Renal Failure Research Articles

Impact of ventricular assist device use on pediatric heart transplant waitlist mortality: Analysis of the scientific registry of transplant recipients database.

Children awaiting heart transplant (Tx) have a high risk of death due to donor organ scarcity. Historically, ventricular assist devices (VADs) reduced waitlist mortality, prompting increased VAD use. We sought to determine whether the VAD survival benefit persists in the current era. Using the Scientific Registry of Transplant Recipients, we identified patients listed for Tx between 3/22/2016 and 9/1/2020. We compared characteristics of VAD and non-VAD groups at Tx listing. Cox proportional hazards models were used to identify risk factors for 1-year waitlist mortality. Among 5054 patients, 764 (15%) had a VAD at Tx listing. The VAD group was older with more mechanical ventilation and renal impairment. Unadjusted waitlist mortality was similar between groups; the curves crossed ~90 days after listing (p = .55). In multivariable analysis, infant age (HR 2.77, 95%CI 2.13-3.60), Black race (HR 1.57, 95%CI 1.31-1.88), congenital heart disease (HR 1.23, 95%CI 1.04-1.46), renal impairment (HR 2.67, 95%CI 2.19-3.26), inotropes (HR 1.28, 95%CI 1.09-1.52), and mechanical ventilation (HR 2.23, 95%CI 1.84-2.70) were associated with 1-year waitlist mortality. VADs were not associated with mortality in the first 90 waitlist days but were protective for those waiting ≥90 days (HR 0.43, 95%CI 0.26-0.71). In the current era, VADs reduce waitlist mortality, but only for those waitlisted ≥90 days. The differential effect by race, size, and VAD type is less clear. These findings suggest that Tx listing without VAD may be reasonable if a short waitlist time is anticipated, but VADs may benefit those expected to wait >90 days.

Mitochondrial DNA 13513G>A Mutation Causing Leber Hereditary Optic Neuropathy Associated With Adult-Onset Renal Failure.

Leber hereditary optic neuropathy (LHON) is one of the more common mitochondrial diseases and is rarely associated with mitochondrial renal disease. We report 3 unrelated patients with a background of adult-onset renal failure who presented to us with LHON and were shown to have a heteroplasmic mitochondrial DNA mutation (m.13513G>A). Retrospective chart review. All 3 patients had a background of chronic renal failure and presented to us with bilateral optic neuropathy (sequential in 2) and were found to have heteroplasmic m.13513G>A mutations in the MT-ND5 gene. Two of the patients were females (aged 30 and 45 years) with chronic kidney disease from their 20s, attributed to pre-eclampsia, one of whom also had diabetes and sudden bilateral hearing loss. One patient was a male (aged 54 years) with chronic kidney disease from his 20s attributed to IgA nephropathy. His mother had diabetes and apparently sudden bilateral blindness in her 70s. Renal biopsy findings were variable and included interstitial fibrosis, acute tubular necrosis, focal segmental glomerulosclerosis, and IgA/C3 tubular casts on immunofluorescence. Mild improvements in vision followed treatment with either idebenone or a combination supplement including coenzyme Q10, alpha-lipoic acid, and B vitamins. Our cases expand the clinical syndromes associated with m.13513G>A to include bilateral optic neuropathy and adult-onset renal disease. This highlights that in patients with bilateral, especially sequential, optic neuropathy a broad approach to mitochondrial testing is more useful than a limited LHON panel. Mitochondrial diseases present a diagnostic challenge because of their clinical and genetic variability.

