Simultaneous Liver Kidney Transplantation in a Primary Type 2 Hyperoxaluria With Corrected TOF and Severe Cardiomyopathy: A Case Report.

Background: Primary type 2 hyperoxaluria is a very rare genetic disorder,1,2 where in the progression to renal failure was assumed to be insidious and not very common.3 PH2 is due to deficient glyoxylate reductase/hydroxypyruvate reductase (GRHPR),1,2 which was thought to have extra-hepatic production also.4 The progression to renal failure in these patient subgroups is well documented in the Literature and the role of SLK (simultaneous liver and kidney transplantation) has not been clearly established.8. Method: We present a case report of a young girl with PH2, who successfully underwent SLK, with evidence of reduction in the urine oxalate levels post SLK. Results: PH2, though a rare genetic disease, has a proven potential to progress to chronic renal failure requiring transplantation, renal transplantation alone has not shown any benefit, these patients can be offered SLK as a primary treatment option, to improve the outcomes, this needs further validation with consensus and studies.

Periodontitis and systemic parameters in chronic kidney disease: Systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review with meta-analysis to assess recent scientific evidence on the association between periodontitis and systemic parameters/conditions in individuals with chronic kidney disease (CKD). MATERIALS AND METHODS: The search for studies was performed in MedLine/PubMed, Scopus, Web of Science, and BIREME databases. Reference lists of selected articles were also searched. Studies with different epidemiological designs evaluating the influence of exposure to periodontitis on serum markers and mortality in individuals with CKD were eligible for inclusion. Three independent reviewers performed the article selection and data extraction. The assessment of methodological quality used the adapted Newcastle Ottawa Scale. Random effects meta-analysis was performed to calculate association measurements and 95% confidence intervals. RESULTS: In total, 3053 records were identified in the database search, with only 25 studies meeting the eligibility criteria and, of these, 10 studies contributed data for meta-analysis. Using a random-effects model, periodontitis was associated with hypoalbuminemia (PRunadjusted = 2.47; 95%CI:1.43-4.26), with high levels of C-reactive protein (PRunadjusted = 1.35; 95%CI%:1.12-1.64), death from cardiovascular disease (RRunadjusted = 2.29; 95%CI:1.67-3.15) and death from all causes (RRunadjusted = 1.73; 95%CI:1.32-2.27). CONCLUSIONS: The findings of this review validated a positive association between periodontitis and serum markers and mortality data in individuals with CKD.

The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data. METHODS: Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population. RESULTS: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0-31.5; standard therapy: 18.5, 95%CI: 14.7-23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9-38.3; standard therapy: 29.6, 95%CI: 25.5-34.7). CONCLUSION: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

Serum Vitamin B12 Deficiency in Chronic Hemodialysis Patients.

Introduction Essential vitamins like folate and vitamin B12 are crucial for many physiological functions. Patients with renal failure undergoing regular hemodialysis in the general population may experience harmful effects from vitamin B12 deficits. Therefore, this study aimed to determine the frequency of vitamin B12 deficiency in hemodialysis patients and its association with other clinical parameters. Methods This cross-sectional study was conducted at the dialysis unit of Patel Hospital and Lifeline Hospital, Karachi, using a non-probability consecutive sampling technique after obtaining ethical approval from Lifeline Hospital (LLH/HR/02-22). The study duration was six months, from January 10, 2023, to July 22, 2023. A total of 135 adult renal failure patients with ages >18 and <70 years on maintenance hemodialysis for >1 year were included in the study. The chi-square test was used to determine the association between vitamin B12 deficiency and age and gender. A p-value of 0.05 was considered statistically significant. Results The study findings showed that out of 135 patients, 82 (60.7%) were males and 53 (39.3%) were females, with a mean age of 50.80 ± 10.03 years. The duration of hemodialysis was approximately 1-2 years in 98 (72.6%) patients, 2-3 years in 27 (20.0%) patients, and 3-4 years in only 9 (6.7%) patients. The mean serum vitamin B-12 levels were 411.61 ± 224.95 pg/ml, with 30 (22.2%) of the subjects being deficient. In terms of duration of hemodialysis, there was a significant association (p= 0.013). Between patients with normal 4 (4%) and deficient 5 (17%) vitamin B12 and 3-4 years of hemodialysis. Conclusion In this study, we found that a significant proportion of patients on chronic hemodialysis had vitamin B12 deficiency. Moreover, vitamin B12 deficiency was significantly associated with duration of hemodialysis. Therefore, we recommend periodic vitamin B12 testing in hemodialysis patients to avoid any associated complications.

