Nephroprotective Effect of the Virgin Olive Oil Polyphenol Hydroxytyrosol in Type 1-like Experimental Diabetes Mellitus: Relationships with Its Antioxidant Effect

The aim of this study was to determine whether hydroxytyrosol administration prevented kidney damage in an experimental model of type 1 diabetes mellitus in rats. Hydroxytyrosol was administered to streptozotocin-diabetic rats: 1 and 5 mg/kg/day p.o. for two months. After hydroxytyrosol administration, proteinuria was significantly reduced (67–73%), calculated creatinine clearance was significantly increased (26–38%), and the glomerular volume and glomerulosclerosis index were decreased (20–30%). Hydroxytyrosol reduced oxidative and nitrosative stress variables and thromboxane metabolite production. Statistical correlations were found between biochemical and kidney function variables. Oral administration of 1 and 5 mg/kg/day of hydroxytyrosol produced an antioxidant and nephroprotective effect in an experimental model of type 1-like diabetes mellitus. The nephroprotective effect was significantly associated with the systemic and renal antioxidant action of hydroxytyrosol, which also influenced eicosanoid production.

Evaluation of standard dosing for selected broad spectrum Hydrophilic antibiotics in critically ill patients with Augmented renal clearance: An observational Study

Background: Inappropriate antibiotics dosing in critically ill patients with augmented renal clearance (ARC) may be associated with pathogens resistance and worse outcomes. Unfortunately, studies regarding the relationship between ARC and clinical outcomes in patients treated with antibiotics medication are rare. The study evaluates the efficacy and clinical outcomes of selected broad-spectrum hydrophilic antibiotics in ARC critically ill patients with confirmed infections. Methods: A retrospective cohort study in adult critically ill patients who were admitted to intensive care units (ICUs) at King Abdulaziz Medical City (KAMC)-Riyadh and received standard dosing of selected broad-spectrum hydrophilic antibiotics (Meropenem, Imipenem, or Piperacillin/Tazobactam) with confirmed infection. All the patients who met our inclusion criteria during the study period (01/01/2018 – 31/12/2019) were included. Eligible patients have been divided into two groups (ARC Vs. non-ARC) according to the calculated creatinine clearance using the Cockcroft-Gault equation. The primary outcome was to assess pathogen eradication at 10-14 days; other outcomes were considered secondary. Multivariate logistic and generalized linear regression analyses were used. We considered a P value of < 0.05 statistically significant. Results: A total of 133 patients were included in the study; 67 Patients had ARC. The distribution of infections and types of pathogens between the groups were the same. The pathogen eradication at 10-14 days was similar between the two groups (OR 1.08; 95% CI, 0.41–2.78 p = 0.88). Moreover, the odds of resistance development and persistence after 3 days were not significantly different between the groups ((OR 0.78; 95% CI, 0.25–2.40 p = 0.66) and (OR 0.88; 95% CI, 0.35–2.18 p = 0.78) respectively). Conclusion: Using standard dosing of Meropenem, Imipenem, or Piperacillin/Tazobactam in ARC patients was not associated with therapy failure. Further randomized clinical and interventional studies are required to confirm our findings.

Evaluation of standard dosing for selected broad spectrum Hydrophilic antibiotics in critically ill patients with Augmented renal clearance: An observational Study

Background: Inappropriate antibiotics dosing in critically ill patients with augmented renal clearance (ARC) may be associated with pathogens resistance and worse outcomes. Unfortunately, studies regarding the relationship between ARC and clinical outcomes in patients treated with antibiotics medication are rare. The study evaluates the efficacy and clinical outcomes of selected broad-spectrum hydrophilic antibiotics in ARC critically ill patients with confirmed infections. Methods: A retrospective cohort study in adult critically ill patients who were admitted to intensive care units (ICUs) at King Abdulaziz Medical City (KAMC)-Riyadh and received standard dosing of selected broad-spectrum hydrophilic antibiotics (Meropenem, Imipenem, or Piperacillin/Tazobactam) with confirmed infection. All the patients who met our inclusion criteria during the study period (01/01/2018 – 31/12/2019) were included. Eligible patients have been divided into two groups (ARC Vs. non-ARC) according to the calculated creatinine clearance using the Cockcroft-Gault equation. The primary outcome was to assess pathogen eradication at 10-14 days; other outcomes were considered secondary. Multivariate logistic and generalized linear regression analyses were used. We considered a P value of < 0.05 statistically significant. Results: A total of 133 patients were included in the study; 67 Patients had ARC. The distribution of infections and types of pathogens between the groups were the same. The pathogen eradication at 10-14 days was similar between the two groups (OR 1.08; 95% CI, 0.41–2.78 p = 0.88). Moreover, the odds of resistance development and persistence after 3 days were not significantly different between the groups ((OR 0.78; 95% CI, 0.25–2.40 p = 0.66) and (OR 0.88; 95% CI, 0.35–2.18 p = 0.78) respectively). Conclusion: Using standard dosing of Meropenem, Imipenem, or Piperacillin/Tazobactam in ARC patients was not associated with therapy failure. Further randomized clinical and interventional studies are required to confirm our findings.

