Chronic Transplant Research Articles

#431 Ionized and total magnesium levels in patients with chronic kidney disease: associated factors and outcomes

Abstract Background and Aims Association between hypo- and/or hypermagnesaemia and cardiovascular (CV) outcomes or mortality showed conflicting results in chronic kidney disease (CKD) and was mostly conducted on total magnesium (tMg) levels and not ionized magnesium (iMg). Thus, the objectives of the present study were to (i) describe the serum iMg concentration in patients at various CKD stages, (ii) measure the correlation between iMg and tMg concentrations, (iii) identify their associated factors and (iv) determine whether serum tMg and/or iMg concentrations are associated with adverse outcomes, such as major adverse cardiovascular events (MACE) and death before kidney replacement therapy (KRT, defined as the initiation of chronic dialysis or kidney transplantation) in CKD patients, after adjustment for confounding factors. Method CKD-REIN is a French prospective cohort of patients with stage 3 to 5 CKD (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²) recruited from 40 nephrology facilities, neither on maintenance dialysis nor transplanted, and followed up for 5 years. Baseline iMg and tMg serum concentrations were centrally measured. Patients were compared by subgroups according to serum tMg tertiles (Tertile 1 (T1): ≤0.73 mmol/L, T2: 0.74-0.81 mmol/L, T3: >0.81 mmol/L). Multivariate linear regressions were used to identify factors associated with iMg and tMg serum concentrations. Adjusted cause-specific Cox proportional hazard models were used to test the association between the risk of first MACE, all-cause mortality, and CV mortality with serum iMg and tMg concentrations at baseline. Results Of the 2, 419 included patients, 66% were men, median age was 68, and the mean eGFR was 34.8 mL/min/1.73 m². Mean serum iMg and tMg concentrations were respectively 0.48 mmol/L and 0.77 mmol/L. They were strongly correlated (r = 0.89, P < .001) and were independently associated with eGFR. Overall, iMg and tMg concentrations were associated with the same factors. The adjusted HR [95% CI] for MACE associated with the baseline serum tMg level was 1.27 [0.95; 1.69] for patients in T1, and 1.56 [1.18; 2.06] for patients in T3, relative to patients in T2. The adjusted HR [95% CI] for MACE associated with baseline serum iMg was 0.93 [0.71; 1.23] for patients in T1, and 1.14 [0.88; 1.48] for patients in T3, relative to patients in T2. The risks of all-cause death (HR [95% CI] = 1.48 [1.11; 1.97]) and CV mortality (HR [95% CI] = 1.98 [1.27; 3.10]) were also increased in T3 of tMg compared with T2. The adjusted risks for mortality (all-cause or CV) associated with the baseline serum iMg level were not significantly different from one tertile to another. Conclusion Our analysis of a large cohort of patients with moderate-to-advanced CKD demonstrated that individuals with higher serum tMg concentrations, although still within the normal range, had a greater likelihood of MACE and mortality. Total magnesium is routinely assayed in hospital laboratories and might be a useful variable to monitor in CKD patients. We failed to demonstrate the added value of iMg when studying its association with CV outcomes and mortality.

#2434 Literature review on the burden of herpes zoster in patients with kidney disease—a need for earlier prevention

