scholarly journals MO335URINARY CYTOKINES REFLECT THE ONGOING RENAL INFLAMMATION IN THE DIAGNOSTIC OF ACUTE TUBULOINTERSTITIAL NEPHRITIS: RESULTS OF A MULTIPLEX BEAD-BASED ASSAY ASSESSMENT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Laura Martinez Valenzuela ◽  
Juliana Draibe ◽  
Xavier Fulladosa ◽  
Francisco Gomez Preciado ◽  
Ernest Nadal ◽  
...  
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Urinary Concentration ◽  
Blood Eosinophil ◽  
Healthy Controls ◽  
Acute Tubulointerstitial Nephritis ◽  
Positive Correlation ◽  
Luminex Assay ◽  
Urinary Levels ◽  
Multiplex Bead

Abstract Background and Aims Acute tubulointerstitial nephritis (ATIN) diagnostic lays on the kidney biopsy given the absence of non-invasive biomarkers for disease demonstration and follow-up. The aim of this study was to evaluate the accuracy of ten urinary inflammatory-related cytokines in the diagnostic of ATIN and its clinical distinction from acute tubular necrosis (ATN). Method Observational prospective study including 21 ATIN and 12 ATN patients, and 6 healthy controls. We determined the urinary levels of 10 inflammation-related cytokines using a multiplex bead-based Luminex assay. We registered clinical, analytical and histological data from the medical records. Results Urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFα and MCP-1 were higher in ATIN compared to healthy controls. In contrast, healthy controls exhibited higher EGF urinary levels compared to ATIN patients. Follow-up samples available from 11/21 ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/CXCL9 and CXCL10 levels. Urinary levels of I-TAC/CXCL11, IL-6 and MCP-1 were significantly higher in ATIN compared to ATN patients, with I-TAC/CXCL11 as the best discriminatory biomarker based on its higher AUC in the ROC curve and likelihood ratio. The combinatory model of the three cytokines increased the sensitivity of the individual biomarkers in the distinction of ATIN/ATN but the best results were obtained when blood eosinophil count and leukocyturia were added to the model. We found a positive correlation of the extent of the tubulointerstitial infiltrate in kidney biopsies with the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10, IL17, IFNα, MCP1 and EGF, indicating the potential renal source of the cytokines Conclusion the higher cytokine levels in ATIN compared to ATN patients and healthy controls, the significant decline after treatment and the positive correlation of the cytokines with the grade of the inflammatory infiltrate allows us to propose I-TAC/CXCL11, CXCL10, IL6 and MCP-1 as candidate biomarkers in this disease.

scholarly journals Urinary Cytokines Reflect Renal Inflammation in Acute Tubulointerstitial Nephritis: A Multiplex Bead-Based Assay Assessment

2021 ◽  
Vol 10 (13) ◽  
pp. 2986
Author(s):  
Laura Martinez Valenzuela ◽  
Juliana Draibe ◽  
Oriol Bestard ◽  
Xavier Fulladosa ◽  
Francisco Gómez-Preciado ◽  
...  
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Urinary Concentration ◽  
Blood Eosinophil ◽  
Acute Tubulointerstitial Nephritis ◽  
Luminex Assay ◽  
Non Invasive ◽  
Urinary Levels ◽  
Histological Data ◽  
The Individual ◽  
Multiplex Bead

