scholarly journals Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury

2021 ◽  
Vol 22 (6) ◽  
pp. 2784
Author(s):  
Linda Awdishu ◽  
Amy Le ◽  
Jordan Amato ◽  
Vidhyut Jani ◽  
Soma Bal ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Exclusion Principle ◽  
Complement C3 ◽  
Proximal Tubule Cell ◽  
Partial Recovery ◽  
Label Free ◽  
First Line Therapy ◽  
Large Patient ◽  
Urinary Exosomes

Background: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. Methods: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O’Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). The mean peak serum creatinine was 3.7 ± 1.4 mg/dL and time to kidney injury was 4.0 ± 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. Conclusion: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.

scholarly journals Acute kidney injury with cardiorenal syndrome; experience from a tertiary care renal unit in Pakistan

2020 ◽  
Vol 10 (4) ◽  
pp. e29-e29
Author(s):  
Rubina Naqvi
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Acute Kidney Injury ◽  
Infective Endocarditis ◽  
Cardiac Failure ◽  
Kidney Injury ◽  
Congestive Cardiac Failure ◽  
Fluid Replacement ◽  
Partial Recovery

Introduction: Acute kidney injury (AKI) is a commonly recognized clinical problem after many morbid conditions related to heart like congenital heart disease surgery, acute or chronic congestive heart failure, acute myocardial infarction, infective endocarditis or cardiomyopathies. Cardio-renal syndrome (CRS) includes a spectrum of disorders involving both the heart and kidneys simultaneously; here acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other. Objectives: To report here, case series of patients with AKI developing in association with CRS. We aim to report different causes of CRS and outcome of patients in this group of patients. Patients and Methods: Subjects for the study reported here comprised a cohort of 34 patients coming to this institution with AKI in association of CRS. AKI was defined according to KDIGO guidelines and CRS based on consensus conference of ADQI in 2012. Type 1or type2 CRS are included in the study. All patients had normal size kidneys on ultrasonography. Results: Thirty-four patients with AKI and CRS were brought to this institute from January 1990 to December 2014; this was contributing 1% to medical causes of total AKI. Among these 25 were males and 9 females; mean age of these patients was 54.06±14.106 years. Causes of CRS were acute myocardial infarction (ST elevated), congestive cardiac failure, infective endocarditis and dilated cardiomyopathy. More than two third of patients were either oliguric or anuric on presentation. Fluid replacement and/or inotropic support required in 79%. Renal replacement therapy in form of hemodialysis was conducted in 64.7% and intermittent peritoneal dialysis in one patient. Complete renal recovery was observed in 19 (56%) patients, while 12 (35%) died during acute phase of illness. CKD-V developed in one patient, 2 patients lost long term follow up, but became dialysis free and renal functions were in improving trends, they were labeled as partial recovery. Secondary insults like hypotension, aggressive diuresis, and volume loss from gastro-intestinal tract or infection were evaluated for any co-relation with outcome but statistically no significant difference was found. Conclusion: CRS can be severe life-threatening condition especially when patients present with circulatory collapse. Diuretics must be used cautiously in patients with congestive cardiac failure. Infective endocarditis with acute right heart failure can lead to CRS.

scholarly journals Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with Cirrhosis

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Linda Awdishu ◽  
Shirley Tsunoda ◽  
Michelle Pearlman ◽  
Chanthel Kokoy-Mondragon ◽  
Majid Ghassemian ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Function ◽  
Kidney Injury ◽  
Meld Score ◽  
Functional Change ◽  
Decompensated Cirrhosis ◽  
Normal Kidney ◽  
Normal Kidney Function ◽  
Urinary Exosomes ◽  
History Of

