Dialysis Patient Perspectives on CKD Advocacy: A Semistructured Interview Study.

BACKGROUND: Health advocacy groups provide education, raise public awareness, and engage in legislative, scientific, and regulatory processes to advance funding and treatments for many diseases. Despite a high burden of chronic kidney disease (CKD) in the United States, public awareness and research funding lag behind those for other disease states. We undertook this study of patients receiving maintenance dialysis to describe knowledge and beliefs about CKD advocacy, understand perceptions regarding advocacy participation, and elicit ideas for generating more advocacy in the dialysis community. STUDY DESIGN: Qualitative study. SETTING & PARTICIPANTS: 48 patients (89% response rate) receiving in-center hemodialysis (n=39), home hemodialysis (n=4), and peritoneal dialysis (n=5) from 14 US states. METHODOLOGY: Semistructured interviews. ANALYTICAL APPROACH: Transcripts were thematically analyzed. RESULTS: 5 themes describing patient perspectives on CKD advocacy were identified: (1) advocacy awareness (advocacy vs engagement knowledge, concrete knowledge, CKD publicity), (2) willingness to participate (personal qualities, internal efficacy, external efficacy), (3) motivations (altruism, providing a purpose, advancement of personal health, self-education), (4) resource availability (time, financial and transportation, health status), and (5) mobilization experience (key figure, mobilization network). Participants displayed operational understanding of advocacy but generally lacked knowledge about specific opportunities for participation. Personal qualities and external efficacy were perceived as important for advocacy participation, as were motivating factors such as altruism and self-education. Resources factored heavily into perceived participation ability. Most participants identified a key figure who invited them to participate in advocacy. In-person patient-delivered communication about advocacy opportunities was identified as critical to enhancing CKD advocacy among patients living on dialysis therapy. LIMITATIONS: Potential selection bias and inclusion of only English-speaking participants may limit generalizability. CONCLUSIONS: Overall, our results suggest that there may be untapped advocacy potential within the dialysis community and highlight the need for local in-person patient-led initiatives to increase patient involvement in CKD advocacy.

A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors.

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.

Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia.

Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.

Impact of increasing operative time on the incidence of early failure and complications following free tissue transfer? A risk factor analysis of 2,008 patients from the ACS-NSQIP database.

BACKGROUND: There is a scarcity of externally valid data that investigate the utility of operative time, a common clinical parameter, as a predictor of free flap failures. Our aim was to assess whether prolonged operative time correlates with early flap failure following free tissue transfer in the acute care setting using the American College of Surgeons National Surgical Quality Improvement Program database. METHODS: The 2005-2011 American College of Surgeons National Surgical Quality Improvement Program databases were reviewed for encounters that entailed a free tissue transfer via a CPT algorithm. Patients identified as having a flap loss were compared with people who did not with regards to operative time and patient comorbidities. Patients were subdivided into the following cohort groups with regards to operative time: <6 hours, 6-12 hours, and >12 hours. Secondary outcome was association between increasing operative time and postoperative complications. RESULTS: Of the 2,008 patients identified, 62 (3.1%) had early flap failure. After multivariable analysis, it was found that progressive operative time was associated with an increased risk of flap failure; 6-12 hours odds ratio was 4.64 and >12 hours odds ratio was 5.65 (P = 0.0140). Higher American Society of Anesthesiologists class (P = 0.0042) was also shown to be significantly associated with flap failure. On secondary analysis, increasing operative time was correlated with the following complications: pneumonia, blood transfusions, prolonged ventilation, wound dehiscence, and wound complications. CONCLUSION: Our results, one of the largest series in the literature, revealed that prolonged operative time was associated with a stepwise increase in the likelihood of early flap failure as well certain postoperative complications. © 2014 Wiley Periodicals, Inc. Microsurgery 37:12-20, 2017.

Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis.

