Chronic End-stage Renal Disease Research Articles

Mechanism of tacrolimus in the treatment of lupus nephritis

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, with more than half of the patients developing lupus nephritis (LN), which significantly contributes to chronic kidney disease (CKD) and end-stage renal disease (ESRD). The treatment of lupus nephritis has always been challenging. Tacrolimus (TAC), an effective immunosuppressant, has been increasingly used in the treatment of LN in recent years. This review aims to explore the mechanisms of action of tacrolimus in treating LN. Firstly, we briefly introduce the pharmacological properties of tacrolimus, including its role as a calcineurin (CaN) inhibitor, exerting immunosuppressive effects by inhibiting T cell activation and cytokine production. Subsequently, we focus on various other immunomodulatory mechanisms of tacrolimus in LN therapy, including its effects on T cells, B cells, and immune cells in kidney. Particularly, we emphasize tacrolimus’ regulatory effect on inflammatory mediators and its importance in modulating the Th1/Th2 and Th17/Treg balance. Additionally, we review its effects on actin cytoskeleton, angiotensin II (Ang II)-specific vascular contraction, and P-glycoprotein activity, summarizing its impacts on non-immune mechanisms. Finally, we summarize the efficacy and safety of tacrolimus in clinical studies and trials. Although some studies have shown significant efficacy of tacrolimus in treating LN, its safety remains a challenge. We outline the potential adverse reactions of long-term tacrolimus use and provide suggestions on effectively monitoring and managing these adverse reactions in clinical practice. In general, tacrolimus, as a novel immunosuppressant, holds promising prospects for treating LN. Of course, further research is needed to better understand its therapeutic mechanisms and ensure its safety and efficacy in clinical practice.

Protocol for a systematic review of the application of the kidney failure risk equation and Oxford classification in estimating prognosis in IgA nephropathy

BackgroundIgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease progression at an individual level is challenging. Accurate risk stratification is important to identify individuals most likely to benefit from treatment. The Kidney Failure Risk Equation (KFRE) has been extensively validated in CKD populations and predicts the risk of ESRD at 2 and 5 years using non-invasive tests; however, its predictive performance in IgAN is unknown. The Oxford classification (OC) describes pathological features demonstrated on renal biopsy that are associated with adverse clinical outcomes that may also inform prognosis. The objective of this systematic review is to compare the KFRE with the OC in determining prognosis in IgAN.MethodsA systematic review will be conducted and reported in line with PRISMA guidelines (PRISMA-P checklist attached as Additional file 1). Inclusion criteria will be cohort studies that apply the KFRE or OC to determine the risk of CKD progression or ESRD in individuals with IgAN. Multiple databases will be searched in duplicate to identify relevant studies, which will be screened first by title, then by abstract and then by full-text analysis. Results will be collated for comparison. Risk of bias and confidence assessments will be conducted independently by two reviewers, with a third reviewer available if required.DiscussionIdentifying individuals at the highest risk of progression to ESRD is challenging in IgAN, due to the heterogeneity of clinical outcomes. Risk prediction tools have been developed to guide clinicians; however, it is imperative that these aids are accurate and reproducible. The OC is based on observations made by specialist renal pathologists and may be open to observer bias, therefore the utility of prediction models incorporating this classification may be diminished, particularly as in the future novel biomarkers may be incorporated into clinical practice.Systematic review registrationPROSPERO CRD42022364569

Polyvascular Disease is Common in Patients Undergoing Carotid Endarterectomy and Lower Extremity Bypass and is Associated With Worse Outcomes