Exploration and Validation of Lead Molecules against Yellow Fever through High Throughput Virtual Screening and Molecular Dynamics Simulation

Background: Yellow fever (YF) is a mosquito-borne flaviviral hemorrhagic fever (VHF) that causes severe hepatitis, renal failure, bleeding, and quick terminal events such as shock and multi-organ failure. There are currently no particular anti-viral medications for the management of the YF virus (YFV). Despite the availability of a commercial YFV vaccination, there are roughly 30,000 fatalities globally each year, with instances rising over the previous 20 years. After being translocated into the endoplasmic reticulum lumen, glycosylated NS1 resides as a membrane-associated dimer, where it is required for viral genome replication. The secreted hexamer NS1 has a role in immune evasion and pathogenesis and has been discovered as a possible diagnostic marker for the early identification of viral infections. Objective: The main aim of this study is to analyze the small molecule as a potent drug candidate against the target NS1 protein. Methods: In this study, Computational approaches, including high throughput virtual screening, molecular docking, and dynamics simulation, were carried out against the target NS1 protein using three different chemical libraries Enamine, Asinex, and NCI. The selected lead compounds were validated through HOMO-LUMO analysis, ADME prediction, and Toxicity parameters to analyze the biological and pharmacological properties of the lead small molecules. Results: From the result, it was concluded that the leads possessed the highest docking scores, interacting with the binding residues, and were stable in the simulation period. Conclusion: Overall findings revealed that the lead three small molecules could act as the potential drug candidate for the target NS1 protein to inhibit the diseasing efficacy of Yellow fever.

Effects of glyphosate herbicide ingestion on kidney function in rats on a balanced diet.

Glyphosate is the most widely used herbicide worldwide and in Brazil. There is currently increasing concern about the effects of glyphosate on human health. The Brazilian Institute for Consumer Protection showed data on the presence of glyphosate in some of Brazil's most consumed ultra-processed products. Currently, regulations on the upper limit for these residues in ultra-processed foods have yet to be established by the National Health Surveillance, and ultra-processed food consumption is independently associated with an increased risk of incident chronic kidney disease. Since an unbalanced diet can interfere with kidney function, this study aims to investigate the effect of daily intake of 5 mg/kg bw glyphosate in conjunction with a balanced diet and the possible impact on renal function in rats. Kidney function, kidney weight, markers of renal injury, and oxidative stress were evaluated. There was a decrease in kidney weight. The main histopathological alterations in renal tissues were vacuolation in the initial stage and upregulation of the kidney injury marker KIM-1. Renal injury is associated with increased production of reactive oxygen species in mitochondria. This study showed changes in the kidney of rats exposed to a balanced diet with glyphosate, suggesting a potential risk to human kidney. Presumably, ultra-processed food that contain glyphosate can potentiate this risk. The relevance of these results lies in drawing attention to the need to regulate glyphosate concentration in ultra-processed foods in the future.

Artificial neural networks analysis predicts long-term fistula function in hemodialysis patients following percutaneous transluminal angioplasty

Kidney failure is particularly common in the United States, where it affects over 700,000 individuals. It is typically treated through repeated sessions of hemodialysis to filter and clean the blood. Hemodialysis requires vascular access, in about 70% of cases through an arteriovenous fistula (AVF) surgically created by connecting an artery and vein. AVF take 6 weeks or more to mature. Mature fistulae often require intervention, most often percutaneous transluminal angioplasty (PTA), also known as fistulaplasty, to maintain the patency of the fistula. PTA is also the first-line intervention to restore blood flow and prolong the use of an AVF, and many patients undergo the procedure multiple times. Although PTA is important for AVF maturation and maintenance, research into predictive models of AVF function following PTA has been limited. Therefore, in this paper we hypothesize that based on patient-specific information collected during PTA, a predictive model can be created to help improve treatment planning. We test a set of rich, multimodal data from 28 patients that includes medical history, AVF blood flow, and interventional angiographic imaging (specifically excluding any post-PTA measurements) and build deep hybrid neural networks. A hybrid model combining a 3D convolutional neural network with a multi-layer perceptron to classify AVF was established. We found using this model that we were able to identify the association between different factors and evaluate whether the PTA procedure can maintain primary patency for more than 3 months. The testing accuracy achieved was 0.75 with a weighted F1-score of 0.75, and AUROC of 0.75. These results indicate that evaluating multimodal clinical data using artificial neural networks can predict the outcome of PTA. These initial findings suggest that the hybrid model combining clinical data, imaging and hemodynamic analysis can be useful to treatment planning for hemodialysis. Further study based on a large cohort is needed to refine the accuracy and model efficiency.

