-
Experimental and Clinical... Mar 2024Encapsulating peritoneal sclerosis is a rare but highly morbid disease process in patients with end-stage kidney disease on peritoneal dialysis. Surgical management has...
Encapsulating peritoneal sclerosis is a rare but highly morbid disease process in patients with end-stage kidney disease on peritoneal dialysis. Surgical management has been described in patients with encapsulation of bowel causing obstruction. Here, we describe a case of surgical management in a patient following kidney transplant with medically refractory ascites and lower extremity edema.
Topics: Humans; Kidney Transplantation; Peritoneal Fibrosis; Kidney Failure, Chronic; Treatment Outcome; Ascites; Edema; Male; Peritoneal Dialysis; Female; Middle Aged; Adult
PubMed: 38695593
DOI: 10.6002/ect.2023.0265 -
Renal Failure Dec 2024Chronic kidney disease (CKD) lacks effective treatments and renal fibrosis (RF) is one of CKD's outcomes. Dickkopf 3 (DKK3) has been identified as an agonist in CKD....
BACKGROUND
Chronic kidney disease (CKD) lacks effective treatments and renal fibrosis (RF) is one of CKD's outcomes. Dickkopf 3 (DKK3) has been identified as an agonist in CKD. However, the underlying mechanisms of DKK3 in CKD are not fully understood.
METHODS
HO-treated HK-2 cells and ureteric obstruction (UUO) mice were used as RF models. Biomarkers, Masson staining, PAS staining, and TUNEL were used to assess kidney function and apoptosis. Oxidative stress and mitochondria function were also evaluated. CCK-8 and flow cytometry were utilized to assess cell viability and apoptosis. Western blotting, IHC, and qRT-PCR were performed to detect molecular expression levels. Immunofluorescence was applied to determine the subcellular localization. Dual luciferase assay, MeRIP, RIP, and ChIP were used to validate the m6A level and the molecule interaction.
RESULTS
DKK3 was upregulated in UUO mouse kidney tissue and HO-treated HK-2 cells. Knockdown of DKK3 inhibited oxidative stress, maintained mitochondrial homeostasis, and alleviated kidney damage and RF in UUO mice. Furthermore, DKK3 silencing suppressed HK-2 cell apoptosis, oxidative stress, and mitochondria fission. Mechanistically, DKK3 upregulation was related to the high m6A level regulated by METTL3. DKK3 activated TCF4/β-catenin and enhanced MFF transcriptional expression by binding to its promoter. Overexpression of MFF reversed in the inhibitory effect of DKK3 knockdown on cell damage.
CONCLUSION
Upregulation of DKK3 caused by m6A modification activated the Wnt/β-catenin pathway to increase MFF transcriptional expression, leading to mitochondrial dysfunction and oxidative stress, thereby promoting RF progression.
Topics: Animals; Humans; Male; Mice; Adaptor Proteins, Signal Transducing; Apoptosis; beta Catenin; Cell Line; Disease Models, Animal; Fibrosis; Intercellular Signaling Peptides and Proteins; Kidney; Mice, Inbred C57BL; Mitochondria; Oxidative Stress; Renal Insufficiency, Chronic; Up-Regulation; Wnt Signaling Pathway
PubMed: 38682264
DOI: 10.1080/0886022X.2024.2343817 -
Tuberkuloz Ve Toraks Mar 2024The gold standard treatment for obstructive sleep apnea syndrome (OSAS) is positive airway pressure therapy (PAP) treatments. PAP treatments reduce complications by...
INTRODUCTION
The gold standard treatment for obstructive sleep apnea syndrome (OSAS) is positive airway pressure therapy (PAP) treatments. PAP treatments reduce complications by reducing apnea and hypopnea attacks by creating airflow at a determined pressure. In our study, we aimed to examine the effect of treatment compliance on kidney and liver functions, apneahypopnea (AHI) index, and lipid profile of patients diagnosed with OSAS and started PAP treatment.
MATERIALS AND METHODS
Patients who were admitted to the sleep laboratory of our hospital between September 2022 and September 2023 and started PAP treatment after PSG were included in our study. Patients who were called for follow-up six months after the initiation of PAP treatment were divided into two groups according to their compliance with PAP treatment. Patients who used the device for at least four hours per night and more than 70% at night were grouped as PAP-compliant patients, while the other patients were grouped as non-PAP-compliant patients.