Modified Zhenwu Tang delays chronic renal failure progression by modulating oxidative stress and hypoxic responses in renal proximal tubular epithelial cells.

Background: Tubulointerstitial fibrosis (TIF) is a critical pathological feature of chronic renal failure (CRF), with oxidative stress (OS) and hypoxic responses in renal proximal tubular epithelial cells playing pivotal roles in disease progression. This study explores the effects of Modified Zhenwu Tang (MZWT) on these processes, aiming to uncover its potential mechanisms in slowing CRF progression. Methods: We used adenine (Ade) to induce CRF in rats, which were then treated with benazepril hydrochloride (Lotensin) and MZWT for 8 weeks. Assessments included liver and renal function, electrolytes, blood lipids, renal tissue pathology, OS levels, the hypoxia-inducible factor (HIF) pathway, inflammatory markers, and other relevant indicators. In vitro, human renal cortical proximal tubular epithelial cells were subjected to hypoxia and lipopolysaccharide for 72 h, with concurrent treatment using MZWT, FM19G11, and N-acetyl-l-cysteine. Measurements taken included reactive oxygen species (ROS), HIF pathway activity, inflammatory markers, and other relevant indicators. Results: Ade treatment induced significant disruptions in renal function, blood lipids, electrolytes, and tubulointerstitial architecture, alongside heightened OS, HIF pathway activation, and inflammatory responses in rats. In vivo, MZWT effectively ameliorated proteinuria, renal dysfunction, lipid and electrolyte imbalances, and renal tissue damage; it also suppressed OS, HIF pathway activation, epithelial-mesenchymal transition (EMT) in proximal tubular epithelial cells, and reduced the production of inflammatory cytokines and collagen fibers. In vitro findings demonstrated that MZWT decreased apoptosis, reduced ROS production, curbed OS, HIF pathway activation, and EMT in proximal tubular epithelial cells, and diminished the output of inflammatory cytokines and collagen. Conclusion: OS and hypoxic responses significantly contribute to TIF development. MZWT mitigates these responses in renal proximal tubular epithelial cells, thereby delaying the progression of CRF.

Aminophylline suppresses chronic renal failure progression by activating SIRT1/AMPK/mTOR-dependent autophagy.

Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.

Preferences of people with chronic kidney disease regarding digital health interventions that promote healthy lifestyle: qualitative systematic review with meta-ethnography.

