The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis

2021 ◽  
pp. ASN.2021030382
Author(s):  
Sarah Moran ◽  
Jennifer Scott ◽  
Michael Clarkson ◽  
Niall Conlon ◽  
Jean Dunne ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Kidney Injury ◽  
Urine Protein ◽  
Prospective Multicenter Study ◽  
Soluble Cd163 ◽  
Anca Associated Vasculitis ◽  
Renal Vasculitis ◽  
Total Urine ◽  
Nephrotic Range Proteinuria ◽  
Positive Results

Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop glomerulonephritis, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (sCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade urinary sCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and 10 controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, urinary sCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic acute kidney injury. Urinary sCD163's specificity declined in AAV patients with nephrotic-range proteinuria and in primary podocytopathy, with 62% of nephrotic patients displaying a "positive" urinary sCD163. In AAV patients with significant proteinuria, urinary sCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions Urinary sCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates urinary sCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

scholarly journals Proteinuria as a Biomarker for COVID-19 Severity

2021 ◽  
Vol 12 ◽  
Author(s):  
Hajar Ouahmi ◽  
Johan Courjon ◽  
Lucas Morand ◽  
Juliette François ◽  
Vincent Bruckert ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Protein Electrophoresis ◽  
Biological Data ◽  
Urine Protein ◽  
Prospective Multicenter Study ◽  
Icu Admission ◽  
Protein Excretion ◽  
D Dimer

BackgroundRenal involvement in syndrome coronavirus 2 (SARS-CoV-2) infection has been retrospectively described, especially acute kidney injury (AKI). However, quantitative proteinuria assessment and its implication in coronavirus disease 2019 (COVID-19) remain unknown.MethodsIn this prospective, multicenter study in France, we collected clinical and biological data including urinary protein to creatine ratio (UPCR) in patients presenting with moderate to severe COVID-19. Clinical outcome was analyzed according to the level of UPCR.Results42/45 patients (93.3%) had renal involvement (abnormal urinary sediment and/or AKI). Significant proteinuria occurred in 60% of patients. Urine protein electrophoresis showed tubular protein excretion in 83.8% of patients with proteinuria. Inflammatory parametersand D-dimer concentrations correlated with proteinuria level. Patients who required intensive care unit (ICU) admission had higher proteinuria (p = 0.008). On multivariate analysis, proteinuria greater than 0.3 g/g was related to a higher prevalence of ICU admission [OR = 4.72, IC95 (1.16–23.21), p = 0.03], acute respiratory distress syndrome (ARDS) [OR = 6.89, IC95 (1.41–53.01, p = 0.02)], nosocomial infections [OR = 3.75, IC95 (1.11–13.55), p = 0.03], longer inpatient hospital stay (p = 0.003).ConclusionRenal involvement is common in moderate to severe SARS-CoV-2 infection. Proteinuria at baseline is an independent risk factor for increased hospitalization duration and ICU admission in patients with COVID-19.

scholarly journals Checkpoint inhibitor-related renal vasculitis and use of rituximab

2020 ◽  
Vol 8 (2) ◽  
pp. e000750 ◽  
Author(s):  
Omar Mamlouk ◽  
Jamie S Lin ◽  
Maen Abdelrahim ◽  
Amanda S Tchakarov ◽  
William F Glass ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Checkpoint Inhibitor ◽  
Treatment Options ◽  
Kidney Injury ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Lung Involvement ◽  
Patients With Cancer ◽  
Anca Associated Vasculitis ◽  
Renal Vasculitis

The percentage of patients with cancer eligible for checkpoint inhibitor (CPI) therapy has increased rapidly over the past few years and approaches 45%. As a result, more cases of CPI-related nephrotoxicity, including a rare subset with vasculitis, are being reported. To elucidate the clinical presentation of CPI-associated renal vasculitis and its possible mechanisms, treatment options and prognosis, we describe cases from a comprehensive cancer center and reviewed the literature for similar cases. We retrospectively reviewed the charts of all patients with cancer from 2014 to 2020 who were diagnosed with CPI-related nephrotoxicity and underwent a kidney biopsy. We identified five cases of renal vasculitis: three patients were diagnosed with seronegative antineutrophil cytoplasm antibody (ANCA)-associated vasculitis, one case with seropositive ANCA-associated vasculitis and one case was diagnosed with IgA vasculitis. Of these cases, four patients were receiving nivolumab, and one patient was receiving tremelimumab. All patients had microscopic hematuria, four out of five patients had negative ANCA serology, one patient had concurrent lung involvement and positive ANCA serology, and all had severe acute kidney injury with creatinine >4.50 mg/dL on diagnosis. All patients were treated by discontinuing CPI and initiating corticosteroids and rituximab. Three patients received plasmapheresis; two of these required renal replacement therapy including the patient with lung involvement. All patients after rituximab had a partial or complete renal response. Two patients died within 8 months of diagnosis due to malignancy progression. None of the patients had a relapse of vasculitis. We demonstrated that CPI can be associated with different types of renal vasculitis that are predominantly ANCA negative and manifest as severe acute kidney injury. Despite the lack of strong evidence, treatment similar to treatment of primary seropositive ANCA-associated vasculitis with corticosteroids and rituximab is well tolerated with favorable renal outcomes.

