose of this work is to develop and validate a new atlas-based metabolite quantification pipeline for edited magnetic resonance spectroscopic imaging (MEGA-MRSI) that enables group comparisons of brain structure-specific GABA levels. By using brain structure masks segmented from high-resolution MPRAGE images and coregistering these to MEGA-LASER 3D MRSI data, an automated regional quantification of neurochemical levels is demonstrated for the example of the thalamus. Thalamic gamma-aminobutyric acid + coedited macromolecules (GABA+) levels from 21 healthy subjects scanned at 3 T were cross-validated both against a single-voxel MEGA-PRESS acquisition in the same subjects and same scan sessions, as well as alternative MRSI processing techniques (ROI approach, four-voxel approach) using Pearson correlation analysis. In addition, reproducibility was compared across the MRSI processing techniques in test-retest data from 14 subjects. The atlas-based approach showed a significant correlation with SV MEGA-PRESS (correlation coefficient r [GABA+] = 0.63, P < 0.0001). However, the actual values for GABA+, NAA, tCr, GABA+/tCr and tNAA/tCr obtained from the atlas-based approach showed an offset to SV MEGA-PRESS levels, likely due to the fact that on average the thalamus mask used for the atlas-based approach only occupied 30% of the SVS volume, ie, somewhat different anatomies were sampled. Furthermore, the new atlas-based approach showed highly reproducible GABA+/tCr values with a low median coefficient of variance of 6.3%. In conclusion, the atlas-based metabolite quantification approach enables a more brain structure-specific comparison of GABA+ and other neurochemical levels across populations, even when using an MRSI technique with only cm-level resolution. This approach was successfully cross-validated against the typically used SVS technique as well as other different MRSI analysis methods, indicating the robustness of this quantification approach.
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    Development and external validation of a diagnostic model for biopsy-proven acute interstitial nephritis using electronic health record data
    (Oxford University Press, 2022) Moledina, Dennis G.; Eadon, Michael T.; Calderon, Frida; Yamamoto, Yu; Shaw, Melissa; Perazella, Mark A.; Simonov, Michael; Luciano, Randy; Schwantes-An, Tae-Hwi; Moeckel, Gilbert; Kashgarian, Michael; Kuperman, Michael; Obeid, Wassim; Cantley, Lloyd G.; Parikh, Chirag R.; Wilson, F. Perry; Medicine, School of Medicine
    Background: Patients with acute interstitial nephritis (AIN) can present without typical clinical features, leading to a delay in diagnosis and treatment. We therefore developed and validated a diagnostic model to identify patients at risk of AIN using variables from the electronic health record. Methods: In patients who underwent a kidney biopsy at Yale University between 2013 and 2018, we tested the association of >150 variables with AIN, including demographics, comorbidities, vital signs and laboratory tests (training set 70%). We used least absolute shrinkage and selection operator methodology to select prebiopsy features associated with AIN. We performed area under the receiver operating characteristics curve (AUC) analysis with internal (held-out test set 30%) and external validation (Biopsy Biobank Cohort of Indiana). We tested the change in model performance after the addition of urine biomarkers in the Yale AIN study. Results: We included 393 patients (AIN 22%) in the training set, 158 patients (AIN 27%) in the test set, 1118 patients (AIN 11%) in the validation set and 265 patients (AIN 11%) in the Yale AIN study. Variables in the selected model included serum creatinine {adjusted odds ratio [aOR] 2.31 [95% confidence interval (CI) 1.42-3.76]}, blood urea nitrogen:creatinine ratio [aOR 0.40 (95% CI 0.20-0.78)] and urine dipstick specific gravity [aOR 0.95 (95% CI 0.91-0.99)] and protein [aOR 0.39 (95% CI 0.23-0.68)]. This model showed an AUC of 0.73 (95% CI 0.64-0.81) in the test set, which was similar to the AUC in the external validation cohort [0.74 (95% CI 0.69-0.79)]. The AUC improved to 0.84 (95% CI 0.76-0.91) upon the addition of urine interleukin-9 and tumor necrosis factor-α. Conclusions: We developed and validated a statistical model that showed a modest AUC for AIN diagnosis, which improved upon the addition of urine biomarkers. Future studies could evaluate this model and biomarkers to identify unrecognized cases of AIN.