BACKGROUND: Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bioaccumulate to precipitate inadvertent bleeding. We wanted to determine whether prescription of dabigatran or rivaroxaban was occurring in the dialysis population and whether these practices were safe. METHODS AND RESULTS: Prevalence plots were used to describe the point prevalence (monthly) of dabigatran and rivaroxaban use among 29977 hemodialysis patients with atrial fibrillation. Poisson regression compared the rate of bleeding, stroke, and arterial embolism in patients who started dabigatran, rivaroxaban, or warfarin. The first record of dabigatran prescription among hemodialysis patients occurred 45 days after the drug became available in the United States. Since then, dabigatran and rivaroxaban use in the atrial fibrillation-end-stage renal disease population has steadily risen where 5.9% of anticoagulated dialysis patients are started on dabigatrian or rivaroxaban. In covariate adjusted Poisson regression, dabigatran (rate ratio, 1.48; 95% confidence interval, 1.21-1.81; P=0.0001) and rivaroxaban (rate ratio, 1.38; 95% confidence interval, 1.03-1.83; P=0.04) associated with a higher risk of hospitalization or death from bleeding when compared with warfarin. The risk of hemorrhagic death was even larger with dabigatran (rate ratio, 1.78; 95% confidence interval, 1.18-2.68; P=0.006) and rivaroxaban (rate ratio, 1.71; 95% confidence interval, 0.94-3.12; P=0.07) relative to warfarin. There were too few events in the study to detect meaningful differences in stroke and arterial embolism between the drug groups. CONCLUSIONS: More dialysis patients are being started on dabigatran and rivaroxaban, even when their use is contraindicated and there are no studies to support that the benefits outweigh the risks of these drugs in end-stage renal disease.

Epidemiology and Mechanisms of De Novo and Persistent Hypertension in the Postpartum Period.

BACKGROUND: The pathophysiology of hypertension in the immediate postpartum period is unclear. METHODS AND RESULTS: We studied 988 consecutive women admitted to a tertiary medical center for cesarean section of a singleton pregnancy. The angiogenic factors soluble fms-like tyrosine kinase 1 and placental growth factor, both biomarkers associated with preeclampsia, were measured on antepartum blood samples. We then performed multivariable analyses to determine factors associated with the risk of developing postpartum hypertension. Of the 988 women, 184 women (18.6%) developed postpartum hypertension. Of the 184 women, 77 developed de novo hypertension in the postpartum period, and the remainder had a hypertensive disorder of pregnancy in the antepartum period. A higher body mass index and history of diabetes mellitus were associated with the development of postpartum hypertension. The antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor positively correlated with blood pressures in the postpartum period (highest postpartum systolic blood pressure [r=0.29, P<0.001] and diastolic blood pressure [r=0.28, P<0.001]). Moreover, the highest tertile of the antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor was independently associated with postpartum hypertension (de novo hypertensive group: odds ratio, 2.25; 95% confidence interval, 1.19-4.25; P=0.01; in the persistent hypertensive group: odds ratio, 2.61; 95% confidence interval, 1.12-6.05; P=0.02) in multivariable analysis. Women developing postpartum hypertension had longer hospitalizations than those who remained normotensive (6.5±3.5 versus 5.7±3.4 days; P<0.001). CONCLUSIONS: Hypertension in the postpartum period is relatively common and is associated with prolonged hospitalization. Women with postpartum hypertension have clinical risk factors and an antepartum plasma angiogenic profile similar to those found in women with preeclampsia. These data suggest that women with postpartum hypertension may represent a group of women with subclinical or unresolved preeclampsia.

Vitamin D-binding protein and vitamin D status of black Americans and white Americans.

BACKGROUND: Low levels of total 25-hydroxyvitamin D are common among black Americans. Vitamin D-binding protein has not been considered in the assessment of vitamin D deficiency. METHODS: In the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort of blacks and whites (2085 participants), we measured levels of total 25-hydroxyvitamin D, vitamin D-binding protein, and parathyroid hormone as well as bone mineral density (BMD). We genotyped study participants for two common polymorphisms in the vitamin D-binding protein gene (rs7041 and rs4588). We estimated levels of bioavailable 25-hydroxyvitamin D in homozygous participants. RESULTS: Mean (±SE) levels of both total 25-hydroxyvitamin D and vitamin D-binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.6±0.2 ng per milliliter vs. 25.8±0.4 ng per milliliter, P<0.001; vitamin D-binding protein, 168±3 µg per milliliter vs. 337±5 µg per milliliter, P<0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D-binding protein and total 25-hydroxyvitamin D, respectively. BMD was higher in blacks than in whites (1.05±0.01 g per square centimeter vs. 0.94±0.01 g per square centimeter, P<0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P<0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxyvitamin D overall (2.9±0.1 ng per milliliter and 3.1±0.1 ng per milliliter, respectively; P=0.71) and within quintiles of parathyroid hormone concentration. CONCLUSIONS: Community-dwelling black Americans, as compared with whites, had low levels of total 25-hydroxyvitamin D and vitamin D-binding protein, resulting in similar concentrations of estimated bioavailable 25-hydroxyvitamin D. Racial differences in the prevalence of common genetic polymorphisms provide a likely explanation for this observation. (Funded by the National Institute on Aging and others.).

