Kidney Injury
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2021 ◽  
Vol 8 ◽  
Yi Cheng ◽  
You Zhang ◽  
Boxiang Tu ◽  
Yingyi Qin ◽  
Xin Cheng ◽  

Objective: This study aimed to explore the association between base excess (BE) and the risk of 30-day mortality among patients with acute kidney injury (AKI) in the intensive care unit (ICU).Methods: This retrospective study included patients with AKI from the Medical Information Mart for Intensive Care (MIMIC)-IV database. We used a multivariate Cox proportional-hazards model to obtain the hazard ratio (HR) for the risk of 30-day mortality among patients with AKI. Furthermore, we utilized a Cox proportional-hazard model with restricted cubic splines (RCS) to explore the potential non-linear associations.Results: Among the 14,238 ICU patients with AKI, BE showed a U-shaped relationship with risk of 30-day mortality for patients with AKI, and higher or lower BE values could increase the risk. Compared with normal base excess (−3~3 mEq/L), patients in different groups (BE ≤ −9 mEq/L, −9 mEq/L < BE ≤ −3 mEq/L, 3 mEq/L < BE ≤ 9 mEq/L, and BE > 9 mEq/L) had different HRs for mortality: 1.57 (1.40, 1.76), 1.26 (1.14, 1.39), 0.97 (0.83, 1.12), 1.53 (1.17, 2.02), respectively. The RCS analyses also showed a U-shaped curve between BE and the 30-day mortality risk.Conclusion: Our results suggest that higher and lower BE in patients with AKI would increase the risk of 30-day mortality. BE measured at administration could be a critical prognostic indicator for ICU patients with AKI and provide guidance for clinicians.

2021 ◽  
Vol 10 (23) ◽  
pp. 5684
Benedikt Frank ◽  
Jordi Kühne Escolà ◽  
Leoni Biermann-Ratjen ◽  
Anika Hüsing ◽  
Yan Li ◽  

Background: Our aim was to investigate the relationship between additional iodinated contrast medium (CM) application for acute stroke imaging and Post-Contrast Acute Kidney Injury (PC-AKI). Methods: We performed a retrospective analysis of consecutive patients with acute stroke who received a CT angiogram (CTA) with or without additional CT perfusion (CTP) at admission between 2017 and 2020. The primary endpoint was the incidence of PC-AKI. Potential causes of renal function impairment were recorded and logistic regression was performed to determine predictors of PC-AKI. Results: Of 3134 cases screened, n = 989 met the predefined inclusion criteria. PC-AKI occurred in 22 (5.4%) patients who received CTA only and 18 (3.1%) patients who received CTA and additional CTP (unadjusted OR, CI; 0.59, 0.29–1.05). In 31/40 (77.5%) patients who suffered PC-AKI, a non-CM-related cause of renal function impairment was identified. Stroke etiology (hemorrhagic vs. ischemic) and indicators of prior kidney disease were independent predictors of PC-AKI. Conclusions: Additional administration of CM for perfusion imaging in acute stroke did not show a relevant influence on the occurrence of PC-AKI. Patients with intracranial hemorrhage and/or prior kidney disease are at particular risk of developing AKI.

2021 ◽  
Vol 22 (1) ◽  
Elisabet Jacobsen ◽  
Simon Sawhney ◽  
Miriam Brazzelli ◽  
Lorna Aucott ◽  
Graham Scotland ◽  

Abstract Background Early and accurate acute kidney injury (AKI) detection may improve patient outcomes and reduce health service costs. This study evaluates the diagnostic accuracy and cost-effectiveness of NephroCheck and NGAL (urine and plasma) biomarker tests used alongside standard care, compared with standard care to detect AKI in hospitalised UK adults. Methods A 90-day decision tree and lifetime Markov cohort model predicted costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) from a UK NHS perspective. Test accuracy was informed by a meta-analysis of diagnostic accuracy studies. Clinical trial and observational data informed the link between AKI and health outcomes, health state probabilities, costs and utilities. Value of information (VOI) analysis informed future research priorities. Results Under base case assumptions, the biomarker tests were not cost-effective with ICERs of £105,965 (NephroCheck), £539,041 (NGAL urine BioPorto), £633,846 (NGAL plasma BioPorto) and £725,061 (NGAL urine ARCHITECT) per QALY gained compared to standard care. Results were uncertain, due to limited trial data, with probabilities of cost-effectiveness at £20,000 per QALY ranging from 0 to 99% and 0 to 56% for NephroCheck and NGAL tests respectively. The expected value of perfect information (EVPI) was £66 M, which demonstrated that additional research to resolve decision uncertainty is worthwhile. Conclusions Current evidence is inadequate to support the cost-effectiveness of general use of biomarker tests. Future research evaluating the clinical and cost-effectiveness of test guided implementation of protective care bundles is necessary. Improving the evidence base around the impact of tests on AKI staging, and of AKI staging on clinical outcomes would have the greatest impact on reducing decision uncertainty.

