Diagnosing acute kidney injury ahead of time in critically ill septic patients using kinetic estimated glomerular filtration rate.

INTRODUCTION: Accurate and actionable diagnosis of Acute Kidney Injury (AKI) ahead of time is important to prevent or mitigate renal insufficiency. The purpose of this study was to evaluate the performance of Kinetic estimated Glomerular Filtration Rate (KeGFR) in timely predicting AKI in critically ill septic patients. METHODS: We conducted a retrospective analysis on septic ICU patients who developed AKI in AmsterdamUMCdb, the first freely available European ICU database. The reference standard for AKI was the Kidney Disease: Improving Global Outcomes (KDIGO) classification based on serum creatinine and urine output (UO). Prediction of AKI was based on stages defined by KeGFR and UO. Classifications were compared by length of ICU stay (LOS), need for renal replacement therapy and 28-day mortality. Predictive performance and time between prediction and diagnosis were calculated. RESULTS: Of 2492 patients in the cohort, 1560 (62.0%) were diagnosed with AKI by KDIGO and 1706 (68.5%) by KeGFR criteria. Disease stages had agreement of kappa = 0.77, with KeGFR sensitivity 93.2%, specificity 73.0% and accuracy 85.7%. Median time to recognition of AKI Stage 1 was 13.2 h faster for KeGFR, and 7.5 h and 5.0 h for Stages 2 and 3. Outcomes revealed a slight difference in LOS and 28-day mortality for Stage 1. CONCLUSIONS: Predictive performance of KeGFR combined with UO criteria for diagnosing AKI is excellent. Compared to KDIGO, deterioration of renal function was identified earlier, most prominently for lower stages of AKI. This may shift the actionable window for preventing and mitigating renal insufficiency.

Cathelicidin protects mice from Rhabdomyolysis-induced Acute Kidney Injury.

Background: Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity. Rhabdomyolysis is a major trigger of AKI. Objectives: Here, we investigated the role of cathelicidins in non-infectious Acute kidney Injury (AKI). Method: Using an experimental model of rhabdomyolysis, we induced AKI in wild-type and cathelicidin-related AMP knockout (CRAMP-/-) mice. Results: We previously demonstrated that CRAMP-/- mice, as opposed wild-type mice, are protected from AKI during sepsis induced by cecal ligation and puncture. Conversely, in the current study, we show that CRAMP-/- mice are more susceptible to the rhabdomyolysis model of AKI. A more in-depth investigation of wild-type and CRAMP-/- mice revealed important differences in the levels of several inflammatory mediators. Conclusion: Cathelicidins can induce a varied and even opposing repertoire of immune-inflammatory responses depending on the subjacent disease and the cellular context.