Mind the gap in kidney care: Translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure,or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Fasciotomy and rate of amputation after tibial fracture in adults: a population-based cohort study.

Limb amputation is a possible outcome of acute compartment syndrome. We undertook this study to investigate the occurrence of fasciotomy and amputation in patients with tibial fractures in the Ontario adult population, aiming to evaluate variables that may be associated with each of these outcomes. Retrospective, population-based cohort study (April 1, 2003-March 31, 2016). Canadian province of Ontario. Patients with tibial fracture, aged 14 years and older. Fasciotomy after tibial fracture. The primary outcomes were fasciotomy and amputation within 1 year of fasciotomy. Secondary outcomes included repeat surgery, new-onset renal failure, and mortality, all within 30 days of fasciotomy. We identified 76,299 patients with tibial fracture; the mean (SD) age was 47 (21) years. Fasciotomy was performed in 1303 patients (1.7%); of these, 76% were male and 24% female. Patients who were younger, male, or experienced polytrauma were significantly more likely to undergo fasciotomy. Limb amputation occurred in 4.3% of patients undergoing fasciotomy, as compared with 0.5% in those without fasciotomy; older age, male sex, presence of polytrauma, and fasciotomy were associated with an increased risk of amputation (age odds ratio [OR] of 1.03 [95% CI, 1.02-1.03], P < 0.0001; sex OR of 2.04 [95% CI, 1.63-2.55], P < 0.0001; polytrauma OR of 9.37 [95% CI, 7.64-11.50], P < 0.0001; fasciotomy OR of 4.35 [95% CI, 3.21-5.90], P < 0.0001), as well as repeat surgery within 30 days (sex OR of 1.54 [95% CI, 1.14-2.07], P = 0.0053; polytrauma OR of 4.24 [95% CI, 3.33-5.38], P < 0.0001). Among tibial fracture patients, those who were male and who experienced polytrauma were at significantly higher risk of undergoing fasciotomy and subsequent amputation. Fasciotomy was also significantly associated with risk of amputation, a finding that is likely reflective of the severity of the initial injury.

Development of compliance theory based on self-regulation in chronic kidney failure patients on hemodialysis

Self-management in regulating diet, fluids, activities, and medication in chronic renal failure patients which getting hemodialysis is still worse. This research aimed to develop the theory of compliance based on self-regulation to increase patient obedience and awareness. A cross-sectional approach of 130 respondents was recruited using simple random sampling. Structural equation modeling partial least square (SEM-PLS) was the statistical analysis for this study. All indicators in the outer model showed outer loading value &amp;gt;0.7, it declared feasible to predict each of the latent variables. The R-square value of appraisal latent was 0.576, Coping was 0.897, and self-care compliance was 0.713. The model was relevant when applied in other research studies with a Q-Square value=0.832. The goodness of fit (GoF) was 0.832&amp;gt;0.36, which means that the model was applied well. The appraisal variable is the strongest variable that influences coping, based on the hypothesis test. The self-regulation-based compliance model for blood pressure, interdialytic weight gain (IDWG), sodium levels, and functional independence can be developed through analysis of the structural model.

Clinico-Epidemiological Profile, Trends, and Health-Related Outcomes of Snakebite Victims: A One-Year Prospective Study from Eastern India.