Background. Acute kidney injury (AKI) is a frequent complication of decompensated cirrhosis with increased mortality. Traditional biomarkers such as serum creatinine are not sensitive for detecting injury without functional change. We hypothesize that urinary exosomes potentially carry markers that differentiate the type of kidney injury in cirrhotic patients. Methods. This is a prospective, single-center, and observational study of adult patients with cirrhosis. The patient groups included healthy normal controls, compensated cirrhosis with normal kidney function, decompensated cirrhosis with normal kidney function, and decompensated cirrhosis with AKI. Data were extracted from the electronic health record including etiology of liver disease, MELD score, history of decompensation, Child-Turcotte-Pugh score, history of AKI, and medication exposures. Urine samples were collected at the time of consent. Urine exosome protein content was analyzed, and proteomic data were validated by immunoblotting. Statistical analysis included partial least squares-discriminant analysis coupled with variable importance in projection identification. Results. Eighteen cirrhotic subjects were enrolled, and six healthy control subjects were extracted from our biorepository. Urine exosomes were isolated, and 1572 proteins were identified. Maltase-glucoamylase was the top discriminating protein confirmed by western blotting. Conclusions. Patients with cirrhosis and AKI have upregulation of renal brush border disaccharidase, MGAM, in urinary exosomes which may differentiate the type of kidney injury in cirrhosis; however, the clinical significance of this requires further validation.

P0602CLINICAL PATTERN, RENAL RECOVERY AND PATIENT OUTCOMES AFTER ACUTE KIDNEY INJURY IN ADULTS IN AN EMERGING COUNTRY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Arunkumar Subbiah ◽  
Sanjay Kumar Agarwal
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Hospital Mortality ◽  
Kidney Injury ◽  
Hospitalized Patients ◽  
Renal Recovery ◽  
Common Source ◽  
Partial Recovery

Abstract Background and Aims Acute Kidney Injury (AKI) is an important determinant of outcome in hospitalized patients. Further, there is a risk for development of Chronic Kidney Disease (CKD) in the future. Though the long-term impact of AKI has been studied in developed countries, there is a paucity of data in this area from the Indian subcontinent. This single-centre study aimed to assess the pattern, clinical spectrum, short-term and long-term outcomes of AKI. Method In this prospective observational cohort study, detailed demographic and clinical data at presentation, during hospital stay and follow-up at 1, 3, 6 and 12 months after discharge were obtained prospectively for a cohort of patients with AKI. Both community (CAAKI) and hospital acquired AKI (HAAKI) were included. Patient with pre-existing CKD were excluded. Outcome variables examined were in-hospital mortality, renal function at discharge and on follow-up after discharge from hospital. Results In our study cohort with 476 patients, majority of the cases were CAAKI (395, 83%). The mean age at presentation was 44.8 ± 18.7 years. Medical causes (84%) contributed to the majority of AKI while the remaining were due to surgical (10%) and obstetrical (6%) causes. Sepsis (176/476; 36.9%) was the most common cause of AKI. The most common source for sepsis was respiratory (41%) followed by urological source (18.7%). The in-hospital mortality rate for patients with AKI was 38%. Age >60 years (HR = 1.51; 95% CI, 1.11 – 2.07), oliguria (HR = 1.48; 95% CI, 1.05 – 2.10), need for ventilator (HR = 2.45; 95% CI, 1.36 – 4.41) and/or inotropes (HR = 14.4; 95% CI, 6.28 – 33.05) were predictors of mortality. At discharge, 146 (30.7%) patients had complete renal recovery, while 149 (31.3%) had partial renal recovery. Oliguria (p < 0.001), hypoalbuminemia (p = 0.001) and need for renal replacement therapy (RRT) (p = 0.01) were significantly associated with partial recovery. Of the 295 patients on follow-up at discharge, 211 (71.5%) patients had normal renal function, 4 (1.4%) died and 33 (11.2%) were lost to follow up; 47(15.9%) patients developed CKD of which 6 (2%) were dialysis dependent. Elderly patients, higher AKIN stage with oliguria and those requiring RRT were more likely to develop CKD. Among these, the need for in-hospital RRT was the single most important factor predicting the risk of CKD (OR 1.77, 95% CI, 1.12-2.78). Conclusion In conclusion, our data shows that AKI in hospitalized patients still has high mortality in emerging countries like India. Though a fairly good percentage of cases recovered, there is a definite risk of CKD development, especially in patients who required RRT during hospitalization.