IntroductionPolyvascular disease is strongly associated with increased risk of cardiovascular morbidity and mortality. However, its prevalence in patients undergoing carotid and lower extremity surgical revascularization and its impact on outcomes are unknown. MethodsThe Vascular Quality Initiative was queried for carotid endarterectomy (CEA) or infrainguinal lower extremity bypass (LEB), 2013-2019. Polyvascular disease was defined as presence of atherosclerotic occlusive disease in > 1 arterial bed: carotid, coronary, and infrainguinal. Primary outcomes were: (1) composite perioperative myocardial infarction (MI) or death and (2) 5-year survival. Patient characteristics and perioperative outcomes were evaluated using chi-square test and multivariable logistic regression. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards multivariable models. ResultsPolyvascular disease was identified in 47% of CEA (39% 2 arterial beds, 7.6% 3 arterial beds; n = 93,736) and 47% of LEB (41% 2 arterial beds, 5.7% 3 arterial beds; n=25,223). For both CEA and LEB, patients with polyvascular disease had more comorbidities including hypertension, congestive heart disease, chronic obstructive pulmonary disease, smoking, diabetes mellitus, and end-stage renal disease (P<0.0001). Perioperative MI/death rates increased with increasing number of vascular beds affected following CEA (0.9% 1 bed vs 1.5% 2 beds vs 2.7% 3 beds, P<0.001) and LEB (2.2% 1 bed vs 5.3% 2 beds vs 6.6% 3 beds, P<0.001). Polyvascular disease was independently associated with perioperative MI/death after CEA (OR 1.59 (95% CI 1.40-1.81), P<.0001) and LEB (OR 1.78 (95% CI 1.52-2.08), P<.0001). Five-year survival was decreased in patients with polyvascular disease after CEA (82% 3 beds vs 88% 2 beds vs 92% 1 bed, P<0.01) and LEB (72% 3 beds vs 75% 2 beds vs 84% 1 bed, P<0.01) in a dose-dependent manner, with the lowest 5 year survival observed in those with 3 arterial beds involved. Polyvascular disease was independently associated with five-year mortality following CEA (HR 1.33 (95% CI 1.24-1.40), P=0.0001) and LEB (HR 1.30 (95% CI 1.20-1.41), P=0.0001). ConclusionPolyvascular disease is common in patients undergoing CEA and LEB and is associated with higher risk of perioperative MI/death and decreased long-term survival. Following revascularization, polyvascular disease patients may be considered for more aggressive cardioprotective medications and closer follow up.

Association of chronic kidney disease and end-stage renal disease with procedural complications and inpatient outcomes of leadless pacemaker implantations across the United States

Leadless pacemakers have emerged as a promising alternative to transvenous pacemakers in patients with kidney disease. However, studies investigating leadless pacemaker outcomes and complications based on kidney dysfunction are limited. To evaluate the association of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with inpatient complications and outcomes of leadless pacemaker implantations. National Inpatient Sample and International Classification of Diseases, Tenth Revision codes were used to identify CKD and ESRD patients who underwent leadless pacemaker implantations in the U.S. from 2016-2020. Study endpoints assessed included inpatient complications, outcomes and resource utilization of leadless pacemaker implantations. A total of 29,005 leadless pacemaker placements were identified. Patients with CKD (n=5,245, 18.1%) and ESRD (n=3,790, 13.1%) were younger and had higher prevalence of important comorbidities than patients without CKD. In crude analysis, ESRD was associated with higher prevalence of major complications, peripheral vascular complications, and inpatient mortality. After multivariable adjustment, CKD and ESRD were associated with inpatient mortality (aOR 1.62, 95% CI 1.40 - 1.86; aOR 1.38, 95% CI 1.18 - 1.63) and prolonged length of stay (aOR 1.55, 95% CI 1.46 - 1.66; aOR 1.81, 95% CI 1.67 - 1.96). ESRD was also associated with higher hospitalization costs (aOR 1.63, 95% CI 1.50 - 1.77) and major complications (aOR 1.62, 95% CI 1.40 - 1.86) after leadless pacemaker implantation. Approximately one-third of patients undergoing leadless pacemaker implantation had CKD or ESRD. CKD and ESRD were associated with greater length and cost of stay, and inpatient mortality.

Treatment of Gout in Patients with CrCl ≤30 mL/min and/or on Hemodialysis: A Review

Gout is highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), owing to impaired uric acid excretion. However, treating gout in this population is challenging due to concerns about medication safety and efficacy with reduced kidney function. This review examines the evidence of various pharmacologic and non-pharmacologic approaches to managing gout in CKD/ESRD. For acute gout flares, there is insufficient evidence to guide optimal dosing of NSAIDs, colchicine, and corticosteroids in advanced CKD. The risks generally outweigh the benefits of NSAIDs and colchicine. Corticosteroids appear safer but require individual risk-benefit assessments. Interleukin-1 inhibitors show promise, but larger studies are needed. For long-term urate lowering, xanthine oxidase inhibitors like allopurinol and febuxostat are preferred over probenecid and other uricosurics. However, studies specifically evaluating urate-lowering therapies in CKD are scarce, resulting in conflicting expert guidelines. Starting with low allopurinol doses and gradual titration can mitigate the risks. Higher allopurinol doses may be needed to reach urate targets in some CKD patients. Febuxostat’s safety in advanced CKD remains debated. Optimal gout management in dialysis patients is also unclear, including when to continue urate-lowering therapy. Overall, gout is often suboptimally treated in CKD/ESRD, highlighting the need for more research to guide therapy in this population. Improving management can significantly reduce the burden of these comorbid diseases.

