Peter A. McCullough M.D.

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.

Zhang, J., M. K. Fallahzadeh and P. A. McCullough (2016). “Aging male spontaneously hypertensive rat as an animal model for the evaluation of the interplay between contrast-induced acute kidney injury and cardiorenal syndrome in humans.” Cardiorenal Med 7(1): 1-10.

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BACKGROUND: Although there are some animal models for biomarkers of contrast-induced acute kidney injury (CI-AKI), for cardiorenal syndrome (CRS) and for acute renal failure, the interplay between CI-AKI and CRS has yet to be evaluated. Insight into the pathogenesis of CRS is urgently needed from animal models in order to foster the discovery and implementation of novel biomarkers for this disease. Specially designed animal models for type 1 and 3 CRS, particularly CI-AKI, have not yet emerged. SUMMARY: We hypothesize that the aging male spontaneously hypertensive rat (SHR) is likely to be a suitable model. The SHR model is able to mimic risk factors for preclinical CRS that appears in the clinical setting, specifically hypertension, age, preexisting damage and dysfunction of the heart and kidney, endothelial dysfunction, increased level of reactive oxygen species, decreased level and bioavailability of nitric oxide (NO), impairment of the L-arginine-NO pathway, and insulin resistance. In the SHR, CI-AKI results in a different profile of AKI biomarkers than is seen with preexisting chronic kidney injury. KEY MESSAGES: The SHR model can be used to evaluate the interaction between CI-AKI and CRS type 1 and 3 and to verify neutrophil gelatinase-associated lipocalin (NGAL) as a reliable CI-AKI biomarker for clinical application. Further research is warranted with a large number of aging male SHRs to prove NGAL as a sensitive, specific, highly predictive, early biomarker for CI-AKI.

McCullough, P. A., J. P. Choi, G. A. Feghali, J. M. Schussler, R. M. Stoler, R. C. Vallabahn and A. Mehta (2016). “Contrast-induced acute kidney injury.” J Am Coll Cardiol 68(13): 1465-1473.

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Coronary angiography and percutaneous intervention rely on the use of iodinated intravascular contrast for vessel and chamber imaging. Despite advancements in imaging and interventional techniques, iodinated contrast continues to pose a risk of contrast-induced acute kidney injury (CI-AKI) for a subgroup of patients at risk for this complication. There has been a consistent and graded signal of risk for associated outcomes including need for renal replacement therapy, rehospitalization, and death, according to the incidence and severity of CI-AKI. This paper reviews the epidemiology, pathophysiology, prognosis, and management of CI-AKI as it applies to the cardiac catheterization laboratory.

Schussler, J. M., A. Vasudevan, L. J. von Bose, J. I. Won and P. A. McCullough (2016). “Comparative efficacy of transradial versus transfemoral approach for coronary angiography and percutaneous coronary intervention.” Am J Cardiol 118(4): 482-488.

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Transradial artery (TRA) approach is associated with fewer vascular complications and reduced mortality in patients at high risk compared with transfemoral approach (TFA). The objective of our study was to compare the characteristics and outcomes of patients who had coronary angiography by TRA and TFA over the course of hospital implementation of this approach. We included 12,928 patients from Baylor University Medical Center and Baylor Heart and Vascular Hospital, Dallas, Texas, who underwent a coronary angiography from January 2008 to March 2015. To control for selection bias and the learning curve, a nested matched study design was used for patients with percutaneous coronary intervention (PCI) with TRA patients matched with TFA by age (+/-2 years) and calendar year of the procedure in a ratio of 1:3. TRA for PCI increased from nearly 0% in 2008 to 9% in 2014. Including patients from 2011 to 2015 for the analysis, patients with TFA were older (65 +/- 12 vs 64 +/- 11) and had lower mean body mass index (30 +/- 7 vs 33 +/- 9 kg/m(2)) than patients with TRA. Patients with TRA had less bleeding, dialysis, pseudoaneurysm, and access site hematomas than the patients with TRA (0.7% vs 0%; p = 0.02). By a conditional logistic regression, we observed fewer complications, readmissions, and in-hospital deaths among TRA patients than the matched TFA patients. In conclusion, patients undergoing angiography with/without PCI through TRA had fewer complications, readmissions, and a shorter length of hospital stay after procedure versus TFA at our hospital.