scholarly journals Development of a practical prediction score for acute renal injury after surgery for Stanford type A aortic dissection

2020 ◽  
Vol 30 (5) ◽  
pp. 746-753
Author(s):  
Ning Dong ◽  
Hulin Piao ◽  
Yu Du ◽  
Bo Li ◽  
Jian Xu ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Risk Score ◽  
Scoring System ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Type A ◽  
Postoperative Management ◽  
Prediction Score ◽  
Improve Patient

Abstract OBJECTIVES Acute kidney injury (AKI) is a common complication of cardiovascular surgery that is associated with increased mortality, especially after surgeries involving the aorta. Early detection and prevention of AKI in patients with aortic dissection may help improve outcomes. The objective of this study was to develop a practical prediction score for AKI after surgery for Stanford type A acute aortic dissection (TAAAD). METHODS This was a retrospective cohort study that included 2 independent hospitals. A larger cohort of 326 patients from The Second Hospital of Jilin University was used to identify the risk factors for AKI and to develop a risk score. The derived risk score was externally validated in a separate cohort of 102 patients from the other hospital. RESULTS The scoring system included the following variables: (i) age >45 years; (ii) body mass index >25 kg/m2; (iii) white blood cell count >13.5 × 109/l; and (iv) lowest perioperative haemoglobin <100 g/l, cardiopulmonary bypass duration >150 min and renal malperfusion. On receiver operating characteristic curve analysis, the score predicted AKI with fair accuracy in both the derivation [area under the curve 0.778, 95% confidence interval (CI) 0.726–0.83] and the validation (area under the curve 0.747, 95% CI 0.657–0.838) cohorts. CONCLUSIONS We developed a convenient scoring system to identify patients at high risk of developing AKI after surgery for TAAAD. This scoring system may help identify patients who require more intensive postoperative management and facilitate appropriate interventions to prevent AKI and improve patient outcomes.

scholarly journals 1310. Implementation of AUC:MIC Pharmacy to Dose in an Academic Medical Center: A Pilot Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S667-S668
Author(s):  
Ann-Marie Idusuyi ◽  
Maureen Campion ◽  
Kathleen Belusko
Keyword(s):  
Medical Center ◽  
Academic Medical Center ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Retrospective Chart Review ◽  
Total Daily Dose ◽  
Therapeutic Goals ◽  
Academic Medical ◽  
Progress Notes ◽  
Implementation Period

Abstract Background The new ASHP/IDSA consensus guidelines recommend area under the curve (AUC) monitoring to optimize vancomycin therapy. Little is known about the ability to implement this recommendation in a real-world setting. At UMass Memorial Medical Center (UMMMC), an AUC pharmacy to dose protocol was created to manage infectious diseases (ID) consult patients on vancomycin. The service was piloted by the pharmacy residents and 2 clinical pharmacists. The purpose of this study was to determine if a pharmacy to dose AUC protocol can safely and effectively be implemented. Methods A first-order kinetics calculator was built into the electronic medical record and live education was provided to pharmacists. Pharmacists ordered levels, wrote progress notes, and communicated to teams regarding dose adjustments. Patients were included based upon ID consult and need for vancomycin. After a 3-month implementation period, a retrospective chart review was completed. Patients in the pre-implementation group were admitted 3 months prior to AUC pharmacy to dose, had an ID consult and were monitored by trough (TR) levels. The AUC group was monitored with a steady state peak and trough level to calculate AUC. The primary outcome evaluated time to goal AUC vs. time to goal TR. Secondary outcomes included number of dose adjustments made, total daily dose of vancomycin, and incidence of nephrotoxicity. Results A total of 64 patients met inclusion criteria, with 37 patients monitored by TR and 27 patients monitored by AUC. Baseline characteristics were similar except for weight in kilograms (TR 80.0 ±25.4 vs AUC 92.0 ±26.7; p=0.049). The average time to goal AUC was 4.13 (±2.08) days, and the average time to goal TR was 4.19 (±2.30) days (p=0.982). More dose adjustments occurred in the TR group compared to the AUC (1 vs 2; p=0.037). There was no difference between the two groups in dosing (TR 15.8 mg/kg vs AUC 16.4 mg/kg; p=0.788). Acute kidney injury occurred in 5 patients in the AUC group and 11 patients in the TR group (p=0.765). Conclusion Fewer dose adjustments and less nephrotoxicity was seen utilizing an AUC based protocol. Our small pilot has shown that AUC pharmacy to dose can be safely implemented. Larger studies are needed to evaluate reduction in time to therapeutic goals. Disclosures All Authors: No reported disclosures