RESULT
It was observed that uric acid, BUN, triglyceride, total cholesterol, ALT, GGT, ALP, and AHI levels of the patients who started PAP treatment decreased after six months (p= 0.001, 0.006, <0.001, 0.006, 0.01, <0.001, <0.001, <0.001 with). It was observed that HDL cholesterol levels increased (p≤ 0.001). It was observed that the change in uric acid, AHI, total cholesterol, and GGT levels in group 1 (n= 36) patients who were compliant with PAP treatment was statistically higher than in group 2 (n= 30) patients (p< 0.001, <0.03, <0.001, 0.008, respectively).
CONCLUSIONS
Uric acid, total cholesterol and GGT are biomarkers that may increase in OSAS due to intermittent hypoxia with the involvement of other systems. Since a decrease in these biomarkers can be observed in the early period depending on treatment compliance, these biomarkers can be used practically in the follow-up of treatment compliance and treatment efficacy.
Topics: Humans; Sleep Apnea, Obstructive; Female; Male; Middle Aged; Patient Compliance; Follow-Up Studies; Adult; Continuous Positive Airway Pressure; Polysomnography; Lipids
PubMed: 38676594
DOI: 10.5578/tt.202401869 -
The Lancet. Digital Health May 2024In the context of immune-mediated inflammatory diseases (IMIDs), COVID-19 outcomes are incompletely understood and vary considerably depending on the patient population...
Machine learning to understand risks for severe COVID-19 outcomes: a retrospective cohort study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US health-care system.
BACKGROUND
In the context of immune-mediated inflammatory diseases (IMIDs), COVID-19 outcomes are incompletely understood and vary considerably depending on the patient population studied. We aimed to analyse severe COVID-19 outcomes and to investigate the effects of the pandemic time period and the risks associated with individual IMIDs, classes of immunomodulatory medications (IMMs), chronic comorbidities, and COVID-19 vaccination status.
METHODS
In this retrospective cohort study, clinical data were derived from the electronic health records of an integrated health-care system serving patients in 51 hospitals and 1085 clinics across seven US states (Providence St Joseph Health). Data were observed for patients (no age restriction) with one or more IMID and for unmatched controls without IMIDs. COVID-19 was identified with a positive nucleic acid amplification test result for SARS-CoV-2. Two timeframes were analysed: March 1, 2020-Dec 25, 2021 (pre-omicron period), and Dec 26, 2021-Aug 30, 2022 (omicron-predominant period). Primary outcomes were hospitalisation, mechanical ventilation, and mortality in patients with COVID-19. Factors, including IMID diagnoses, comorbidities, long-term use of IMMs, and COVID-19 vaccination status, were analysed with multivariable logistic regression (LR) and extreme gradient boosting (XGB).
FINDINGS
Of 2 167 656 patients tested for SARS-CoV-2, 290 855 (13·4%) had confirmed COVID-19: 15 397 (5·3%) patients with IMIDs and 275 458 (94·7%) without IMIDs. In the pre-omicron period, 169 993 (11·2%) of 1 517 295 people who were tested for COVID-19 tested positive, of whom 23 330 (13·7%) were hospitalised, 1072 (0·6%) received mechanical ventilation, and 5294 (3·1%) died. Compared with controls, patients with IMIDs and COVID-19 had higher rates of hospitalisation (1176 [14·6%] vs 22 154 [13·7%]; p=0·024) and mortality (314 [3·9%] vs 4980 [3·1%]; p<0·0001). In the omicron-predominant period, 120 862 (18·6%) of 650 361 patients tested positive for COVID-19, of whom 14 504 (12·0%) were hospitalised, 567 (0·5%) received mechanical ventilation, and 2001 (1·7%) died. Compared with controls, patients with IMIDs and COVID-19 (7327 [17·3%] of 42 249) had higher rates of hospitalisation (13 422 [11·8%] vs 1082 [14·8%]; p<0·0001) and mortality (1814 [1·6%] vs 187 [2·6%]; p<0·0001). Age was a risk factor for worse outcomes (adjusted odds ratio [OR] from 2·1 [95% CI 2·0-2·1]; p<0·0001 to 3·0 [2·9-3·0]; p<0·0001), whereas COVID-19 vaccination (from 0·082 [0·080-0·085]; p<0·0001 to 0·52 [0·50-0·53]; p<0·0001) and booster vaccination (from 2·1 [2·0-2·2]; p<0·0001 to 3·0 [2·9-3·0]; p<0·0001) status were associated with better outcomes. Seven chronic comorbidities were significant risk factors during both time periods for all three outcomes: atrial fibrillation, coronary artery disease, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, chronic liver disease, and cancer. Two IMIDs, asthma (adjusted OR from 0·33 [0·32-0·34]; p<0·0001 to 0·49 [0·48-0·51]; p<0·0001) and psoriasis (from 0·52 [0·48-0·56] to 0·80 [0·74-0·87]; p<0·0001), were associated with a reduced risk of severe outcomes. IMID diagnoses did not appear to be significant risk factors themselves, but results were limited by small sample size, and vasculitis had high feature importance in LR. IMMs did not appear to be significant, but less frequently used IMMs were limited by sample size. XGB outperformed LR, with the area under the receiver operating characteristic curve for models across different time periods and outcomes ranging from 0·77 to 0·92.