OBJECTIVES: Diet and physical activity are crucial for people with chronic kidney disease (CKD) to maintain good health. Digital health interventions can increase access to lifestyle services. However, consumers' perspectives are unclear, which may reduce the capacity to develop interventions that align with specific needs and preferences. Therefore, this review aims to synthesise the preferences of people with CKD regarding digital health interventions that promote healthy lifestyle. DESIGN: Qualitative systematic review with meta-ethnography. DATA SOURCES: Databases Scopus, CENTRAL, MEDLINE, CINAHL and SPORTDiscus were searched between 2000 and 2023. ELIGIBILITY CRITERIA: Primary research papers that used qualitative exploration methods to explore the preferences of adults with CKD (≥18 years) regarding digital health interventions that promoted diet, physical activity or a combination of these health behaviours. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened title, abstract and full text. Discrepancies were resolved by a third reviewer. Consumers' quotes were extracted verbatim and synthesised into higher-order themes and subthemes. RESULTS: Database search yielded 5761 records. One record was identified following communication with a primary author. 15 papers were included. These papers comprised 197 consumers (mean age 51.0±7.2), including 83 people with CKD 1-5; 61 kidney transplant recipients; 53 people on dialysis. Sex was reported in 182 people, including 53% male. Five themes were generated regarding consumers' preferences for digital lifestyle interventions. These included simple instruction and engaging design; individualised interventions; virtual communities of care; education and action plans; and timely reminders and automated behavioural monitoring. CONCLUSION: Digital health interventions were considered an important mechanism to access lifestyle services. Consumers' preferences are important to ensure future interventions are tailored to specific needs and goals. Future research may consider applying the conceptual framework of consumers' preferences in this review to develop and evaluate the effect of a digital lifestyle intervention on health outcomes. PROSPERO REGISTRATION NUMBER: CRD42023411511.

Serum interleukin 18 level in kidney diseases and age.

Background: Interleukin-18 (IL-18), also known as interferon-gamma inducing factor is a protein which in humans is encoded by the IL18 gene, it is a member of the IL 1 family and has a molecular weight of 18 kDa. Innate and adaptive immunity can be regulated by IL-18, and disorders involving its dysregulation might result in inflammatory or autoimmune conditions. Aim of the Work: To distinguish between acute kidney injury (AKI) and chronic renal failure (CRF), this research investigates the utility of IL-18 as a novel biomarker and examines how age affects its level. Materials and Methods: Three hundred participants were included and divided into three groups using the following methodology. Group I consisted of 100 control subjects who were split up by age and gender. Group II consisted of 100 AKI patients who were divided into two groups and subgroups based on age and gender. Group III, which consisted of 100 CRF (hemodialyzed patients), was divided into two groups and subgroups, as patients with acute renal injury and previously healthy people. Patients' blood was drawn to conduct a laboratory investigation blood urea, serum creatinine, sodium, potassium, pH, GFR and PCO2. Results: Patients with CRF had higher serum levels of IL-18 than patients with AKI, regardless of gender, and both groups of patients had levels of IL-18 that rise with age. Conclusion: IL-18 is a reliable indicator for the differentiation between AKI and CRF patients receiving hemodialysis and its level correlates with age independent with gender.

Coexisting presentation of two rare genetic variants of autosomal dominant polycystic kidney disease and Alport syndrome.

Alport syndrome and autosomal dominant polycystic kidney disease are monogenic causes of chronic kidney disease and end-stage kidney failure. We present a case of a man in his 60s with progressive chronic kidney disease, bilateral sensorineural hearing loss and multiple renal cysts. Genetic analysis revealed a heterozygous variant in COL4A3 (linked to Alport syndrome) and in the GANAB gene (associated with a milder form of autosomal dominant polycystic kidney disease). Although each variant confers a mild risk of developing end-stage kidney disease, the patient presented a pronounced and accelerated progression of chronic kidney disease, which goes beyond what would be predicted by adding up their individual effects. This suggests a potential synergic effect of both variants, which warrants further investigation.

Association between non-registration of chronic kidney disease and mortality and cardiovascular outcome: a time-to-event analysis of retrospective primary care data.