scholarly journals Poor Glycemic Control Can Increase the Plasma Kidney Injury Molecule-1 Concentration in Normoalbuminuric Children and Adolescents with Diabetes Mellitus

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 417
Author(s):  
Moon Bae Ahn ◽  
Kyoung Soon Cho ◽  
Seul Ki Kim ◽  
Shin Hee Kim ◽  
Won Kyoung Cho ◽  
...  
Keyword(s):  
Glycosylated Hemoglobin ◽  
Significant Risk ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Significant Risk Factor ◽  
Controlled Study ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Diabetic Children ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Diabetic nephropathy (DN) is a serious microvascular complication in childhood diabetes and microalbuminuria has been a solid indicator in the assessment of DN. Nevertheless, renal injury may still occur in the presence of normoalbuminuria (NA) and various tubular injury biomarkers have been proposed to assess such damage. This case-controlled study aimed to evaluate plasma and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (KIM-1) levels in diabetic children particularly in those with normo- and high-NA stages and determine their role in predicting DN. Fifty-four children/adolescents with type 1 and 2 diabetes and forty-four controls aged 7–18 years were included. The baseline clinical and laboratory characteristics including plasma and urinary biomarkers were compared. The plasma KIM-1 levels were significantly higher in diabetic children than in the controls and in high-NA children than normo-NA children. Glycosylated hemoglobin (HbA1c) was identified as a significant risk factor for increased plasma KIM-1. The optimal cutoff for HbA1c when the plasma KIM-1 was > 23.10 pg/mL was 6.75% with an area under the curve of 0.77. For diabetic children with mildly increased albuminuria, the plasma KIM-1 complementary to MA may help increase the yield of detecting DN. Our findings also suggested an HbA1c cutoff of 6.75% correlated with increased plasma KIM-1.

scholarly journals An unusual precipitant of acute heart failure—ANCA-associated vasculitis in a patient with ischaemic cardiomyopathy: a case report

2020 ◽  
Author(s):  
Krishna Prasad ◽  
Pruthvi C Revaiah ◽  
Krishna Santosh Vemuri ◽  
Parag Barwad
Keyword(s):  
Heart Failure ◽  
Renal Failure ◽  
Acute Heart Failure ◽  
Acute Decompensated Heart Failure ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Left Ventricular ◽  
Alveolar Haemorrhage ◽  
Coronary Syndrome ◽  
Anca Associated Vasculitis ◽  
Renal Vasculitis

Abstract Background Antineutrophil cytoplasmic antibody (ANCA)-associated pulmonary renal vasculitis is an uncommon disease entity. Its presentation as acute heart failure for the first time in a patient with established coronary artery disease (CAD) is even rarer. We present here a case of such an association and an approach to managing this clinical situation. Case summary A 60-year-old male patient presented to the emergency room with recent-onset dyspnoea New York Heart Association Class IV. He was having hypertension, uncontrolled diabetes mellitus, chronic kidney disease (CKD), and CAD. He also underwent a percutaneous coronary intervention to left anterior descending in the past for acute coronary syndrome and had moderate left ventricular dysfunction. He was being managed as a case of acute decompensated heart failure (ADHF) and was mechanically ventilated. Suddenly his ventilator requirement increased and endotracheal aspirate contained blood. The chest radiograph showed bilateral hilar infiltrates. Simultaneously he also had recurrent episodes of ventricular tachycardia (VT) requiring direct current (DC) cardioversion. Blood investigations showed deranged renal function and severe hyperkalaemia, but no evidence of coagulopathy. High-resolution computed tomography chest showed features of diffuse alveolar haemorrhage. Further investigations revealed high titres of c-ANCA and raised inflammatory biomarkers. A diagnosis of ANCA-associated vasculitis presenting as acute on CKD with dyselectrolytaemia (hyperkalaemia) leading to VT was made. Apart from standard management for associated illness, he was treated with plasma exchange, steroids, and cyclophosphamide to which he responded and was later on discharged. Discussion Antineutrophil cytoplasmic antibody-related pulmonary renal vasculitis can lead to rapidly progressing renal failure and may present as ADHF in a patient with existent CAD. The associated VT storm in our patient can be attributed to hyperkalaemia secondary to acute renal failure. A multidisciplinary approach is required for the successful management of such a complex clinical scenario.