Ultrafiltration Rate and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Observational data have demonstrated an association between higher ultrafiltration rates and greater mortality among hemodialysis patients. Prior studies were small and did not consider potential differences in the association across body sizes and other related subgroups. No study has investigated ultrafiltration rates normalized to anthropometric measures beyond body weight. Also, potential methodological shortcomings in prior studies have led to questions about the veracity of the ultrafiltration rate-mortality association. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: 118,394 hemodialysis patients dialyzing in a large dialysis organization, 2008 to 2012. PREDICTORS: Mean 30-day ultrafiltration rates were dichotomized at 13 and 10mL/h/kg, separately and categorized using various cutoff points. Ultrafiltration rates normalized to body weight, body mass index, and body surface area were investigated. OUTCOMES: All-cause mortality. MEASUREMENTS: Multivariable survival models were used to estimate the association between ultrafiltration rate and all-cause mortality. RESULTS: At baseline, 21,735 (18.4%) individuals had ultrafiltration rates > 13mL/h/kg and 48,529 (41.0%) had ultrafiltration rates > 10mL/h/kg. Median follow-up was 2.3 years, and the mortality rate was 15.3 deaths/100 patient-years. Compared with ultrafiltration rates ≤ 13mL/h/kg, ultrafiltration rates > 13mL/h/kg were associated with greater mortality (adjusted HR, 1.31; 95% CI, 1.28-1.34). Compared with ultrafiltration rates ≤ 10mL/h/kg, ultrafiltration rates > 10mL/h/kg were associated with greater mortality (adjusted HR, 1.22; 95% CI, 1.20-1.24). Findings were consistent across subgroups of sex, race, dialysis vintage, session duration, and body size. Higher ultrafiltration rates were associated with greater mortality when normalized to body weight, body mass index, and body surface area. LIMITATIONS: Residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Regardless of the threshold implemented, higher ultrafiltration rate was associated with greater mortality in the overall study population and across key subgroups. Randomized controlled trials are needed to investigate whether ultrafiltration rate reduction improves clinical outcomes.

Changes in Kidney Function After Transjugular Intrahepatic Portosystemic Shunts Versus Large-Volume Paracentesis in Cirrhosis: A Matched Cohort Analysis.

BACKGROUND: Patients with cirrhosis and refractory ascites have physiologic and hormonal dysregulation that contributes to decreased kidney function. Placement of a transjugular intrahepatic portosystemic shunt (TIPS) can reverse these changes and potentially improve kidney function. We sought to evaluate change in estimated glomerular filtration rate (eGFR) following TIPS placement. STUDY DESIGN: Retrospective, matched cohort analysis. SETTINGS & PARTICIPANTS: Patients who underwent first-time TIPS placement for refractory ascites in 1995 to 2014. Frequency matching was used to generate a comparator group of patients with cirrhosis and ascites treated with serial large-volume paracentesis (LVP) in a 1:1 fashion. PREDICTOR: TIPS placement compared to serial LVP. OUTCOME: Change in eGFR over 90 days' follow-up. MEASUREMENTS: Multivariable regression stratified by baseline eGFR<60 versus ≥60mL/min/1.73m(2); analysis of effect modification between TIPS placement and baseline eGFR. RESULTS: 276 participants (TIPS, n=138; serial LVP, n=138) were analyzed. After 90 days, eGFRs increased significantly after TIPS placement in participants with baseline eGFRs<60mL/min/1.73m(2) compared to treatment with serial LVP (21 [95% CI, 13-29] mL/min/1.73m(2); P<0.001) and was no different in those with eGFRs≥60mL/min/1.73m(2) (1 [95% CI, -9 to 12] mL/min/1.73m(2); P=0.8). There was significant effect modification between TIPS status and baseline eGFR (P=0.001) in a model that included all participants. LIMITATIONS: Outcomes restricted by clinically recorded data; clinically important differences may still exist between the TIPS and LVP cohorts despite good statistical matching. CONCLUSIONS: TIPS placement was associated with significant improvement in kidney function. This was most prominent in participants with baseline eGFRs<60mL/min/1.73m(2). Prospective studies of TIPS use in populations with eGFRs<60mL/min/1.73m(2) are needed to evaluate these findings.