scholarly journals Cumulative fluid accumulation is associated with the development of acute kidney injury and non-recovery of renal function: a retrospective analysis

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Jing Zhang ◽  
Siobhan Crichton ◽  
Alison Dixon ◽  
Nina Seylanova ◽  
Zhiyong Y. Peng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Fluid Balance ◽  
Tertiary Care ◽  
Kidney Injury ◽  
Renal Recovery ◽  
Partial Recovery ◽  
Factors Associated ◽  
Cumulative Fluid Balance

Abstract Background Acute kidney injury (AKI) is common in patients in the intensive care unit (ICU) and may be present on admission or develop during ICU stay. Our objectives were (a) to identify factors independently associated with the development of new AKI during early stay in the ICU and (b) to determine the risk factors for non-recovery of AKI. Methods We retrospectively analysed prospectively collected data of patients admitted to a multi-disciplinary ICU in a single tertiary care centre in the UK between January 2014 and December 2016. We identified all patients without AKI or end-stage renal failure on admission to the ICU and compared the outcome and characteristics of patients who developed AKI according to KDIGO criteria after 24 h in the ICU with those who did not develop AKI in the first 7 days in the ICU. Multivariable logistic regression was applied to identify factors associated with the development of new AKI during the 24–72-h period after admission. Among the patients with new AKI, we identified those with full, partial or no renal recovery and assessed factors associated with non-recovery. Results Among 2525 patients without AKI on admission, the incidence of early ICU-acquired AKI was 33.2% (AKI I 41.2%, AKI II 35%, AKI III 23.4%). Body mass index, Sequential Organ Failure Assessment score on admission, chronic kidney disease (CKD) and cumulative fluid balance (FB) were independently associated with the new development of AKI. By day 7, 69% had fully recovered renal function, 8% had partial recovery and 23% had no renal recovery. Hospital mortality was significantly higher in those without renal recovery. Mechanical ventilation, diuretic use, AKI stage III, CKD, net FB on first day of AKI and cumulative FB 48 h later were independently associated with non-recovery with cumulative fluid balance having a U-shape association. Conclusions Early development of AKI in the ICU is common and mortality is highest in patients who do not recover renal function. Extreme negative and positive FB were strong risk factors for AKI non-recovery.

scholarly journals Kidney Tubular Damage Secondary to Deferasirox: Systematic Literature Review

Children ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 1104
Author(s):  
Martin Scoglio ◽  
Maria Domenica Cappellini ◽  
Emanuela D’Angelo ◽  
Mario G. Bianchetti ◽  
Sebastiano A. G. Lava ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Kidney Injury ◽  
The United States ◽  
Kidney Damage ◽  
Tubular Damage ◽  
Acid Base ◽  
Electrolyte Disorders ◽  
First Line Therapy

Deferasirox is a first-line therapy for iron overload that can sometimes cause kidney damage. To better define the pattern of tubular damage, a systematic literature review was conducted on the United States National Library of Medicine, Excerpta Medica, and Web of Science databases. Twenty-three reports describing 57 individual cases could be included. The majority (n = 35) of the 57 patients were ≤18 years of age and affected by thalassemia (n = 46). Abnormal urinary findings were noted in 54, electrolyte or acid–base abnormalities in 46, and acute kidney injury in 9 patients. Latent tubular damage was diagnosed in 11 (19%), overt kidney tubular damage in 37 (65%), and an acute kidney injury in the remaining nine (16%) patients. Out of the 117 acid–base and electrolyte disorders reported in 48 patients, normal-gap metabolic acidosis and hypophosphatemia were the most frequent. Further abnormalities were, in decreasing order of frequency, hypokalemia, hypouricemia, hypocalcemia, and hyponatremia. Out of the 81 abnormal urinary findings, renal glucosuria was the most frequent, followed by tubular proteinuria, total proteinuria, and aminoaciduria. In conclusion, a proximal tubulopathy pattern may be observed on treatment with deferasirox. Since deferasirox-associated kidney damage is dose-dependent, physicians should prescribe the lowest efficacious dose.