Abstract Background and Aims Kidney disease (KD), including end stage renal disease (ESRD), is a global health problem. Both are associated with impaired immune systems, which can lead to infections. Complications such as cardiovascular disease and various infections are leading causes of morbidity and mortality in KD patients. Notably, patients with KD have an increased risk of herpes zoster (HZ). While the link between ESRD and renal transplant with increased HZ risk is understood, knowledge gaps regarding the burden of HZ across the KD spectrum still exist. This review aims to describe the risk and impact of HZ across the KD spectrum in order to guide preventive care strategies for patients with renal diseases. Method A structured literature review was conducted in PubMed using a combination of keywords and Medical Subject Heading (MeSH) terms to identify studies related to HZ risk in adult KD patients aged ≥18 years published in the English language between 01/11/2003–31/10/2023. Data extracted from published studies included the burden of HZ infection in patients with KD (risk of HZ and related complications), impact of HZ on underlying KD, and the efficacy/effectiveness of HZ vaccines among patients with KD. Results A total of 47 studies were identified (Randomized controlled trials [RCT] = 2; observational studies = 45) in this review (Fig. 1). Included studies presented evidence from regions in Europe (n = 18), Asia (n = 17), North America (n = 7), South America (n = 1), multinational (n = 2) and Australia (n = 1); country not reported in one study. Evidence from observational studies (n = 37) reported a high risk of HZ infection and related complications, such as disseminated HZ, and recurrent HZ across the KD spectrum, including chronic KD, polycystic KD, hemodialysis, peritoneal dialysis and kidney transplant patients. Infection with HZ was reported to accelerate KD progression and increased the risk of ESRD and cardiovascular events. In general, for ESRD patients with an inpatient HZ diagnosis, mortality increased with age, followed by malnutrition and bacteremia/septicemia. Studies reporting vaccine efficacy (n = 2) and effectiveness results (n = 8) suggest that HZ vaccination was associated with a reduced risk of HZ when compared to unvaccinated individuals. Furthermore, the recombinant zoster vaccine (RZV) was found to be immunogenic in kidney transplant recipients, with immunogenicity persisting through 12 months post-vaccination. An RCT post-hoc analysis showed high vaccine efficacy in patients aged ≥50 years with medical conditions at enrollment, including KD, which was consistent with the overall population. A favorable benefit-risk profile was reported in randomized and observational studies. Studies evaluating the effectiveness of the zoster live-attenuated vaccine (ZVL) found a lower risk of HZ in patients with ESRD immunized against HZ compared to unvaccinated individuals. In many countries, vaccination guidelines specifically recommended immunization of people with KD to protect against HZ. However, ZVL is contraindicated for immunocompromised (e.g. kidney transplant) patients. Conclusion Findings indicate that HZ has a significant HZ burden across the KD spectrum, which may negatively impact renal disease progression. With effective vaccines offering durable protection against HZ and its complications, the immunization of renal patients at earlier stages could enhance healthcare management and patient outcomes.

#1280 Temporal trends in chronic kidney disease and mortality after acute kidney injury

Abstract Background and Aims In 2015, the International Society of Nephrology formulated the “0by25” initiative, which aims to eliminate all preventable deaths due to acute kidney injury (AKI) by 2025. Numerus publications have added focus to the importance of clinical awareness and improved treatment for AKI. Ideally, this should translate to lower rates of AKI-associated adverse outcomes such as chronic kidney disease (CKD) and death. To our knowledge, there are no studies describing temporal trends in the incidence of CKD following AKI. Moreover, only a few studies have examined the temporal trends in mortality following AKI and these studies included highly selected groups of patients not representative of general hospitalized patients and to an even lesser degree the general population. Hence, further examination of the prognosis after AKI is required to understand temporal trends in the quality of care for AKI and establish a foundation for both preventive and therapeutic measures. Therefore, we examined the temporal trends in CKD and mortality after AKI in Denmark. Method We identified adult individuals with AKI from 1 January 2007 to 31 December 2018 using population-based plasma creatinine (pCr) data covering both the primary care and hospital settings. AKI was defined in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. CKD after AKI was defined as ≥2 eGFR measurements from primary care or planned outpatient hospital visits <60 mL/min/1.73 m2 separated by a period of ≥90 days or by a hospital diagnoses code related to chronic dialysis or kidney transplantation. Information on all-cause death was obtained from the Danish Civil Registration System. Annual crude and sex-and-age-standardized 1-year incidence rates of CKD and mortality after AKI were estimated using direct standardization. Results During the 2007-2018 period, 406,207 AKIs were identified in 274,269 distinct Danish residents. The mean age at the time of first AKI was 72 years (IQR, 61; 81) and 137,185 (50%) of first-time AKIs occurred in males. Twenty-eight percent of individuals had a Charlson Comorbidity Index (CCI) score of 0, while 42% had a CCI score of 1-2, and 30% a CCI score ≥3. The mean age, sex, and CCI score distributions were stable across the study period. The age- and sex-standardized incidence rate of CKD after AKI ranged from 102 (95% CI, 99-106) per 1000 person-years in 2018 to 126 (95% CI, 119-133) per 1000 person-years in 2014. Besides a peak in 2014, the incidence of CKD after AKI showed little variation throughout the period. The age-and sex-standardized mortality rate after AKI ranged from 317 (95% CI, 311-323) per 1000 person-years in 2018 to 392 (95% CI, 379-406) per 1000 person-years in 2007. From 2007 to 2013 there was a stable decline in the mortality rate after AKI. From 2014 to 2018 the rate showed little variation. Conclusion The rate of CKD after AKI was stable throughout the period, while there was a decline in mortality after AKI, especially in the years from 2007 to 2013. The decline in mortality after AKI is encouraging; however, the stable rate of CKD after AKI, despite increasing knowledge on AKI treatment and CKD prevention, warrants an evaluation of the contemporary quality of care for AKI in Denmark.