Hemodialysis arteriovenous fistula as first option not necessary in elderly patients.

OBJECTIVE: Kidney Disease Outcomes Quality Initiative guidelines recommend arteriovenous fistulas as the preferred access for hemodialysis patients. However, this may not hold across all populations of patients, especially the elderly, given their comorbidities and relatively reduced life expectancy. Therefore, we investigated whether fistulas held benefit over arteriovenous grafts as hemodialysis access in elderly patients. METHODS: We retrospectively searched a vascular access database to compare the outcomes for 138 fistulas and 44 grafts that were placed in elderly patients (≥75 years old) during a 4-year period at a tertiary medical center. RESULTS: The primary failure rate was higher for the fistulas compared with the grafts (odds ratio, 2.89; P = .008), and more fistulas required one or more interventions before their successful use compared with grafts (31% vs 10%, respectively; P = .03). In addition, the time to catheter-free dialysis was longer for fistulas than for grafts (P < .001). However, the primary and secondary patency rates were comparable between the fistulas and grafts and between the different access locations. The all-cause mortality rates were also comparable between the fistula and graft groups. CONCLUSIONS: Despite the Fistula First Initiative recommendations, grafts need not be discounted as a first-line hemodialysis access option in select elderly patients.

Racial Disparities in End-of-Life Communication and Preferences among Chronic Kidney Disease Patients.

BACKGROUND: Previous studies on end-of-life (EOL) care among patients with chronic kidney disease (CKD) have been largely limited to White hemodialysis patients. In this study, we sought to explore racial variability in EOL communication, care preferences and advance care planning (ACP) among patients with advanced CKD prior to decisions regarding the initiation of dialysis. METHODS: We performed a cross-sectional study between 2013 and 2015 of Black and White patients with stage IV or V CKD (per the Modified Diet in Renal Disease estimation of GFR <30 ml/min/1.73 m2) from 2 academic centers in Boston. We assessed experiences with EOL communication, ACP, EOL care preferences, hospice knowledge, spiritual/religious and cultural beliefs, and distrust of providers. RESULTS: Among 152 participants, 41% were Black. Black patients were younger, had less education, and lower income than White patients (all p < 0.01). Black patients also had less knowledge of hospice compared to White patients (17 vs. 61%, p < 0.01). A small fraction of patients (8%) reported having EOL discussions with their nephrologists and the majority had no advance directives. In multivariable analyses, Blacks were more likely to have not communicated EOL preferences (adjusted OR 2.70, 95% CI 1.08-6.76) and more likely to prefer life-extending treatments (adjusted OR 3.06, 95% CI 1.23-7.60) versus Whites. CONCLUSIONS: As Black and White patients with advanced CKD differ in areas of EOL communication, preferences, and hospice knowledge, future efforts should aim to improve patient understanding and promote informed decision-making.

Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study.

BACKGROUND: Whereas several longitudinal metabolomics studies have been conducted in individuals with normal estimated glomerular filtration rate (eGFR) at baseline, disease progression among individuals with established chronic kidney disease (CKD) has not been rigorously examined. METHODS: We performed a nested case-control study of rapid CKD progression in the Chronic Renal Insufficiency Cohort Study, profiling baseline plasma from 200 individuals each with eGFR slope <-3 ml/min/1.73 m2/year (cases) or between -1 and +1 ml/min/1.73 m2/year (controls), matched on baseline eGFR and proteinuria. To directly assess how the kidney modulates circulating metabolites, we profiled plasma from the aorta and renal vein of 25 hospital-based individuals. RESULTS: At baseline, cases and controls had a mean eGFR of 41.7 ± 13.3 and 45.0 ± 14.5 ml/min/1.73 m2, respectively. Ten plasma metabolites were nominally associated with CKD progression in logistic regression models adjusted for age, sex, race/ethnicity, hypertension, systolic and diastolic blood pressure, diabetes, eGFR and proteinuria; no metabolite achieved the Bonferroni-adjusted significance threshold (p < 0.0003). In a cross-sectional analysis, all 6 of the metabolites that were higher in cases than controls were significantly associated with eGFR at baseline. By contrast, threonine, methionine and arginine were lower in cases than in controls and had no association with baseline eGFR. Furthermore, in the hospital-based cohort that underwent renal arteriovenous sampling, these 3 metabolites were net released from the kidney. Combining these metabolites into a panel of markers further strengthened their association with CKD progression. CONCLUSION: Our results motivate interest in arginine, methionine and threonine as potential indicators of renal metabolic function and markers of renal prognosis.

