scholarly journals Neuroblastoma Amplified Sequence Gene Mutations Inducing Acute Kidney and Liver Injury in an Adolescent Female

2020 ◽  
Vol 10 (3) ◽  
pp. 117-123
Author(s):  
Roy Rafael Dayan ◽  
O.N. Ray Bignall II ◽  
Sheryl Johnson ◽  
Francisco Flores ◽  
Oded Volovelsky
Keyword(s):  
Liver Injury ◽  
Gene Mutation ◽  
Gene Mutations ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Compound Heterozygous ◽  
Adolescent Female ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Tubular Necrosis ◽  
Causative Relation

Acute liver injury (ALI) in children is a life-threatening event, and a definitive etiology can be identified in approximately 50% of cases. Neuroblastoma amplified sequence (NBAS) gene mutations have been associated with a broad phenotypic spectrum of this disease, ranging from recurrent episodes of fever-induced liver injuries to multiorgan involvement, including frequent infections as well as skeletal and immunological abnormalities. Here, we describe an adolescent female with a confirmed compound heterozygous NBAS gene mutation who presented with an episode of ALI complicated by severe acute kidney injury (AKI). The kidney injury was most probably driven by an intrinsic insult, as noted by elevated neutrophil gelatinase-associated lipocalin levels and a kidney biopsy demonstrating severe tubular damage consistent with acute tubular necrosis. While the patient’s liver function and mental status showed significant improvement with supportive care, recovery of kidney function was delayed, and the patient required acute hemodialysis. We suggest a causative relation between the NBAS gene mutation and severe AKI.

scholarly journals Postangiography Increases in Serum Creatinine and Biomarkers of Injury and Repair

2020 ◽  
Vol 15 (9) ◽  
pp. 1240-1250 ◽  
Author(s):  
Caroline Liu ◽  
Maria K. Mor ◽  
Paul M. Palevsky ◽  
James S. Kaufman ◽  
Heather Thiessen Philbrook ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Serious Adverse Events ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Iodinated Contrast ◽  
Injury And Repair ◽  
Kidney Injury Molecule 1 ◽  
Major Adverse Kidney Events

Background and objectivesIt is unknown whether iodinated contrast causes kidney parenchymal damage. Biomarkers that are more specific to nephron injury than serum creatinine may provide insight into whether contrast-associated AKI reflects tubular damage. We assessed the association between biomarker changes after contrast angiography with contrast-associated AKI and 90-day major adverse kidney events and death.Design, setting, participants, & measurementsWe conducted a longitudinal analysis of participants from the biomarker substudy of the Prevention of Serious Adverse Events following Angiography trial. We measured injury (kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, IL-18) and repair (monocyte chemoattractant protein-1, uromodulin, YKL-40) proteins from plasma and urine samples at baseline and 2–4 hours postangiography. We assessed the associations between absolute changes and relative ratios of biomarkers with contrast-associated AKI and 90-day major adverse kidney events and death.ResultsParticipants (n=922) were predominately men (97%) with diabetes (82%). Mean age was 70±8 years, and eGFR was 48±13 ml/min per 1.73 m2; 73 (8%) and 60 (7%) participants experienced contrast-associated AKI and 90-day major adverse kidney events and death, respectively. No postangiography urine biomarkers were associated with contrast-associated AKI. Postangiography plasma kidney injury molecule-1 and IL-18 were significantly higher in participants with contrast-associated AKI compared with those who did not develop contrast-associated AKI: 428 (248, 745) versus 306 (179, 567) mg/dl; P=0.04 and 325 (247, 422) versus 280 (212, 366) mg/dl; P=0.009, respectively. The majority of patients did not experience an increase in urine or plasma biomarkers. Absolute changes in plasma IL-18 were comparable in participants with contrast-associated AKI (−30 [−71, −9] mg/dl) and those without contrast-associated AKI (−27 [−53, −10] mg/dl; P=0.62). Relative ratios of plasma IL-18 were also comparable in participants with contrast-associated AKI (0.91; 0.86, 0.97) and those without contrast-associated AKI (0.91; 0.85, 0.96; P=0.54).ConclusionsThe lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.