Snakebite envenomation is a significant life-threatening public health problem in Southeast Asia (SEA). In this region, India reported the largest number of snakebite deaths from 2000 to 2019 (1.2 million), with an average of 58,000 deaths yearly. This prospective observational study was carried out among snakebite victims at the emergency department (ED) of a tertiary care public sector hospital in eastern India. A total of 145 cases of venomous snakebite were investigated. More than half (n = 81, 56%) of the snakebite victims were between 17 to 45 years. Most of the snakebite victims were male (68%) and were farmers (53%) by occupation. The majority of snakebites occurred during the daytime (76%) and while outdoors (67%). Most victims sustained a bite on the lower extremity (71%). The peak incidence of snakebites occurred from June to September (69%). Three-quarters of all patients were unaware of the required first aid measures following a snakebite. Among the 145 venomous snakebites, 48 were presumptively identified as the Indian cobra, 32 by the Indian krait, 56 by the Russel's viper, and 9 by saw-scaled viper. The mean duration from the snakebite to the onset of systemic effects in the Indian cobra was 52 ± 14.28 min, 66 ± 18.35 min in the Indian krait, 42 ± 13.47 min in Russel's viper, and 48 ± 16.38 min in saw-scaled viper. Respiratory failure was the commonly observed complication following an elapid envenomation. The mortality rate was 2.1% among the patients treated with antivenom. Snakebite is considered an occupational hazard in India, commonly affecting the young population in their productive period. The peak incidence was during monsoon season, and the majority had neurotoxic envenomation following an elapid bite (55%) that contributed to the increased mortality and morbidity among young adults. Of the 145 patients, the majority (84%) recovered fully with treatment; 16% of the victims developed morbidity viz cellulitis, respiratory failure, acute renal failure, compartment syndrome, local tissue necrosis, intracerebral hemorrhage, and disseminated intravascular coagulation. Appropriate first aid measures and timely medical intervention can significantly improve the treatment outcome following snakebites.

Comparison of safety and efficacy between Nirmatrelvir-ritonavir and molnupiravir in the treatment of COVID-19 infection in patients with advanced kidney disease: a retrospective observational study

Nirmatrelvir-ritonavir is used in patients with coronavirus disease 2019 (COVID-19) with normal or mild renal impairment (eGFR ≥30ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease (eGFR <30ml/min per 1.73m2). We performed a retrospective territory-wide observational study evaluating the safety and efficacy of nirmatrelvir-ritonavir when compared with molnupiravir in the treatment of patients with COVID-19 with advanced kidney disease. We adopted target trial emulation using data from a territory-wide electronic health record database on eligible patients aged ≥18 years with advanced kidney disease (history of eGFR <30ml/min per 1.73m2) who were infected with COVID-19 and were prescribed with either molnupiravir or nirmatrelvir-ritonavir within five days of infection during the period from 16 March 2022 to 31 December 2022. A sequence trial approach and 1:4 propensity score matching was applied based on the baseline covariates including age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index (CCI), hospitalisation, eGFR, renal replacement therapy, comorbidities (cancer, respiratory disease, myocardial infarction, ischaemic stroke, diabetes, hypertension), and drug use (renin-angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, nitrates, lipid lowering agents, insulins, oral antidiabetic drugs, antiplatelets, immuno-suppressants, corticosteroids, proton pump inhibitors, histamine H2 receptor antagonists, monoclonal antibody infusion) within past 90 days. Individuals were followed up from the index date until the earliest outcome occurrence, death, 90 days from index date or the end of data availability. Stratified Cox proportional hazards regression adjusted with baseline covariates was used to compare the risk of outcomes between nirmatrelvir-ritonavir recipients and molnupiravir recipients which include (i) all-cause mortality, (ii) intensive care unit (ICU) admission, (iii) ventilatory support, (iv) hospitalisation, (v) hepatic impairment, (vi) ischaemic stroke, and (vii) myocardial infarction. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (≤5; >5), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). A total of 4886 patients were included (nirmatrelvir-ritonavir: 1462; molnupiravir: 3424). There were 347 events of all-cause mortality (nirmatrelvir-ritonavir: 74, 5.06%; molnupiravir: 273, 7.97%), 10 events of ICU admission (nirmatrelvir-ritonavir: 4, 0.27%; molnupiravir: 6, 0.18%), 48 events of ventilatory support (nirmatrelvir-ritonavir: 13, 0.89%; molnupiravir: 35, 1.02%), 836 events of hospitalisation (nirmatrelvir-ritonavir: 218, 23.98%; molnupiravir: 618, 28.14%), 1 event of hepatic impairment (nirmatrelvir-ritonavir: 0, 0%; molnupiravir: 1, 0.03%), 8 events of ischaemic stroke (nirmatrelvir-ritonavir: 3, 0.22%; molnupiravir: 5, 0.16%) and 9 events of myocardial infarction (nirmatrelvir-ritonavir: 2, 0.15%; molnupiravir: 7, 0.22%). Nirmatrelvir-ritonavir users had lower rates of all-cause mortality (absolute risk reduction (ARR) at 90 days 2.91%, 95% CI: 1.47-4.36%) and hospitalisation (ARR at 90 days 4.16%, 95% CI: 0.81-7.51%) as compared with molnupiravir users. Similar rates of ICU admission (ARR at 90 days-0.09%, 95% CI:-0.4 to 0.2%), ventilatory support (ARR at 90 days 0.13%, 95% CI:-0.45 to 0.72%), hepatic impairment (ARR at 90 days 0.03%, 95% CI:-0.03 to 0.09%), ischaemic stroke (ARR at 90 days-0.06%, 95% CI:-0.35 to 0.22%), and myocardial infarction (ARR at 90 days 0.07%, 95% CI:-0.19 to 0.33%) were found between nirmatrelvir-ritonavir and molnupiravir users. Consistent results were observed in relative risk adjusted with baseline characteristics. Nirmatrelvir-ritonavir was associated with significantly reduced risk of all-cause mortality (HR: 0.624, 95% CI: 0.455-0.857) and hospitalisation (HR: 0.782, 95% CI: 0.64-0.954). Patients with COVID-19 with advanced kidney disease receiving nirmatrelvir-ritonavir had a lower rate of all-cause mortality and hospital admission when compared with molnupiravir. Other adverse clinical outcomes were similar in both treatment groups. Health and Medical Research Fund (COVID1903010), Health Bureau, The Government of the Hong Kong Special Administrative Region, China.