Background: Acute tubulointerstitial nephritis (ATIN) diagnosis lays on histological assessment through a kidney biopsy, given the absence of accurate non-invasive biomarkers. The aim of this study was to evaluate the accuracy of different urinary inflammation-related cytokines for the diagnostic of ATIN and its distinction from acute tubular necrosis (ATN). Methods: We included 33 patients (ATIN (n = 21), ATN (n = 12)), and 6 healthy controls (HC). We determined the urinary levels of 10 inflammation-related cytokines using a multiplex bead-based Luminex assay at the time of biopsy and after therapy, and registered main clinical, analytical and histological data. Results: At the time of biopsy, urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFα and MCP-1 were significantly higher in ATIN compared to HC. A positive correlation between the extent of the tubulointerstitial cellular infiltrates in kidney biopsies and the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10, IL17, IFNα, MCP1 and EGF was observed. Notably, I-TAC/CXCL11, IL-6 and MCP-1 were significantly higher in ATIN than in ATN, with I-TAC/CXCL11 as the best discriminative classifier AUC (0.77, 95% CI 0.57–0.95, p = 0.02). A combinatory model of these three urinary cytokines increased the accuracy in the distinction of ATIN/ATN compared to the individual biomarkers. The best model resulted when combining the three cytokines with blood eosinophil and urinary leukocyte counts (LR = 9.76). Follow-up samples from 11ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/CXCL9 and CXCL10 levels. Conclusions: Urinary I-TAC/CXCL11, CXCL10, IL6 and MCP-1 levels accurately distinguish patients developing ATIN from ATN and healthy individuals and may serve as novel non-invasive biomarkers in this disease.

scholarly journals P0196ACUTE TUBULOINTERSTITIAL NEPHRITIS (ATIN) INDUCED BY CHECKPOINT INHIBITORS (ICI) VERSUS CLASSICAL ATIN. ARE THEY THE SAME DISEASE?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Laura Martinez Valenzuela ◽  
Juliana Draibe ◽  
Clara Garcia Carro ◽  
Irene Agraz ◽  
Xavier Fulladosa ◽  
...  
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Laboratory Data ◽  
Specific Treatment ◽  
Latency Period ◽  
Response To Treatment ◽  
Acute Tubulointerstitial Nephritis ◽  
Diagnostic Time ◽  
Renal Histology

Abstract Background and Aims The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased during the past years. A new subtype of ATIN apparently different from classical drug related ATIN has emerged, which has been related to the administration of immune check point inhibitors (ICI). We herein investigated these differences between ICI related ATIN and non-ICI related ATIN, in terms of clinical features, response to treatment with steroids, and the kidney function evolution. Method A total of 47 patients diagnosed with acute tubulointerstitial nephritis (ATIN) from two centers were recruited. Of these, 13 patients presented with ATIN during the treatment with ICI, and 34 patients were diagnosed with ATIN attributed to other drugs. The main demographical, clinical and analytical variables such as gender, age, and current medication were recorded. The type of malignancy, oncological treatment, dose of ICI, and presence of extra-renal immune-related adverse-events were also reviewed. Renal biopsy diagnostic, time to drug withdrawal and ATIN specific treatment, as well as laboratory data during the follow-up were also studied. Results Patients diagnosed with ICI related ATIN presented with lower creatinine (ICI ATIN 3.8±1.03mg/dl vs. classical ATIN 5.98±4.15, p=0.007) at diagnostic and higher urinary leukocyte count (ICI ATIN 263.2±418.04 vs. classical ATIN 133.55±284.62, p=0.048) as compared to patients with non-ICI related ATIN. Time elapsed from the initiation of the culprit drug to the ATIN diagnostic was longer in ICI ATIN compared to classical ATIN (197.07±184.99 vs 114.4±352.16 days, p=0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower in ICI related ATIN compared to non-ICI related patients. Conclusion In this study we analyzed the differences between ICI ATIN and the classical ATIN. We found that ICI ATIN patients presented a larger latency period after offending drug initiation, milder acute kidney injury, and slower creatinine amelioration as compared to the classical ATIN. These results may be in part ascribed to potential differences in the pathological mechanisms in ATIN development, suggesting that ICI ATIN and the classical ATIN may be different disease with similar renal histology.

scholarly journals Acute tubulointerstitial nephritis induced by checkpoint inhibitors versus classical acute tubulointerstitial nephritis: are they the same disease?