OBJECTIVE: Patients with impaired kidney function and increased albuminuria are at risk of developing cardiovascular disease (CVD). Previous research has revealed that a substantial proportion of patients with chronic kidney disease (CKD) do not get a registered diagnosis in the electronic health record of the general practitioner. The aim of this study was to investigate the association between non-registration of CKD and all-cause mortality and cardiovascular outcome. DESIGN AND SETTING: A retrospective study in primary care. METHODS: The analyses were carried out in the INTEGO database, a general practice-based morbidity registration network in Flanders, Belgium. The study used INTEGO data from the year 2018 for all patients ≥18 years old, including 10 551 patients. To assess the risk of mortality and CVD, a time-to-event analysis was performed. Cox proportional hazard model was used to evaluate the association between non-registration and incidence of all-cause mortality and cardiovascular events with mortality as a competing risk. Subgroup analyses were performed for estimated glomerular filtration rate stages (3A, 3B, 4 and 5). Multiple imputation was done following the methodology of Mamouris et al. RESULTS: Mortality was higher in patients with non-registered CKD compared with patients with registered CKD (HR 1.29, 95% CI 1.19 to 1.41). Non-registration of CKD was not associated with an increased risk for the development of CVD (HR 0.92, 95% CI 0.77 to 1.11). CONCLUSION: An association between non-registration and all-cause mortality was identified, although no such association was apparent for CVD.

Hemodynamic effects of low versus high dialysate bicarbonate concentration in hemodialysis patients.

INTRODUCTION: Hemodialysis treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with hemodynamic instability. The aim of this study was to perform a detailed comparison of high and low dialysate bicarbonate in terms of blood pressure, intradialytic hemodynamic parameters, orthostatic blood pressure, and electrolytes. METHODS: Fifteen hemodialysis patients were examined in a single-blind, randomized, controlled, crossover study. Participants underwent a 4-h hemodialysis session with dialysate bicarbonate concentration of 30 or 38 mmol/L with 1 week between interventions. Blood pressure was monitored throughout hemodialysis, while cardiac output, total peripheral resistance, stroke volume, and central blood volume were assessed with ultrasound dilution technique (Transonic). Orthostatic blood pressure was measured pre- and post-hemodialysis. FINDINGS: With similar ultrafiltration (UF) volume (2.6 L), systolic blood pressure (SBP) tended to decrease more during high dialysate bicarbonate compared to low dialysate bicarbonate; the mean (95% confidence interval) between treatment differences in SBP were: 8 (-4; 20) mmHg (end of hemodialysis) and 7 (0; 15) mmHg (post-hemodialysis). Stroke volume decreased whereas total peripheral resistance increased significantly more during high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment differences: Stroke volume: 12 (1; 23) mL; Total peripheral resistance: -2.9 (-5.3; -0.5) mmHg/(L/min). Cardiac output tended to decrease more with high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment difference 0.7 (0.0; 1.4) L/min. High dialysate bicarbonate caused alkalosis, hypocalcemia, and lower plasma potassium, whereas patients remained normocalcemic with normal pH during low dialysate bicarbonate. Orthostatic blood pressure response after dialysis did not differ significantly. DISCUSSION: The use of high dialysate bicarbonate compared to low dialysate bicarbonate was associated with hypocalcemia, alkalosis, and a more pronounced hypokalemia. During hemodialysis with UF, a better preservation of blood pressure, stroke volume, and cardiac output may be achieved with low dialysate bicarbonate compared to high dialysate bicarbonate.

Melittin induces autophagy to alleviate chronic renal failure in 5/6-nephrectomized rats and angiotensin II-induced damage in podocytes.