Microbial Analysis in Chronic Rhinosinusitis Patients with Chronic Kidney Disease and End-Stage Renal Disease.

This study aimed to elucidate the bacterial profile of chronic rhinosinusitis (CRS) in patients with end-stage renal disease (ESRD) and chronic kidney disease (CKD) compared with nonrenal patients, guiding antibiotic selection for clinicians. We retrospectively analyzed 13,906 inpatients from the Chang Gung Research Database who underwent sinus surgery (2004-2018). Patients were categorized into ESRD-CRS, CKD-CRS, and non-CKD-CRS based on the estimated glomerular filtration rate. Bacterial cultures from surgical samples were classified as facultative anaerobes or aerobes (e.g., Klebsiella pneumoniae [KP], Pseudomonas aeruginosa [Ps.a]), anaerobes, and fungi and ranked by prevalence. Data from 47 ESRD-CRS, 230 CKD-CRS, and 13,123 non-CKD-CRS patients were analyzed. In ESRD-CRS, the predominant species were KP (31.6%), Ps.a (21.1%), and Coagulase-negative Staphylococcus (CoNS, 15.8%). CKD-CRS showed Staphylococcus epidermidis (27.7%), CoNS (20.5%), and Ps.a (20.5%). Non-CKD-CRS had Staphylococcus epidermidis (29.8%), CoNS (25.0%), and Staphylococcus aureus (15.5%). For anaerobes, ESRD-CRS was dominated by Fusobacterium nucleatum (10.5%) and Peptostreptococcus micros (10.5%), whereas CKD-CRS and non-CKD-CRS showed Propionibacterium acnes as a primary strain (14.5% and 28.7%, respectively). For CRS in ESRD, antibiotics targeting KP and Fusobacterium nucleatum are recommended. In CKD-CRS, a focus on Staphylococcus epidermidis and Propionibacterium acnes is suggested. 4 Laryngoscope, 2024.

Prevalence and characteristics of patients prescribed opioids and central nervous system depression agents on discharge to hospice care.

Hospice patients with end-stage liver disease (ESLD) have an increased risk of adverse drug events due to physiological changes and changes in pharmacokinetic and pharmacodynamic properties of medications; however, the use of opioid and central nervous system (CNS) depressant prescribing among patients with ESLD is prevalent. This study quantified the frequency and distribution of opioid and concomitant respiratory and CNS depressant prescribing among hospice patients with ESLD compared to other common hospice diagnoses of cancer, chronic obstructive pulmonary disorder (COPD), heart failure, and end-stage renal disease. This was a cross-sectional study of adult (age 18 years or older) decedents of a large hospice chain. Patients included had a primary diagnosis of liver, cancer, cardiovascular, or respiratory disease. Among 119,424 hospice decedents, mean age of 77.9 years (standard deviation =13.5 years), 54.6% were female, and 58.9% were of a non-Hispanic white race. There was a similar frequency of prescribing a "scheduled" and "as needed [pro re nata (PRN)]" opioid or benzodiazepine in patients with ESLD compared to other common hospice diagnoses. In addition, there was a high prevalence of concurrent opioid and benzodiazepine prescriptions among patients with ESLD compared to cardiovascular and respiratory disease at admission (65.4% vs. 63.9% and 64.9%). Opioid requirements, oral morphine equivalent (OME) median [interquartile range (IQR)] at discharge were similar between cancer, liver, and respiratory disease, 120 OME [60-300], 120 OME [50-240], and 120 OME [50-240], respectively. We observed a high frequency of opioid and CNS depressant prescribing in a hospice patient population with ESLD which was similar to other common admitting hospice diagnoses.

Change Over Time in Pre–End-Stage Renal Disease 24-Hour Urine Creatinine as Muscle Mass Surrogate and Post–End-Stage Renal Disease Mortality