1555. Risk of Developing Acute Kidney Injury in Patients Receiving Piperacillin–Tazobactam and Vancomycin Compared with Those on Piperacillin–Tazobactam and Telavancin

Background The combination of piperacillin–tazobactam (PIP-TAZO) and vancomycin is associated with an increased frequency of acute kidney injury (AKI) in patients when compared with either agent alone. Like vancomycin, telavancin is also used for gram-positive infections and has been reported to cause AKI, but there is a paucity of data regarding the development of AKI with the combination of PIP-TAZO and telavancin. The purpose of this study was to compare the incidence of AKI in patients receiving PIP-TAZO with concomitant vancomycin or telavancin. Methods This retrospective cohort study included patients admitted between November 2016 and March 2019 who received at least 2 days of either vancomycin or telavancin in combination with PIP-TAZO. Patients were excluded if they had a baseline calculated creatinine clearance of less than 20 milliliters per minute or were receiving renal replacement therapy. Any cases of AKI were defined as a serum creatinine increase of 0.3 milligrams per deciliter (mg/dL) or an increase in creatinine of 1.5 times baseline when observed within 7 days of the studied antibiotic combinations. Statistical analysis was performed to compare baseline characteristics and the development of AKI between the two groups. Results Ninety-four patients with an average age of 55 years met the inclusion criteria. Forty-seven patients were included in both treatment arms. There were no statistically significant differences observed between study group baseline characteristics. All patients received PIP-TAZO 3.375 grams every 8 hours as a 4-hour infusion and the average telavancin dose was 7.5 mg/kg. Seventeen of 94 (18%) patients developed AKI, 8(17%) in the vancomycin and PIP-TAZO group and 9 (19%) in the telavancin and PIP-TAZO group (P = 1.0). No patients required dialysis. Conclusion The development of AKI appears to be similar when comparing vancomycin and PIP-TAZO to telavancin and PIP-TAZO in our population. It is noteworthy that PIP-TAZO was given as an extended infusion and telavancin dosing was lower than the manufacturer recommendations in this evaluation. Additional studies are warranted to further examine the occurrence of AKI with these antibiotic combinations. Disclosures All authors: No reported disclosures.

Chemotherapy for Muscle-Invasive Bladder Cancer: Better Late Than Never?

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 64-year-old man with a history of cigarette smoking but no significant comorbidities presented with hematuria and dysuria. Computed tomography scans demonstrated a mass and thickening of the bladder wall and no evidence of metastasis. His laboratory evaluation showed normal blood cell counts and comprehensive metabolic panel with a calculated creatinine clearance of more than 60 mL per minute. A transurethral resection of the bladder tumor and biopsy identified transitional cell carcinoma or urothelial carcinoma invading the muscularis propria of the bladder. On the basis of the bladder-confined mass on computed tomography scan, the tumor was assigned a clinical stage of cT2N0. The patient was advised to undergo neoadjuvant chemotherapy followed by radical cystectomy (RC). The patient had multiple concerns regarding neoadjuvant chemotherapy, particularly toxicities, especially the possibility of chronic neurologic and renal toxicities, and the potential harm from delay of RC, especially if the bladder cancer was resistant to chemotherapy. After a discussion of approximately 1 hour, he elected to proceed with upfront RC and extended lymph node dissection in conjunction with construction of a neobladder. Pathology revealed pathologic extravesical urothelial carcinoma, with disease in one of 25 lymph nodes removed (ypT3N1). Four weeks after RC, he returned to discuss further management with the medical oncologist. He exhibited an Eastern Cooperative Oncology Group performance status of 0, normal blood cell counts, and a calculated creatinine clearance of more than 60 mL per minute.

What is the role of hemodialysis for dabigatran-associated major bleeding?

A 70-year-old male with a history of atrial fibrillation who is being anticoagulated with dabigatran etexilate presents to the emergency room with melena. He reports taking his most recent dose of dabigatran more than 2 hours ago. On examination, he is hypotensive and tachycardic, and he continues to have melanotic stools. Laboratory testing reveals a calculated creatinine clearance of 15 mL/min, a prothrombin time of 16.5 seconds (reference range: 11.8-15.2 seconds), an international normalized ratio of 1.2 (reference range: 0.9-1.2), and an activated partial thromboplastin time of 50 seconds (reference range: 22.2-33.0 seconds). You are asked by the emergency medicine physician whether hemodialysis should be considered to decrease the patient's plasma dabigatran level.

Effect of Waxy Maize-derived Hydroxyethyl Starch 130/0.4 on Renal Function in Surgical Patients

Background: The aim of this meta-analysis was to evaluate renal safety with the active substance of the latest generation of waxy maize-derived hydroxyethyl starch in surgical patients. The authors focused on prospective, randomized, controlled studies that documented clinically relevant variables with regard to renal effects of waxy maize-derived hydroxyethyl starch 130/0.40. Materials and methods: The authors carefully searched for all available prospective, randomized studies and evaluated the greatest delta from baseline values in renal safety variables (serum creatinine values, calculated creatinine clearance, incidence of renal replacement therapy, and acute renal failure). The authors included 17 studies that analyzed patients (n = 1,230) undergoing a variety of surgical procedures. Results: For maximum serum creatinine values, the effect size estimate was 0.068 (95% CI = −0.227 to 0.362), P = 0.65. For calculated creatinine clearance values, pooled risk difference was 0.302 (95% CI = −0.098 to 0.703), P = 0.14. For incidence of acute renal failure, pooled risk difference was 0.0003 (95% CI = −0.018 to 0.019), P = 0.98. For incidence of renal replacement therapy, pooled risk difference was −0.003 (95% CI = −0.028 to 0.022), P = 0.85. Conclusions: The authors found no evidence for renal dysfunction caused by modern waxy maize-derived hydroxyethyl starch 130/0.40 in surgical patients.