BACKGROUND/OBJECTIVES: Chronic renal failure (CRF) is a complex pathological condition that lacks a cure. Certain Chinese medicines, such as melittin, a major component in bee venom, have shown efficacy in treating CRF patients. On the other hand, the mechanisms underlying the therapeutic effects of melittin are unclear. MATERIALS/METHODS: A 5/6 nephrectomy model (5/6 Nx) of renal failure was established on rats for in vivo assays, and mouse podocyte clone 5 (MPC5) mouse podocyte cells were treated with angiotensin II (AngII) to establish an in vitro podocyte damage model. The 24-h urine protein, serum creatinine, and blood urea nitrogen levels were evaluated after one, 2, and 4 weeks. Hematoxylin and eosin staining, Masson staining, and periodic acid-Schiff staining were used to examine the pathological changes in kidney tissues. A cell counting kit 8 assay was used to assess the cell viability. Reverse transcription polymerase chain reaction and Western blot were used to assess the mRNA and protein levels in the cells, respectively. RESULTS: In the rat 5/6 Nx, melittin reduced the 24-h urinary protein excretion and the serum creatinine and blood urea nitrogen levels. Furthermore, the renal pathology was improved in the melittin-treated 5/6 Nx rats. Melittin promoted podocin, nephrin, Beclin 1, and the LC3II/LC3I ratio and inhibited phosphorylated mammalian target of rapamycin (mTOR)/mTOR in 5/6 Nx-induced rats and AngII-induced MPC5 mouse podocyte cells. Moreover, inhibiting autophagy with 3-MA weakened the effects of melittin on podocin, nephrin, and the LC3II/LC3I ratio in podocytes. CONCLUSION: Melittin may offer protection against kidney injury, probably by regulating podocyte autophagy. These results provide the theoretical basis for applying melittin in CRF therapy.

Causal relationship between gut microbiota and chronic renal failure: a two-sample Mendelian randomization study.

Background: Observational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure. Methods: Employing genome-wide association study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings. Results: According to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71-0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08-1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02-1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03-1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00-1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02-1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09-1.28, p < 0.001) may be risk factors for chronic renal failure. However, after correction for multiple comparisons using False Discovery Rate, only the associations with Escherichia-Shigella and Howardella remain significant, indicating that the other genera have suggestive associations. Sensitivity analyses did not reveal any pleiotropy or heterogeneity. Conclusion: Our two-sample Mendelian randomization study suggests that the genera Escherichia-Shigella and Howardella are risk factors for chronic renal failure, and they may serve as potential targets for future therapeutic interventions. However, the exact mechanisms of action are not yet clear, necessitating further research to elucidate their precise roles fully.

Short versus long-acting erythropoiesis-stimulating agents for anemia management in Egyptian hemodialysis patients.

BACKGROUND: Chronic kidney disease (CKD) often results in renal anemia, impacting the well-being of patients and causing various negative consequences. Erythropoiesis-stimulating agents (ESAs) offer promising solutions for managing anemia in CKD. This study aimed to evaluate and compare the effectiveness, safety profile, and cost-effectiveness of short-acting (Eprex®) and long-acting (Aranesp®) ESAs. METHOD: This comparative prospective cohort cost-effectiveness study was carried out over 6 months among adult Egyptian hemodialysis patients of either gender. Participants were categorized into two groups based on the type of ESA administered: the Eprex group, receiving epoetin alfa, and the Aranesp group, receiving darbepoetin alfa. These two treatment groups' efficacy, safety, and cost were analyzed and compared. RESULTS: Of 127 hemodialysis patients, 60 (47.2%) received Eprex, while 67 (52.8%) were treated with Aranesp. Target hemoglobin (Hb) was achieved by 50.6% of patients in the Eprex group versus 63.4% in the Aranesp group, with a significant difference (P < 0.001). Both treatment groups exhibited a similar safety profile, while Aranesp® was considered the cost-saving protocol. CONCLUSION: In hemodialysis Egyptian patients, Aranesp with extended dosing intervals proved to be more effective in achieving target Hb with comparable adverse effect profiles, a substantial cost-saving strategy, and offered time-saving advantages for medical staff workload compared to Eprex. TRIAL REGISTRATION: The Clinicaltrial.gov registration ID is NCT05699109 (26/01/2023).

Omentin reduces venous neointimal hyperplasia in arteriovenous fistula through hypoxia-inducible factor-1 alpha inhibition.