#2020 The use of the target trial approach in kidney failure: a systematic methodological review

Abstract Background and Aims The concept of target trial emulation has recently been introduced and implemented in nephrology as a complement to when randomized trials may not be feasible. Thereby critical questions in the comparative effectiveness and safety of interventions during kidney failure can be addressed. This methodological systematic review aims to evaluate the scope, validity and robustness of the target trial approach for studying outcomes in patients with kidney disease. Method MEDLINE, Embase, and reference lists were searched up until 1st June 2023 to identify studies on kidney disease patients that use target trial emulation. Dual study selection (AA, PK) was undertaken, with a third reviewer settling disagreements (JP). Interventional observational studies were eligible that used target trial emulation to mimic a hypothetical trial where the conduct of a randomized trial was unfeasible, unethical, or untimely. We included studies across the range of chronic kidney diseases, i.e., predialysis, dialysis and transplantation; studies assessing acute disease states (including acute kidney injury) were excluded as well as non-primary research (i.e., case series/editorials/reports/narrative reviews). The quality of reporting and risk of bias was assessed independently by three reviewers and differences resolved through consensus with a fourth reviewer. The critical appraisal was piloted using a previously published reporting checklist and refined throughout the process. Results The systematic search yielded 2883 studies, of which 649 duplicates were removed. From 2232 studies, 367 full-text studies were assessed for eligibility according to target trial emulation criteria and 74 studies were included. A large number of studies (47) focused on patients with kidney failure undergoing renal replacement therapy, mainly haemodialysis. 30 studies were reported before 2019. Of the 74 studies, 46 focused on pharmacological interventions, six on surgical interventions, four on transplantation and 18 on other interventions. Studies used either registries (41), health administration data (4), insurance data (5), electronic health records (15), study databases (8) or other (1). It should be noted that in multiple instances more than one data source was used. The majority (66) of studies did not explicitly mention target trial emulation in the title or abstract. Only a minority (8) of studies explicitly prespecified a target trial protocol. To mitigate confounding, studies mainly focused on exact matching of the groups by using inverse probability weighting and propensity score matching. Conclusion In the past decade the use of the target trial emulation framework in nephrology has substantially increased. However, reporting and quality of study conduct is variable and shows the clear need for a reporting framework to increase clarity and reliability, and to understand to what extent study findings are generalisable into clinical practice to improve health outcomes

Tubulointerstitial nephritis with IgG4-positive plasma cell infiltration and tertiary lymphoid tissue in a patient with cryoglobulinemic vasculitis: a case report.

Tertiary lymphoid tissue (TLT) develops at sites of chronic immune stimulation, including infection, autoimmune disease, transplant rejection, and cancer. Recently, TLT has been focused on an indicator for poor renal prognosis in various kidney diseases. In cryoglobulinemic vasculitis (CV), specific glomerular and vascular lesions are seen; however, tubulointerstitial lesions are usually nonspecific. We herein report the case of a 74-year-old man with idiopathic CV with rare tubulointerstitial lesions, such as tubulointerstitial nephritis (TIN) with IgG4-positive plasma cell infiltration and TLT. To our knowledge, this is the first report identifying TLT in the kidney biopsy in a patient with CV. Glucocorticoid improved the renal outcome. The association between CV and TIN with TLT remains unknown.