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    Estimation of glomerular filtration rate for drug dosing in patients with very high or low body mass index
    (Wiley, 2022) Donker, Erik M.; Bet, Pierre; Nurmohamed, Azam; Serné, Erik; Burchell, George Louis; Friedman, Allon N.; Bouquegneau, Antoine; Lemoine, Sandrine; Ebert, Natalie; Cirillo, Massimo; van Agtmael, Michiel A.; Bartelink, Imke H.; Medicine, School of Medicine
    An accurate estimated glomerular filtration rate (eGFR) is essential in drug dosing. This study demonstrates the limitations of indexed (ml/min/1.73 m2 ) and de-indexed (ml/min) eGFR based drug dosing in patients with obesity or underweight. This systematic study aimed to determine the most appropriate approach to estimate the GFR for standardized eGFR based drug dosing in these patients. (Raw) data of 12 studies were selected to investigate the accuracy and bias of both the indexed and de-indexed estimations of the Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), and of the Cockcroft-Gault (CG) in patients with obesity or underweight. Accuracy was calculated as the proportion of eGFR values within 30% of the measured GFR (P30) using an inert tracer (e.g., iohexol, inulin, 51 Cr-EDTA, or iothalamate clearance). An accuracy of at least 80% was considered acceptable. GFR values estimated with the CG, MDRD, and CKD-EPI differ significantly within a patient with obesity or underweight regardless of whether it is indexed or de-indexed. All studies, with two exceptions, show that all three equations are inaccurate for patients with underweight or class II obesity (P30: 55%-94%). De-indexing eGFR improves not or modestly the accuracy, and mostly remains below the 80% (P30: 62%-100%). CG was highly inaccurate in obese and underweight patients (P30: 7%-82%). Although these results show that CG is obsolete, the accuracy of MDRD and CKD-EPI is low in patients with obesity or underweight and de-indexing is not the solution. Better education and more accurate methods for appropriate drug dosing (e.g., measured GFR with inert tracer, therapeutic drug monitoring, or 24-h creatinine clearance) are recommended.
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    Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges
    (Dovepress, 2021-07-08) Batte, Anthony; Berrens, Zachary; Murphy, Kristin; Mufumba, Ivan; Sarangam, Maithri L.; Hawkes, Michael T.; Conroy, Andrea L.; Pediatrics, School of Medicine
    Acute kidney injury (AKI) is emerging as a complication of increasing clinical importance associated with substantial morbidity and mortality in African children with severe malaria. Using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI, an estimated 24-59% of African children with severe malaria have AKI with most AKI community-acquired. AKI is a risk factor for mortality in pediatric severe malaria with a stepwise increase in mortality across AKI stages. AKI is also a risk factor for post-discharge mortality and is associated with increased long-term risk of neurocognitive impairment and behavioral problems in survivors. Following injury, the kidney undergoes a process of recovery and repair. AKI is an established risk factor for chronic kidney disease and hypertension in survivors and is associated with an increased risk of chronic kidney disease in severe malaria survivors. The magnitude of the risk and contribution of malaria-associated AKI to chronic kidney disease in malaria-endemic areas remains undetermined. Pathways associated with AKI pathogenesis in the context of pediatric severe malaria are not well understood, but there is emerging evidence that immune activation, endothelial dysfunction, and hemolysis-mediated oxidative stress all directly contribute to kidney injury. In this review, we outline the KDIGO bundle of care and highlight how this could be applied in the context of severe malaria to improve kidney perfusion, reduce AKI progression, and improve survival. With increased recognition that AKI in severe malaria is associated with substantial post-discharge morbidity and long-term risk of chronic kidney disease, there is a need to increase AKI recognition through enhanced access to creatinine-based and next-generation biomarker diagnostics. Long-term studies to assess severe malaria-associated AKI's impact on long-term health in malaria-endemic areas are urgently needed.
