Background: Recent studies have identified the combination of vancomycin with piperacillin-tazobactam (VPT) to be associated with increased nephrotoxicity. Multiple, large cohort studies have found this widely used combination to have a higher risk of nephrotoxicity than other regimens in a variety of populations. Summary: This review summarizes the epidemiology and clinical features of VPT-associated acute kidney injury (AKI). Potential mechanisms involved in the pathogenesis of this phenomenon are also discussed. Key Message: VPT-associated nephrotoxicity is a recently recognized clinical entity. Clinical strategies to minimize the risk of toxicity in this setting include antimicrobial stewardship, monitoring of kidney function, and emerging data supporting the potential role for novel biomarkers in predicting and managing AKI.

Background: The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective 2-center observational study investigating the utility of urinary biomarker combinations for the diagnostic and prognostic assessment of acute kidney injury (AKI) in a heterogeneous adult intensive care unit (ICU) population. The objective of this study is to evaluate whether serial urinary biomarker measurements, in combination with a simple clinical model, could improve biomarker performance in the diagnostic prediction of severe AKI and clinical outcomes such as death and need for renal replacement therapy (RRT). Methods: Urine was collected daily from patients admitted to the ICU, for a total of 7 post-admission days. Urine biomarker concentrations (neutrophil gelatinase-associated lipocalin [NGAL], α-glutathione S-transferase [GST], π-GST, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], Cystatin C, creatinine, and albumin) were measured. Urine biomarkers were combined with a clinical prediction of AKI model, to determine ability to predict AKI (any stage, within 2 days or 7 days of ICU admission), or a ­30-day composite clinical outcome (RRT – or death). Results: A total of 257 (38%) patients developed AKI within 7 days of ICU admission. Of those who developed AKI, 106 (41%) patients met stage 3 AKI within 7 days of ICU admission and 208 patients of the entire study cohort (31%) met the composite clinical endpoint of in-hospital mortality or RRT within 30 days of ICU admission. The addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI (area under the curve [AUC] of 0.9 from 0.87, p = 0.369) and the prediction of 30-day RRT or death (AUC 0.83 from 0.79, p = 0.139). Conclusion: A clinical model incorporating severity of illness, patient demographics, and chronic illness with currently available clinical biomarkers of renal function was strongly predictive of development of AKI and associated clinical outcomes in a heterogeneous adult ICU population. The addition of urinary NGAL/albumin to this simple clinical model improved the prediction of severe AKI, need for RRT and death, but not at a statistically or clinically significant level, when compared to the clinical model alone.

This study shows PD to be an acceptable modality of renal replacement therapy in elderly patients, with no observed differences in survival, technique survival or complication rates. Co-morbidities appear to play a stronger role in predicting survival than age alone. Assisted PD is a viable option in those unable to undergo PD independently.

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Background Acute Kidney Injury (AKI) is common in hospitalized patients and is associated with high morbidity and mortality. The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective cohort study of critically ill patients (n = 717). We hypothesised that novel urinary biomarkers would predict progression of AKI and associated outcomes. Methods The primary (diagnostic) analysis assessed the ability of biomarkers levels at the time of early Stage 1 or2 AKI to predict progression to higher AKI Stage, RRT or Death within 7 days of ICU admission. In the secondary (prognostic) analysis, we investigated the association between biomarker levels and RRT or Death within 30 days. Results In total, 186 patients had an AKI within 7 days of admission. In the primary (diagnostic) analysis, eight of the 14 biomarkers were independently associated with progression. The best predictors were Cystatin C (aOR 5.2; 95% CI, 1.3-23.6), IL-18 (aOR 5.1; 95% CI, 1.8-15.7), Albumin (aOR 4.9; 95% CI, 1.5-18.3) and NGAL (aOR 4.6; 95% CI, 1.4-17.9). ROC and Net Reclassification Index analyses similarly demonstrated improved prediction by these biomarkers. In the secondary (prognostic) analysis of Stage 1-3 AKI cases, IL-18, NGAL, Albumin, and MCP-1 were also independently associated with RRT or Death within 30 days. Conclusions Among 14 novel urinary biomarkers assessed, Cystatin C, IL-18, Albumin and NGAL were the best predictors of Stage 1-2 AKI progression. These biomarkers, after further validation, may have utility to inform diagnostic and prognostic assessment and guide management of AKI in critically ill patients.