Risk Factors and Outcomes Associated With Heart Failure With Preserved and Reduced Ejection Fraction in People With Chronic Kidney Disease.

Heart failure (HF) is associated with poor outcomes in people with chronic kidney disease, yet it is unknown whether outcomes differ by HF subtype. This study aimed to examine associations of incident HF with preserved ejection fraction (HFpEF) versus HF with reduced ejection fraction (HFrEF) with progression to end-stage kidney disease (ESKD) and mortality. We studied individuals with chronic kidney disease in the CRIC study (Chronic Renal Insufficiency Cohort) who were free of HF at cohort entry. Incident HF hospitalizations were adjudicated and classified into HFpEF (ejection fraction, ≥50%) or HFrEF (ejection fraction, <50%) based on echocardiograms performed during the hospitalization or at a research study visit. ESKD was defined as need for chronic dialysis or kidney transplant. Cox proportional hazards were used to evaluate the association of time-updated HF subtype with risk of ESKD and mortality, adjusting for demographics, comorbidities, and medication use. Among the 3557 study participants without HF at cohort entry, mean age was 57 years and mean estimated glomerular filtration rate was 45 mL/min per 1.73 m2. A total of 682 participants had incident HF. Incidence rates for HFpEF and HFrEF were 0.9 (95% CI, 0.8-1.0) and 0.7 (95% CI, 0.6-0.8) per 100 person-years, respectively (Pdifference=0.005). Associations of incident HF with progression to ESKD were not statistically different for HFpEF (hazard ratio, 2.06 [95% CI, 1.66-2.56]) and HFrEF (hazard ratio, 1.80 [95% CI, 1.36-2.38]; P=0.42). The associations with mortality were stronger for HFrEF (hazard ratio, 2.73 [95% CI, 2.24-3.33]) compared with HFpEF (hazard ratio, 1.99 [95% CI, 1.65-2.40]; P=0.0002). In a chronic kidney disease population, the rates of HFpEF hospitalizations were greater than that of HFrEF. Risk of ESKD was high but not statically different across HF subtypes. There was a stronger association of HFrEF with mortality. Prevention and treatment of both HFpEF and HFrEF should be central priorities to improve outcomes in chronic kidney disease.

269 Gastrointestinal Bleeding (GIB) in Advanced Chronic Kidney Disease and Kidney Transplant (KT) Recipients: A National Analysis

269 Gastrointestinal Bleeding (GIB) in Advanced Chronic Kidney Disease and Kidney Transplant (KT) Recipients: A National Analysis

(168) - Targeting Immunometabolism in Chronic Lung Transplant Rejection

(168) - Targeting Immunometabolism in Chronic Lung Transplant Rejection

Multichannel bridges and NSC synergize to enhance axon regeneration, myelination, synaptic reconnection, and recovery after SCI

Regeneration in the injured spinal cord is limited by physical and chemical barriers. Acute implantation of a multichannel poly(lactide-co-glycolide) (PLG) bridge mechanically stabilizes the injury, modulates inflammation, and provides a permissive environment for rapid cellularization and robust axonal regrowth through this otherwise inhibitory milieu. However, without additional intervention, regenerated axons remain largely unmyelinated (<10%), limiting functional repair. While transplanted human neural stem cells (hNSC) myelinate axons after spinal cord injury (SCI), hNSC fate is highly influenced by the SCI inflammatory microenvironment, also limiting functional repair. Accordingly, we investigated the combination of PLG scaffold bridges with hNSC to improve histological and functional outcome after SCI. In vitro, hNSC culture on a PLG scaffold increased oligodendroglial lineage selection after inflammatory challenge. In vivo, acute PLG bridge implantation followed by chronic hNSC transplantation demonstrated a robust capacity of donor human cells to migrate into PLG bridge channels along regenerating axons and integrate into the host spinal cord as myelinating oligodendrocytes and synaptically integrated neurons. Axons that regenerated through the PLG bridge formed synaptic circuits that connected the ipsilateral forelimb muscle to contralateral motor cortex. hNSC transplantation significantly enhanced the total number of regenerating and myelinated axons identified within the PLG bridge. Finally, the combination of acute bridge implantation and hNSC transplantation exhibited robust improvement in locomotor recovery. These data identify a successful strategy to enhance neurorepair through a temporally layered approach using acute bridge implantation and chronic cell transplantation to spare tissue, promote regeneration, and maximize the function of new axonal connections.