Sequential plasma angiogenic factors levels in women with suspected preeclampsia.

BACKGROUND: Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. OBJECTIVE: Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. STUDY DESIGN: We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. RESULTS: During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th to 75th) soluble fms-like tyrosine kinase/placental growth factor ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P < .001). The median (25th to 75th) absolute change per day in soluble fms-like tyrosine kinase levels (pg/mL) was 491.0 pg/mL (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/mL (-177.9, 449.0) among women without adverse outcomes (P = .01). Similarly the absolute change per day for soluble fms-like tyrosine kinase/placental growth factor ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) between the two groups (P = .004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 and 14 (0-39) below a ratio of 85 (P < .001). The positive predictive value for plasma soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 at admission for indicated delivery within 2 weeks was 91% (83-99%). Admission plasma soluble fms-like tyrosine kinase/placental growth factor ratio positively correlated with pre-delivery uterine artery resistive index (r = 0.35; P = .004). CONCLUSION: Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine kinase/placental growth factor ratios delivered sooner than women with low soluble fms-like tyrosine kinase/placental growth factor levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.

Relationship Between Comorbid Conditions and Utilization Patterns of Immediate Breast Reconstruction Subtypes Post-mastectomy.

There is limited information on the influence of a patient's comorbid status on the type of immediate breast reconstruction (IBR) selected. Our aim was to provide a population-based review of the relationship between baseline comorbid conditions and IBR subtype selected. This is a retrospective cohort study using the National Surgical Quality Improvement Program database to identify IBR recipients. Multivariable regression analyses was performed to identify the association between comorbidity and IBR subtype selection (prosthetic, pedicled, and free autologous). A total of 48,096 mastectomy patients were identified, of which 17,404 patients received IBR. IBR patients were younger (51 ± 10.4 versus 61.5 ± 13.6 years) and had a lower body mass index (27.1 ± 6.4 versus 28.9 ± 7.3) relative to patients who did not pursue IBR (p < 0.001 for all). Overall, IBR patients had a significantly lower incidence of comorbid conditions. In adjusted models, patients aged 45-64 years were more likely to pursue pedicled-autologous reconstruction (OR: 1.43, p < 0.001) and those older than 65 years were less likely to undergo free-autologous reconstruction (OR: 0.64, p = 0.02). Class I and II obesity was associated with pedicled (class I OR: 1.57, class II OR: 1.41) and free transfer (class I OR: 1.81, class II OR: 1.66) autologous IBR utilization (all p < 0.001). Also, smoking was related to increased chance of prosthetic reconstruction while preoperative radiotherapy was linked to free-autologous IBR. IBR patients were noted to be healthier than their non-IBR counterparts, and each IBR subtype was associated with a particular comorbidity profile. This has significant implications with regard to creation of an IBR-predictive model. Such a tool will improve preoperative counseling and decision making.

Metabolomic profiling in the prediction of gestational diabetes mellitus.

