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Cureus May 2024This case report discusses the management of anti-neutrophil cytoplasmic antibodies (ANCA)-negative rapid progressive glomerulonephritis (RPGN) in a 68-year-old man with...
This case report discusses the management of anti-neutrophil cytoplasmic antibodies (ANCA)-negative rapid progressive glomerulonephritis (RPGN) in a 68-year-old man with a complex medical history, presenting with fatigue, edema, and acute renal failure. Despite the absence of positive biomarkers for specific RPGN types, the clinical progression suggested microscopic polyangiitis, leading to intensive immunosuppressive therapy with cyclophosphamide and rituximab. The patient's condition was further complicated by the coexistence of nephritic and nephrotic syndromes, requiring nuanced management strategies, including prolonged hemodialysis. After initial treatment failure, remission was eventually achieved, allowing cessation of dialysis and significant recovery of renal function. This case highlights the challenges of diagnosing and managing ANCA-negative RPGN, particularly the importance of a tailored, dynamic approach to treatment in resource-limited settings. The recovery observed underscores the potential for renal function improvement even after prolonged periods of intensive therapy, reinforcing the need for persistence and adaptability in managing complex RPGN cases.
PubMed: 38947646
DOI: 10.7759/cureus.61390 -
IScience Jun 2024Aging is closely associated with inflammation, which affects renal function reserve (RFR) in the kidneys. This study aims to investigate the impact of reduced RFR...
Aging is closely associated with inflammation, which affects renal function reserve (RFR) in the kidneys. This study aims to investigate the impact of reduced RFR reduction on kidney aging and the influence of renal inflammation and RFR reduction on this process. Natural aging rats and those subjected to unilateral nephrectomy (UNX), 1/6 nephrectomy (1/6NX), and unilateral ureteral obstruction (UUO) were observed at 6, 12, 18, and 21 months. Our findings suggest that RFR reduction and renal inflammation can accelerate kidney aging, and inflammation contributes more. Metabolomics analysis revealed alterations in amino acid metabolism contribute to RFR decline. Furthermore, experiments confirmed the involvement of pentose phosphate pathway (PPP) in promoting aging though inflammation. Our research provides novel insights into for the mechanism of kidney aging and provides indirect support for clinical treatment decisions, such as addressing kidney inflammation, stones, or tumors that may necessitate partial or complete nephrectomy.
PubMed: 38947529
DOI: 10.1016/j.isci.2024.110045 -
IScience Jun 2024The development of targeted drugs for the early prevention and management of chronic kidney disease (CKD) is of great importance. However, the success rates and...
The development of targeted drugs for the early prevention and management of chronic kidney disease (CKD) is of great importance. However, the success rates and cost-effectiveness of traditional drug development approaches are extremely low. Utilizing large sample genome-wide association study data for drug repurposing has shown promise in many diseases but has not yet been explored in CKD. Herein, we investigated actionable druggable targets to improve renal function using large-scale Mendelian randomization and colocalization analyses. We combined two population-scale independent genetic datasets and validated findings with cell-type-dependent eQTL data of kidney tubular and glomerular samples. We ultimately prioritized two drug targets, opioid receptor-like 1 and F12, with potential genetic support for restoring renal function and subsequent treatment of CKD. Our findings explore the potential pathological mechanisms of CKD, bridge the gap between the molecular mechanisms of pathogenesis and clinical intervention, and provide new strategies in future clinical trials of CKD.
PubMed: 38947510
DOI: 10.1016/j.isci.2024.109953 -
Heliyon Jun 2024Acute kidney injury (AKI) frequently emerges as a consequential non-neurological sequel to traumatic brain injury (TBI), significantly contributing to heightened...