scholarly journals P0614URINARY EXOSOMAL MICRORNA-21 AS A MARKER OF SCRUB TYPHUS-ASSOCIATED ACUTE KIDNEY INJURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
In O Sun ◽  
Kwang Young Lee ◽  
A Young Cho
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Scrub Typhus ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Diagnostic Value ◽  
Cross Sectional Study ◽  
Total Leukocyte Count ◽  
Cross Sectional ◽  
Exosomal Mirna

Abstract Background and Aims Urinary microRNA (miRNA)-21 is reported to be a biomarker for detection of acute kidney injury (AKI). Analysis of urinary exsome may serve as a novel diagnostic approach in kidney disease. The aim of this study is to investigate the clinical significance of urinary exosomal miRNA-21 for AKI in patients with scrub typhus. Method In a cross-sectional study, we collected 138 urine samples at the time of admission from 145 patients with scrub typhus. For 25 patients with scrub typhus-associated AKI and 25 age, sex-matched scrub typhus patient without AKI, we measured miRNA-21 in urinary exosomal fraction and compared diagnostic value in predictiong AKI. Results Compared with patients in the non-AKI group, patients in the AKI group were more likely to have one or more comorbidity such as diabetes (50% vs. 5%, P<0.01) and chronic kidney disease (8% vs. 0%, P<0.01). Total leukocyte count were higher in patients with AKI than in those without AKI (10.40 × 103/ mL vs. 6.40 × 103/mL, P<0.01). The levels of urinary miRNA-21 were higher in the AKI group than in the non-AKI group. Urinary exosomal miRNA-21 levels correlated directly with serum neutrophil gelatinase-associated lipocalin values and total leukocyte counts and inversely with estimated glomerular filtration rate. The receiver operator characteristics curve analysis for urinary exosomal miRNA-21 showed good discriminative power for the diagnosis of scrub typhus-associated AKI, with area under the curve value of 0.907. Conclusion Urinary exosomal miRNA-21 could be a surrogate markers for the diagnosis of scrub typhus–associated AKI.

scholarly journals Neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in children after cardiac surgery

2016 ◽  
Vol 56 (4) ◽  
pp. 230
Author(s):  
Meta Herdiana Hanindita ◽  
Riskky Vitria Prasetyo ◽  
Ninik Asmaningsih Soemyarso ◽  
I Ketut Alit Utamayasa ◽  
Paul Tahalele
Keyword(s):  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Creatinine Clearance ◽  
Sensitivity And Specificity ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Schwartz Formula ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Plasma Ngal ◽  
Neutrophil Gelatinase

Background Acute kidney injury (AKI) is still diagnosed by measuring the estimated creatinine clearance (eCCl), despite the fact that it may not change until 50% or more of kidney function has been lost. AKI after cardiac surgery is related to prolonged intensive care, decreased quality of life, and increased long term mortality. Neutrophil gelatinase-associated lipocalin (NGAL) represents an early biomarker of AKI, which may be useful for assessing AKI in cardiac patients.Objective To determine the validity of urinary and plasma NGAL as biomarkers for AKI in children after cardiac surgery.Methods Subjects were children who underwent cardiac surgery in Dr. Soetomo Hospital, Surabaya, Indonesia from August 2013 to January 2014. Serial urine and blood samples were analyzed for NGAL before surgery, as well as at 2h, 4h, 12h, and 24h after surgery. The AKI was established based on pRIFLE criteria. Estimated creatinine clearance (eCCl) was calculated from the estimated glomerular filtration rate (eGFR), according to age by the traditional Schwartz formula. Serum creatinine was assayed by the Jaffe method before surgery, as well as at 12h, 24h, 48h, and 72h after surgery.Results Of 20 subjects, 5 developed AKI. Urinary and plasma NGAL increased markedly at 2h postoperatively, as compared to eGFR which showed a rise at 12-48 h after cardiac surgery. Analysis of 2h post-operative urinary NGAL at a cut off value of 11.270ng/mL yielded an area under the curve (AUC) of 1.00 (95%CI 2.63 to 12.13), with sensitivity and specificity of 100% each for AKI. In addition, 2h post-operative plasma NGAL at a cut off value of 8.385 ng/mL yielded an AUC of 1.00 (95%CI 3.71 to 12.15) with sensitivity and specificity of 100% each for AKI.Conclusion Urinary and plasma NGAL are valid as early biomarkers for AKI in children after cardiac surgery.

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