scholarly journals Renal Recovery in Critically Ill Adult Patients Treated With Veno-Venous or Veno-Arterial Extra Corporeal Membrane Oxygenation: A Retrospective Cohort Analysis

2020 ◽  
Vol 7 (2) ◽  
pp. 104-112
Author(s):  
Braghadheeswar Thyagarajan ◽  
Mariana Murea ◽  
Deanna N. Jones ◽  
Amit K. Saha ◽  
Gregory B. Russell ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Critically Ill ◽  
Retrospective Cohort ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Renal Recovery ◽  
Partial Recovery ◽  
Va Ecmo ◽  
Ecmo Treatment ◽  
Vv Ecmo

Abstract Introduction Patients on extracorporeal membrane oxygenator (ECMO) therapy are critically ill and often develop acute kidney injury (AKI) during hospitalisation. Little is known about the association of exposure to and the effect of the type of ECMO and extent of renal recovery after AKI development. Aim of the study In patients who developed AKI, renal recovery was characterised as complete, partial or dialysis-dependent at the time of hospital discharge in both the Veno-Arterial (VA) and Veno-Venous (VV) ECMO treatment groups. Material and methods The study consisted of a single-centre retrospective cohort that includes all adult patients (n=125) who received ECMO treatment at a tertiary academic medical centre between 2015 to 2019. Data on demographics, type of ECMO circuit, comorbidities, exposure to nephrotoxic factors and receipt of renal replacement therapy (RRT) were collected as a part of the analysis. Acute Kidney Injury Network (AKIN) criteria were used for the diagnosis and classification of AKI. Group differences were assessed using Fisher’s exact tests for categorical data and independent t-tests for continuous outcomes. Results Sixty-four patients received VA ECMO, and 58 received VV ECMO. AKI developed in 58(91%) in the VA ECMO group and 51 (88%) in the VV ECMO group (p=0.77). RRT was prescribed in significantly higher numbers in the VV group 38 (75%) compared to the VA group 27 (47%) (p=0.0035). At the time of discharge, AKI recovery rate in the VA group consisted of 15 (26%) complete recovery and 5 (9%) partial recovery; 1 (2%) remained dialysis-dependent. In the VV group, 22 (43%) had complete recovery (p=0.07), 3(6%) had partial recovery (p=0.72), and 1 (2%) was dialysis-dependent (p>0.99). In-hospital mortality was 64% in the VA group and 49% in the VV group (p=0.13). Conclusions Renal outcomes in critically ill patients who develop AKI are not associated with the type of ECMO used. This serves as preliminary data for future studies in the area.

scholarly journals Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury

2020 ◽  
Vol 117 (27) ◽  
pp. 15874-15883 ◽  
Author(s):  
Yuhei Kirita ◽  
Haojia Wu ◽  
Kohei Uchimura ◽  
Parker C. Wilson ◽  
Benjamin D. Humphreys
Keyword(s):  
Acute Kidney Injury ◽  
Proximal Tubule ◽  
Communication Networks ◽  
Rat Kidney ◽  
Kidney Injury ◽  
Human Kidney ◽  
Cellular Responses ◽  
Acute Injury ◽  
Proximal Tubule Cell ◽  
Tubule Cell

After acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma, and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the molecular events that drive these processes are poorly understood. Here, we use single nucleus RNA sequencing of a mouse model of AKI to characterize cell states during repair from acute injury. We identify a distinct proinflammatory and profibrotic proximal tubule cell state that fails to repair. Deconvolution of bulk RNA-seq datasets indicates that this failed-repair proximal tubule cell (FR-PTC) state can be detected in other models of kidney injury, increasing during aging in rat kidney and over time in human kidney allografts. We also describe dynamic intercellular communication networks and discern transcriptional pathways driving successful vs. failed repair. Our study provides a detailed description of cellular responses after injury and suggests that the FR-PTC state may represent a therapeutic target to improve repair.