2021 ◽  
Vol 12 ◽  
Swastika Sur ◽  
Mark Nguyen ◽  
Patrick Boada ◽  
Tara K. Sigdel ◽  
Hans Sollinger ◽  

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p < 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p < 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7307
Dong Zhang ◽  
Mojiao Zhao ◽  
Yumei Li ◽  
Dafang Zhang ◽  
Yong Yang ◽  

Xanthine oxidase (XOD) inhibition has long been considered an effective anti-hyperuricemia strategy. To identify effective natural XOD inhibitors with little side effects, we performed a XOD inhibitory assay-coupled isolation of compounds from Smilacis Glabrae Rhizoma (SGR), a traditional Chinese medicine frequently prescribed as anti-hyperuricemia agent for centuries. Through the in vitro XOD inhibitory assay, we obtained a novel XOD inhibitor, 5-O-caffeoylshikimic acid (#1, 5OCSA) with IC50 of 13.96 μM, as well as two known XOD inhibitors, quercetin (#3) and astilbin (#6). Meanwhile, we performed in silico molecular docking and found 5OCSA could interact with the active sites of XOD (PDB ID: 3NVY) with a binding energy of −8.6 kcal/mol, suggesting 5OCSA inhibits XOD by binding with its active site. To evaluate the in vivo effects on XOD, we generated a hyperuricemia mice model by intraperitoneal injection of potassium oxonate (300 mg/kg) and oral gavage of hypoxanthine (500 mg/kg) for 7 days. 5OCSA could inhibit both hepatic and serum XOD in vivo, together with an improvement of histological and multiple serological parameters in kidney injury and HUA. Collectively, our results suggested that 5OCSA may be developed into a safe and effective XOD inhibitor based on in vitro, in silico and in vivo evidence.

Nephron ◽  
2021 ◽  
pp. 1-7
Tolga Yildirim ◽  
Ebru Gok-Oguz ◽  
Neriman Sila Koc ◽  
Muge Uzerk-Kibar ◽  
Meral Uner ◽  

<b><i>Introduction:</i></b> Patients with AA amyloidosis may present with acute kidney injury that progresses to end-stage kidney disease in a short period of time. Acute allergic tubulointerstitial nephritis (aTIN) is a frequent cause of acute kidney injury in patients with AA amyloidosis. Although aTIN has a favorable prognosis in the general population, the course of aTIN in patients with AA amyloidosis was not previously reported. In this retrospective study, we determined the prognosis of aTIN superimposed on AA amyloidosis. <b><i>Methods:</i></b> Thirty-two patients with combined pathological diagnosis of AA amyloidosis + aTIN and 32 patients with isolated aTIN were compared in terms of 1-year renal functions after the biopsies were performed with an indication of acute kidney injury. Baseline renal functions and number of patients requiring hemodialysis at the time of biopsy was similar in both groups. <b><i>Results:</i></b> At the end of the 12-month follow-up period, 29 of 32 patients in the amyloidosis + aTIN group and 1 of 32 patients in the isolated aTIN group required dialysis. Most of these patients with AA amyloidosis had completely normal renal function before the episode of acute kidney injury and had clear exposures to drugs associated with aTIN. <b><i>Conclusion:</i></b> In contrary to the patients without AA amyloidosis, patients with AA amyloidosis have extremely high risk of permanent renal failure in case of development of aTIN. Great caution should be exercised in prescribing drugs that are associated with aTIN, in patients with AA amyloidosis.

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