Guanhua Chen

Disparities in Electronic Health Record Patient Portal Use in Nephrology Clinics

BACKGROUND AND OBJECTIVESnElectronic health record (EHR) patient portals allow individuals to access their medical information with the intent of patient empowerment. However, little is known about portal use in nephrology patients. We addressed this gap by characterizing adoption of an EHR portal, assessing secular trends, and examining the association of portal adoption and BP control (<140/90 mmHg).nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnPatients seen between January 1, 2010, and December 31, 2012, at any of four university-affiliated nephrology offices who had at least one additional nephrology follow-up visit before June 30, 2013, were included. Sociodemographic characteristics, comorbidities, clinical measurements, and office visits were abstracted from the EHR. Neighborhood median household income was obtained from the American Community Survey 2012.nnnRESULTSnOf 2803 patients, 1098 (39%) accessed the portal. Over 87% of users reviewed laboratory results, 85% reviewed their medical information (e.g., medical history), 85% reviewed or altered appointments, 77% reviewed medications, 65% requested medication refills, and 31% requested medical advice from their renal provider. In adjusted models, older age, African-American race (odds ratio [OR], 0.50; 95% confidence interval [95% CI], 0.39 to 0.64), Medicaid status (OR, 0.53; 95% CI, 0.36 to 0.77), and lower neighborhood median household income were associated with not accessing the portal. Portal adoption increased over time (2011 versus 2010: OR, 1.38 [95% CI, 1.09 to 1.75]; 2012 versus 2010: OR, 1.95 [95% CI, 1.44 to 2.64]). Portal adoption was correlated with BP control in patients with a diagnosis of hypertension; however, in the fully adjusted model this was somewhat attenuated and no longer statistically significant (OR, 1.11; 95% CI, 0.99 to 1.24).nnnCONCLUSIONnWhile portal adoption appears to be increasing, greater attention is needed to understand why vulnerable populations do not access it. Future research should examine barriers to the use of e-health technologies in underserved patients with CKD, interventions to address them, and their potential to improve outcomes.

Fibroblast growth factor 23 levels are elevated and associated with severe acute kidney injury and death following cardiac surgery

Fibroblast growth factor 23 (FGF23) is elevated in chronic kidney disease and associated with increased mortality, but data on FGF23 in humans with acute kidney injury (AKI) are limited. Here we tested whether FGF23 levels rise early in the course of AKI following cardiac surgery and if higher postoperative FGF23 levels are independently associated with severe AKI and adverse outcomes. Plasma C-terminal FGF23 (cFGF23) levels were measured preoperatively, at the end of cardiopulmonary bypass, and on postoperative days 1 and 3 in 250 patients undergoing cardiac surgery. We also measured intact FGF23, parathyroid hormone, phosphate, and vitamin D metabolites in a subgroup of 18 patients with severe AKI and 18 matched non-AKI controls. Beginning at the end of cardiopulmonary bypass, cFGF23 levels were significantly and consistently higher in patients who developed AKI compared with those who did not. The early increase in cFGF23 predated changes in other mineral metabolites. The levels of intact FGF23 also increased in patients who developed severe AKI, but the magnitude wasxa0lower than cFGF23. In analyses adjusted for age, preoperative eGFR, and cardiopulmonary bypass time, higher cFGF23 levels at the end of cardiopulmonary bypass were significantly associated with greater risk of severe AKI and the need for renal replacement therapy or death. Thus, cFGF23 levels rise early in AKI following cardiac surgery and are independently associated with adverse postoperative outcomes.

Acute kidney injury is a risk factor for subsequent proteinuria

Acute kidney injury (AKI) is associated with subsequent chronic kidney disease (CKD), but the mechanism is unclear. To clarify this, we examined the association of AKI and new-onset or worsening proteinuria during the 12 months following hospitalization in a national retrospective cohort of United States Veterans hospitalized between 2004-2012. Patients with and without AKI were matched using baseline demographics, comorbidities, proteinuria, estimated glomerular filtration rate, blood pressure, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACEI/ARB) use, and inpatient exposures linked to AKI. The distribution of proteinuria over one year post-discharge in the matched cohort was compared using inverse probability sampling weights. Subgroup analyses were based on diabetes, pre-admission ACEI/ARB use, and AKI severity. Among the 90,614 matched AKI and non-AKI pairs, the median estimated glomerular filtration rate was 62 mL/min/1.73m2. The prevalence of diabetes and hypertension were 48% and 78%, respectively. The odds of having one plus or greater dipstick proteinuria was significantly higher during each month of follow-up in patients with AKI than in patients without AKI (odds ratio range 1.20-1.39). Odds were higher in patients with Stage II or III AKI (odds ratios 1.32-1.81) than in Stage I AKI (odds ratios 1.18-1.32), using non-AKI as the reference group. Results were consistent regardless of diabetes status or baseline ACEI/ARB use. Thus, AKI is a risk factor for incident or worsening proteinuria, suggesting a possible mechanism linking AKI and future CKD. The type of proteinuria, physiology, and clinical significance warrant further study as a potentially modifiable risk factor in the pathway from AKI to CKD.