scholarly journals A study of pregnancy related acute kidney injury and its outcome at a tertiary care centre, civil hospital, Ahmadabad, Gujarat, India

2019 ◽  
Vol 8 (10) ◽  
pp. 4020
Author(s):  
Komal K. Agrawal ◽  
Mahima Jain
Keyword(s):  
Acute Kidney Injury ◽  
Tertiary Care ◽  
Kidney Injury ◽  
Causative Factor ◽  
Partial Recovery ◽  
Loss Of Function ◽  
Contributing Factors ◽  
Tertiary Care Centre ◽  
Stage Renal Disease ◽  
In Pregnancy

Background: Pregnancy related acute kidney injury (PRAKI) is acute kidney injury occurring during pregnancy, labour, delivery, and/or postpartum period. Proper management of PRAKI is challenging because (i) both maternal and fetal health must be considered and (ii) the cardiovascular and renal adaptations of pregnancy add to the complexity of diagnosis and management. A multi discipilinary team is often needed to optimize all aspects of the pregnant women’s care.Methods: To study association and contributing factors in pregnancy related Acute Kidney injury, a retrospective study of 39 cases of acute kidney injury complicating pregnancies was carried out in department of obstetrics and gynaecology, B. J. Medical college over a period of 6 months, and results were studied and analysed. Etiological-factors, associated liver pathology, coagulation abnormality, thrombocytopenia, sepsis, recovery status and fetomaternal outcome were studied and results were tabulated. AKI was analysed in terms of maximal stage of renal injury attained as per risk, injury, failure, loss of function, and end-stage renal disease (RIFLE) criteria.Results: The incidence of ARF in pregnancy was found to be 0.3%. Hypertension and its related complications were the most common causative factor. 59.5% of cases required hemodialysis and except for 6 cases (14.3%) all had complete or at least partial recovery from failure.Conclusions: AKI complicating pregnancies are not uncommon in tertiary care centres. If recognized and treated promptly, recovery is assured in majority of 85.7% of cases. Early identification and prompt management of pre-eclampsia and sepsis can prevent majority of ARF cases.

scholarly journals Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury

2020 ◽  
Author(s):  
Yuhei Kirita ◽  
Haojia Wu ◽  
Kohei Uchimura ◽  
Parker C. Wilson ◽  
Benjamin D. Humphreys
Keyword(s):  
Acute Kidney Injury ◽  
Proximal Tubule ◽  
Rna Sequencing ◽  
Therapeutic Target ◽  
Kidney Injury ◽  
Cellular Responses ◽  
Acute Injury ◽  
Proximal Tubule Cell ◽  
Tubule Cell ◽  
Single Nucleus

AbstractAfter acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the molecular events that drive these processes are poorly understood. Here, we use single nucleus RNA sequencing of a mouse model of AKI to characterize cell states during repair from acute injury. We identify a distinct proinflammatory and profibrotic proximal tubule cell state that fails to repair. Deconvolution of bulk RNA-seq datasets indicates that this “failed-repair proximal tubule cell” or FR-PTC, state can be detected in other models of kidney injury, increasing in the aging rat kidney and over time in human kidney allografts. We also describe dynamic intercellular communication networks and discern transcriptional pathways driving successful vs. failed repair. Our study provides a detailed description of cellular responses after injury and suggests that the FR-PTC state may represent a therapeutic target to improve repair.Significance StatementSingle nucleus RNA sequencing revealed gene expression changes during repair after acute kidney injury. We describe a small population of proximal tubule cells that fail to repair (FR-PTC). Since this subpopulation expresses abundant pro-inflammatory and profibrotic genes, it may represent a new therapeutic target to improve repair and reduce fibrosis after AKI.

Sign in / Sign up

Export Citation Format

Share Document