An Indian surgeon's perspective on management of asymptomatic gallstones.

Cholelithiasis is widely prevalent in India, with a majority of patients being asymptomatic while a small proportion experiencing mild complications. In the laparoscopic era, the rate of cholecystectomies has increased owing to early recovery and fewer complications. In asymptomatic patients, the risk of complications must be balanced against the treatment benefit. Recent guidelines suggest no prophylactic cholecystectomy in asymptomatic patients. We aimed to find out the Indian surgeons' perspective on asymptomatic gallstone management. A cross-sectional e-survey was conducted of practicing surgeons, onco-surgeons and gastrointestinal-surgeons in India. The survey had questions regarding their perspective on laparoscopic cholecystectomy and treatment modalities in asymptomatic gallstones. A total of 196 surgeons responded to the survey. Their mean age was 42.3 years. Overall, 111 (57%) respondents worked in the private sector. Most surgeons (164) agreed that the rate of cholecystectomy has increased since the advent of laparoscopy; 137 (70%) respondents agreed that they would not operate on patients without risk factors. Common bile duct stones, chronic hemolytic diseases, transplant recipients, and diabetes mellitus were the risk factors. Majority of the participants agreed on not performing a cholecystectomy in patients with asymptomatic gallstones. There exists a lack of consensus among Indian surgeons on asymptomatic gallstone management in India. Where the majority of cases are asymptomatic and do not require surgery, certain comorbidities can influence the line of treatment in individual patients. Currently, the treatment guidelines for asymptomatic patients need to be established as cholecystectomies may be overperformed due to the fear of development of complications.

Indications and results of intestinal transplantation for short bowel syndrome after mesenteric ischemia

Intestinal transplantation (ITx) is the only causal treatment for complicated chronic intestinal failure after mesenteric ischemia and impending failure of parenteral supplementation. Isolated or combined ITx with the inclusion of the intestine is associated with demanding immunological, perioperative and infection associated challenges. The characterization of chronic intestinal failure, the indications, transplant survival, transplantation techniques and success rates. Collection, summary and critical appraisal of international guidelines, the guidelines of the German Medical Chamber, and the international literature. The first successful ITx were performed in 1987 and 1988 at the University of Kiel Germany and the University of Pittsburgh, USA. The number of ITx rose continuously but in phases from the end of the 1990s to over 200 per year but has currently decreased to 100-150 per year due to optimized intestinal rehabilitation. While the 1‑year and 3‑year transplant survival rates were 30% and 20% before 1991, they increased in phases up to 60% and 50%, respectively, after 1995 and have now achieved almost 80% and 70%, respectively. The substantial improvement in the results of ITx can be partly explained by progress in operative techniques, intensive care medicine and a better understanding of mucosal immunity; however, optimized strategies in immunosuppression as well as prevention of infectious diseases and malignancies have also made decisive contributions.

Retroperitoneal lymphadenopathy: An underappreciated contributor to acute kidney failure in patients with cancer

Introduction: Retroperitoneal lymphadenopathy represents a unique and infrequent complication within various malignancies. This case report exemplifies the intricate diagnostic challenges that arise when identifying nondilated obstructive nephropathy in the context of retroperitoneal lymphadenopathy due to diffuse large B-cell lymphoma (DLBCL), particularly when conventional imaging fails to reveal the hallmark feature of hydronephrosis. Case description: We present a 66-year-old male with relapsed chronic lymphocytic leukemia post-allogeneic stem cell transplantation. His direct admission to the hematology/oncology service was due to failure to thrive. Despite the absence of hydronephrosis on imaging, the patient developed volume overload and increased serum creatinine levels. An ultrasound unveiled mild bilateral collecting system dilation, while laboratory findings did not provide valuable insight into the underlying etiology. A Lasix renal scan confirmed split renal function with minimal bilateral excretion. High clinical suspicion resulted in an MRI scan showing interval enlargement of retroperitoneal lymph nodes and pelvicaliectasis, which prompted urological and interventional radiology involvement. Conclusions: This case underscores the complexity of diagnosing retroperitoneal lymphadenopathy and pelvicaliectasis, in DLBCL, particularly when hydronephrosis is absent on imaging. It emphasizes the significance of clinical acumen, collaboration among specialties, and the use of advanced imaging techniques. Timely recognition of nondilated obstructive nephropathy in the setting of retroperitoneal lymphadenopathy is pivotal for guiding appropriate management strategies and optimizing patient outcomes in the intricate clinical setting.