INTERPRETATION
Our results suggest that age, chronic comorbidities, and not being fully vaccinated might be greater risk factors for severe COVID-19 outcomes in patients with IMIDs than the use of IMMs or the IMIDs themselves. Overall, there is a need to take age and comorbidities into consideration when developing COVID-19 guidelines for patients with IMIDs. Further research is needed for specific IMIDs (including IMID severity at the time of SARS-CoV-2 infection) and IMMs (considering dosage and timing before a patient's first COVID-19 infection).
FUNDING
Pfizer, Novartis, Janssen, and the National Institutes of Health.
Topics: Humans; COVID-19; Retrospective Studies; Male; Female; Comorbidity; Middle Aged; United States; Aged; Machine Learning; SARS-CoV-2; Immunomodulating Agents; Adult; Risk Factors; COVID-19 Vaccines; Hospitalization
PubMed: 38670740
DOI: 10.1016/S2589-7500(24)00021-9 -
Renal Failure Dec 2024Iguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of...
Iguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of action, iguratimod has been observed to have antifibrotic effects in the lung and skin; however, its effect on renal fibrosis remains unknown. This study aimed to investigate whether iguratimod could affect renal fibrosis progression. Three different concentrations of iguratimod (30 mg/kg/day, 10 mg/kg/day, and 3 mg/kg/day) were used to intervene in unilateral ureteral obstruction (UUO) model mice. Iguratimod at 10 mg/kg/day was observed to be effective in slowing UUO-mediated renal fibrosis. In addition, stimulating bone marrow-derived macrophages with IL-4 and/or iguratimod, or with TGF-β and iguratimod or SRC inhibitors , suggested that iguratimod mitigates the progression of renal fibrosis in UUO mice, at least in part, by inhibiting the IL-4/STAT6 signaling pathway to attenuate renal M2 macrophage infiltration, as well as by impeding SRC activation to reduce macrophage-myofibroblast transition. These findings reveal the potential of iguratimod as a treatment for renal disease.
Topics: Animals; Ureteral Obstruction; Mice; Macrophages; Disease Models, Animal; Fibrosis; Sulfonamides; Interleukin-4; STAT6 Transcription Factor; Male; Myofibroblasts; Chromones; Kidney; Signal Transduction; Transforming Growth Factor beta; Kidney Diseases; Mice, Inbred C57BL; Immunosuppressive Agents
PubMed: 38666363
DOI: 10.1080/0886022X.2024.2327498 -
JAMA Network Open Apr 2024Many veterans who served in Afghanistan and Iraq during Operations Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) were deployed to military bases with open... (Observational Study)
Observational Study
IMPORTANCE
Many veterans who served in Afghanistan and Iraq during Operations Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) were deployed to military bases with open burn pits and exposed to their emissions, with limited understanding of the long-term health consequences.
OBJECTIVE
To determine the association between deployment to military bases where open burn pits were used for waste disposal and the subsequent risk of developing respiratory and cardiovascular diseases.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective observational cohort study used Veterans Health Administration medical records and declassified deployment records from the Department of Defense to assess Army and Air Force veterans who were deployed between 2001 and 2011 and subsequently received health care from the Veterans Health Administration, with follow-up through December 2020. Data were analyzed from January 2023 through February 2024.
