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Diagnostics (Basel, Switzerland) Jul 2023Acute kidney injury (AKI) is common in cirrhotic patients affecting almost 20% of these patients. While multiple etiologies can lead to AKI, pre-renal azotemia seems to... (Review)
Review
Acute kidney injury (AKI) is common in cirrhotic patients affecting almost 20% of these patients. While multiple etiologies can lead to AKI, pre-renal azotemia seems to be the most common cause of AKI. Irrespective of the cause, AKI is associated with worse survival with the poorest outcomes observed in those with hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). In recent years, new definitions, and classifications of AKI in cirrhosis have emerged. More knowledge has also become available regarding the benefits and drawbacks of albumin and terlipressin use in these patients. Diagnostic tools such as urinary biomarkers and point-of-care ultrasound (POCUS) became available and they will be used in the near future to differentiate between different causes of AKI and direct management of AKI in these patients. In this update, we will review these new classifications, treatment recommendations, and diagnostic tools for AKI in cirrhotic patients.
PubMed: 37510105
DOI: 10.3390/diagnostics13142361 -
Frontiers in Immunology 2023Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Therefore, efforts to understand DKD pathophysiology and prevent its...
INTRODUCTION
Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide. Therefore, efforts to understand DKD pathophysiology and prevent its development at the early phase are highly warranted.
METHODS
Here, we analyzed kidneys from healthy mice, diabetic mice, and diabetic mice treated with the sodium-glucose cotransporter 2 inhibitor dapagliflozin using ATAC and RNA sequencing. The findings were verified at the protein levels and in cultured cells.
RESULTS
Our combined method of ATAC and RNA sequencing revealed , , and as the key candidate genes associated with hyperglycemia, azotemia, and albuminuria. Their protein levels were altered together with multiple other inflammatory cytokines in the diabetic kidney, which was alleviated by dapagliflozin treatment. Cell culture of immortalized renal tubular cells and macrophages unraveled that dapagliflozin could directly effect on these cells as an anti-inflammatory agent independent of glucose concentrations. We further proved that dapagliflozin attenuated ischemia/reperfusion-induced chronic kidney injury and renal inflammation in mice.
DISCUSSION
Overall, our data emphasize the importance of inflammatory factors to the pathogenesis of DKD, and provide valuable mechanistic insights into the renoprotective role of dapagliflozin.
Topics: Animals; Mice; Diabetic Nephropathies; Blood Glucose; Diabetes Mellitus, Experimental; Sodium-Glucose Transporter 2 Inhibitors; Nephritis; Inflammation
PubMed: 38022502
DOI: 10.3389/fimmu.2023.1205834 -
Scientific Reports Dec 2023To explore whether ferroptosis is involved in focal segmental glomerulosclerosis (FSGS) and its mechanism. The FSGS rat model was constructed by single nephrectomy...
To explore whether ferroptosis is involved in focal segmental glomerulosclerosis (FSGS) and its mechanism. The FSGS rat model was constructed by single nephrectomy combined with fractional tail vein injection of doxorubicin. 24-hour urine protein, serum biochemistry, HE, PAS and Masson pathological staining were measured to assess renal injury. Glomerular and morphological changes of ferroptosis were observed by transmission electron microscopy. Iron content in renal tissue was assessed by Prussian blue staining and iron detection. GSH/GSSG kit was used to detect the content and proportion of reduced/oxidized glutathione. Lipid peroxidation related proteins including MDA expression was assessed by colorimetry. The iron metabolism biomarkers such as hepcidin, ferroportin and TFR, ferroptosis biomarkers such as GPX4, ACSL4, and ferritinophagy biomarkers such as LC3II/LC3I, NCOA4, and FTH1 were detected by Western blot. Significant urinary protein, hyperlipidemia, azotemia, increased serum creatinine and hypoproteinemia were observed in FSGS rats. Histology and electron microscopy showed segmental sclerosis of glomeruli, compensatory enlargement of some glomeruli, occlusion of capillary lumen, balloon adhesion, increased mesangial matrix, atrophy of some tubules, and renal interstitial fibrosis in renal tissue of FSGS rats. The morphology of glomerular foot processes disappeared; the foot processes were extensively fused and some foot processes detached. Mitochondria became smaller, membrane density increased, and mitochondrial cristae decreased or disappeared. In addition, iron deposition was observed in renal tissue of FSGS rats. Compared with the control group, the levels of GSH, GSH/GSSG, GPX4, and ferroportin were reduced and the expression of GSSG, MDA, ACSL4, hepcidin, and TFR was increased in the renal tissue of FSGS rats; meanwhile, the expression of LC3II/LC3I and NCOA4 was increased and the expression of FTH1 was decreased. Ferroptosis is involved in the pathological progression of FSGS, which is probably associated with activation of ferritinophagy. This represents a potential therapeutic target for FSGS.