LncRNA SNHG14 silencing attenuates the progression of diabetic nephropathy via the miR-30e-5p/SOX4 axis.

Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in DN were explored. Streptozotocin (STZ)-induced DN mouse models and high glucose (HG)-treated human mesangial cells (MCs) were used to detect SNHG14 expression. SNHG14 silencing plasmids were applied to examine the function of SNHG14 on proliferation and fibrosis in HG-treated MCs. Potential targets of SNHG14 were predicted using bioinformatics tools and verified by luciferase reporter, RNA pulldown, and northern blotting assays. The functional role of SNHG14 in DN in vivo was detected by injection with adenoviral vector carrying sh-SNHG14 into DN mice. Serum creatinine, blood urea nitrogen, blood glucose, 24-h proteinuria, relative kidney weight, and renal pathological changes were examined in DN mice. SNHG14 expression was elevated in the kidneys of DN mice and HG-treated MCs. SNHG14 silencing inhibited proliferation and fibrosis of HG-stimulated MCs. SNHG14 bound to miR-30e-5p to upregulate SOX4 expression. In rescue assays, SOX4 elevation diminished the effects of SNHG14 silencing in HG-treated MCs, and SOX4 silencing reversed the effects of SNHG14 overexpression. In in vivo studies, SNHG14 downregulation significantly ameliorated renal injuries and renal interstitial fibrosis in DN mice. SNHG14 silencing attenuates kidney injury in DN mice and reduces proliferation and fibrotic phenotype of HG-stimulated MCs via the miR-30e-5p/SOX4 axis.

Self-regulatory-based compliance module improve chronic kidney failure patients condition

Adherence is very important to pay attention to in health management and the quality of life among end-stage renal disease (ESRD) patients, in the fact that adherence is still lacking. This study aimed to analyze the effect of self-regulatory-based compliance modules improving interdialytic weight gains (IDWG), blood pressure (BP), sodium levels, and functional independence. A quantitative research design with a quasi-experiment approach (pre and post-test control study). A total of 28 samples for each group were taken using purposive sampling. Self-regulation based on health promotion was given using module and IDWG, sodium levels, BP measured with laboratories and physical examination, and Functional Independence measured using a questionnaire. Wilcoxon signed-rank test and Mann-Whitney test were the selected analyses for this study. There was a significant effect on self-regulation-based compliance to IDWG (p=0.012), sodium levels (p=0.001), systolic pressure (p=0.003), and functional independence (p=0.002) in the intervention group. A significant difference was also shown between the two groups (p&amp;lt;0.05). The self-regulation-based compliance module showed improved patient compliance in terms of fluid restriction, taking drugs, paying attention to diet, and managing activities. Adherence to patients increases good outcomes in controlling IDWG, BP, sodium levels, and functional independence in ESRD patients.

