Research Spotlight

McCullough, P. A., C. T. Chan, E. D. Weinhandl, J. M. Burkart and G. L. Bakris (2016). “Intensive hemodialysis, left ventricular hypertrophy, and cardiovascular disease.” Am J Kidney Dis 68(5s1): S5-s14.

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The prevalence of cardiovascular disease, including cardiac arrhythmia, coronary artery disease, cardiomyopathy, and valvular heart disease, is higher in hemodialysis (HD) patients than in the US resident population. Cardiovascular disease is the leading cause of death in HD patients and the principal discharge diagnosis accompanying 1 in 4 hospital admissions. Furthermore, the rate of hospital admissions for either heart failure or fluid overload is persistently high despite widespread use of beta-blockers and renin-angiotensin system inhibitors and attempts to manage fluid overload with ultrafiltration. An important predictor of cardiovascular mortality and morbidity in dialysis patients is left ventricular hypertrophy (LVH). LVH is an adaptive response to increased cardiac work, typically caused by combined pressure and volume overload, resulting in cardiomyocyte hypertrophy and increased intercellular matrix. In new dialysis patients, the prevalence of LVH is 75%. Regression of LVH may reduce cardiovascular risk, including the incidence of heart failure, complications after myocardial infarction, and sudden arrhythmic death. Multiple randomized clinical trials show that intensive HD reduces left ventricular mass, a measure of LVH. Short daily and nocturnal schedules in the Frequent Hemodialysis Network trial reduced left ventricular mass by 14 (10%) and 11 (8%) g, respectively, relative to 3 sessions per week. Comparable efficacy was observed in an earlier trial of nocturnal HD. Intensive HD also improves cardiac rhythm. Clinical benefits have been reported only in observational studies. Daily home HD is associated with 17% and 16% lower risks for cardiovascular death and hospitalization, respectively; admissions for cerebrovascular disease, heart failure, and hypertensive disease, which collectively constitute around half of cardiovascular hospitalizations, were less likely with daily home HD. Relative to peritoneal dialysis, daily home HD is likewise associated with lower risk for cardiovascular hospitalization. In conclusion, intensive HD likely reduces left ventricular mass and may lead to lower risks for adverse cardiac events.

McCullough, P. A., A. Vasudevan, L. R. Lopez, C. Swift, M. Peterson, J. Bennett-Firmin, R. Schiffmann and T. Bottiglieri (2016). “Oxidative stress reflected by increased f2-isoprostanes is associated with increasing urinary 11-dehydro thromboxane b2 levels in patients with coronary artery disease.” Thromb Res 148: 85-88.

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Acetylsalicylic acid (ASA, aspirin) is widely prescribed as an aid in primary and secondary prevention of coronary artery disease (CAD) as it inhibits > 95% of platelet cyclooxygenase-1 (COX-1) activity, reducing the production of thromboxane A2 (TxA2) [1]. However, the non-platelet inflammatory COX-2 pathway remains active minimally affected by ASA. Based on the clinical development of complications or on laboratory tests, an inadequate response to ASA has been referred to as “aspirin resistance” [2] which is associated with increased risk of adverse outcomes [3]. Oxidative stress has been recently recognized as a relevant underlying mechanism to explain incomplete ASA response. Along with the enzymatic pathways (COX-1; COX-2), there is a non-enzymatic arachidonic acid pathway that produces F2-isoprostanes by oxidative stress damage which can directly activate platelets by stimulating platelet thromboxane prostanoid receptors (TPR) [4] and is not affected by ASA [5]. 8-isoprostaglandin-F2α (8-isoPGF2α) is considered a reliable laboratory biomarker of in vivo oxidative stress and a reliable noninvasive measurement of lipid peroxidation [6]. We investigated the association of oxidative stress (urinary 8-isoPGF2α) and the adequacy of inhibition of COX-1 (urinary 11-dehydro thromboxane B2 [11dhTxB2]).

McCullough, P. A., T. Ball, K. M. Cox and M. D. Assar (2016). “Use of oral anticoagulation in the management of atrial fibrillation in patients with esrd: Pro.” Clin J Am Soc Nephrol 11(11): 2079-2084.

