Peter A. McCullough M.D.

Ostermann, M., P. A. McCullough, L. G. Forni, S. M. Bagshaw, M. Joannidis, J. Shi, K. Kashani, P. M. Honore, L. S. Chawla and J. A. Kellum (2017). “Kinetics of urinary cell cycle arrest markers for acute kidney injury following exposure to potential renal insults.” Crit Care Med: 2017 Nov [Epub ahead of print].

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OBJECTIVES: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 predict the development of acute kidney injury following renal insults of varied aetiology. To aid clinical interpretation, we describe the kinetics of biomarker elevations around an exposure. DESIGN: In an ancillary analysis of the multicenter SAPPHIRE study, we examined the kinetics of the urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor binding protein 7] in association with exposure to common renal insults (major surgery, IV radiocontrast, vancomycin, nonsteroidal anti-inflammatory drugs, and piperacillin/tazobactam). SETTING: Thirty-five sites in North America and Europe between September 2010 and June 2012. PATIENTS: Seven hundred twenty-three critically ill adult patients admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the urinary [tissue metalloproteinase-2]*[insulin growth factor binding protein 7] kinetics from the day prior to exposure up to 5 days after exposure in patients developing acute kidney injury stage 2-3, stage 1, or no acute kidney injury by Kidney Disease Improving Global Outcome criteria. Among the 723 patients, 679 (94%) had at least one, 70% had more than one, and 35% had three or more exposures to a known renal insult. There was a significant association between cumulative number of exposures up to study day 3 and risk of acute kidney injury (p = 0.02) but no association between the specific type of exposure and acute kidney injury (p = 0.22). With the exception of radiocontrast, patients who developed acute kidney injury stage 2-3 after one of the five exposures, had a clear rise and fall of urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor binding protein 7] from the day of exposure to 24-48 hours later. In patients without acute kidney injury, there was no significant elevation in urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor binding protein 7]. CONCLUSIONS: Exposure to potential renal insults is common. In patients developing acute kidney injury stage 2-3, the kinetics of urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor binding protein 7] matched the exposure except in the case of radiocontrast.

Rangaswami, J., R. O. Mathew and P. A. McCullough (2017). “Resuscitation for the specialty of nephrology: Is cardionephrology the answer?” Kidney Int: 2017 Nov [Epub ahead of print].

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The specialty of nephrology faces major fellowship recruitment challenges, with ongoing declining interest among internal medicine residents. The field of Cardionephrology can help instill new interest and enthusiasm in choosing nephrology as a career amongst trainee physicians.

Vasudevan, A., K. M. Tecson, J. Bennett-Firmin, T. Bottiglieri, L. R. Lopez, M. Peterson, M. Sathyamoorthy, R. Schiffmann, J. M. Schussler, C. Swift, C. E. Velasco and P. A. McCullough (2017). “Prognostic value of urinary 11-dehydro-thromboxane b2 for mortality: A cohort study of stable coronary artery disease patients treated with aspirin.” Catheter Cardiovasc Interv: 2017 Nov [Epub ahead of print].

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AIM: There is a variable cardiovascular risk reduction attributable to aspirin because of individual differences in the suppression of thromboxane A2 and its downstream metabolite 11-dehydro-thromboxane B2 (11dhTxB2 ). The aim of this study is to evaluate the optimal cut point of urinary 11dhTxB2 for the risk of mortality in aspirin-treated coronary artery disease (CAD) patients. METHODS AND RESULTS: This was a prospective cohort study including stable CAD patients who visited the Baylor Heart and Vascular Hospital in Dallas or the Texas Heart Hospital Baylor Plano, TX between 2010 and 2013. The outcome of all-cause mortality was ascertained from chart review and automated sources. The 449 patients included in this analysis had a mean age of 66.1 +/- 10.1 years. 67 (14.9%) patients died within 5 years; 56 (87.5%) of the 64 patients with known cause of death suffered a cardiovascular related mortality. Baseline ln(urinary 11dhTxB2 /creatinine) ranged between 5.8 and 11.1 (median = 7.2) with the higher concentrations among those who died (median: 7.6) than those who survived (median = 7.2, P < 0.001). Using baseline ln(11dhTxB2 ) to predict all-cause mortality, the area under the curve was 0.70 (95% CI: 0.64-0.76). The optimal cut point was found to be ln(7.38) = 1597.8 pg/mg, which had the following decision statistics: sensitivity = 0.67, specificity = 0.62, positive predictive value = 0.24, negative predictive value = 0.92, and accuracy = 0.63. CONCLUSION: Our data indicate the optimal cut point for urine 11dhTxB2 is 1597.8 (pg/mg) for the risk prediction of mortality over five years in stable patients with CAD patients treated with aspirin.

McCullough, P. A., G. David, T. M. Todoran, E. S. Brilakis, M. P. Ryan and C. Gunnarsson (2017). “Iso-osmolar contrast media and adverse renal and cardiac events after percutaneous cardiovascular intervention.” J Comp Eff Res: 2017 Nov [Epub ahead of print].

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AIM: To assess the relationship between type of contrast media (CM), iso-osmolar contrast media (IOCM) or low-osmolar contrast media (LOCM), and major adverse renal and cardiovascular events (MARCE). MATERIALS & METHODS: Coronary or peripheral angioplasty visits were stratified into CM cohorts: IOCM or LOCM. Multivariable regression analysis used hospital fixed effects to assess the relationship between MARCE events and type of CM. RESULTS: Among 333,533 visits (357 hospitals), the incidence of MARCE was 7.41%. After controlling for observable and unobservable time invariant within-hospital characteristics, administration of IOCM versus LOCM was associated with a 0.69% absolute and 9.32% relative risk reduction in MARCE rate. CONCLUSION: Our study indicates that as compared with LOCM, IOCM may be associated with reduction of MARCE events in coronary or peripheral angioplasty patients.

Packer, M. (2017). “Early worsening of renal function after treatment with antihyperglycemic drugs: A consistent finding in large-scale trials.” Am J Med: 2017 Nov [Epub ahead of print].

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Prolonged hyperglycemia in type 2 diabetes exerts adverse structural and functional effects on the kidney, and sustained lowering of blood glucose for a decade or longer has been shown to reduce the risk of progression to end-stage renal disease. 1 However, during the first months or years of treatment with an antihyperglycemic drug, patients may experience worsening of renal function regardless of the agent used to lower blood glucose. There is minimal recognition of this phenomenon in the medical literature. The most persuasive evidence supporting the occurrence of early worsening of renal function after initiation of treatment with antidiabetic drugs is derived from randomized controlled clinical trials with different antihyperglycemic agents. Sequential changes in estimated glomerular filtration rate (or in serum creatinine) have been reported in 5 large-scale trials completed since regulatory agencies issued a new guidance on diabetes in 2008. 2