Novel DIO1 gene mutation acting as phenotype modifier for novel compound heterozygous TPO gene mutations causing congenital hypothyroidism

Thyroid ◽  
2021 ◽  
Author(s):  
Aryel E Furman ◽  
Zeina Hannoush ◽  
Francisco X Barrera Echegoyen ◽  
Alexandra M Dumitrescu ◽  
Samuel Refetoff ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Congenital Hypothyroidism ◽  
Gene Mutations ◽  
Compound Heterozygous

P0704PROTECTIVE EFFECT OF DUAL ACTING LIGAND TARGETING A2A AND A3 ADENOSINE RECEPTOR ON OBSTRUCTION-INDUCED KIDNEY INJURY IN MICE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Eun Seon Pak ◽  
Jiyoun Lee ◽  
Hunjoo Ha
Keyword(s):  
Protein Expression ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Public Health Problem ◽  
Cellular Damage ◽  
Control Group ◽  
Tubular Damage ◽  
Tubular Necrosis ◽  
A3 Adenosine Receptor ◽  
Sirius Red

Abstract Background and Aims Chronic kidney disease (CKD) has been a worldwide public health problem, and the current therapeutic strategies against CKD are limited. Adenosine plays a significant role in protection against cellular damage in the regions with high metabolism. All 4 known subtypes of adenosine receptors such as A1AR, A2AAR, A2BAR, and A3AR are expressed in the kidney. While A2AAR agonists protect the kidney against inflammation, our previous study has demonstrated that an A3AR regulator effectively prevented diabetic kidney injury. The present study examined the preventive effect of LJ-4459, a newly synthesized dual acting ligand targeting A2AAR and A3AR, on unilateral ureteral obstruction (UUO)-induced kidney injury in mice. Method UUO surgery was performed in 6-week-old male C57BL/6 mice. LJ-4459 was administered by oral gavage at dose of either 1 or 10 mg/kg per day. The control group was administered an equal volume of vehicle (0.25% carboxymethyl cellulose). Results LJ-4459 effectively prevented tubular damage presented by significantly reduced NGAL expression and tubular necrosis in the obstructed kidney. LJ-4459 effectively inhibited elevation of a-SMA, collagen I, and collagen IV protein expression as well as picro sirius red staining in the obstructed kidney, suggesting antifibrotic effect of LJ-4459. LJ-4459 also inhibited inflammation as estimated by significantly reduced F4/80 positive-stained area and protein expression of p-NF-kB and ICAM1. Conclusion The results suggest that LJ-4459 may become a potential therapeutic agent against interstitial fibrosis, a common feature of CKD.

scholarly journals Molecular Characterization and Frequencies of Different Genetic Ameliorating Factors in Transfusion Dependent Thalassemia Patients from District Peshawar

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4816-4816
Author(s):  
Gulrukh Mehmood ◽  
Abid Sohail Taj ◽  
Arshi Naz ◽  
Tariq Masood Khan
Keyword(s):  
Gene Mutation ◽  
Conflicts Of Interest ◽  
Globin Gene ◽  
Severe Disease ◽  
Genetic Modifier ◽  
Gene Mutations ◽  
Clinical Severity ◽  
Health Concern ◽  
Compound Heterozygous ◽  
Globin Genes

Background Thalassemia is one of the most common genetic blood disorders worldwide. The carrier rate of β thalassemia in Pakistan is found to be around 5-7%, rendering it a major health concern. Approximately 5000 children are diagnosed with thalassemia major every year in Pakistan due to consanguineous marriages. More than 200 causative molecular defects have been identified in β-globin genes. About 20 mutations account for 90% of the abnormal β-genes. Clinical severity of β-thalassemia is modified by different factors. The important ones include the type of disease causing mutation and the ability to produce α and γ globin chains. A better understanding of these ameliorating factors may have a significant impact on disease management. Objectives 1. To re-assess diagnoses among local multi-transfused thalassemia syndrome patients. 2. To determine frequency of various genetic determinants of milder phenotypes of thalassemia among study patients. Methods Transfusion dependent thalassemia patients, upto 15 years age, were enrolled from Fatimid Foundation, Peshawar Pakistan. A comprehensive questionnaire encompassing demographic and clinical data was filled out for each patient. Genetic analyses for 2 alpha (α) and 13 prevalent beta (β) gene mutations and for polymorphisms at Xmn1-HBG2 and BCL11A were carried out on blood samples of the patients at National Institute of Blood Diseases, Karachi Pakistan. The data collected was analysed at Khyber Medical University (KMU) Peshawar Pakistan. Results A total of 54 transfusion dependent thalassemia patients were enrolled into the study. Homozygous or compound heterozygous combinations of β-globin gene mutations were identified in all the study patients. Eleven patients were found to have a co-existing heterozygous α (3.7kb) deletion, two patients had Xmn1-HBG2 polymorphism and 38 had BCL11A polymorphism. Homozygous Fr 8-9 was the most frequent mutation, found in 19 (35.2%) patients. Only 13 patients were found to have isolated β-globin gene mutations. In total, 46 (85.2%) study patients were identified to have an ameliorating genetic factor (a co-existing α-globin gene mutation, an Xmn1-HBG2 polymorphism or a BCL11A polymorphism) besides the main β-globin gene mutation. Conclusion It was concluded that co-existing genetic ameliorating factors are frequently found in transfusion dependent β-thalassemia patients of Peshawar District. These factors impart a milder phenotype to an otherwise severe disease. It is hence suggested that β-thalassemia patients from District Peshawar be screened for these factors and due consideration be paid by the physician in devising management plans. Key Words Thalassemia, Genetic modifier in thalassemia, Transfusion dependent Anaemia, Xmn1 polymorphism Disclosures No relevant conflicts of interest to declare.