Long term evolution of endothelial function during kidney transplantation

BackgroundEndothelial dysfunction is an important precursor to the development of atherosclerosis, and has been suggested to play a role in the increased cardiovascular risk in patients with end stage renal disease. Endothelial function improves rapidly following post kidney transplantation, but the long term change remains unclear. Hypothesizing that endothelial function would remain improved long term post kidney transplantation, we evaluated the longitudinal change of endothelial function, measured by flow-mediated dilation (FMD) of the brachial artery, from months 1 to 24 post transplantation. Given the previously reported association of fibroblast growth factor 23 (FGF-23) with endothelial dysfunction, we also examined changes in the association between FGF-23 levels and the change in FMD following kidney transplantation.MethodsWe performed a prospective cohort study of 149 kidney transplant recipients, measuring endothelial function by FMD at months 1, 12, and 24 post-transplant. FGF-23 levels were measured at months 1 and 24 post-transplant. Linear mixed effects models were used to assess both the unadjusted and adjusted outcomes.ResultsThe cohort (mean age 49u2009±u200913xa0years) was 74xa0% male and 75xa0% white. The median FMD was 6.3xa0% (IQR: 3.4, 10.2), 5.4xa0% (IQR: 3.1, 8.5), and 5.6xa0% (IQR: 3.5, 9.1) at 1, 12, and 24xa0months, respectively. After adjustment for covariates, compared to month 1, no change occurred in FMD at 12xa0months (−0.66xa0%; 95xa0% CI: −1.81xa0%, 0.49xa0%; Pu2009=u20090.262) or 24xa0months (−0.25xa0%; 95%CI: −1.76xa0%, 1.26xa0%; Pu2009=u20090.746). FGF-23 decreased significantly over time (Pu2009=u20090.024), but there was no significant association between FGF-23 and FMD (Pu2009=u20090.799).ConclusionEndothelial function remained stable at 12 and 24xa0months from 1xa0month post-kidney transplant, indicating that the improved endothelial function seen with transplant is maintained up to 2xa0years post transplantation. There was also no significant association between FGF-23 and endothelial function following kidney transplantation.

High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients

BACKGROUND AND OBJECTIVESnProtein energy wasting and systemic inflammation are prevalent in maintenance hemodialysis (MHD) patients. Omega-3 (ω-3) fatty acids have anti-inflammatory properties and have been shown to improve protein homeostasis. We hypothesized that administration of high-dose (2.9 g/d) ω-3 would be associated with decreased muscle protein breakdown in MHD patients with systemic inflammation.nnnDESIGN, SETTING, PARTICIPANTS & MEASUREMENTSnThis is a substudy from a randomized, placebo-controlled study (NCT00655525). Patients were recruited between September 2008 and June 2011. Primary inclusion criteria included signs of chronic inflammation (average C-reactive protein of ≥5 mg/L over three consecutive measurements), lack of active infectious or inflammatory disease, no hospitalization within 1 month prior to the study, and not receiving steroids (>5 mg/d) and/or immunosuppressive agents. The primary outcomes were forearm muscle and whole body protein breakdown and synthesis before and after the intervention. The patients received ω-3 (n=11) versus placebo (n=9) for 12 weeks. Analysis of covariance was used to compare outcome variables at 12 weeks. Models were adjusted for a propensity score that was derived from age, sex, race, baseline high sensitivity C-reactive protein, diabetes mellitus, and fat mass because the groups were not balanced for several characteristics.nnnRESULTSnCompared with placebo, ω-3 supplementation was significantly associated with decreased muscle protein breakdown at 12 weeks (-31, [interquartile range, -98--13] versus 26 [interquartile range, 13-87] µg/100 ml per min; P=0.01), which remained significant after multivariate adjustment (-46, [95% confidence interval, -102 to -1] µg/100 ml per min). ω-3 Supplementation resulted in decreased forearm muscle protein synthesis while the rate in the placebo group increased; however, there is no longer a statistically significant difference in skeletal muscle protein synthesis or in net protein balance after multivariate adjustment. There was no statistically significant effect of ω-3 supplementation on whole body protein synthesis or breakdown.nnnCONCLUSIONSnHigh-dose ω-3 supplementation over 12 weeks in MHD patients with systemic inflammation was associated with attenuation of forearm muscle protein breakdown but did not influence skeletal muscle protein synthesis, skeletal muscle net protein balance or any component of the whole-body protein balance. These results should be interpreted cautiously given the imbalance in the two groups and the short duration of the intervention.