AIMS/HYPOTHESIS: Metabolomic profiling in populations with impaired glucose tolerance has revealed that branched chain and aromatic amino acids (BCAAs) are predictive of type 2 diabetes. Because gestational diabetes mellitus (GDM) shares pathophysiological similarities with type 2 diabetes, the metabolite profile predictive of type 2 diabetes could potentially identify women who will develop GDM. METHODS: We conducted a nested case-control study of 18- to 40-year-old women who participated in the Massachusetts General Hospital Obstetrical Maternal Study between 1998 and 2007. Participants were enrolled during their first trimester of a singleton pregnancy and fasting serum samples were collected. The women were followed throughout pregnancy and identified as having GDM or normal glucose tolerance (NGT) in the third trimester. Women with GDM (n = 96) were matched to women with NGT (n = 96) by age, BMI, gravidity and parity. Liquid chromatography-mass spectrometry was used to measure the levels of 91 metabolites. RESULTS: Data analyses revealed the following characteristics (mean ± SD): age 32.8 ± 4.4 years, BMI 28.3 ± 5.6 kg/m(2), gravidity 2 ± 1 and parity 1 ± 1. Six metabolites (anthranilic acid, alanine, glutamate, creatinine, allantoin and serine) were identified as having significantly different levels between the two groups in conditional logistic regression analyses (p < 0.05). The levels of the BCAAs did not differ significantly between GDM and NGT. CONCLUSIONS/INTERPRETATION: Metabolic markers identified as being predictive of type 2 diabetes may not have the same predictive power for GDM. However, further study in a racially/ethnically diverse population-based cohort is necessary.

Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease.

Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb.

24,25-Dihydroxyvitamin d3 and vitamin D status of community-dwelling black and white Americans.

BACKGROUND: 24,25-Dihydroxyvitamin D [24,25(OH)2D] is a metabolite of 25-hydroxyvitamin D (25D). Blacks frequently have low total 25D without manifestations of vitamin D deficiency, suggesting that total serum 25D may incorrectly reflect vitamin D status in different racial groups. The ratio of serum 24,25(OH)2D to 25D [vitamin D metabolite ratio (VMR)] represents a new candidate biomarker for vitamin D status. METHODS: We measured 24,25(OH)2D3 and 25D3 by mass spectrometry in a random community cohort of black (n = 212) and white (n = 164) Americans to evaluate VMR as a marker for vitamin D status. We measured parathyroid hormone concentrations by immunoassay to compare VMR and 25D3 against a physiological indicator of vitamin D deficiency. RESULTS: Serum 24,25(OH)2D3 strongly correlated with 25D3 in both black and white study participants (r = 0.90, P < 0.001 and r = 0.86, P < 0.001 respectively). Blacks had lower mean 25D3 than whites [17.0 (7.8) vs 27.5 (11.3) ng/mL; 42.4 (19.5) vs 68.6 (28.2) nmol/L, P < 0.001] and lower mean 24,25(OH)2D3 [2.1 (1.3) vs 3.6 (2.0) ng/mL; 5.1 (3.1) vs 8.7 (4.8) nmol/L, P < 0.001]. In contrast to total 25D3 concentrations, mean VMR values were similar in blacks and whites [11.9 (4.0) vs 12.5 (3.4), P = 0.16, respectively] and were negatively correlated with parathyroid hormone concentrations in both races (rs = -0.26, P < 0.001, and rs = -0.25, P < 0.001, respectively). CONCLUSIONS: Our results provide further evidence that measurement of total 25D for assessment of vitamin D status in patients of African descent deserves reevaluation and suggest that alternative measures such as VMR should be considered.

Racial disparities in the type of postmastectomy reconstruction chosen.

BACKGROUND: Racial disparities remain for women undergoing immediate breast reconstruction (IBR) after mastectomy. Understanding patterns of racial disparities in IBR utilization may present opportunities to tailor policies aimed at optimizing care across racial groups. The aim of this study was to determine if racial disparities exist for types of IBR chosen. METHODS: A national, retrospective cohort study used the 2005-2011 American College of Surgeons National Surgical Quality Improvement Program database. Multivariable logistic regression models were created to detect the odds by race for receiving each subtype of IBR after mastectomy-prosthetic, pedicled-transfer autologous tissue, or free-transfer autologous tissue. Secondary outcome was trends in IBR rates over time. RESULTS: There were 44,597 women identified in the data set who underwent mastectomy. Thirty-seven percent of women (N = 16, 642) were noted to undergo IBR after mastectomy. Prosthetic reconstruction (84.4%, n = 37, 640) was the most common form of IBR compared with pedicled-autologous reconstruction (15.4%, n = 6868) and free transfer autologous reconstruction (4.9%, n = 2185), P < 0.001. In multivariate analysis, minorities had lower odds of undergoing IBR compared with whites (odds ratio [OR] 0.37 and 95% confidence interval [CI] 0.33-0.42 for Asians, OR 0.57 and 95% CI 0.52-0.61 for blacks, and OR 0.64 and 95% CI 0.58-0.71 for Hispanics, all P < 0.001). Compared with whites, Hispanics (OR 0.70, 95% CI 0.58-0.83) and blacks (OR 0.53, 95% CI 0.46-0.60) were less likely to use prosthetic reconstruction and more likely to use free-transfer autologous reconstruction (OR 1.66, 95% CI 1.26-2.18 for Hispanics, OR 2.13, 95% CI 1.73-2.63 for blacks), all P < 0.001. Racial disparities persisted from 2005-2011; as minority patients were less likely to undergo IBR than whites (P < 0.001). CONCLUSIONS: Utilization of IBR may be a sensitive measure of disparities in access to high-quality care and underlying cultures. Strategies aimed at reducing racial disparities in IBR should be tailored to specific patterns of disparities among Asian, black, and Hispanic women.