Arteriovenous fistula (AVF) failure often involves venous neointimal hyperplasia (VNH) driven by elevated hypoxia-inducible factor-1 alpha (HIF-1α) in the venous wall. Omentin, known for its anti-inflammatory and anti-hyperplasia properties, has an uncertain role in early AVF failure. This study investigates omentin's impact on VNH using a chronic renal failure (CRF) rabbit model. The CRF rabbit model of AVF received omentin-expressing adenoviral vector or control ß-gal vector to assess omentin's effects on VNH. Human vascular smooth muscle cells (HVSMCs), stimulated with tumor necrosis factor-α (TNF-α), were exposed to recombinant human omentin (Rh-OMT) to study its influence on cell proliferation and migration. The AMP-activated protein kinase (AMPK) inhibitor compound C and the mammalian target of rapamycin (mTOR) activator MHY1485 were employed to explore omentin's mechanisms in VNH reduction through HIF-1α inhibition. Omentin treatment reduced VNH in CRF rabbits, concomitant with HIF-1α down-regulation and the suppression of downstream factors, including vascular endothelial growth factor and matrix metalloproteinases. Rh-OMT inhibited TNF-α-induced HVSMC proliferation and migration by modulating both cell cycle and cell adhesion proteins. Additionally, omentin reduced HIF-1α expression through the AMPK/mTOR pathway activation. Notably, the blockade of AMPK/mTOR signaling reversed omentin-mediated inhibition of VNH, cell proliferation, and migration, both in vivo and in vitro. In conclusion, omentin mitigates VNH post-AVF creation by restraining HIF-1α via AMPK/mTOR signaling. Strategies boosting circulating omentin levels may offer promise in averting AVF failure.

Mycobacterium senegalense catheter-related bloodstream infection.

Catheter-related bloodstream infection (CRBSI) is one of the common healthcare-acquired infections imposing a high burden of morbidity and mortality on the patients. Non-tuberculous mycobacterium is a rare aetiology for CRBSI and poses challenges in laboratory diagnosis and clinical management. This is a case of a woman in her early 60s with underlying end-stage renal failure, diabetes mellitus and hypertension presented with a 2-week history of high-grade fever postregular haemodialysis, vomiting, lethargy and altered mental status.Blood cultures from a permanent catheter and peripheral taken concurrently yielded Mycobacterium senegalense, identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, which established the diagnosis of CRBSI atypically presented with concurrent acute intracranial bleeding and cerebrovascular infarction at initial presentation. She was started on a combination of oral azithromycin, oral amikacin and intravenous imipenem, and the permanent catheter was removed. Despite the treatments instituted, she developed septicaemia, acute myocardial infarction and macrophage activation-like syndrome, causing the patient's death.

Global trends in chronic kidney disease-related mortality: a systematic review protocol.

INTRODUCTION: In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic. METHODS AND ANALYSIS: We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics. ETHICS AND DISSEMINATION: A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023416084.

Are there lost opportunities in chronic kidney disease? A region-wide cohort study.

OBJECTIVES: Identify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention. DESIGN AND SETTING: Observational, population-wide study of residents in the Stockholm and Skåne regions of Sweden between 1 January 2015 and 31 December 2020. PARTICIPANTS: All patients who did not yet have a diagnosis of CKD in healthcare but had CKD according to laboratory measurements of CKD biomarkers available in electronic health records. OUTCOME MEASURES: We assessed the proportions of the patient population that received a subsequent diagnosis of CKD in healthcare, that used guideline-directed pharmacological therapy (statins, renin-angiotensin aldosterone system inhibitors (RAASi) and/or sodium-glucose cotransporter-2 inhibitors (SGLT2i)) and that experienced adverse outcomes (all-cause mortality, cardiovascular mortality or major adverse cardiovascular events (MACE)). The potential to prevent adverse outcomes in CKD was assessed using simulations of guideline-directed pharmacological therapy in untreated subsets of the study population. RESULTS: We identified 99 382 patients with undiagnosed CKD during the study period. Only 33% of those received a subsequent diagnosis of CKD in healthcare after 5 years. The proportion that used statins or RAASi was of similar size to the proportion that didn't, regardless of how advanced their CKD was. The use of SGLT2i was negligible. In simulations of optimal treatment, 22% of the 21 870 deaths, 27% of the 14 310 cardiovascular deaths and 39% of the 22 224 MACE could have been avoided if every patient who did not use an indicated medication for their laboratory-confirmed CKD was treated with guideline-directed pharmacological therapy for CKD. CONCLUSIONS: While we noted underdiagnosis and undertreatment of CKD in this large contemporary population, we also identified a substantial realisable potential to improve CKD outcomes and reduce its burden by treating patients early with guideline-directed pharmacological therapy.