Acute kidney injury (AKI) frequently emerges as a consequential non-neurological sequel to traumatic brain injury (TBI), significantly contributing to heightened mortality risks. The intricate interplay of oxidative stress in the pathophysiology of TBI underscores the centrality of the Keap1-Nrf2/HO-1 signaling pathway as a pivotal regulator in this context. This study endeavors to elucidate the involvement of the Keap1-Nrf2/HO-1 pathway in modulating oxidative stress in AKI subsequent to TBI and concurrently explore the therapeutic efficacy of dimethyl fumarate (DMF). A rat model of TBI was established via the Feeney free-fall method, incorporating interventions with varying concentrations of DMF. Assessment of renal function ensued through measurements of serum creatinine and neutrophil gelatinase-associated lipocalin. Morphological evaluation of renal pathology was conducted employing quantitative hematoxylin and eosin staining. The inflammatory response was scrutinized by quantifying interleukin (IL)-6, IL-1β, and tumor necrosis factor-α levels. Oxidative stress levels were discerned through quantification of malondialdehyde and superoxide dismutase. The apoptotic cascade was examined via the terminal deoxynucleotidyl transferase dUTP deletion labeling assay. Western blotting provided insights into the expression dynamics of proteins affiliated with the Keap1-Nrf2/HO-1 pathway and apoptosis. The findings revealed severe kidney injury, heightened oxidative stress, inflammation, and apoptosis in the traumatic brain injury model. Treatment with DMF effectively reversed these changes, alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 signaling pathway, ultimately conferring protection against AKI. Activating Keap1-Nrf2/HO-1 signaling pathway may be a potential therapeutic strategy for attenuating oxidative stress-induced AKI after TBI.
PubMed: 38947486
DOI: 10.1016/j.heliyon.2024.e32377 -
Journal of Cancer 2024Kidney clear cell carcinoma (KIRC) commonly presents with metastases upon diagnosis, highlighting the critical need to identify more precise biomarkers for early...
Kidney clear cell carcinoma (KIRC) commonly presents with metastases upon diagnosis, highlighting the critical need to identify more precise biomarkers for early detection, intervention, and personalized treatment. Although The REEP family has been investigated in cancer development, the specific relationship between REEP4 and cancer remains unclear. In our study, we employed bioinformatics analysis and conducted fundamental experiments to evaluate the potential of REEP4 as a biomarker for predicting the prognosis and therapeutic efficacy of KIRC. Comparing KIRC tumor tissues to normal tissues, we observed a significant upregulation in REEP4 expression, with higher levels of REEP4 correlating positively with tumor malignancy. Further COX regression analysis, as well as single and multifactorial analyses, confirmed that high REEP4 expression indicated lower survival rates in KIRC. Gene function analysis also identified associations between REEP4 and critical pathways such as the cell cycle, along with its involvement in protein binding. Furthermore, our investigation of the immune response suggests that a favorable immunotherapeutic response is linked to a reduction in REEP4 expression. Subsequently, we conducted in experiments to confirm the overexpression of REEP4 in KIRC tumor tissues and renal cancer cells. In summary, our study revealed a close association between REEP4 expression and KIRC, emphasizing its correlation with prognosis and the immune response. These findings suggest that REEP4 is a potential biomarker for KIRC.
PubMed: 38947393
DOI: 10.7150/jca.96135 -
World Journal of Gastroenterology Jun 2024Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver...
BACKGROUND
Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure.
AIM
To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.
METHODS
The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired -tests, Mann-Whitney tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups.
RESULTS
In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality.
CONCLUSION
Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.
Topics: Humans; Hepatectomy; Heparin; Male; Female; Middle Aged; Liver Failure; Liver Neoplasms; Aged; Anticoagulants; Treatment Outcome; Postoperative Complications; Retrospective Studies; Length of Stay; Risk Factors; Intensive Care Units; Propensity Score
PubMed: 38947296
DOI: 10.3748/wjg.v30.i22.2881 -
MedRxiv : the Preprint Server For... Jun 2024Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.
BACKGROUND
Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.
AIM
To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension.
METHODS
We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data.
RESULTS
Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials.
CONCLUSIONS
RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication.
CLINICAL PERSPECTIVE
What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.