Relationship of hemoglobin levels with outcomes in deceased donor kidney transplant: a retrospective cohort study.

Anemia is frequent in patients undergoing replacement therapy for kidney failure. Anemia in the pre- and post-transplantation period might be related to kidney transplant outcomes. The current study therefore sought to assess the relationship between anemia, delayed allograft function (DGF), chronic kidney allograft dysfunction (CAD), and death from any cause following kidney transplantation from a deceased donor. This was a retrospective study with 206 kidney transplant patients of deceased donors. We analyzed deceased donors' and kidney transplant patients' demographic data. Moreover, we compared biochemical parameters, anemia status, and medicines between DGF and non-DGF groups. Afterward, we performed a multivariate analysis. We also evaluated outcomes, such as CAD within one year and death in ten years. We observed a lower frequency of pre-transplant hemoglobin concentration (Hb) but higher frequency of donor-serum creatinine and red blood transfusion within one week after transplantation in the group with DGF. In addition, there was an independent association between Hb concentration before transplantation and DGF [OR 0.252, 95%CI: 0.159-0.401; p < 0.001]. There was also an association between Hb concentration after six months of kidney transplantation and both CAD [OR 0.798, 95% CI: 0.687-0.926; p = 0.003] and death from any cause. An association was found between pre-transplantation anemia and DGF and between anemia six months after transplantation and both CAD and death by any cause. Thus, anemia before or after transplantation affects the outcomes for patients who have undergone kidney transplantation from a deceased donor.

Intelligent Document Processing for Disease Detection

Abstract: This project endeavors to develop an intelligent document processing pipeline tailored specifically for medical reports, with a primary focus on samples from Dr Lal Path lab and targeting prevalent diseases leading to kidney failures such as glomerulonephritis, chronic kidney disease, polycystic kidney disease, hypertensive nephropathy, and lupus nephritis. The proposed pipeline integrates cutting-edge technologies including the YOLOv8 object detection model for precise cropping of tabular data, Paddle OCR for accurate extraction of information from tabular images, and Fuzzy Wuzzy NLP library for filtering pertinent data from the extracted information necessary for the subsequent machine learning model. The goal is to employ a neural network model to predict potential kidney failure based on the processed medical data. This holistic approach amalgamates advanced computer vision, natural language processing, and machine learning techniques to streamline the analysis of medical reports, potentially enhancing diagnostic accuracy and clinical decision-making in nephrology.

Anesthetic management of a high-risk patient with complex medical conditions: A case report of multimodal analgesia and regional nerve blocks in urgent transfemoral amputation

This case article presents the anesthetic management of a patient with complex medical conditions and surgical requirements. The patient had secondary hyperparathyroidism due to chronic renal failure, resulting in hypocalcemia. The patient required a transfemoral amputation due to progressive bacterial infection and global foot gangrene. The urgency of the operation prevented preoperative preparation and necessitated careful consideration of the patient's cardiovascular and respiratory challenges. Due to the patient's facial deformity and limited neck mobility, general anesthesia was not feasible. Instead, a multimodal analgesia approach was adopted, utilizing regional nerve blocks targeting various nerves involved in lower limb innervation. This approach, combined with sedation, provided effective surgical anesthesia.