Topics: Rats; Animals; Glomerulosclerosis, Focal Segmental; Hepcidins; Ferroptosis; Glutathione Disulfide; Biomarkers; Iron
PubMed: 38097813
DOI: 10.1038/s41598-023-49697-8 -
Journal of Clinical Medicine Jul 2023The aims of this study were to analyze prevalence and severity of vascular risk factors in older patients referred to our clinic due to onset of Very Late-Onset...
BACKGROUND
The aims of this study were to analyze prevalence and severity of vascular risk factors in older patients referred to our clinic due to onset of Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP) and to create a specific phenotype based on pathophysiological insight rather than age of onset.
METHODS
In a longitudinal study, 103 (M = 39, F = 64; mean age of 80.32 ± 7.65 years) patients were evaluated with cognitive, neuropsychiatric, and functional assessment scales. Blood concentration of hemoglobin (Hb), mean corpuscular volume (MCV), platelets, total protein test (TPT), creatinine, azotemia, glycemia, total cholesterol (TC), triglycerides (TG), uric acid (UA), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), folate, vitamin B12 (Vit-B12), and homocysteine were measured. Presence/absence of tobacco use, alcohol consumption, psychoactive substance use, hypertension, hyperlipidemia, diabetes mellitus, and history of vascular disease were collected.
RESULTS
Females were more apathetic than males (NPI-Apathy: = 0.040). Males had a significantly higher level of Hb ( = 0.019) and UA ( = 0.001), and a lower level of platelets ( = 0.004) and Ca ( = 0.003), and used more tobacco ( = 0.046) and alcohol ( = 0.024) than females. Comparing patients < 80 and ≥80 years, we found differences in frequency of vascular risk factors among men ( = 0.027). In total, 102 patients were treated for psychosis (59.16% of them were using atypical antipsychotics).
CONCLUSIONS
The results of this study could be useful for a progressive demonstration of the causal relationship between cardiac and cerebral vascular events and VLOSLP.
PubMed: 37510946
DOI: 10.3390/jcm12144831 -
JNMA; Journal of the Nepal Medical... Oct 2023Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in...
UNLABELLED
Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in the background, eventually leading to multiorgan dysfunction and death. The incidence of primary amyloidosis is estimated at 5.1-12.8 cases per million, with a poor prognosis. We report a case of a 69-year male with lower back pain, shortness of breath, and anasarca diagnosed as primary systemic amyloidosis by serum-free light chain assay and kidney needle biopsy. He was started on intravenous bortezomib and dexamethasone. Though he adhered to his medications, with time he developed renal insufficiency marked by azotemia following which hemodialysis was performed. Primary systemic amyloidosis is a rare clinical condition with a very poor prognosis. Further studies are needed to understand the proper pathophysiology and treatment of the disease.
KEYWORDS
cardiomyopathies; case reports; primary amyloidosis.
Topics: Humans; Male; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Bortezomib; Renal Insufficiency; Prognosis
PubMed: 38289775
DOI: 10.31729/jnma.8297 -
Journal of Inflammation Research 2024To identify subclasses of acute pancreatitis (AP) patients in the intensive care unit (ICU) by analyzing blood urea nitrogen (BUN) trajectories.