Lipid parameters, adipose tissue distribution and prognosis prediction in chronic kidney Disease patients

BackgroundLipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis.PurposeExplore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3–5.MethodsThis is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3–5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness..Results255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis..ConclusionComprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3–5.

Impact of sarcopenia on clinical outcomes in pediatric chronic liver disease post-liver transplantation: prevalence and implications.

The purpose of this retrospective single-center study was to determine the frequency of sarcopenia and its association with mortality and other morbidities in children with chronic liver disease who had undergone liver transplantation. Sarcopenia, a muscle-wasting syndrome, is common in patients with advanced liver disease and is associated with increased morbidity and mortality. While sarcopenia in adults has been extensively studied, there is little information in this regard about children and adolescents with chronic liver diseases. The study included 108 children and adolescents who had undergone liver transplantation. Sarcopenia was measured using skeletal muscle index at the third lumbar vertebral level and assessed using abdominal computed tomography imaging. The frequency of sarcopenia in the studied population was found to be 45.7%. Patients with sarcopenia were more likely to be male (P<0.0001), older (P<0.0001), and had lower height-for-age z-scores (P=0.012). Genetic/metabolic diseases were the most common underlying cause of sarcopenia in children. Except for a higher rate of transplant rejection in the sarcopenia group (P=0.035), there was no significant difference in mortality rates (P=0.688) or post-LT complications between the two groups. One year after LT, computed tomography-derived body composition parameters revealed no significant differences between children who survived and those who did not. Our findings indicated a high frequency of sarcopenia in children with chronic liver disease, implying that more research is needed to better understand its impact on clinical outcomes in this population.

Oral Health in Children with Chronic Kidney Disease, Hemodialysis, and Renal Transplantation: A Comprehensive Narrative Review of the Oral Manifestations and Dental Implications.

Chronic kidney disease (CKD) in children presents multifaceted challenges, impacting various aspects of health, including oral health. This narrative review provides a comprehensive synthesis of literature focusing on the oral health status of pediatric CKD patients, encompassing oral manifestations, dental considerations, and management challenges associated with hemodialysis and kidney transplantation. A comprehensive search strategy was employed, utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, to identify relevant literature on oral manifestations in children with CKD, including those undergoing hemodialysis or renal transplantation. Search terms were carefully selected to capture studies examining enamel hypoplasia, dental caries, delayed tooth eruption, gingival diseases, periodontal diseases, radiographic alterations, craniofacial development, dry mouth, and changes in the oral mucosa. Our narrative review meticulously selected articles through a systematic process. Ultimately, 12 studies meeting the inclusion criteria were included in the review. Relevant data from each included study were independently extracted and synthesized, focusing on oral manifestations and their implications in pediatric CKD patients. The synthesized findings were organized and presented in a structured manner within the review article, considering their clinical implications and informing recommendations for dental management of children with CKD. This article highlights the importance of a coordinated effort between nephrologists, dentists, and other healthcare professionals in providing holistic care for pediatric CKD patients. A comprehensive understanding of the oral health status of these children, along with proactive dental management strategies, contributes to improved overall health outcomes and a better quality of life. This review aims to serve as a valuable resource for the oral healthcare providers involved in the care of pediatric CKD patients.

Perceptions and Information-Seeking Behavior Regarding COVID-19 Vaccination Among Patients With Chronic Kidney Disease in 2023: A Cross-Sectional Survey.