Loss of muscle mass and sarcopenia are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD), and sarcopenia can worsen insidiously in patients with advancing CKD. The temporal dynamics of sarcopenia in patients with progressive loss of kidney function, and its association with future outcomes, is unclear. In a contemporary national cohort of incident ESRD US veterans, we selected 661 patients who had at least 2 24-hour urine creatinine (24hrUC) measurements, a surrogate of muscle mass, performed during the 3-year prelude period prior to ESRD transition. We estimated 24hrUC slopes in mixed effects models. To assess the temporal dynamics of pre-ESRD changes in 24hrUC and its association with changing eGFR, we separately fitted in mixed effects models a penalized spline regression of 24hrUC on time and on eGFR. We examined the association of 24hrUC slopes with postdialysis all-cause mortality using Cox models adjusted for confounders. The mean slope of 24hrUC versus time was -78mg/year (95% confidence interval: -102 to -54), with a steeper decline noted in the last year prior to ESRD. More severe decreases in 24hrUC were associated with higher all-cause mortality: a 100mg/year decrease in 24hrUC was associated with a multivariable adjusted death hazard ratio of 1.41 (95% confidence interval: 1.00-1.98, P=.05). Patients with advanced CKD lose a substantial proportion of their muscle mass each year during pre-ESRD prelude. Loss of muscle mass accelerates near ESRD transition, and more loss of muscle mass is associated with higher mortality after ESRD transition.

Health-related quality of life among patients undergoing hemodialysis in a tertiary center in South Kerala

IntroductionHealth-related quality of life is essential for evaluating treatment quality in chronic diseases, providing valuable patient perspectives for medical decisions. Chronic kidney disease and end-stage renal disease significantly affect Health-related quality of life. The study aimed to assess the Health-related quality of life and the factors affecting it in end-stage renal disease patients on maintenance hemodialysis. MethodsA cross-sectional study was conducted in a tertiary care center in Kerala from November 2021 to December 2022.A validated Kidney Disease Quality of Life in the local language Malayalam was used for data collection. Patients over the age of 18 who have end-stage renal disease and have been on maintenance dialysis for at least 3 months and agreed to participate were included in the study by consecutive sampling method. ResultsAmong the 124 patients studied, the physical component had the lowest mean score (38.11 ± 20.87), mental component displayed a higher score compared to the physical (47.33 ± 16.88), indicating moderate level of mental well-being. Kidney Disease Component Summary had the highest mean score (61.73 ± 9.42).Younger patients had better mental-health related quality of life, while age did not significantly affect physical or disease-specific health related quality of life. Gender differences appeared, with males reporting higher physical-health related quality of life. Discussion and conclusionThe study highlights the quality of life and its association with socio-personal variables. To enhance the well-being of end-stage renal disease patients in Kerala, public health initiatives should prioritize elderly females with limited education, tailoring interventions to address their specific issues.

Cost-effectiveness of switching from tenofovir disoproxil fumarate to tenofovir alafenamide versus entecavir for chronic hepatitis B patients in Greece.

Aim: This study assessed the clinical impact and cost-effectiveness of switching from tenofovir disoproxil fumarate (TDF) to either tenofovir alafenamide (TAF) or entecavir (ETV) in a Greek chronic hepatitis B (CHB) population. Patients & methods: A Markov model from the perspective of a third-party payer in Greece quantified the health and economic benefits of switching from TDF to either TAF or ETV over a lifetime horizon. Results: Over a lifetime, patients who switch from TDF to TAF versus patients who switch from TDF to ETV had an overall lower incidence of compensated cirrhosis (0.4% lower), decompensated cirrhosis (0.04% lower) and hepatocellular carcinoma (0.25% lower). Chronic kidney disease and end-stage renal disease were also lower in patients who switch to TAF; major osteoporotic fractures were similar for both groups. While total costs were higher for switching from TDF to TAF versus TDF to ETV due to the higher cost of TAF, switching from TDF to TAF versus ETV was cost effective with an incremental cost-effectiveness ratio of €17,113 per quality-adjusted life year. Conclusion: Switching from TDF to TAF in patients living with CHB is a cost effective strategy to reduce adverse liver disease outcomes, while improving bone- and renal-related safety outcomes.

Aging and Diabetic Kidney Disease: Emerging Pathogenetic Mechanisms and Clinical Implications.

Diabetic kidney disease (DKD) is one of the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. With the overpowering trend of aging, the prevalence of DKD in the elderly is progressively increasing. Genetic factors, abnormal glucose metabolism, inflammation, mitochondrial dysregulation, and oxidative stress all contribute to the development of DKD. Conceivably, during aging, these pathobiological processes are likely to be intensified, and this would further exacerbate the deterioration of renal functions in elderly patients, ultimately leading to ESRD. Currently, the pathogenesis of DKD in the elderly is not very well-understood. This study describes an appraisal of the relationship between diabetic nephropathy and aging while discussing the structural and functional changes in the aged kidney, the impact of related mechanisms on the outcome of DKD, and the latest advances in targeted therapies.

Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis.

Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD). This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease. A comprehensive systematic review provides a clear conclusion and high-level evidence for the association between ELMO1 gene and DKD for future application in personalized medicine. A comprehensive search of electronic databases, per PRISMA instructions, was conducted in Scopus, EMBASE, Web of Science, and PubMed databases from 1980 to January 2023. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using appropriate models. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and assess the robustness of the findings. A total of 5794 diabetes patients with DKD, 4886 diabetes patients without DKD, and 2023 healthy controls were included in the 17 studies that made up this systematic review. In the investigation of DM (Diabetes Mellitus) with DKD vs. DM without DKD, the susceptibility for DKD for the EMLO1 rs741301 polymorphism indicated a significant difference under the dominant, homozygote, and recessive genetic models. The susceptibility for DKD for the EMLO1 rs1345365, rs10255208, and rs7782979 polymorphisms demonstrated a significant difference under the allele genetic models in the analysis of DM with DKD vs. DM without DKD groups. There was a considerable increase in DKD risk in the Middle East when the population was stratified by the region. The findings of the meta-analysis show that there are a significant connection between the EMLO1 rs741301 polymorphism and DKD susceptibility in overall analyses; as well as rs1345365, rs10255208, and rs7782979 polymorphisms; especially in the Middle East region.

P434 Incidence of chronic end-stage renal disease in patients with inflammatory bowel disease: a population-based cohort study from the French National Health Insurance Database

Abstract Background Renal disorders are among the extra-intestinal manifestations of inflammatory bowel disease (IBD), and treatments may also lead to renal failure. However, the incidence of end-stage renal disease (ESRD), defined as the need for renal replacement therapy (dialysis and/or renal transplantation(RT)), is poorly known. The primary objective of our study was to assess the incidence of ESRD in IBD patients, and to compare it with the non-IBD population. Methods We conducted a prognostic cohort study based on data from the French National Health Insurance Database(SNDS). Prevalent cases of IBD affiliated to the general health insurance scheme during the period 2011-2020 were identified on the basis of declarations long-term diseases ALD 24 or the presence of 2 hospital stays for IBD with ICD-10 codes or a single stay with reimbursement of specific treatments. Incident cases of ESRD were identified on the basis of a stay with a RT or a period with dialysis sessions for at least 45 days. Crude incidence rates of ESRD were calculated over the period for the IBD and the non-IBD population, with their 95% confidence intervals. Results A total of 280,283 IBD patients were included in the study over the period 2011-2020, 134,567 with ulcerative colitis(UC) and 145,716 with Crohn’s disease(CD). The mean age at study inclusion was 39.8 (± 17.1) years. The M/F sex ratio was 0.9. The mean age at incidence of ESRD in the non-IBD population was 65.0 (±17.0) years, the M/F sex ratio cases was 1.7. Among IBD patients, 534 patients began replacement therapy by dialysis or RT, they were younger than non-IBD patients (60.3(±16.7)years, P&amp;lt;0.001).The mean incidence rate of ESRD over the period was 26.4 per 100,000 person-years (IC95% 23.1-29.6), 480 (89.9%) patients entered ESRD by dialysis, and 54 (10.1%) by preemptive RT. In the non-IBD population the mean rate of ESRD was 15.9 per 100,000 person-years (IC95% 14.8- 17.1; P&amp;lt;0.0001 compared with IBD): 79,606 (94.5%) patients entered ESRD by dialysis, and 4,634 (5.5%) by RT (as compared with IBD,P&amp;lt;0.001). In subgroup analysis, the mean incidence rate of ESRD was 22.8 per 100,000 person-years (IC95% 18.9-26.7) in UC patients and 29.5 (IC95% 25.3-33.6) in CD patients. The rates of preemptive RT were 12.4% in UC patients (87.6% dialysis) and 8.6% in CD patients (91.4% dialysis). Over a median follow-up of 6.8 years, the survival rate after ESRD was 40.8% in ESRD-IBD patients VS 34.2% in ESRD non-IBD patients (P&amp;lt;0.001). Conclusion This study shows that the incidence of ESRD is significantly higher in IBD than in the non-IBD population, confirming the need for regular monitoring of renal function in our patients. The high incidence of RT confirms that access to transplantation is not restricted in this population.

Clinical-grade human skin-derived ABCB5+ mesenchymal stromal cells exert anti-apoptotic and anti-inflammatory effects in vitro and modulate mRNA expression in a cisplatin-induced kidney injury murine model.