Calibration drift in regression and machine learning models for acute kidney injury

ObjectivenPredictive analytics create opportunities to incorporate personalized risk estimates into clinical decision support. Models must be well calibrated to support decision-making, yet calibration deteriorates over time. This study explored the influence of modeling methods on performance drift and connected observed drift with data shifts in the patient population.nnnMaterials and MethodsnUsing 2003 admissions to Department of Veterans Affairs hospitals nationwide, we developed 7 parallel models for hospital-acquired acute kidney injury using common regression and machine learning methods, validating each over 9 subsequent years.nnnResultsnDiscrimination was maintained for all models. Calibration declined as all models increasingly overpredicted risk. However, the random forest and neural network models maintained calibration across ranges of probability, capturing more admissions than did the regression models. The magnitude of overprediction increased over time for the regression models while remaining stable and small for the machine learning models. Changes in the rate of acute kidney injury were strongly linked to increasing overprediction, while changes in predictor-outcome associations corresponded with diverging patterns of calibration drift across methods.nnnConclusionsnEfficient and effective updating protocols will be essential for maintaining accuracy of, user confidence in, and safety of personalized risk predictions to support decision-making. Model updating protocols should be tailored to account for variations in calibration drift across methods and respond to periods of rapid performance drift rather than be limited to regularly scheduled annual or biannual intervals.

Longitudinal Assessment of Cardiac Morphology and Function Following Kidney Transplantation

Abnormal cardiac morphology is a risk factor for cardiovascular complications in kidney transplant patients. A supraphysiologic level of fibroblast growth factor 23 (FGF‐23) has been associated with myocardial hypertrophy in this patient population. Our aim was to evaluate the change in cardiac morphology and function following kidney transplantation and to evaluate the association between the change in FGF‐23 concentrations and cardiac morphology.

Leucine disposal rate for assessment of amino acid metabolism in maintenance hemodialysis patients

BackgroundProtein energy wasting (PEW) is common in patients undergoing maintenance hemodialysis (MHD) and closely associated with poor outcomes. Insulin resistance and associated alterations in amino acid metabolism are potential pathways leading to PEW. We hypothesized that the measurement of leucine disposal during a hyperinsulinemic- euglycemic-euaminoacidemic clamp (HEAC) procedure would accurately measure the sensitivity to insulin for its actions on concomitant carbohydrate and protein metabolism in MHD patients.MethodsWe examined 35 MHD patients and 17 control subjects with normal kidney function by hyperinsulinemic-euglycemic clamp (HEGC) followed by HEAC clamp procedure to obtain leucine disposal rate (LDR) along with isotope tracer methodology to assess whole body protein turnover.ResultsThe glucose disposal rate (GDR) by HEGC was 5.1u2009±u20092.1xa0mg/kg/min for the MHD patients compared to 6.3u2009±u20093.9xa0mg/kg/min for the controls (pu2009=u20090.38). The LDR during HEAC was 0.09u2009±u20090.03xa0mg/kg/min for the MHD patients compared to 0.11u2009±u20090.05xa0mg/kg/min for the controls (pu2009=u20090.009). The LDR level was correlated with whole body protein synthesis (ru2009=u20090.25; pu2009=u20090.08), with whole body protein breakdown (ru2009=u2009−0.38 pu2009=u20090.01) and net protein balance (ru2009=u20090.85; pu2009<u20090.001) in the overall study population. Correlations remained significant in subgroup analysis. The GDR derived by HEGC and LDR correlated well in the controls (ru2009=u20090.79, pu2009<u20090.001), but less so in the MHD patients (ru2009=u20090.58, pu2009<u20090.001).ConclusionsLeucine disposal rate reliably measures amino acid utilization in MHD patients and controls in response to high dose insulin.