People living with chronic kidney disease (CKD) face an increased risk of severe outcomes such as hospitalization or death from COVID-19. COVID-19 vaccination is a vital approach to mitigate the risk and severity of infection in patients with CKD. Limited information exists regarding the factors that shape COVID-19 vaccine uptake, including health information-seeking behavior and perceptions, within the CKD population. The objectives were to describe among CKD patients, (1) health information-seeking behavior on COVID-19, (2) their capacity to comprehend and trust COVID-19 information from different sources, and (3) their perceptions concerning COVID-19 infection and vaccination. Cross-sectional web-based survey administered in British Columbia and Ontario from February 17, 2023, to April 17, 2023. Chronic kidney disease G3b-5D patients and kidney transplant recipients (CKD G1T-5T) enrolled in a longitudinal COVID-19 vaccine serology study. The survey consisted of a questionnaire that included demographic and clinical data, perceived susceptibility of contracting COVID-19, the ability to collect, understand, and trust information on COVID-19, as well as perceptions regarding COVID-19 vaccination. Descriptive statistics were used to present the data with values expressed as count (%) and chi square tests were performed with a significance level set at P ≤ .05. A content analysis was performed on one open-ended response regarding respondents' questions surrounding COVID-19 infection and vaccination. Among the 902 patients who received the survey via email, 201 completed the survey, resulting in a response rate of 22%. The median age was 64 years old (IQR 53-74), 48% were male, 51% were university educated, 32% were on kidney replacement therapies, and 57% had received ≥5 COVID-19 vaccine doses. 65% of respondents reported that they had sought out COVID-19-related information in the last 12 months, with 91% and 84% expressing having understood and trusted the information they received, respectively. Those with a higher number of COVID-19 vaccine doses were associated with having sought out (P =.017), comprehended (P < .001), and trusted (P =. 005) COVID-19-related information. Female sex was associated with expressing more concern about contracting COVID-19 (P = .011). Most respondents strongly agreed to statements regarding the benefits of COVID-19 vaccination. Respondents' questions about COVID-19 infection and vaccination centered on 4 major themes: COVID-19 vaccination strategy, vaccine effectiveness, vaccine safety, and the impact of COVID-19 infection and vaccination on kidney health. This survey was administered within the Canadian health care context to patients with CKD who had at least 1 COVID-19 vaccine dose. Race/ethnicity of participants was not captured. In this survey of individuals with CKD, COVID-19 information-seeking behavior was high and almost all respondents understood and trusted the information they received. Perceptions toward the COVID-19 vaccine and booster were mostly favorable.

Unlocking Macrophage Secrets: Histone Deacetylases in Chronic Transplant Rejection.

Solid organ transplantation (SOT) offers life-saving therapy for patients with organ failure, yet chronic rejection remains a significant challenge despite advances in immunosuppression. Macrophages are central to chronic rejection, orchestrating fibrosis, and tissue damage. Since it became clear that histone deacetylases (HDACs), a family of epigenetic regulators, modulate macrophage function and polarization and eventually affect fibrosis progression, the HDACs modulation has gained great importance. This review explores the role of HDACs in chronic rejection, focusing on their impact on macrophage polarization and fibrosis. While some HDACs promote M2 polarization and fibrosis, others inhibit these processes, highlighting the complexity of HDAC function. Targeting HDACs holds promise as a therapeutic strategy for chronic rejection, offering a potential approach for intervention in transplant recipients. However, further research is needed to elucidate the specific roles of individual HDAC isoforms and their inhibition in chronic rejection.

Application potential of senolytics in clinical treatment.

Of the factors studied in individual ageing, the accumulation of senescent cells has been considered as an essential cause of organ degeneration to eventually initiate age-related diseases. Cellular senescence is attributed to the accumulation of damage for an inducement in the activation of cell cycle inhibitory pathways, resulting the cell permanently withdraw from the cell proliferation cycle. Further, senescent cells will activate the inflammatory factor secretion pathway to promote the development of various age-related diseases. Senolytics, a small molecule compound, can delay disease development and extend mammalian lifespan. The evidence from multiple trials shows that the targeted killing of senescent cells has a significant clinical application for the treatment of age-related diseases. In addition, senolytics are also significant for the development of ageing research in solid organ transplantation, which can fully develop the potential of elderly organs and reduce the age gap between demand and supply. We conclude that the main characteristics of cellular senescence, the anti-ageing drug senolytics in the treatment of chronic diseases and organ transplantation, and the latest clinical progress of related researches in order to provide a theoretical basis for the prevention and treatment of ageing and related diseases.