OBJECTIVE
To identify subclasses of acute pancreatitis (AP) patients in the intensive care unit (ICU) by analyzing blood urea nitrogen (BUN) trajectories.
METHODS
AP patients in West China Hospital System (development cohort) and three public databases in the United States (validation cohort) were included. Latent class trajectory modelling was used to identify subclasses based on BUN trajectories within the first 21 days after ICU admission. Clinical characteristics and outcomes were compared, and results were externally validated.
RESULTS
The study comprised 2971 and 930 patients in the development and validation cohorts, respectively, with five subclasses: Class 1 ("Moderate-azotemia, slow decreasing"), Class 2 ("Non-azotemia"), Class 3 ("Severe-azotemia, slow decreasing"), Class 4 ("Moderate-azotemia, rapid increasing"), and Class 5 ('Moderate-azotemia, slow increasing) identified. Azotemia patients showed significantly higher 30-day mortality risk in development and validation cohorts. Specifically, Class 4 patients exhibited notably highest mortality risk in both the development cohort (HR 5.32, 95% CI 2.62-10.82) and validation cohort (HR 6.23, 95% CI 2.93-13.22). Regarding clinical characteristics, AP patients in Class 4 showed lower mean arterial pressure and a higher proportion of renal disease. We also created an online early classification model to further identify Class 4 patients among all patients with moderate azotemia at baseline.
CONCLUSION
This multinational study uncovers heterogeneity in BUN trajectories among AP patients. Patients with "Moderate-azotemia, rapid increasing" trajectory, had a higher mortality risk than patients with severe azotemia at baseline. This finding complements studies that solely rely on baseline BUN for risk stratification and enhanced our understanding of longitudinal progression of AP.
PubMed: 38828047
DOI: 10.2147/JIR.S460142 -
The Canadian Veterinary Journal = La... Mar 2024To describe the findings, treatment, and outcome of small intestinal volvulus (SIV) in 47 cows.
OBJECTIVE
To describe the findings, treatment, and outcome of small intestinal volvulus (SIV) in 47 cows.
ANIMALS AND PROCEDURE
Retrospective analysis of medical records. Comparison of the findings for 18 surviving and 29 non-surviving cows.
RESULTS
The most common abnormal vital signs were tachycardia (68.0%), tachypnea (59.6%), and decreased rectal temperature (51.1%). Signs of colic occurred in 66.0% of cows in the study. Rumen motility was reduced or absent in 93.6% of cows, and intestinal motility in 76.6%. Clinical signs on ballottement and/or percussion and simultaneous auscultation were positive on the right side in 78.7% of cows. Transrectal examination showed dilated small intestines in 48.9% of cows. The rectum contained little or no feces in 93.6% of cows. The principal laboratory abnormalities were hypocalcemia (74.1%), hypokalemia (73.8%), azotemia (62.8%), hypermagnesemia (61.6%), and hemoconcentration (60.0%). The principal ultrasonographic findings were dilated small intestines (87.1%) and reduced or absent small intestinal motility (85.2%). Forty-one of the 47 cows underwent right flank laparotomy and the SIV was reduced in 21 cows. When comparing the clinical and laboratory findings of 18 surviving and 29 non-surviving cows, the groups differed significantly with respect to severely abnormal general condition (16.7 37.9%), rumen stasis (22.2 79.3%), intestinal atony (16.7 48.3%), serum urea concentration (6.5 9.8 mmol/L), and serum magnesium concentration (0.98 1.30 mmol/L). In summary, 38.3% of the cows were discharged and 61.7% were euthanized before, during, or after surgery.
CONCLUSION AND CLINICAL RELEVANCE
An acute course of disease, little or no feces in the rectum, and dilated small intestines were characteristic of SIV in this study population.
Topics: Humans; Female; Cattle; Animals; Pregnancy; Intestinal Volvulus; Retrospective Studies; Intestine, Small; Rectum; Feces; Magnesium; Cattle Diseases
PubMed: 38434172
DOI: No ID Found