INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America. METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes. RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 μg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] μg/g creatinine) from prerenal AKI (45 [0, 154] μg/g) or HRS (110 [50, 393] μg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] μg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival ( P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02). DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing. Multi-center study of consecutive patients with COVID-19 receiving CRRT. Primary outcome was CRRT filter loss. Sixty-five patients were analyzed, including 17 using an anti-factor Xa protocol to guide systemic heparin dosing. Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 [2.5, 33.5] h. There was no difference in first or second filter loss between the anti-Xa protocol and standard of care anticoagulation groups, however fewer patients lost their third filter in the protocolized group (55% vs. 93%) resulting in a longer median third filter survival time (24 [15.1, 54.2] vs. 17.3 [9.5, 35.1] h, p = 0.04). The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is reasonable approach to anticoagulation in this population.

Background/Aims The MELD score was developed to predict survival after transjugular intrahepatic portosystemic shunt (TIPS) placement. Given changes in practice patterns and development of new prognostic tools in cirrhosis, we aimed to evaluate common models to predict mortality after TIPS placement. Methods Analysis of consecutive patients who underwent TIPS placement for ascites or bleeding. Performance to predict 90-day mortality was assessed by C statistic for six models (MELD, MELD-Na, CLIF-C ACLF, Child-Pugh, Platelet-Albumin-Bilirubin, and Emory score). Added predictive value to MELD score was assessed for univariate predictors of 90-day mortality. Stratified analysis by TIPS indication, emergent placement status, and TIPS stent type was performed. Results 413 patients were analyzed (248 with variceal bleeding, 165 with refractory ascites). 90-day mortality was 27% (113/413). Mean MELD score was 15 ± 7.9. MELD score best predicted mortality for all patients (c = 0.779), for variceal bleeding (c = 0.844), and for emergent TIPS (c = 0.817). CLIF-C ACLF score best predicted mortality for refractory ascites (c = 0.707). Addition of sodium to the MELD score did not improve predictive value across multiple strata. Addition of hemoglobin improved MELD score’s predictive value in variceal bleeding. Addition of age improved MELD score’s predictive value in refractory ascites. Conclusions MELD score best predicted 90-day mortality. Addition of sodium to the MELD score did not improve its performance, though mortality prediction was improved using Age-MELD for ascites and Hemoglobin-MELD for bleeding. An individualized risk stratification approach may be best when considering candidates for TIPS placement.

Background: Continuous renal replacement therapy (CRRT) is commonly employed in the intensive care unit (ICU), though there are no guidelines around the transition between CRRT and intermittent hemodialysis (iHD). Accelerated venovenous hemofiltration (AVVH) is a modality utilizing higher hemofiltration rates (4–5 L/h) with shorter session durations (8–10 h) to “accelerate” the clearance and volume removal that normally is spread out over a 24-h period in CRRT. We examined AVVH as a transition therapy between CRRT and iHD, with the aim of decreasing time on CRRT and providing a more graduated transition for hemodynamically unstable patients requiring RRT. Methods: Retrospective cohort study describing the clinical outcomes and quality initiative experience of the integration of AVVH into the CRRT program at an academic tertiary care center. Outcomes of interest included mortality, ICU length of stay and readmission rates, and technical characteristics of treatments. Results: In total, 97 patients received a total of 298 AVVH treatments (3.1 ± 3.3 treatments per patient). Totally, 271/298 (91%) treatments were completed successfully. During an average treatment time of 9.5 ± 1.6 h with 4.2 ± 0.5 L/h ­replacement fluid rate, urea reduction ratio was 23 ± 26% per 10-h treatment, and net ultrafiltration volume was 2.4 ± 1.3 L/treatment. Inpatient mortality was 32%, mean total hospital length of stay was 54 ± 47 days. Sixty-four out of 97 (66%) patients recovered renal function by discharge. Among those who transferred out of the ICU, 7/62 (11%) patients required readmission to the ICU after developing hypotension on iHD. Conclusion: AVVH can serve as a transition therapy between CRRT and iHD in the ICU and has the potential to decrease total time on CRRT, improve patient mobility, and sustain low ICU readmission rates. Future study is needed to analyze the implications on resource use and cost of this modality.