Biological profile of secondary hyperparathyroidism in chronic renal failure patients

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease, especially in hemodialysis patients. It is characterized by overproduction of parathyroid hormone in response to chronic deterioration of renal function. The aim of this retrospective study was to determine the average time to develop secondary hyperparathyroidism, analyze the initial phosphocalcic profiles, and evaluate the evolution of these profiles in hemodialysis patients, following the recommendations of the KDOQI 2003 and KDIGO 2009 groups. The study included 134 hemodialysis patients from two private dialysis centers. Data were collected from patients' medical records and analyzed using SPSS software. The results showed that the average time to develop secondary hyperparathyroidism was 3.15 years according to KDOQI recommendations and 4.64 years according to KDIGO recommendations based on parathyroid hormone levels. The initial assessment revealed an imbalance in phosphocalcic metabolism in approximately 20.1% to 22.5% of patients, a proportion that increased to 27.5% during follow-up, according to both sets of recommendations. In conclusion, secondary hyperparathyroidism is an inevitable complication of chronic kidney disease, affecting the vital and functional prognosis of hemodialysis patients. Diagnosis primarily relies on parathyroid hormone levels, associated with phosphocalcemia, vitamin D, and PAL analyses. Treatment aims mainly to maintain blood levels of calcium, phosphorus, and vitamin D within recommended limits and to reduce parathyroid response to phosphocalcic disturbances.

Hazard functioning modeling for dextrose fluids associated hemodilution; Cox-regressional analysis for patients’ Hematocrit Hemoglobin Ratio

Aims: This study looks at the cox-regressional relationships between hematocrit to hemoglobin ratio (HHR) and a group of outcomes of interest (cOI). These outcomes include death from any cause, acute myocardial infarction, stroke, and severe dilutional hyponatraemia incidence. Additionally other outcome of interest in this study will be prolongation of admission days, infection rate, acute kidney injury, and mandating the transition to the critical unit and mechanical ventilation intubation. The study also will investigate the performances of the tested ratio and will explore their sensitivity, specificity, and accuracy indexes. Methods: Between 2018 and 2022, a retrospective study was conducted at the King Hussein Medical Centre in Amman, Jordan, involving 926 patients. The study aimed to determine the potential risk of dilution of red blood cells in circulation caused by dextrose-containing fluids in patients with chronic kidney disease. The study aimed to determine the ideal threshold levels of the investigated ratio (HHR) to enhance clinical outcomes and safety margins, particularly in patients with severe renal impairment or chronic kidney disease in a hospital setting. The study included patients with fluctuating kidney function, renal replacement therapy, uncontrolled diabetes, and conditions necessitating specific fluid regimens. The study used binary logistic regression and cox-regression proportional hazard modelling to examine the correlation between the hematocrit to haemoglobin ratio and the composite outcomes of interest (cOI) in patients from Jordan. The findings suggest that higher cOI likelihood indicates a more advantageous condition, while lower values suggest a less advantageous condition. Results: A retrospective study at the KHMC in Amman, Jordan, involved 1306 patients from 2018 to 2022. The study focused on the hematocrit to haemoglobin ratio (HHR) and achieved correct classification rates of 70.8%. The best HHR was 2.555:1, with a 42.8% chance of occurring at this level. Cox-Regression Proportional Hazard Modelling revealed a censored percentage of 83.4% in HHR&gt;2.555 stratum and 51.5% in HHR≤2.555 stratum. The study found a high percentage of HD patients processed in the analysis. Conclusion: Intravenous dextrose fluids associated hemodilutional state is linked to all-cause mortality in admitted medically and surgically patients and cardiovascular death. Low ratio increases the risk. Factors such as malnutrition and kidney function loss contribute to prognosis. Future studies should focus on mechanistic pathways, optimal targets, age, and sociodemographic factors.

Targeted Restoration of GPX3 Attenuates Renal Ischemia/Reperfusion Injury by Balancing Selenoprotein Expression and Inhibiting ROS-mediated Mitochondrial Apoptosis.

