Pathologies of acute tubular necrosis

Perazella MA. Clinical Approach to Diagnosing Acute and Chronic Tubulointerstitial Disease. Adv Chronic Kidney Dis. 2017 Mar;24(2):57-63. Full-text for Emory users.

Abbreviations: ATIN, acute tubulointerstitial nephritis; CTIN, chronic
tubulointerstitial nephritis; NSAIDs, nonsteroidal anti-inflammatory
drugs; PPIs, proton pump inhibitors; SLE, systemic lupus erythematosis;
TIN, tubulointerstitial nephritis; TINU, tubulointerstitial nephritis
uveitis; DRESS, drug related eosinophilia systemic syndrome. (Perazella, p. 59)
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Vancomycin-Related Acute Kidney Injury

Zasowski EJ, et al. Identification of Vancomycin Exposure-Toxicity Thresholds in Hospitalized Patients Receiving Intravenous Vancomycin. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01684-17.

Evidence supports vancomycin therapeutic-drug monitoring by area under the concentration-time curve (AUC), but data to establish an AUC upper limit are limited and published nephrotoxicity thresholds range widely. The objective of this analysis was to examine the association between initial vancomycin AUC and nephrotoxicity. This was a multicenter, retrospective cohort study of adult patients receiving intravenous vancomycin from 2014 to 2015. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/liter and 50% from baseline on consecutive measurements. Vancomycin exposure profile during the initial 48 h of therapy was estimated using maximum a posteriori probability Bayesian estimation. Vancomycin AUC and minimum-concentration (Cmin) thresholds most strongly associated with nephrotoxicity were identified via classification and regression tree (CART) analysis. Predictive performances of CART-derived and other candidate AUC thresholds was assessed through positive and negative predictive value and receiver operating characteristic curves. Poisson regression was used to quantify the association between exposure thresholds and nephrotoxicity while adjusting for confounders. Among 323 patients included, nephrotoxicity was significantly higher in patients with AUCs from 0 to 48 h (AUC0-48) of ≥1,218 mg · h/liter, AUC0-24 of ≥677 mg · h/liter, AUC24-48 of ≥683 mg · h/liter, and day 1 Cmin (Cmin24) of ≥18.8 mg/liter. Vancomycin exposure in excess of these thresholds was associated with a 3- to 4-fold-increased risk of nephrotoxicity in Poisson regression. The predictive performance of AUC for nephrotoxicity was maximized at daily AUC values between 600 and 800 mg · h/liter. Although these data support an AUC range for vancomycin-associated nephrotoxity rather than a single threshold, available evidence suggests that a daily AUC limit of 700 mg · h/liter is reasonable.

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Risk of Acute Kidney Injury After IV Contrast Media Administration

Hinson JS, Ehmann MR, Fine DM, et al. Risk of Acute Kidney Injury After Intravenous Contrast Media Administration. Ann Emerg Med. 2017 May;69(5):577-586.e4.

Full-text for Emory users.

Results: “Rates of acute kidney injury were similar among all groups. Contrast administration was not associated with increased incidence of acute kidney injury (contrast-induced nephropathy criteria odds ratio=0.96, 95% confidence interval 0.85 to 1.08; and Acute Kidney Injury Network/Kidney Disease Improving Global Outcomes criteria odds ratio=1.00, 95% confidence interval 0.87 to 1.16). This was true in all subgroup analyses regardless of baseline renal function and whether comparisons were made directly or after propensity matching. Contrast administration was not associated with increased incidence of chronic kidney disease, dialysis, or renal transplant at 6 months. Clinicians were less likely to prescribe contrast to patients with decreased renal function and more likely to prescribe intravenous fluids if contrast was administered.”

The benefit of urinary alkalinization and mannitol in the treatment of rhabdomyolysis

One discussion this week included the benefits of urinary alkalinization and mannitol in treating rhabdomyolysis (RM).

Reference: Bada A, Smith N, and Surgical Critical Care Guidelines Committee. Rhabdomyolysis: Prevention and Treatment. SurgicalCritical 2018, Jul 24.

Summary: RM is the dissolution muscle and release of potentially toxic intracellular components into the systemic circulation. RM has the potential to cause myoglobinuric ARF in 10-15% of such patients. Overall, 10-15% of ARF in the United States is from RM.

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