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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Article of interest: Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kidney Injury in Adults With Chronic Kidney Disease: The Kompas RCT.

Timal RJ, et al Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kidney Injury in Adults With Chronic Kidney Disease: The Kompas Randomized Clinical Trial. JAMA Intern Med. 2020 Feb 17. [Epub ahead of print]

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RESULTS: Of 554 patients randomized, 523 were included in the intention-to-treat analysis. The median (interquartile range) age was 74 (67-79) years; 336 (64.2%) were men and 187 (35.8%) were women. The mean (SD) relative increase in creatinine level 2 to 5 days after contrast administration compared with baseline was 3.0% (10.5) in the no prehydration group vs 3.5% (10.3) in the prehydration group (mean difference, 0.5; 95% CI, -1.3 to 2.3; P < .001 for noninferiority). Postcontrast acute kidney injury occurred in 11 patients (2.1%), including 7 of 262 (2.7%) in the no prehydration group and 4 of 261 (1.5%) in the prehydration group, which resulted in a relative risk of 1.7 (95% CI, 0.5-5.9; P = .36). None of the patients required dialysis or developed acute heart failure. Subgroup analyses showed no evidence of statistical interactions between treatment arms and predefined subgroups. Mean hydration costs were €119 (US $143.94) per patient in the prehydration group compared with €0 (US $0) in the no prehydration group (P < .001). Other health care costs were similar.

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.

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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.”

Readmission rates following parathyroidectomy for renal disease

One discussion this week included readmission rates following parathyroidectomy.

References: Ferrandino R, et al. Unplanned 30-day readmissions after parathyroidectomy in patients with chronic kidney disease: a nationwide analysis. Otolaryngology – Head and Neck Surgery. 2017 Dec;157(6):955-965. doi:10.1177/0194599817721154.

Summary: A retrospective cohort study was performed using the 2013 Nationwide Readmissions Database (NRD) of the Healthcare Cost and Utilization Project (HCUP) from the Agency for Healthcare Research and Quality (AHRQ). In a total of 2756 parathyroidectomies performed in patients with chronic kidney disease, 17.2%  had at least one unplanned readmission rate within the first 30-days, and 2.4% had more than one readmission. Overall, readmission rates for chronic kidney disease patients are nearly 5-times that of the general population (Ferrandino et al, 2017).

Hypocalcemia/hungry bone syndrome accounted for 40% of readmissions. While readmissions occurred uniformly throughout the 30 days after discharge, those for hypocalcemia/hungry bone syndrome peaked in the first 10 days and decreased over time.

Weight loss/malnutrition at time of parathyroidectomy and length of stay of 5-6 days conferred increased risk of readmission with adjusted odds ratios of 3.31 and 1.87, respectively. Relative to primary hyperparathyroidism, parathyroidectomies performed for secondary hyperparathyroidism were associated with higher risk of readmission.

The authors conclude: “While there are few patient-specific predictors of readmission, we note that the bulk of these readmissions can be attributed to hypocalcemia. To improve readmission rates after parathyroidectomy in CKD patients, we propose focusing on accurate, appropriate medication reconciliation, and optimizing communication and transitions of care to outside facilities (skilled nursing, dialysis, etc.) to facilitate the comprehensive care of this high-risk patient population” (Ferrandino et al, p.964).

Additional Reading: Sharma J, et al. Improved long-term survival of dialysis patients after near-total parathyroidectomy. Journal of the American College of Surgeons. 2012 Apr;214(4):400-407. doi:10.1016/j.jamcollsurg.2011.12.046.

Westerdahl J, et al. Risk factors for postoperative hypocalcemia after surgery for primary hyperparathyroidism. Archives of Surgery. 2000 Feb;135(2):142-147.