Chronic End-stage Renal Disease Research Articles

#1656 Ezetimibe improves diabetic nephropathy by upregulating Nrf2 to alleviate endoplasmic reticulum stress

Abstract Background and Aims Diabetic nephropathy (DN), a prevalent complication of diabetes mellitus, stands as the primary contributor to chronic kidney disease and end-stage renal disease. The progression of diabetic nephropathy is facilitated by endoplasmic reticulum stress and the excessive generation of reactive oxygen species (ROS). In addition to its cholesterol-lowering properties, recent research has revealed that ezetimibe also ameliorates insulin resistance and glucose intolerance abnormalities, and is also beneficial in chronic kidney disease. However, the specific impact of ezetimibe on diabetic nephropathy and the underlying mechanism remain unknown. Therefore, the objective of this research is to investigate the effect of ezetimibe on diabetic nephropathy and elucidate its mechanism. Method In vivo experiments were conducted using C57BL/6J mice, with a total of 24 mice randomly assigned to three groups: NC, DM, and EZE (10 mg/kg/day). In vitro experiments involved the treatment of human renal proximal tubular (HK-2) cells with ezetimibe (50 μM) and high glucose (30 mmol/L) for 48 hours. Then, combined with histopathological examination, biochemical evaluation, TUNEL stain, western blot analysis, Si-RNA transfection, transmission electron microscopy and ROS probe were used to detect the renal morphology and function, oxidative stress and endoplasmic reticulum homeostasis level. Results The results demonstrated that a 10-week treatment with ezetimibe led to significant improvements in urine volume, beta-N-acetylglucosaminidase (NAG), and the urinary albumin/creatinine ratio (ACR). The administration of ezetimibe in the treatment exhibited enhancements in glomerular hypertrophy and renal tubular vacuolization, as well as mesangial matrix expansion and glomerular basement membrane thickness, in diabetic mice. Additionally, ezetimibe treatment resulted in a reduction in ROS formation by upregulating the expression of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), through the activation of NF-E2-related factor-2 (Nrf2). Furthermore, ezetimibe administration partially reversed the increased expression of endoplasmic reticulum stress-related proteins, including activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), and C/EBP homologous protein (CHOP), in DN mice. Ezetimibe demonstrated inhibitory effects on the accumulation of ROS and alleviated endoplasmic reticulum stress in HK-2 cells treated with high glucose. Furthermore, electron microscopy analysis revealed that ezetimibe effectively reduced the distension and dilation of the endoplasmic reticulum. However, the anti-endoplasmic reticulum stress effect of ezetimibe was significantly diminished following transfection with si-Nrf2. These findings suggest that ezetimibe exerts its anti-endoplasmic reticulum stress effect, at least in part, by enhancing antioxidant capacity and reducing ROS levels through the upregulation of Nrf2. Conclusion In summary, our research findings demonstrate the notable contribution of endoplasmic reticulum stress to the progression of DN. Through the up-regulation of Nrf2, ezetimibe effectively mitigates ROS generation in the context of DN, consequently ameliorating the adverse consequences of ERS, restoring equilibrium within the endoplasmic reticulum, and ultimately safeguarding against renal cell demise. Ezetimibe is an attractive potential therapy for the treatment of DN.

#1346 Inpatient and outpatient service review of a Greek reference centre for glomerular diseases

Abstract Background and Aims The glomerulonephritis (GN) is a rare and complicated disease with high demand of hospital resources while the chronic kidney disease and end-stage renal disease present increased prevalence in these patients. Method We retrospectively assessed the inpatient and outpatient service of a Greek reference centre for glomerular diseases during the pre-Covid-19 period 2018-2020. Results 267 patients (38% female, median age 65 ± 23 years) included. All patients underwent a kidney biopsy by the nephrologist without complications. ANCA associated GN (18%), Focal Segmental Glomerulosclerosis/Minimal Change Disease (17.5%), IgA nephropathy (17%), Membranous Nephropathy (12.6%), Lupus Nephritis (5%), Membranoproliferative GN (3%), Fibrillary GN (3%), Monoclonal Gammopathy of Renal Significance (3.3%) and IgG4-related disease (2%.) are encompassed. We reported median 75 new patients per year. Regarding the inpatient service, we observed an increasing trend to the hospitalizations during this period (274, 452, 461 hospitalizations in 2018, 2019, 2020 respectively). The AAGN was the most common disease of hospitalizations through this period (53% in 2018, 33% in 2019, 39% in 2020), whereas the second most common was the FSGS/MCD (28% in 2018, 13% in 2019, 23.8% in 2020). The outpatient's service review also revealed an increasing number of visits per person per year (279, 456 and 464 total visits in 2018, 2019 and 2020 respectively). The disease with the highest number of visits per person was reported the AAV (median 3.25 visits per patient per year). All the patients were managed in adherence to the latest guidelines for GN in collaboration with a multidisciplinary team, consisting of nephrologist, rheumatologist, cardiologist, and pathologist. Finally, we reported complete response at 76% of the patients and in terms of renal improvement, 46% presented eGFR≥60 ml/min/1.73 m2, 45% eGFR<60 ml/min/1.73 m2 and only 9% progressed to ESRD after the first year of treatment. Conclusion Patients with GN present an increased need for hospitalization and regular outpatient visits. Addressing these diseases necessitates the expertise of a multidisciplinary team to provide comprehensive care that maximizes the potential for sustained positive long-term outcomes.