2020 ◽  
Author(s):  
Juliana B Draibe ◽  
Clara García-Carro ◽  
Laura Martinez-Valenzuela ◽  
Irene Agraz ◽  
Xavier Fulladosa ◽  
...  
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Laboratory Data ◽  
Specific Treatment ◽  
Latency Period ◽  
Response To Treatment ◽  
Acute Tubulointerstitial Nephritis ◽  
Oncological Treatment ◽  
Culprit Drug

Abstract Background The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased over recent years. A new subtype of ATIN, apparently different from classical drug-related ATIN, has emerged that has been related to the administration of immune checkpoint inhibitors (ICIs). We investigated these differences between ICI-related ATIN (ICI ATIN) and non-ICI-related ATIN in terms of clinical features, response to treatment with steroids and the evolution of kidney function. Methods A total of 47 patients diagnosed with ATIN from two centres were recruited. Of these, 13 patients presented with ATIN during ICI treatment and 34 were diagnosed with ATIN attributed to other drugs. The main demographic, clinical and analytical variables such as gender, age and current medication were recorded. The type of malignancy, oncological treatment, ICI dose and presence of extrarenal immune-related adverse events were also reviewed. Renal biopsy diagnosis, time to drug withdrawal and ATIN-specific treatment, as well as laboratory data during follow-up, were also studied. Results Patients diagnosed with ICI ATIN presented with lower creatinine (ICI ATIN 3.8 ± 1.03  versus classical ATIN 5.98 ± 4.15 mg/dL, P = 0.007) at diagnosis and higher urinary leucocyte counts (ICI ATIN 263.2 ± 418.04 versus classical ATIN 133.55 ± 284.62, P = 0.048) compared with patients with non-ICI-related ATIN. Time from initiation of the culprit drug to ATIN diagnosis was longer in patients with ICI ATIN than in those with classical ATIN (197.07 ± 184.99 versus 114.4 ± 352.16 days, P = 0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower for ICI ATIN compared with non-ICI-related ATIN. Conclusions In this study, we analysed differences between ICI ATIN and classical ATIN. We found that patients with ICI ATIN presented with a larger latency period after culprit drug initiation, milder acute kidney injury and slower creatinine amelioration compared with those with classical ATIN. These results may, in part, be ascribed to potential differences in the pathological mechanisms involved in ATIN development, suggesting that ICI and classical ATIN may be different diseases with similar renal histologies.

scholarly journals Acute tubulointerstitial nephritis and polyclonal hypergammaglobulinaemia: Which is the culprit?

2018 ◽  
Vol 8 (4) ◽  
Author(s):  
Ana E. Sirvent ◽  
Ricardo Enríquez ◽  
Tania Muci ◽  
Francisco Javier Ardoy-Ibañez ◽  
Isabel Millán ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Serum Creatinine ◽  
Renal Biopsy ◽  
Proton Pump ◽  
Tubulointerstitial Nephritis ◽  
Systemic Disease ◽  
Acute Tubulointerstitial Nephritis ◽  
Long Period

Proton pump inhibitors (PPIs) are among the most frequent implicated drugs in acute tubulointerstitial nephritis (ATIN), nevertheless it is important to report cases with atypical profiles. A 80-year-old female, exposed during 34 months to omeprazole, presented with polyclonal hypergammaglobulinaemia and renal failure. After stopping omeprazole there was a partial improvement in serum creatinine and IgG. Renal biopsy revealed ATIN; immunohistochemistry for IgG4 was negative. Treatment with steroids and mycophenolate sodium improved renal function and normalized immunoglobulins. The lack of data of other entities and the patient’s evolution strongly point omeprazole as the culprit. After 27 months of follow-up, she remains clinical and analytically stable. ATIN caused by PPIs may appear after a long period of exposure and may be accompanied by analytical anomalies that simulate a systemic disease.

scholarly journals Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis

2020 ◽  
Vol 9 (7) ◽  
pp. 2135
Author(s):  
Raquel Esteras ◽  
Jonathan G. Fox ◽  
Colin C. Geddes ◽  
Bruce Mackinnon ◽  
Alberto Ortiz ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Tubulointerstitial Nephritis ◽  
Kidney Injury ◽  
Common Cause ◽  
Acute Tubulointerstitial Nephritis ◽  
Acute Dialysis