EXPOSURE
Duration of deployment to military bases with open burn pits.
MAIN OUTCOMES AND MEASURES
Diagnosis of asthma, chronic obstructive pulmonary disease, interstitial lung disease, hypertension, myocardial infarction, congestive heart failure, ischemic stroke, and hemorrhagic stroke.
RESULTS
The study population included 459 381 OEF and OIF veterans (mean [SD] age, 31.6 [8.7] years; 399 754 [87.0%] male). Median (IQR) follow-up from end of deployment was 10.9 (9.4-12.7) years. For every 100 days of deployment to bases with burn pits, veterans experienced increased adjusted odds for asthma (adjusted odds ratio [aOR], 1.01; 95% CI, 1.01-1.02), chronic obstructive pulmonary disease (aOR, 1.04; 95% CI, 1.02-1.07), hypertension (aOR, 1.02; 95% CI, 1.02-1.03), and ischemic stroke (aOR, 1.06; 95% CI, 0.97-1.14). Odds of interstitial lung disease, myocardial infarction, congestive heart failure, or hemorrhagic stroke were not increased. Results based on tertiles of duration of burn pit exposures were consistent with those from the continuous exposure measures.
CONCLUSIONS AND RELEVANCE
In this cohort study, prolonged deployment to military bases with open burn pits was associated with increased risk of developing asthma, COPD, and hypertension. The results also point to a possible increased risk in ischemic stroke. The novel ability to use integrated data on deployment and health outcomes provides a model for additional studies of the health impact of environmental exposures during military service.
Topics: Humans; Male; Retrospective Studies; Female; Adult; Afghan Campaign 2001-; Cardiovascular Diseases; United States; Iraq War, 2003-2011; Military Deployment; Veterans; Military Personnel; Middle Aged; Respiratory Tract Diseases; Open Waste Burning
PubMed: 38662371
DOI: 10.1001/jamanetworkopen.2024.7629 -
Iranian Journal of Kidney Diseases Mar 2024One of the most significant clinical features of chronic kidney disease is renal interstitial fibrosis (RIF). This study aimed to investigate the role and mechanism...
INTRODUCTION
One of the most significant clinical features of chronic kidney disease is renal interstitial fibrosis (RIF). This study aimed to investigate the role and mechanism of Shenqi Pill (SQP) on RIF.
METHODS
RIF model was established by conducting unilateral ureteral obstruction (UUO) surgery on rat or stimulating human kidney-2 (HK-2) cell with transforming growth factor β1 (TGFβ1). After modeling, the rats in the SQP low dose group (SQP-L), SQP middle dose group (SQP-M) and SQP high dose group (SQP-H) were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the TGFβ1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing serum. In in vivo assays, serum creatinine (SCr) and blood urea nitrogen (BUN) content were measured, kidney histopathology was evaluated., and α-smooth muscle actin (α-SMA) expression was detected by immunohistochemistry. Interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content, inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were assessed. Meanwhile, cell viability, inflammatory cytokines content, α-SMA expression, IKBα and P65 phosphorylation were detected in vitro experiment. Results. SQP exhibited reno-protective effect by decreasing SCr and BUN content, improving renal interstitial damage, blunting fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after the treatment with SQP-containing serum, viability and α-SMA expression were remarkably decreased in TGFβ1-stimulated HK-2 cell. Furthermore, SQP markedly down-regulated IL-1β, IL-6, and TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro. Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa B (NF-κB) pathway related inflammatory response, which indicates that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.
Topics: Animals; Humans; Rats; Actins; Blood Urea Nitrogen; Cell Line; Creatinine; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Fibrosis; Kidney; NF-kappa B; NF-KappaB Inhibitor alpha; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Transforming Growth Factor beta1; Ureteral Obstruction
PubMed: 38660700
DOI: 10.5254/kv5ap920 -
Iranian Journal of Kidney Diseases Mar 2024We recently discovered that microvesicles (MVs) derived from mesenchymal stem cells (MSCs) overexpressing miRNA-34a can alleviate experimental kidney injury in mice....