scholarly journals Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway

2020 ◽  
Vol 134 (15) ◽  
pp. 2055-2073
Author(s):  
Yu-Lien Tsai ◽  
Chih-Wei Liu ◽  
Chien-Fu Hsu ◽  
Chia-Chang Huang ◽  
Ming-Wei Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatorenal Syndrome ◽  
Rat Kidney ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Obeticholic Acid ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Duct Ligation ◽  
Renal Tubular

Abstract Backgrounds/Aims: The present study explores the potential of chronic treatment with the Foresaid X receptor (FXR) agonist obeticholic acid (OCA), which inhibits oxidative stress-related pathogenesis, in ascitic cirrhotic rats with hepatorenal syndrome (HRS) developed 6 weeks after bile duct ligation (BDL). Methods: Systemic, splanchnic, and renal hemodynamics and pathogenic cascades were measured in ascitic BDL and sham rats receiving 2-weeks of either vehicle or OCA treatments (sham-OCA and BDL-OCA groups), and NRK-52E cells, rat kidney tubular epithelial cells. Results: Chronic OCA treatment significantly normalized portal hypertension, glomerular filtration rate, urine output, renal blood flow; decreased ascites, renal vascular resistance, serum creatinine, and the release of renal tubular damage markers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury moleculae-1 (uKim-1) in BDL-OCA rats. In the BDL group, inhibition of the renal oxidative stress (8-iso-PGF2α)-activated cyclooxygenase-thromboxane A2 [COX-TXA2] pathway, apoptosis, and tubular injury accompanied by a decrease in hyper-responsiveness to the vasoconstrictor 8-iso-PGF2α in perfused kidneys. In vitro experiments revealed that 8-iso-PGF2α induced oxidative stress, release of reactive oxygen species, and cell apoptosis, which were reversed by concomitant incubation with the FXR agonist. Conclusions: Through the inhibition of renal 8-iso-PGF2α production and the down-regulation of the COX-TXA2 pathway, our study suggests that chronic OCA treatment can ameliorate the HRS in ascitic cirrhotic rats. Thus, OCA is an agent with antioxidative stress, antivasoconstrictive, antiapoptotic properties which benefit ascitic, cirrhotic rats with systemic, hepatic, and renal abnormalities.

scholarly journals Development of acute kidney injury with massive granular casts and microscopic hematuria in patients with COVID-19: two case presentations with literature review

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Takuya Fujimaru ◽  
Keiki Shimada ◽  
Takayuki Hamada ◽  
Kimio Watanabe ◽  
Yugo Ito ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Literature Review ◽  
Clinical Characteristics ◽  
Kidney Injury ◽  
Microscopic Hematuria ◽  
Tubular Damage ◽  
Case Presentation ◽  
Tubular Necrosis ◽  
Case Presentations

Abstract Background Complications of acute kidney injury (AKI) are common in patients with coronavirus disease in 2019 (COVID-19). However, clinical characteristics of COVID-19-associated AKI are poorly described. We present two cases of severe COVID-19 patients with AKI. Case presentation A 77-year-old woman was suspected of having vancomycin-associated AKI, and a 45-year-old man was suspected of having heme pigment-induced AKI caused by rhabdomyolysis. The granular cast, which is known to be a valuable diagnostic tool for confirming the diagnosis of acute tubular necrosis, was detected in both patients at the onset of AKI. Interestingly, both patients also developed microscopic hematuria at the occurrence of AKI, and one patient had elevated d-dimer and low platelet levels simultaneously. Conclusions Some reports suggested that COVID-19-associated microangiopathy contributed to the kidney damage. Therefore, it is possible that our patients might have accompanied renal microangiopathy, and that this pathological background may have caused exaggerated tubular damage by vancomycin or heme pigment. The etiology of AKI in patients with COVID-19 is multifactorial. Superimposition of nephrotoxin(s) and virus-associate intra-renal microangiopathy may be a crucial trigger of kidney injury leading to severe AKI in COVID-19 patients. Therefore, in COVID-19 patients, risk factors for AKI should be taken into consideration to prevent its progression into severe AKI.