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury. Although haematuria is a risk factor for the development of renal disease, no previous study has analyzed the significance of haematuria in ATIN. Retrospective, observational analysis of 110 patients with biopsy-proven ATIN was conducted. Results: Haematuria was present in 66 (60%) ATIN patients. A higher percentage of ATIN patients with haematuria had proteinuria than patients without haematuria (89.4% vs. 59.1%, p = 0.001) with significantly higher levels of proteinuria (median (interquartile range) protein:creatinine ratio 902.70 (513–1492) vs. 341.00 (177–734) mg/g, p <0.001). Moreover, those patients with more haematuria intensity had a higher urinary protein:creatinine ratio (1352.65 (665–2292) vs. 849.60 (562–1155) mg/g, p = 0.02). Those patients with higher proteinuria were more likely to need renal replacement therapy (22.7 vs. 0%, p = 0.03) and to suffer relapse (4 vs. 0%, p = 0.03). At the end of follow up, haematuric ATIN patients had higher serum creatinine levels (3.19 ± 2.91 vs. 1.91 ± 1.17 mg/dL, p = 0.007), and a trend towards a higher need for acute dialysis (7 vs. 1%, p = 0.09) and renal replacement therapy (12.1 vs. 2.3%, p = 0.12). Haematuria is common in ATIN and it is associated with worse renal function outcomes.

scholarly journals MO160COVID-19 INFECTION AND ACUTE TUBULOINTERSTITIAL NEPHRITIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Juan Carlos León ◽  
Irene Agraz ◽  
Ander Vergara Arana ◽  
Natalia Ramos Terrada ◽  
Clara García Carro ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Function ◽  
Nosocomial Pneumonia ◽  
Tubulointerstitial Nephritis ◽  
Kidney Injury ◽  
Acute Tubulointerstitial Nephritis ◽  
History Of

Abstract Background COVID-19 infection manifests as pneumonia associated with multiple organ failure, and death. Acute kidney injury is a risk factor for mortality. There is limited scientific literature on COVID-19 infection and allergic tubulointerstitial nephritis, its clinical course and short- and long-term prognosis. Method We performed a retrospective study where medical records of 60 patients with histological diagnosis of allergic tubulointerstitial nephritis from January 2009 to November 2020. In these patients, we studied the incidence of COVID-19 infection, clinical characteristics and prognosis from March to the actual date. Results Of 60 patients with allergic tubulointerstitial nephritis, 6 (10%) patients were diagnosed with COVID-19. The first case, an 85-year-old woman with a history of metastatic melanoma treated with nivolumab and allergic tubulointerstitial nephritis by immunobiological agents in 2018, diagnosed with mild COVID-19 infection in April 2020 without deterioration of renal function in controls at 3 and 6 months of follow-up. The second case, a 51-year-old woman with a history of large B-cell lymphoma with plasmacytic differentiation and progression to multiple myeloma of lambda light chains and allergic tubulointerstitial nephritis due to chemotherapy since 2019, admitted for acute pyelonephritis and PRES syndrome secondary to first dose of bortezomib complicated with COVID-19 nosocomial pneumonia and acute pancreatitis treated with corticosteroids and broad spectrum antibiotic therapy; she died of abdominal refractory septic shock. The third patient, a 64-year-old man without prior renal impairment, was admitted for severe COVID-19 pneumonia and acute kidney injury secondary to acute tubulointerstitial nephritis of uncertain etiology that required orotracheal intubation and continuous veno-venous hemodiafiltration for a week who received methylprednisolone in bolus for 3 days and continued treatment with corticosteroid therapy with complete recovery of renal function and improvement in proteinuria at 3 months of follow-up. The fourth patient, an 82-year-old woman with acute kidney injury AKIN 3 secondary to acute allergic tubulointerstitial nephritis related to ciprofloxacin complicated with severe COVID-19 nosocomial pneumonia, who died despite ventilatory support and high-dose steroids therapy and tocilizumab. The fifth patient, a 75-year-old with a history of metastatic lung adenocarcinoma treated with immunobiological agents and allergic tubulointerstitial nephritis in  2018, admitted in march 2020 for mild COVID-19 pneumonia treated with steroids and hydroxychloroquine without deterioration of respiratory and kidney function.  The sixth patient, an 86-years-old man with acute kidney injury AKIN 3 due to acute allergic tubulointerstitial nephritis secondary to proton-binding inhibitors and nosocomial COVID-19 infección with improvement of kidney function with steroids therapy only.  Conclusion Our 6 patients with allergic tubulointerstitial nephritis and COVID-19 infection presented different spectrum of the disease. It seems that nosocomial COVID-19 infection in patients admitted with recent diagnosis of acute allergic tubulointerstitial nephritis presented a worse clinical prognosis compared with long-term diagnosed acute tubulointerstitial nephritis. Further studies with a larger sample size are needed.