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    Should we CLICK on chlorthalidone for treatment-resistant hypertension in chronic kidney disease?
    (Oxford University Press, 2022-12-20) Agarwal, Rajiv; Medicine, School of Medicine
    Treatment-resistant hypertension is common among patients with advanced chronic kidney disease (CKD). In people with preserved kidney function, spironolactone is an evidence-based treatment. However, the risk for hyperkalemia limits its use in people with more advanced CKD. In the Chlorthalidone in Chronic Kidney Disease (CLICK) trial, 160 patients with stage 4 CKD and poorly controlled hypertension as confirmed by 24-hour ambulatory blood pressure (ABP) monitoring were randomly assigned to either placebo or chlorthalidone 12.5 mg daily in a 1:1 ratio stratified by prior loop diuretic use. The primary endpoint was the change in 24-hour systolic ABP from baseline to 12 weeks. The trial showed a treatment-induced reduction of 24-hour systolic ABP by 10.5 mmHg. Of the 160 patients randomized, 113 (71%) had resistant hypertension, of which 90 (80%) were on loop diuretics and the mean number of antihypertensive medications prescribed was 4.1 (standard deviation 1.1). In this subgroup of patients with treatment-resistant hypertension, the adjusted change from baseline to 12 weeks in the between-group difference in 24-hour systolic ABP was -13.9 mmHg (95% CI -19.4 to -8.4; P < .0001). Furthermore, compared with placebo, the urine albumin:creatinine ratio in the chlorthalidone group at 12 weeks was 54% lower (95% CI -65 to -40). Following randomization, hypokalemia, reversible increases in serum creatinine, hyperglycemia, dizziness, orthostatic hypotension and hyperuricemia occurred more frequently in the chlorthalidone group. Chlorthalidone has the potential to improve BP control among patients with advanced CKD and treatment-resistant hypertension. However, caution is advised when treating patients, especially when they are on loop diuretics.
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    Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study
    (American Society of Nephrology, 2018-07-06) Stremke, Elizabeth R.; McCabe, Linda D.; McCabe, George P.; Martin, Berdine R.; Moe, Sharon M.; Weaver, Connie M.; Peacock, Munro; Hill Gallant, Kathleen M.; Department of Medicine, IU School of Medicine
    BACKGROUND AND OBJECTIVES: Twenty-four-hour urine phosphorus is commonly used as a surrogate measure for phosphorus intake and absorption in research studies, but its reliability and accuracy are unproven in health or CKD. This secondary analysis sought to determine the reliability and accuracy of 24-hour urine phosphorus as a biomarker of phosphorus intake and absorption in moderate CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eight patients with stage 3-4 CKD participated in 2-week balance studies with tightly controlled phosphorus and calcium intakes. Thirteen 24-hour urine collections per patient were analyzed for variability and reliability of 24-hour urine phosphorus and phosphorus-to-creatinine ratio. The accuracy of 24-hour urine phosphorus to predict phosphorus intake was determined using a published equation. The relationships of 24-hour urine phosphorus with phosphorus intake, net absorption, and retention were determined. RESULTS: There was wide day-to-day variation in 24-hour urine phosphorus within and among subjects (coefficient of variation of 30% and 37%, respectively). Two 24-hour urine measures were needed to achieve ≥75% reliability. Estimating dietary phosphorus intake from a single 24-hour urine resulted in underestimation up to 98% in some patients and overestimation up to 79% in others. Twenty-four-hour urine phosphorus negatively correlated with whole-body retention but was not related to net absorption. CONCLUSIONS: From a sample of eight patients with moderate CKD on a tightly controlled dietary intake, 24-hour urine phosphorus was highly variable and did not relate to dietary phosphorus intake or absorption, rather it inversely related to phosphorus retention.