#2460 Haemodialysis-related periarticular calcifications as cause of recurrent severe inflammatory state

Abstract Background and Aims End stage chronic kidney disease (CKD) and haemodialysis (HD) are associated with disturbances in mineral and bone turnover ultimately leading to chronic kidney disease–mineral and bone disorder (CKD-MBD), which affects more than 90 % of patients with stage 5D CKD. The primary changes observed in CKD–MBD involve elevated phosphorus levels, decreased calcium levels, insufficient serum vitamin D, and heightened release of parathyroid hormone from the parathyroid glands, leading to secondary hyperparathyroidism. CKD-MBD leads to vascular calcification, increasing cardiovascular risk. There is also a correlation between abnormal bone remodeling activity in CKD-MBD and the likelihood of calcification in soft tissues. In rare instances, profound calcification occurs in periarticular tissues, resulting in severe inflammation and manifesting as systemic disease with articular involvement clinically. The objective of this case report is to demonstrate a recurrent inflammatory condition caused by severe periarticular calcification in a patient on HD. Case report We present a case of a middle-aged white male diagnosed with hypertension, hypercholesterolemia, chronic obstructive pulmonary disease, hepatitis C, and end-stage renal disease caused by hydronephrosis. He was undergoing HD since July 2020. From summer 2021 the patient experienced recurrent fever and arthralgias in the hips, elbows, and shoulders. Frequent acute hospitalizations were needed due to recurring fevers and severe inflammatory response with markedly elevated acute phase reactants (CRP was repeatedly >200 mg/l), raising suspicion of infection. Laboratory and imaging tests however showed no clear signs of infection, and antibiotic therapy was ineffective. An x-ray of the right AC-joint showed multiple periarticular calcifications dorsally from the AC-joint. Later, due to severe pain and swelling an MRI-scan of right elbow joint was conducted, revealing an osteomyelitis-suspect finding of the olecranon, and olecranon bursitis. No bacteria were detected in the punctate of olecranon bursa. X-ray scans of the elbows revealed bilateral soft tissue calcification dorsally from the proximal ulna. The x-ray scan of the right shoulder revealed calcific expansion in the AC-joint area, leading to total destruction of the lateral part of the clavicle. MRI and CT scans showed severe periarticular calcification around AC- and glenohumeral joints without inflammatory involvement of the synovium. Bony erosions were observed due to the pressure of calcified tissue on the bone. Whole-body CT-scan showed no sites of infection but there was a periarticular calcification observed around the hip joints. A PET-CT scan of the whole body, neck, and upper extremities revealed no signs of malignancy or infections, but there was an increased uptake of 18F-fluorodeoxyglucose detected in several periarticular sites, indicating a multi-site inflammatory process resulting from severe periarticular calcifications. A dual-energy CT-scan of upper extremities was performed, excluding the accumulation of monosodium urate crystals. The cycle of multiple hospitalizations and antibacterial therapies was broken with the diagnosis of CKD and HD-related inflammatory periarticular calcification. Initially, the inflammation was addressed with high-dose glucocorticoids. However, the dose was successfully tapered during the first month of treatment, and the patient continued to do well on a maintenance dose of 5 mg/day of prednisolone. Subsequently, hospitalizations, antibiotics, or surgical procedures were no longer required. Conclusion Severe CKD and HD cause disturbances in mineral and bone metabolism, that can lead to periarticular calcification. Like in our presented case, multi-site calcifications may mimic infection or autoimmune rheumatoid conditions making the way to correct diagnosis cumbersome and costly. Imaging techniques help us distinguish periarticular deposits from inflammatory and infectious arthritis. In our case low-dose prednisolone effectively reduced inflammation, obviating hospitalizations and minimizing healthcare burden.

Diabetes and Renal Complications: An Overview on Pathophysiology, Biomarkers and Therapeutic Interventions.

Diabetic kidney disease (DKD) is a major microvascular complication of both type 1 and type 2 diabetes. DKD is characterised by injury to both glomerular and tubular compartments, leading to kidney dysfunction over time. It is one of the most common causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Persistent high blood glucose levels can damage the small blood vessels in the kidneys, impairing their ability to filter waste and fluids from the blood effectively. Other factors like high blood pressure (hypertension), genetics, and lifestyle habits can also contribute to the development and progression of DKD. The key features of renal complications of diabetes include morphological and functional alterations to renal glomeruli and tubules leading to mesangial expansion, glomerulosclerosis, homogenous thickening of the glomerular basement membrane (GBM), albuminuria, tubulointerstitial fibrosis and progressive decline in renal function. In advanced stages, DKD may require treatments such as dialysis or kidney transplant to sustain life. Therefore, early detection and proactive management of diabetes and its complications are crucial in preventing DKD and preserving kidney function.

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.

Anakinra for Refractory Pseudogout in Patients with End-stage Renal Disease on Haemodialysis.

Calcium pyrophosphate deposition (CPPD) arthritis is the second most common type of crystal-induced arthritis after gout. Acute flares are commonly treated with non-steroidal anti-inflammatory drugs, intra-articular or short-term systemic glucocorticoids or colchicine. However, since there is no pharmacological treatment to reduce CPPD crystal burden, relapsing or chronic CPPD arthritis may be challenging to treat, particularly in patients with end-stage renal disease who are at risk for toxicity of the above medications. Since IL-1β appears to be driving CPPD arthritis, we treated two patients with chronic CPPD arthritis and end-stage renal disease on haemodialysis with the IL-1β receptor antagonist anakinra. In both patients, arthritis resolved quickly, while continuation of anakinra maintained remission and allowed complete glucocorticoid withdrawal. Therefore, anakinra may be a safe and effective option both for short and long-term treatment of CPPD arthritis in patients on chronic renal replacement therapy.

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.