scholarly journals The Role of Congestion in Cardiorenal Syndrome Type 2: New Pathophysiological Insights into an Experimental Model of Heart Failure

2015 ◽  
Vol 6 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Annalisa Angelini ◽  
Chiara Castellani ◽  
Grazia Maria Virzì ◽  
Marny Fedrigo ◽  
Gaetano Thiene ◽  
...  
Keyword(s):  
Heart Failure ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Heart Tissue ◽  
Heart Cell ◽  
Tubular Damage ◽  
Syndrome Type ◽  
Neutrophil Gelatinase Associated Lipocalin

Background: In cardiorenal syndrome type 2 (CRS2), the role of systemic congestion in heart failure (HF) is still obscure. We studied a model of CRS2 [monocrotaline (MCT)-treated rats] secondary to pulmonary hypertension and right ventricular (RV) failure in order to evaluate the contribution of prevalent congestion to the development of kidney injury. Methods: Ten animals were treated with MCT for 4 weeks until they developed HF. Eleven animals were taken as controls. Signs of hypertrophy and dilatation of the right ventricle demonstrated the occurrence of HF. Brain natriuretic peptide (BNP), serum creatinine (sCreatinine), both kidney and heart neutrophil gelatinase-associated lipocalin (NGAL), matrix metallopeptidase 9 (MMP9), serum cytokines as well as kidney and heart cell death, as assessed by TUNEL, were studied. Results: Rats with HF showed higher BNP levels [chronic HF (CHF) 4.8 ± 0.5 ng/ml; controls 1.5 ± 0.2 ng/ml; p < 0.0001], marked RV hypertrophy and dilatation (RV mass/RV volume: CHF 1.46 ± 0.31, controls 2.41 ± 0.81; p < 0.01) as well as pleural and peritoneal effusions. A significant increase in proinflammatory cytokines and sCreatinine was observed (CHF 3.06 ± 1.3 pg/ml vs. controls 0.54 ± 0.23 pg/ml; p = 0.04). Serum (CHF 562.7 ± 93.34 ng/ml vs. controls 245.3 ± 58.19 ng/ml; p = 0.02) as well as renal and heart tissue NGAL levels [CHF 70,680 ± 4,337 arbitrary units (AU) vs. controls 32,120 ± 4,961 AU; p = 0.001] rose significantly, and they were found to be complexed with MMP9 in CHF rats. A higher number of kidney TUNEL-positive tubular cells was also detected (CHF 114.01 ± 45.93 vs. controls 16.36 ± 11.60 cells/mm2; p = 0.0004). Conclusion: In this model of CHF with prevalent congestion, kidney injury is characterized by tubular damage and systemic inflammation. The upregulated NGAL complexed with MMP9 perpetuates the vicious circle of kidney/heart damage by enhancing the enzymatic activity of MMP9 with extracellular matrix degradation, worsening heart remodeling.

scholarly journals Clinical Characteristics and Gene Mutation Analysis of the Chinese Han Population with Gitelman Syndrome: 3 Case Reports and a Literature Review

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Xueting Li ◽  
Ruofei Chen ◽  
Mingwei Chen
Keyword(s):  
Gene Mutation ◽  
Mutation Analysis ◽  
Clinical Characteristics ◽  
Clinical Phenotype ◽  
Gene Mutations ◽  
Gitelman Syndrome ◽  
Chinese Patients ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Gene Mutation Analysis

The present study reported clinical characteristics and the results of gene mutation analysis of 3 Chinese patients with Gitelman syndrome (GS). Three patients manifested with normal blood pressure, recurrent hypokalemia, and metabolic alkalosis. Only case 2 had obvious hypomagnesemia. Gene sequencing showed a compound heterozygous mutation in SCL12A3 in case 1 and a homozygous mutation in SCL12A3 in case 2. Heterozygous mutations in SCL12A3 and CLCNKB were found in case 3. Then, the literature was reviewed. The keyword “Gitelman syndrome” was inputted into the PubMed, Wanfang Database, and CNK to search all Chinese patients with GS diagnosed by gene mutations and to extract complete clinical data from December 1998 to 2018. Finally, a total of 124 cases of GS were included. No significant differences in the levels of serum potassium and magnesium were observed among the different gene mutations, and the serum magnesium levels in adults were lower than those of the juvenile. GS with reduced blood magnesium had a serious clinical phenotype. Therefore, GS had a diverse phenotype, and its final diagnosis required genetic profiling. The relationship of gene mutation and clinical phenotype needed further study.

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