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Warfarin has had a thin margin of benefit over risk for the prevention of stroke and systemic embolism in patients with ESRD because of higher bleeding risks and complications of therapy. The successful use of warfarin has been dependent on the selection of patients with nonvalvular atrial fibrillation at relatively high risk of stroke and systemic embolism and lower risks of bleeding over the course of therapy. Without such selection strategies, broad use of warfarin has not proven to be beneficial to the broad population of patients with ESRD and nonvalvular atrial fibrillation. In a recent meta-analysis of use of warfarin in patients with nonvalvular atrial fibrillation and ESRD, warfarin had no effect on the risks of stroke (hazard ratio, 1.12; 95% confidence interval, 0.69 to 1.82; P=0.65) or mortality (hazard ratio, 0.96; 95% confidence interval, 0.81 to 1.13; P=0.60) but was associated with increased risk of major bleeding (hazard ratio, 1.30; 95% confidence interval, 1.08 to 1.56; P<0.01). In pivotal trials, novel oral anticoagulants were generally at least equal to warfarin for efficacy and safety in nonvalvular atrial fibrillation and mild to moderate renal impairment. Clinical data for ESRD are limited, because pivotal trials excluded such patients. Given the very high risk of stroke and systemic embolism and the early evidence of acceptable safety profiles of novel oral anticoagulants, we think that patients with ESRD should be considered for treatment with chronic anticoagulation provided that there is an acceptable bleeding profile. Apixaban is currently indicated in ESRD for this application and may be preferable to warfarin given the body of evidence for warfarin and its difficulty of use and attendant adverse events.

Morfin, J. A., R. J. Fluck, E. D. Weinhandl, S. Kansal, P. A. McCullough and P. Komenda (2016). “Intensive hemodialysis and treatment complications and tolerability.” Am J Kidney Dis 68(5s1): S43-s50.

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Hemodialysis (HD) treatment can be difficult to tolerate. Common complications are intradialytic hypotension (IDH) and long time to recovery after an HD session. IDH, as defined by nadir systolic blood pressure < 90mmHg and intradialytic decline > 30mmHg, occurs in almost 8% of HD sessions. IDH may be caused by aggressive ultrafiltration in response to interdialytic weight gain, can lead to myocardial stunning and cardiac arrhythmias, and is associated with increased risk for death. Long recovery time after a treatment session is also common. In DOPPS (Dialysis Outcomes and Practice Patterns Study), recovery time was 2 to 6 hours for 41% of HD patients and longer than 6 hours for 27%; recovery time was linearly associated with increased risks for death and hospitalization. Importantly, both decreases in blood pressure and feeling washed out or drained have been identified by patients as more important outcomes than death or hospitalization. Intensive HD likely reduces the likelihood of IDH. In the Frequent Hemodialysis Network trial, short daily and nocturnal schedules reduced the per-session probability of IDH by 20% and 68%, respectively, relative to 3 sessions per week. Due to lower ultrafiltration volume and/or rate, intensive HD may reduce intradialytic blood pressure variability. In a cross-sectional study, short daily and nocturnal schedules were associated with slower ultrafiltration and less dialysis-induced myocardial stunning than 3 sessions per week. In FREEDOM (Following Rehabilitation, Economics, and Everyday-Dialysis Outcome Measurements), a prospective cohort study of short daily HD, recovery time was reduced after 12 months from 8 hours to 1 hour, according to per-protocol analysis. Recovery time after nocturnal HD may be minutes. In conclusion, intensive HD can improve the tolerability of HD treatment by reducing the risk for IDH and decreasing recovery time after HD. These changes may improve the patient centeredness of end-stage renal disease care.

Shahbazov, R., G. Yoshimatsu, W. Z. Haque, O. S. Khan, G. Saracino, M. C. Lawrence, P. T. Kim, N. Onaca, B. Naziruddin and M. F. Levy (2016). “Clinical effectiveness of a pylorus-preserving procedure on total pancreatectomy with islet autotransplantation.” Am J Surg: 2016 Oct [Epub ahead of print].

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BACKGROUND: The impact of pylorus preserving procedures (PP) on total pancreatectomy with islet autotransplantation (TPIAT) has not been examined. This study aimed to investigate the clinical impact of the PP on TPIAT. METHODS: The Baylor Simmons Transplant Institute database was queried to identify seventy-three patients who underwent TPIAT from 2006 to 2014. All patients were investigated in postoperative complications, long-term nutritional status, and graft function. RESULTS: Patients with PP did not face worse outcomes in terms of delayed gastric emptying and length of hospital stay. Also, nutritional status and metabolic outcome, such as body weight, serum albumin level, serum vitamin level, HbA1c level, graft survival rate and insulin independent rate, were similar between both groups. CONCLUSIONS: Clinical results including the graft function indicated that patients undergoing TPIAT with PP did not amplify surgical complications such as delayed gastric emptying and showed no significant advantage of nutrition and metabolic outcome.