McDonald, Jennifer S.

e20033 Background: HDMTX is an important component of lymphoma therapy due to its central nervous system penetration. Although HDMTX can be safely administered to most patients, it can cause significant toxicity with those who have prolonged exposure to high plasma concentrations of MTX due to delayed elimination. Therefore, serum MTX concentration monitoring is still a standard approach for identifying patients at high risk of developing MTX toxicity. A majority of MTX is excreted within the first 48 hours of infusion. Higher MTX plasma concentrations at 48 hrs increase the likelihood of delayed MTX elimination. This study will assess baseline characteristics associated with high 48-hour MTX levels (≥ 1µM) which has been associated with increased risk of complications. Methods: A retrospective review of the electronic medical record was conducted to identify lymphoma patients who received HDMTX from 1/1/2002 to 12/31/18. Baseline demographics including age, gender, comorbidities, body surface area, BMI, weight and baseline chronic kidney disease (CKD) were recorded. Demographics, HDMTX dosing per protocol (3.5g/m2 vs 8g/m2), HDMTX adjusted by renal function (CrCl < 100), and ratio of MTX dose to BSA (MTX/BSA) were compared to 48 hour MTX levels. Analysis was performed in JMP 15. Results: 2553 cycles were of HDMTX were identified. There was a significant association of increasing age, (p = 0.039), male patients (p < 0.001), 8g/m2 dosing (p < 0.001), higher MTX dose (p < 0.001), MTX/BSA (p < 0.001), GFR by CKD-EPI (p < 0.001) and lower number of comorbidities (p < 0.001) with 48-hour MTX levels ≥1. There was no significant association of 48-hour MTX levels ≥1 and GFR by Cockcroft-Gault (p = 0.73), baseline CKD (p = 0.78), and renal adjusted HDMTX (p = 0.52). Multivariate analysis revealed significance for MTX/BSA, gender, BSA, GFR by CKDEPI (p < 0.001), and age (P = 0.0002). Conclusions: Hematologists should be aware that age, gender, GFR by CKD-EPI, and ratio of MTX dose to BSA are associated with elevated 48-hour MTX levels ≥1.

8549 Background: Proteinuria evaluation is essential for diagnosing and monitoring of renal involvement in light chain (AL) amyloidosis. A 24 hour protein collection (24h UP) is the gold standard for proteinuria assessment however it is cumbersome and can be inaccurate. A spot urine albumin to creatinine ratio (uACR) has been proposed as a convenient method to estimate 24hUP. We aimed to validate the correlation between uACR and 24hUP in a large cohort of patients. Methods: We retrospectively studied systemic AL amyloidosis patients evaluated between 2010 and 2019 at Mayo Clinic, with a uACR and 24hUP collected less than 7 days apart. Linear regression analysis was used to construct a prediction model for 24hUP with uACR as the primary predictor. Possible confounders (age, gender, body mass index, morning versus afternoon spot urine collection, estimated glomerular filtration rate) for the primary relationship between uACR and 24h UP were evaluated in the model. We used receiver operating characteristic (ROC) analysis to identify the best uACR cutoff to predict significant proteinuria (defined as a 24hUP > 500mg). Results: We included 665 patients, with a median age of 66 years (IQR 59-72). The spot urine was collected in the morning (before 1200 hours) in 382 (57%) patients, and in the afternoon in 283 (43%) patients. The median 24hUP was 321 (IQR 129-2512.5) mg, median uACR was 107 (IQR 13.5-1845) mg/g, and median serum creatinine was 1.2 (IQR 1-1.8) mg/dL. The uACR correlated well with 24h UP (Pearson’s r= 0.83, 95% CI 0.80-0.85). Linear regression showed that E (24h UPi) = 362 + 1.05(uACRi), and this model was statistically and clinically significant (p < 0.001 and R2 of 0.68, respectively). Age, gender, body mass index, eGFR, and time of day of spot urine collection did not confound the primary relationship between uACR and 24hUP, and no collinearity was observed. A uACR cutoff of > 280 mg/g was the best predictor of a 24hUP > 500 mg (area under the ROC curve 0.98, sensitivity 92%, specificity 97%). For simplicity, we assessed the predictive value of uACR > 300 mg/g for 24h UP > 500 mg. Among patients with 24huACR > 300 mg/g 264 (96%) had a 24hUP > 500 mg, and 31 (7%) of patients with uACR < 300 mg/g had a 24h UP > 500 mg (p < 0.001). Conclusions: In systemic AL amyloid patients, we showed that uACR on a random urine sample correlated well with 24h UP, and can be used to estimate proteinuria with a linear regression model. Based on these findings, and the convenience of uACR testing for patients, we propose that uACR should be used to monitor renal response to AL amyloidosis therapy.

Background and Purpose— Because of the perceived risk of contrast-induced acute kidney injury (AKI), many centers require pre-imaging serum creatinine levels, potentially delaying care. We performed a systematic review and meta-analysis evaluating AKI rates in patients with acute ischemic stroke receiving computed tomographic angiography (CTA) and computed tomographic perfusion (CTP). Methods— We searched MEDLINE, EMBASE, and the Web of Science through December 2016 for studies reporting on AKI in patients with acute ischemic stroke receiving CTA/CTP. Using a random-effects model, estimates were pooled across studies. Outcomes of interest were (1) the odds of AKI in patients receiving CTA/CTP versus noncontrast computed tomography, (2) overall rate of AKI and hemodialysis in patients with acute ischemic stroke undergoing CTA/CTP, and (3) the odds of CTA/CTP-associated AKI among patients with and without chronic kidney disease. Results— Fourteen studies were included (6 case–control studies and 8 single-arm studies) with 5727 CTA/CTP and 981 noncontrast computed tomography patients. In case–control studies, AKI was significantly lower among CTA/CTP patients compared with noncontrast computed tomography patients (odds ratio=0.47; 95% confidence interval=0.33–0.68; P <0.01). Adjusting for baseline creatinine, there was no difference in AKI rates between groups (odds ratio=0.34; 95% confidence interval=0.10–1.21). The overall rate of AKI in CTA/CTP patients was 3% (95% confidence interval=2%–4%). The overall rate of hemodialysis in the CTA/CTP group was 0.07% (3 of 4373). There was no difference in AKI among CTA/CTP patients with and without chronic kidney disease (odds ratio=0.63; 95% confidence interval=0.34–1.12). Conclusions— Nonrandomized evidence suggests that CTA/CTP are not associated with statistically significant increase in risk of AKI in patients with stroke, even those with known chronic kidney disease.

ABSTRACT Intravenous radiographic contrast medium and amphotericin B are commonly required in the care of patients with fungal infections. Both interventions have proposed nephrotoxicity through similar mechanisms. We systematically examined patients who received coadministration of liposomal amphotericin B (AmBisome; GE Healthcare) and intravenous contrast medium within a 24-h period and compared the results for those patients with the results for patients who underwent non-contrast medium studies. We found 114 cases and 85 controls during our study period. Overall, no increased risk of renal injury was seen with coadministration of these 2 agents. Adjustment for age, baseline kidney function, and other clinical factors through propensity score adjustment did not change this result. Our observations suggest that, when clinically indicated, coadministration of contrast medium and liposomal amphotericin B does not present excess risk compared with that from the administration of liposomal amphotericin B alone.