Acute kidney injury (AKI) is characterized by a rapid reduction in renal function and glomerular filtration rate (GFR). The broadly used anti-cancer chemotherapeutic agent cisplatin often induces AKI as an adverse drug side effect. Therapies targeted at the reversal of AKI and its potential progression to chronic kidney disease or end-stage renal disease are currently insufficiently effective. Mesenchymal stromal cells (MSCs) possess diverse immunomodulatory properties that confer upon them significant therapeutic potential for the treatment of diverse inflammatory disorders. Human dermal MSCs expressing ATP-Binding Cassette member B5 (ABCB5) have shown therapeutic efficacy in clinical trials in chronic skin wounds or recessive dystrophic epidermolysis bullosa. In preclinical studies, ABCB5+ MSCs have also shown to reverse metabolic reprogramming in polycystic kidney cells, suggesting a capacity for this cell subset to improve also organ function in kidney diseases. Here, we aimed to explore the therapeutic capacity of ABCB5+ MSCs to improve renal function in a preclinical rat model of cisplatin-induced AKI. First, the anti-apoptotic and immunomodulatory capacity was compared against research-grade adipose stromal cells (ASCs). Then, cross-species immunomodulatory capacity was checked, testing first inhibition of mitogen-driven peripheral blood mononuclear cells and then modulation of macrophage function. Finally, therapeutic efficacy was evaluated in a cisplatin AKI model. First, ABCB5+ MSCs suppressed cisplatin-induced apoptosis of human conditionally-immortalized proximal tubular epithelial cells in vitro, most likely by reducing oxidative stress. Second, ABCB5+ MSCs inhibited the proliferation of either human or rat peripheral blood mononuclear cells, in the human system via the Indoleamine/kynurenine axis and in the murine context via nitric oxide/nitrite. Third, ABCB5+ MSCs decreased TNF-α secretion after lipopolysaccharide stimulation and modulated phagocytosis and in both human and rat macrophages, involving prostaglandin E2 and TGF-β1, respectively. Fourth, clinical-grade ABCB5+ MSCs grafted intravenously and intraperitoneally to a cisplatin-induced AKI murine model exerted modulatory effects on mRNA expression patterns toward an anti-inflammatory and pro-regenerative state despite an apparent lack of amelioration of renal damage at physiologic, metabolic, and histologic levels. Our results demonstrate anti-inflammatory and pro-regenerative effects of clinical grade ABCB5+ MSCs in vitro and in vivo and suggest potential therapeutic utility of this cell population for treatment or prevention of cisplatin chemotherapy-induced tissue toxicity.

High Ferritin and Low Total Iron-Binding Capacity in Plasma Predict All-Cause Mortality During the First 3 Years of Hemodialysis in Patients with End-Stage Chronic Kidney Disease.

To determine all-cause mortality rate and the predictive value of plasma ferritin and total iron-binding capacity (TIBC) concentrations for mortality during the first 3 years of hemodialysis in patients with end-stage chronic renal disease (ESRD). We conducted a study on 174 ESRD patients (estimated Glomerular Filtration Rate < 15 mL/min/1.73m2). The plasma TIBC level was quantified by the ELISA method in all patients at the time before hemodialysis. Based on TIBC concentration, patients were divided equally into 2 groups. Each group had 87 patients. Patients were initiated on hemodialysis, and patients who died from any cause during the first 3 years of hemodialysis were recorded. The all-cause mortality rate of ESRD patients in the first 3 years of maintenance hemodialysis was 22.9%. Plasma high hs-CRP, high ferritin, and low TIBC concentrations were independent factors associated with all-cause mortality in the patients. Plasma ferritin (cut-off value = 454.2 ng/L) and TIBC (cut-off value = 39.84 µmol/L) were predictors of all-cause mortality, AUC is: 0.772; 0.723, p < 0.001. Plasma ferritin and TIBC were good predictors of all-cause mortality in ESRD patients during the first 3 years of hemodialysis.

The Terminalia chebula retz extract treats hyperuricemic nephropathy by inhibiting TLR4/myd88/NF-κb axis