scholarly journals Usefulness of 99mTc-dimercaptosuccinic acid renal scan in the diagnosis and follow-up of acute tubulointerstitial nephritis in children

2017 ◽  
Vol 10 (5) ◽  
pp. 655-660
Author(s):  
Enrico Vidal ◽  
Elisabetta Miorin ◽  
Pietro Zucchetta ◽  
Elisa Benetti ◽  
Germana Longo ◽  
...  
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Dimercaptosuccinic Acid ◽  
Acute Tubulointerstitial Nephritis ◽  
Renal Scan

Hippocampal and amygdala volume changes in patients with major depression and healthy controls during a three year follow-up

2005 ◽  
Vol 38 (05) ◽  
Author(s):  
TS Frodl ◽  
T Zetzsche ◽  
G Schmitt ◽  
T Schlossbauer ◽  
MW Jäger ◽  
...  
Keyword(s):  
Major Depression ◽  
Healthy Controls ◽  
Volume Changes ◽  
Amygdala Volume

Acute tubulointerstitial nephritis in children and chronic kidney disease

2019 ◽  
Vol 26 (5) ◽  
pp. 290-294 ◽  
Author(s):  
S. Clavé ◽  
C. Rousset-Rouvière ◽  
L. Daniel ◽  
M. Tsimaratos
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tubulointerstitial Nephritis ◽  
Acute Tubulointerstitial Nephritis

scholarly journals Cardiac involvement in COVID-19 patients: mid-term follow up by cardiovascular magnetic resonance

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Hui Wang ◽  
Ruili Li ◽  
Zhen Zhou ◽  
Hong Jiang ◽  
Zixu Yan ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Cardiac Involvement ◽  
Global Longitudinal Strain ◽  
Cine Imaging ◽  
Black Blood ◽  
Healthy Controls ◽  
Term Outcome ◽  
Post Contrast

Abstract Background Coronavirus disease 2019 (COVID-19) induces myocardial injury, either direct myocarditis or indirect injury due to systemic inflammatory response. Myocardial involvement has been proved to be one of the primary manifestations of COVID-19 infection, according to laboratory test, autopsy, and cardiovascular magnetic resonance (CMR). However, the middle-term outcome of cardiac involvement after the patients were discharged from the hospital is yet unknown. The present study aimed to evaluate mid-term cardiac sequelae in recovered COVID-19 patients by CMR Methods A total of 47 recovered COVID-19 patients were prospectively recruited and underwent CMR examination. The CMR protocol consisted of black blood fat-suppressed T2 weighted imaging, T2 star mapping, left ventricle (LV) cine imaging, pre- and post-contrast T1 mapping, and late gadolinium enhancement (LGE). LGE were assessed in mixed both recovered COVID-19 patients and healthy controls. The LV and right ventricle (RV) function and LV mass were assessed and compared with healthy controls. Results A total of 44 recovered COVID-19 patients and 31 healthy controls were studied. LGE was found in 13 (30%) of COVID-19 patients. All LGE lesions were located in the mid myocardium and/or sub-epicardium with a scattered distribution. Further analysis showed that LGE-positive patients had significantly decreased LV peak global circumferential strain (GCS), RV peak GCS, RV peak global longitudinal strain (GLS) as compared to non-LGE patients (p < 0.05), while no difference was found between the non-LGE patients and healthy controls. Conclusion Myocardium injury existed in 30% of COVID-19 patients. These patients have depressed LV GCS and peak RV strains at the 3-month follow-up. CMR can monitor the COVID-19-induced myocarditis progression, and CMR strain analysis is a sensitive tool to evaluate the recovery of LV and RV dysfunction.

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