We recently discovered that microvesicles (MVs) derived from mesenchymal stem cells (MSCs) overexpressing miRNA-34a can alleviate experimental kidney injury in mice. In this study, we further explored the effects of miR34a-MV on renal fibrosis in the unilateral ureteral obstruction (UUO) models. Methods. Bone marrow MSCs were modified by lentiviruses overexpressing miR-34a, and MVs were collected from the supernatants of MSCs. C57BL6/J mice were divided into control, unilateral ureteral obstruction (UUO), UUO + MV, UUO + miR-34aMV and UUO + miR-34a-inhibitor-MV groups. MVs were injected to mice after surgery. The mice were then euthanized on day 7 and 14 of modeling, and renal tissues were collected for further analyses by Hematoxylin and eosin, Masson's trichrome, and Immunohistochemical (IHC) staining. Results. The UUO + MV group exhibited a significantly reduced degree of renal interstitial fibrosis with inflammatory cell infiltration, tubular epithelial cell atrophy, and vacuole degeneration compared with the UUO group. Surprisingly, overexpressing miR-34a enhanced these effects of MSC-MV on the UUO mice. Conclusion. Our study demonstrates that miR34a further enhances the effects of MSC-MV on renal fibrosis in mice through the regulation of epithelial-to-mesenchymal transition (EMT) and Notch pathway. miR-34a may be a candidate molecular therapeutic target for the treatment of renal fibrosis. DOI: 10.52547/ijkd.7673.
Topics: Animals; Male; Mice; Cell-Derived Microparticles; Disease Models, Animal; Epithelial-Mesenchymal Transition; Fibrosis; Kidney; Kidney Diseases; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice, Inbred C57BL; MicroRNAs; Signal Transduction; Ureteral Obstruction
PubMed: 38660698
DOI: 10.5254/s9bdqs74 -
BMC Public Health Apr 2024Multimorbidity is prevalent among older adults and is associated with adverse health outcomes, including high emergency department (ED) utilization. Social determinants...
BACKGROUND
Multimorbidity is prevalent among older adults and is associated with adverse health outcomes, including high emergency department (ED) utilization. Social determinants of health (SDoH) are associated with many health outcomes, but the association between SDoH and ED visits among older adults with multimorbidity has received limited attention. This study aimed to examine the association between SDoH and ED visits among older adults with multimorbidity.
METHODS
A cross-sectional analysis was conducted among 28,917 adults aged 50 years and older from the 2010 to 2018 National Health Interview Survey. Multimorbidity was defined as the presence of two or more self-reported diseases among 10 common chronic conditions, including diabetes, hypertension, asthma, stroke, cancer, arthritis, chronic obstructive pulmonary disease, and heart, kidney, and liver diseases. The SDoH assessed included race/ethnicity, education level, poverty income ratio, marital status, employment status, insurance status, region of residence, and having a usual place for medical care. Logistic regression models were used to examine the association between SDoH and one or more ED visits.
RESULTS
Participants' mean (± SD) age was 68.04 (± 10.66) years, and 56.82% were female. After adjusting for age, sex, and the number of chronic conditions in the logistic regression model, high school or less education (adjusted odds ratio [AOR]: 1.10, 95% confidence interval [CI]: 1.02-1.19), poverty income ratio below the federal poverty level (AOR: 1.44, 95% CI: 1.31-1.59), unmarried (AOR: 1.19, 95% CI: 1.11-1.28), unemployed status (AOR: 1.33, 95% CI: 1.23-1.44), and having a usual place for medical care (AOR: 1.46, 95% CI 1.18-1.80) was significantly associated with having one or more ED visits. Non-Hispanic Black individuals had higher odds (AOR: 1.28, 95% CI: 1.19-1.38), while non-Hispanic Asian individuals had lower odds (AOR: 0.71, 95% CI: 0.59-0.86) of one or more ED visits than non-Hispanic White individuals.
CONCLUSION
SDoH factors are associated with ED visits among older adults with multimorbidity. Systematic multidisciplinary team approaches are needed to address social disparities affecting not only multimorbidity prevalence but also health-seeking behaviors and emergent healthcare access.
Topics: Humans; Male; Female; Multimorbidity; Aged; Social Determinants of Health; Cross-Sectional Studies; Emergency Service, Hospital; Middle Aged; United States; Health Surveys; Aged, 80 and over; Chronic Disease; Emergency Room Visits
PubMed: 38658873
DOI: 10.1186/s12889-024-18613-8