Ethnopharmacological relevanceHyperuricemic nephropathy (HN) is a renal injury caused by hyperuricemia and is the main cause of chronic kidney disease and end-stage renal disease. ShiWeiHeZiSan, which is composed mainly of components of Terminalia chebula Retz. And is recorded in the Four Medical Tantras, is a typical traditional Tibetan medicinal formula for renal diseases. Although T. chebula has been reported to improve renal dysfunction and reduce renal cell apoptosis, the specific mechanism of the nephroprotective effects of T. chebula on HN is still unclear. Aim of the studyThis study was conducted to evaluate the effects and specific mechanism of T. chebula extract on HN through network pharmacology and in vivo and in vitro experiments. Materials and methodsPotassium oxalate (1.5 g/kg) and adenine (50 mg/kg) were combined for oral administration to establish the HN rat model, and the effects of T. chebula extract on rats in the HN model were evaluated by renal function indices and histopathological examinations. UPLC-Q-Exactive Orbitrap/MS analysis was also conducted to investigate the chemical components of T. chebula extract, and the potential therapeutic targets of T. chebula in HN were predicted by network pharmacology analysis. Moreover, the activation of potential pathways and the expression of related mRNAs and proteins were further observed in HN model rats and uric acid-treated HK-2 cells. ResultsT. chebula treatment significantly decreased the serum uric acid (SUA), blood urea nitrogen (BUN) and serum creatinine (SCr) levels in HN rats and ameliorated renal pathological injury and fibrosis. A total of 25 chemical components in T. chebula extract were identified by UPLC-Q-Exactive Orbitrap/MS analysis, and network pharmacology analysis indicated that the NF-κB pathway was the potential pathway associated with the therapeutic effects of T. chebula extract on HN. RT‒PCR analysis, immunofluorescence staining and ELISA demonstrated that the mRNA and protein levels of TLR4 and MyD88 were significantly decreased in the renal tissue of HN rats after treatment with T. chebula extract at different concentrations, while the phosphorylation of P65 and the secretion of TNF-α and IL-6 were significantly inhibited. The results of in vitro experiments showed that T. chebula extract significantly decreased the protein levels of TLR4, MyD88, p-IκBα and p-P65 in uric acid-treated HK-2 cells and inhibited the nuclear translocation of p65 in these cells. In addition, the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) and fibrotic genes (α-SMA and fibronectin) was significantly downregulated by T. chebula extract treatment, while E-cadherin expression was significantly upregulated. ConclusionT. chebula extract exerts nephroprotective effects on HN, such as anti-inflammatory effects and fibrosis improvement, by regulating the TLR4/MyD88/NF-κB axis, which supports the general use of T. chebula in the management of HN and other chronic kidney diseases.

Rituximab as add-on therapy in patients with resistant lupus nephritis who have failed induction or maintenance therapy with other agents: A real-world experience from a single center in Mumbai.

Lupus nephritis (LN) is associated with poor outcomes and a significant risk of progression to end-stage renal disease (ESRD). Some patients with resistant LN do not respond adequately to current treatment options and need alternative strategies or therapies. The objective is to evaluate the efficacy and safety of rituximab as a re-induction therapy (Re-RTX) followed by maintenance therapy for patients with resistant LN. Twenty-four patients with resistant LN (failed initial induction therapy or severe relapse after remission) were analyzed. Re-RTX was co-administered with other immunosuppressants. The primary KDIGO criteria outcomes included renal response (complete and partial), disease progression, relapses, and infections. The median age was 28years (IQR 24.5-42), and the female-to-male ratio was 11:1. All patients had active LN, and 91.3% had proliferative LN. Baseline creatinine was 1.075mg% (IQR 0.7-1.38), and mean urine protein-to-creatinine ratio (UPCR) was 4.9 (IQR 2.8-6.65). Of the patients receiving RTX as re-induction therapy, 66.6% (16/24) had failed initial induction therapy with other immunosuppressants, whereas 33.3% (8/24) had severe relapse during maintenance therapy.Re-RTX had a favorable renal response at 6months, with 91.7% of the patients responding (20.8% complete response and 70.8% partial response). At 12months, 58.3% of the patients maintained a renal response (25% complete response and 33.3% partial response). Approximately one-third of patients relapsed within a year.Fourteen patients (58.3%) continued RTX maintenance therapy with two different treatment regimens. At 6months, Regimen-1 (500mg every 6months) resulted in a partial response in 43% (3/7) and relapse in 57% (4/7) of patients. Regimen 2 (1g dose per year) achieved a complete response in 28.5% (2/7) and a partial response in 71.5% (5/7) with no relapses at 6months.At a median follow-up of 29months, adverse renal outcomes were observed in 29.16% of the patients with progression to advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). The overall use of Re-RTX was considered safe, with a reported infection prevalence of 16%, which is comparable to the existing data. Re-RTX demonstrated efficacy and safety as an induction therapy for resistant LN. However, the response waned after 1year, underscoring the need for optimized maintenance therapy.