BackgroundAcute interstitial nephritis is an immune-related adverse event that can occur in patients receiving immune checkpoint inhibitor therapy. Differentiating checkpoint inhibitor-associated acute interstitial nephritis from other causes of acute kidney injury in patients with cancer is challenging and can lead to diagnostic delays and/or unwarranted immunosuppression. In this case report, we assess the use of 18F-flourodeoxyglucose positron-emission tomography imaging as an alternative diagnostic modality in the evaluation of potential acute interstitial nephritis.Case presentationA 55-year-old woman with metastatic vulvar melanoma underwent treatment with two cycles of ipilimumab plus nivolumab, followed by seven cycles of nivolumab combined with radiation therapy. During her treatment, she developed non-oliguric acute kidney injury to a creatinine of 4.5 mg/dL from a baseline of 0.5 mg/dL. A clinical diagnosis of acute interstitial nephritis was made, and steroids were initiated, with rapid improvement of her acute kidney injury. Retrospectively, four positron-emission tomography scans obtained for cancer staging purposes were reviewed. We found a markedly increased 18F-flourodeoxyglucose uptake in the renal cortex at the time acute interstitial nephritis was diagnosed compared to baseline. In three cases of acute kidney injury due to alternative causes there was no increase in 18F-flourodeoxyglucose uptake from baseline.ConclusionsTo our knowledge, this is the first report describing increased 18F-flourodeoxyglucose uptake in the renal cortex in a patient with checkpoint inhibitor-associated acute interstitial nephritis. Our findings suggest that 18F-flourodeoxyglucose positron-emission tomography may be a valuable test for diagnosing immune-mediated nephritis, particularly in patients where timely kidney biopsy is not feasible.

The desymmetrization of ten prochiral diols by phosphoryl transfer with a titanium-BINOLate complex is discussed. The phosphorylation of nine 1,3-propane diols is achieved in yields of 50–98%. Enantiomeric ratios as high as 92:8 are achieved with diols containing a quaternary C-2 center incorporating a protected amine. The chiral ligand, base, solvent, and stoichiometry are evaluated along with a nonlinear effect study to support an active catalyst species that is oligomeric in chiral ligand. The use of pyrophosphates as the phosphorylating agent in the desymmetrization facilitates a user-friendly method for enantioselective phosphorylation with desirable protecting groups (benzyl, o-nitrobenzyl) on the phosphate product.

Eligible patients included low/intermediate risk prostate cancer cT1-2, N0 M0, Gl 6-7, PSA <20 with an IPSS 12. Intermediate risk patients received up to six mo. of ADT. IPSS scores were obtained prior to treatment, last week of treatment at 6 wks., 3 mo. and then every 6 mo.; EPIC-SF12/Max-PC prior to treatment 6 wks., 3 mo. and then every 6 mo. Toxicity (CTCAE4.0) at baseline, weekly during treatment, 6 wks., 3 mo. and then every 6 mo. Cumulative incidence estimation was used to calculate toxicity incidence rate and Mann-Whitney test was used to compare QOL scores between two arms. All p-values were two-sided. Results: As of January 2017, 54 pts had completed treatment, with 11.5 mo. median follow-up (mean 17.2). A total of 70% of the patients were intermediate risk. Patients were evenly distributed by age, Gleason score, t stage, risk group, race, and ADT use. Between the two arms there was no difference in the cumulative incident of grade 2+ GU toxicity (PZ0.97) or GI toxicity (PZ0.181). Fifteen mo. rates were 19%v 12% GU, and 12% v 0% GI. One grade 3 toxicity (EHRT) was observed. There was no significant difference in EPIC-SF12 or Max-PC scores at any time point between the 2 arms in sum score or change from baseline. For IPSS there were statistically significant differences at 6wks (pZ0.0049), 9mo (pZ0.0009), 15mo (pZ0.0076) in favor of AHRT (lower IPSS score). Conclusion: There were no differences in early GI and GU toxicities or PRO measures between AHRT and EHRT. This early analysis suggests that AHRT has decreased urinary symptoms as measured by IPSS. While we await clinical efficacy data, these data suggest little difference in toxicity with AHRT, partially alleviating concerns related to the toxicity of this regimen.

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