PubMed: 38946962
DOI: 10.1101/2024.06.12.24308869 -
Cancer Innovation Apr 2024von Hippel-Lindau (VHL) disease is a rare autosomal dominant multiorgan disease characterized by several benign and malignant tumors rich in vascular, as well as cysts...
von Hippel-Lindau (VHL) disease is a rare autosomal dominant multiorgan disease characterized by several benign and malignant tumors rich in vascular, as well as cysts in other organs. A great clinical treatment strategy is significantly warranted for good prognosis of patients with VHL disease. Herein, we reported a case of a 45-year-old woman diagnosed with VHL disease with spinal hemangioblastoma (HB) and clear cell renal cell carcinoma (ccRCC). Four years after the resection of the right kidney, a recurrent RCC in the right kidney and a malignant lesion in the left kidney were observed. This patient was started on sorafenib (800 mg, daily) and tislelizumab (200 mg per 3 weeks). After 6 months of treatment, the size of renal cell carcinoma was dramatically reduced and renal function improved. More importantly, she achieved partial response during the whole treatment. Microscopically, intramedullary masses resection was done and the HB in T4-5 thoracic spinal was removed. Neurologic symptoms such as numbness and pain were remarkably alleviated. Additionally, tislelizumab-induced elevation in liver transaminase levels and hypothyroidism were revered by hepatoprotector and levothyroxine, respectively. In short, comprehensive treatment strategies may benefit patients with VHL disease, especially with HB and ccRCC.
PubMed: 38946932
DOI: 10.1002/cai2.94 -
Journal of Cellular Physiology Jun 2024The small Rho GTP-binding proteins are important cell morphology, function, and apoptosis regulators. Unlike other Rho proteins, RhoB can be subjected to either...
The small Rho GTP-binding proteins are important cell morphology, function, and apoptosis regulators. Unlike other Rho proteins, RhoB can be subjected to either geranylgeranylation (RhoB-GG) or farnesylation (RhoB-F), making that the only target of the farnesyltransferase inhibitor (FTI). Fluorescence resonance energy transfer experiments revealed that RhoB is activated by hyperosmolarity. By contrast, hyposmolarity did not affect RhoB activity. Interestingly, treatment with farnesyltransferase inhibitor-277 (FTI-277) decreased the cell size. To evaluate whether RhoB plays a role in volume reduction, renal collecting duct MCD4 cells and Human Kidney, HK-2 were transiently transfected with RhoB-wildtype-Enhance Green Fluorescence Protein (RhoB-wt-EGFP) and RhoB-CLLL-EGFP which cannot undergo farnesylation. A calcein-based fluorescent assay revealed that hyperosmolarity caused a significant reduction of cell volume in mock and RhoB-wt-EGFP-expressing cells. By contrast, cells treated with FTI-277 or expressing the RhoB-CLLL-EGFP mutant did not properly respond to hyperosmolarity with respect to mock and RhoB-wt-EGFP expressing cells. These findings were further confirmed by 3D-LSCM showing that RhoB-CLLL-EGFP cells displayed a significant reduction in cell size compared to cells expressing RhoB-wt-EGFP. Moreover, flow cytometry analysis revealed that RhoB-CLLL-EGFP expressing cells as well as FTI-277-treated cells showed a significant increase in cell apoptosis. Together, these data suggested that: (i) RhoB is sensitive to hyperosmolarity and not to hyposmolarity; (ii) inhibition of RhoB farnesylation associates with an increase in cell apoptosis, likely suggesting that RhoB might be a paramount player controlling apoptosis by interfering with responses to cell volume change.
PubMed: 38946197
DOI: 10.1002/jcp.31343 -
Internal Medicine (Tokyo, Japan) 2024Thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) syndrome is an inflammatory disorder with an unclear pathogenesis. We herein report a case...
Thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) syndrome is an inflammatory disorder with an unclear pathogenesis. We herein report a case of TAFRO syndrome in remission in a patient who experienced recurrent intracranial bleeding despite a normal platelet count and coagulation system. A further investigation suggested the presence of anti-glycoprotein VI (GPVI) autoantibodies in the plasma, which induced platelet dysfunction and bleeding tendency. No new bleeding or relapse of TAFRO syndrome occurred after immunosuppressive therapy was initiated. These findings may help elucidate the autoimmune pathogenesis of TAFRO syndrome.
Topics: Humans; Autoantibodies; Recurrence; Syndrome; Platelet Membrane Glycoproteins; Cerebral Hemorrhage; Thrombocytopenia; Fever; Female; Middle Aged; Male; Blood Platelet Disorders
PubMed: 38945933
DOI: 10.2169/internalmedicine.2799-23