MENTAL HEALTH DISORDERS SUBSEQUENT TO GESTATIONAL DIABETES MELLITUS DIFFER BY RACE/ETHNICITY.

INTRODUCTION: The relationship between gestational diabetes mellitus (GDM) and postpregnancy mental health disorders has been inconsistently reported. Additionally, race/ethnicity data are limited. We sought to elucidate the intersection of these relationships. METHODS: We analyzed 18,109 women aged 18-40 with self-reported race/ethnicity. Women with (n = 659) and without (n = 14,461) GDM were followed for a median of 4.4 (interquartile range 1.4-6.8) and 4.0 (1.5-6.4) years, respectively, for incident mental health disorders. Multivariable repeated measures analyses were conducted to examine associations between GDM and postpregnancy mental health disorders, race/ethnicity, and the interaction of these factors. RESULTS: Women with compared to women without GDM were older (mean ± standard deviation, 32 ± 5 vs. 30 ± 5 years; P < .001) and had higher body mass index (29.0 ± 7.2 vs. 25.3 ± 5.2 kg/m(2) ; P < .001). GDM was associated with increased risk for depression and anxiety after adjusting for age and pregnancy complications; however, loss of significance in the fully adjusted model for depression (odds ratio [95% CI]: 1.29 [0.98, 1.70]; P = .064) and anxiety (1.14 [0.83, 1.57], P = .421) suggested that clinical and socioeconomic factors influence this relationship. Hispanic compared to white women had a greater risk for depression (1.40 [1.15, 1.72]; P = .001), even after multivariable adjustment. The interaction between GDM and race was evident in complication-adjusted but not fully adjusted models. CONCLUSIONS: The incidence of mental health disorders subsequent to GDM was attenuated after adjustment for clinical and socioeconomic factors. Moreover, race/ethnicity influenced this relationship. Further investigation is warranted to clarify potential underlying mechanisms.

Shear wave elastography in chronic kidney disease: a pilot experience in native kidneys.

BACKGROUND: There currently is a need for a non-invasive measure of renal fibrosis. We aim to explore whether shear wave elastography (SWE)-derived estimates of tissue stiffness may serve as a non-invasive biomarker that can distinguish normal and abnormal renal parenchymal tissue. METHODS: Participants with CKD (by estimated GFR) and healthy volunteers underwent SWE. Renal elasticity was estimated as Young's modulus (YM) in kilopascals (kPa). Univariate Wilcoxon rank-sum tests were used. RESULTS: Twenty-five participants with CKD (median GFR 38 mL/min; quartile 1, quartile 3 28, 42) and 20 healthy controls without CKD underwent SWE performed by a single radiologist. CKD was associated with increased median YM (9.40 [5.55, 22.35] vs. 4.40 [3.68, 5.70] kPa; p = 0.002) and higher median intra-subject inter-measurement estimated YM's variability (4.27 [2.89, 9.90] vs. 1.51 [1.21, 2.05] kPa; p < 0.001). CONCLUSIONS: SWE-derived estimates of renal stiffness and intra-subject estimated stiffness variability are higher in patients with CKD than in healthy controls. Renal fibrosis is a plausible explanation for the observed difference in YM. Further studies are required to determine the relationship between YM, estimated renal stiffness, and renal fibrosis severity.