Renal ischemia/reperfusion (IR) injury is the leading cause of acute kidney injury in both autologous and transplanted kidneys. Low-level glutathione peroxidase 3 (GPX3) is associated with renal IR injury. The exact mechanism of targeted GPX3 restoration in renal IR injury has yet to be determined. The distribution of GPX3 in different tissues and organs of the body was investigated. The level of GPX3 in renal IR injury was assessed. To confirm the action of GPX3 and its mechanisms, IR models were used to introduce adeno-associated virus 9 containing GPX3, as well as hypoxia/reoxygenation-exposed normal rat kidney cells that consistently overexpressed GPX3. Reverse molecular docking was used to confirm whether GPX3 was a target of ebselen. GPX3 is abundant in the kidneys and decreases in expression during renal IR injury. GPX3 overexpression reduced renal IR injury and protected tubular epithelial cells from apoptosis. Proteomics analysis revealed a strong link between GPX3 and mitochondrial signaling, cellular redox state, and different expression patterns of selenoproteins. GPX3 inhibited reactive oxygen species-induced mitochondrial apoptosis and balanced the disordered expression of selenoproteins. GPX3 was identified as a stable selenoprotein that interacts with ebselen. Ebselen enhanced the level of GPX3 and reduced IR-induced mitochondrial damage and renal dysfunction. Targeted restoration of GPX3 attenuates renal IR injury by balancing selenoprotein expression and inhibiting reactive oxygen species-mediated mitochondrial apoptosis, indicating that GPX3 could be a potential therapeutic target for renal IR injury.

Population pharmacokinetics of imetelstat, a first-in-class oligonucleotide telomerase inhibitor.

Imetelstat is a novel, first-in-class, oligonucleotide telomerase inhibitor in development for the treatment of hematologic malignancies including lower-risk myelodysplastic syndromes and myelofibrosis. A nonlinear mixed-effects model was developed to characterize the population pharmacokinetics of imetelstat and identify and quantify covariates that contribute to its pharmacokinetic variability. The model was developed using plasma concentrations from 7 clinical studies including 424 patients with solid tumors or hematologic malignancies who received single-agent imetelstat via intravenous infusion at various dose levels (0.4-11.7 mg/kg) and schedules (every week to every 4 weeks). Covariate analysis included factors related to demographics, disease, laboratory results, renal and hepatic function, and antidrug antibodies. Imetelstat was described by a two-compartment, nonlinear disposition model with saturable binding/distribution and dose- and time-dependent elimination from the central compartment. Theory-based allometric scaling for body weight was included in disposition parameters. The final covariates included sex, time, malignancy, and dose on clearance; malignancy and sex on volume of the central compartment; and malignancy and spleen volume on concentration of target. Clearance in females was modestly lower, resulting in nonclinically relevant increases in predicted exposure relative to males. No effects on imetelstat pharmacokinetics were identified for mild-to-moderate hepatic or renal impairment, age, race, and antidrug antibody status. All model parameters were estimated with adequate precision (relative standard error < 29%). Visual predictive checks confirmed the capacity of the model to describe the data. The analysis supports the imetelstat body-weight-based dosing approach and lack of need for dose individualizations for imetelstat-treated patients.

Dying Patients' Quality of Care for Five Common Causes of Death: A Nationwide Mortality Follow-Back Survey.

Background: The importance of high-quality care for terminal patients is being increasingly recognized; however, quality of care (QOC) and quality of death and dying (QOD) for noncancer patients remain unclear. Objectives: To clarify QOC and QOD according to places and causes of death. Design, Subjects: A nationwide mortality follow-back survey was conducted using death certificate data for cancer, heart disease, stroke syndrome, pneumonia, and kidney failure in Japan. The questionnaire was distributed to 115,816 bereaved family members between February 2019 and February 2020. Measurements included QOC, QOD, and symptoms during the last week of life. Analyses used generalized estimating equations adjusting for age, sex, and region. Results: Valid responses were returned by 62,576 (54.0%). Family-reported QOC and QOD by the place of death were significantly higher at home than in other places across all causes of death (for all combinations with hospital p < 0.01). In stroke syndrome and pneumonia, QOD significantly differed between hospital and home (stroke syndrome: 57.1 vs. 72.4, p < 0.001, effect size 0.77; pneumonia: 57.3 vs. 71.1, p < 0.001, effect size 0.78). No significant differences were observed in QOC and QOD between cancer and noncancer. The prevalence of symptoms was higher for cancer than for other causes of death. Conclusions: QOC and QOD were higher at home than in other places of death across all causes of death. The further expansion of end-of-life care options is crucial for improving QOC and QOD for all terminal patients.