Inspiratory Muscle Training in Patients Living with Chronic Kidney Disease and Receiving Hemodialysis: Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: People living with chronic kidney disease (CKD) and receiving hemodialysis (HD) have impaired respiratory muscle strength and endurance. The objective of this study was to systematically review the effects of inspiratory muscle training (IMT) on respiratory muscle strength, functional capacity, lung function, quality of life, endothelial function, and oxidative stress in people living with CKD and receiving HD. METHODS: An electronic search was conducted from inception to June 2023. Randomized controlled trials that evaluated the effects of IMT on respiratory muscle strength, functional capacity, lung function, endothelial function, quality of life, or oxidative stress in adults living with CKD and receiving HD, compared with control, placebo IMT, or conventional physical therapy, were included. RESULTS: Eight studies were included, totaling 246 people. The meta-analysis showed that IMT increased the maximum inspiratory pressure (MIP) by 22.53 cm H2O, the maximum expiratory pressure (MEP) by 19.54 cm H2O, and the distance covered in the 6-minute walk test by 77.63 m. Changes in lung function and quality of life were not observed. It was not possible to quantitatively analyze data on endothelial function and oxidative stress. CONCLUSIONS: IMT improves MIP, MEP, and functional capacity in people living with CKD and receiving HD. IMT did not demonstrate significant results for lung function and quality of life. Effects on endothelial function and oxidative capacity remain uncertain. IMPACT: Inspiratory muscle training improves MIP, MEP, and functional capacity in people living with CKD and receiving HD, compared with conventional physical therapy or controls or placebo intervention. Increases in functional capacity in this population are extremely important because of the relationship with the survival of these people.

Protective effect of cilostazol on vascular injury in rats with acute ischemic stroke complicated with chronic renal failure.

Chronic renal failure (CRF) resulting in vascular calcification, which does damage to blood vessels and endothelium, is an independent risk factor for stroke. It has been reported that cilostazol has a protective effect on the focal cerebral ischemic infarct. However, its impact on vascular injury in CRF combined stroke and its molecular protection mechanism have not been investigated. In this study, we carried out the effect of cilostazol on CRF combined stroke rats, and the results confirmed that it improved the neurobehavior, renal function as well as pathologic changes in both the kidney and brain. In addition, the inflammation and oxidative stress factors in the kidney and brain were suppressed. Moreover, the rates of brain edema and infarction were decreased. The injured brain-blood barrier (BBB) was recovered with less Evans blue extravasation and more expressions of zonula occludens-1(ZO-1) and occludin. More cerebral blood flow (CBF) in the ipsilateral hemisphere and more expression of CD31 and vascular endothelial growth factor (VEGF) in brain and kidney were found in the cilostazol group. Furthermore, cell apoptosis and cell autophagy became less, on the contrary, proteins of vascular endothelial growth factor receptor 2 (VEGFR2) after the cilostazol treatment were increased. More importantly, this protective effect is related to the pathway of Janus Kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and the hypoxia inducible factor-1α (HIF-1α). In conclusion, our results confirmed that cilostazol exerted a protective effect on the brain and kidney function, specifically in vascular injury, oxidative stress, cell apoptosis, cell autophagy, and inflammation response in CRF combined with stroke rats which were related to the upregulation of JAK/STAT3/mTOR signal pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00217-w.