Impact of chronic kidney disease and end-stage renal disease on outcomes after complex endovascular and open aortic aneurysm repair

ObjectiveChronic kidney disease (CKD) and end-stage renal disease are traditionally associated with worse outcomes after endovascular aortic repair (EVAR) and open aneurysm repair (OAR) of abdominal aortic aneurysms (AAAs). However, there needs to be more data on complex AAA repair involving the aorta's visceral segment. This study stratifies complex AAA repair outcomes by CKD severity and dialysis dependence. MethodsAll patients undergoing elective OAR and fenestrated/branched EVAR (F-BEVAR) for complex AAA with preoperative renal function data captured by the Vascular Quality Initiative between January 2003 and September 2020 were analyzed. Patients were stratified by CKD class as follows: normal/mild (CKD 1 and 2), moderate (CKD class 3a), moderate to severe (CKD 3b), severe (CKD class 4 and 5), and dialysis. Only patients with clamp sites above one of the renal arteries were included for complex OAR. For F-BEVAR, patients with proximal landing zones below zone 5 (above celiac artery) were included, and distal landing zones between zones 1 and 5 were excluded. Primary outcomes were perioperative and 1-year mortality. Predictors of mortality were identified by Cox multivariate regression models. ResultsWe identified 7849 elective complex AAA repairs: 4230 (54%) complex OARs and 3619 (46%) F-BEVARs. Most patients were White (89%) and male (74%), with an average age of 72 ± 8 years. The patients who underwent F-BEVAR were older and had more comorbidities. Elective F-BEVAR for complex AAA started in 2012 and increased from 1.4% in 2012 to 58% in 2020 (P < .001). The OAR cohort had more perioperative complications, but less 1-year mortality. The normal/mild CKD cohort had the highest 1-year survival compared with other groups after both complex OAR and F-BEVAR. On Cox regression analysis, when compared with CKD 1-2, worsening CKD stage (CKD 3b: hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.82-3.40; P < .001; CKD 4-5: HR, 1.9; 95% CI, 1.16-3.26; P = .011; and dialysis: HR, 4.4; 95% CI, 2.53-7.72; P < .001) were independently associated with 1-year survival after F-BEVAR. After complex OAR, worsening CKD stage but not dialysis was associated with 1-year mortality compared with CKD 1-2 (CKD 3b: HR, 1.6; 95% CI, 1.13-2.35; P = .009; CKD 4-5: HR, 3.4; 95% CI, 2.03-5.79; P < .001). ConclusionsCKD severity is an essential predictor of perioperative and 1-year mortality after complex AAA repair, irrespective of the treatment modality, which may reflect the natural history of CKD. Consideration should be given to raising the threshold for elective AAA repair in patients with moderate to severe CKD and end-stage renal disease, given the high 1-year mortality rate.

Development of Dialysis and Leakage Detection on Different Technology

Dialysis is the treatment for chronic kidney disease (CKD) patients, including acute or end-stage renal disease (ESRD), by performing the filtration of toxic or waste substances from the patient’s body. Haemodialysis (HD) and peritoneal dialysis (PD) are common treatments for dialysis patients with the use of extracorporeal dialysis machines such as haemodialysis machines or automated peritoneal dialysis (APD) for HD and PD, respectively. For HD, is required a dialyser act as a single-use consumable during the treatment of the patient. However, the major concern on the haemodialysis machine might be the issue on false sense during the treatment. The leakage detector of the dialysis machine is important to detect and sense the parameters when that is a leakage event, such as blood leakage at the dialyser or arteriovenous fistula (AVF) dysfunction. Thus, this study provides a review of leakage detection that has been developed with different methodologies of the sensing unit on a haemodialysis machine.

[Chinese clinical practice guideline for acute kidney injury].

Acute kidney injury (AKI), a common and severe disease, is associated with a high risk of developing chronic kidney disease (CKD) and end-stage renal disease (ESRD), which is a global health burden with high morbidity and mortality. Although many foreign clinical practice guidelines have standardized the management and treatment of AKI, there is a lack of overall guidance for AKI which is suitable for our national conditions. Thus, an expert group in related fields were organized by the National Clinical Research Center for Kidney Diseases and Chinese Nephrologist Association to collaborate to complete the Chinese Clinical Practice Guideline for Acute Kidney Injury based on the latest existing evidence-based medical evidence both domestically and internationally. The guideline systematically introduces the definition and epidemiological feature, diagnosis and monitoring of AKI, pharmacological approaches to prevent or treat AKI, and management of renal replacement therapy, management of AKI on special populations, and the outcome and prognosis of AKI, aiming to provide reasonable recommendations for all level clinicians in China.