Blockade of BLyS inhibits B-cell responses and antibody production for the prevention of chronic transplant rejection

BACKGROUNDChronic rejection, closely related to the activation of B cells and donor-specific antibody (DSA) production, has unsatisfactory therapeutic outcomes. B lymphocyte stimulator (BLyS) is a major regulatory factor that controls the activation and differentiation of B cells. However, it remains unclear whether BLyS blockade can regulate B and plasma cells in the transplantation setting and affect chronic rejection. Here, we investigated the efficacy of the BLyS inhibitors belimumab and telitacicept in controlling B-cell response and preventing chronic rejection. METHODSThe effects of belimumab and telitacicept on B-cell activation, differentiation and antibody production in vitro were determined. A chronic rejection model in mouse was established by allogeneic cardiac transplantation with CTLA4-Ig treatment. Allograft survival, histology, DSA levels, and B-cell responses were analyzed to evaluate the chronic rejection-preventive effects of belimumab and telitacicept. RESULTSIn vitro experiments confirmed that belimumab and telitacicept inhibited B-cell activation and differentiation and reduced antibody production. In vivo experiments indicated that they significantly prolonged allograft survival, attenuated chronic rejection through significant suppression of myocardial ischemic necrosis and interstitial fibrosis, and reduced DSA-IgG levels, C4d deposition, and inflammatory cell infiltration. Furthermore, the frequencies of B cells, plasma cells and IgG producing cells in the recipients’ spleen, lymph nodes, bone marrow, and blood were decreased after BLyS inhibitors treatment. CONCLUSIONSThis study demonstrated that belimumab and telitacicept inhibit B-cell responses and antibody production and alleviate chronic transplant rejection. Therefore, BLyS inhibitors are expected to be used for the prevention of chronic rejection in clinical practice.

AD Biomarkers in Chronic Kidney Disease and Kidney Transplant

AbstractBackgroundBlood biomarkers of Alzheimer’s disease (AD) are elevated in chronic kidney disease (CKD). Whether this is due to deceased kidney clearance or increased production, and how they change with kidney transplant (KT), is unclear.MethodWe examined serum AD biomarkers from CKD patients pre‐ to post‐KT and compared findings with controls without CKD or AD. Analyses were performed on a Simoa HD‐X, using pTau181 and Neuro 4 Plex E assays.Age was used for covariate adjustment in linear mixed models (LMM) analyzing phosphorylated tau 181 (ptau181), neurofilament light (NfL), amyloid beta (AB42, AB40, 42/40), and glial fibrillary acidic protein (GFAP). Change in p‐tau181 was our primary outcome. LMM included age and levels for control, pre‐KT, or 12‐weeks or 1‐year post‐KT. Based on residual patterns, the natural log (In) of each measure was used for final analyses. Linear contrasts were used to generate estimated differences between group/time points from age‐adjusted models. These included averaged pre‐KT, post‐KT, and control comparisons. Two degree‐of‐freedom tests compared the post‐KT measures to pre‐KT and controls.ResultThe 59 CKD patients were 52±12 years old and 13 controls were 51±8 years old. Pre‐KT, ln(p‐tau181) was higher than controls (p&lt;0.0001) and post‐KT (p&lt;0.0001) (Figure). Post‐KT p‐tau181 greatly decreased but remained higher than controls (p = 0.0004). There was no difference between 12 weeks and 1 year post‐KT levels (p = 0.70). ln(pTau) increased with age (p = 0.06). ln(NfL) followed a similar pattern; pre‐KT levels were higher than controls (p&lt;0.0001) and post‐KT (p&lt;0.0001). Post‐KT levels decreased but remained higher than controls (p&lt;0.0001). 12‐week and 1‐year post‐KT levels did not differ (p = 0.57). Levels increased with age (p&lt;0.0001). Pre‐KT AB42 was higher than controls (p&lt;0.0001) and post‐KT (p&lt;0.0001). Post‐KT, levels decreased but remained higher than controls (p = 0.005) and continued declining 1‐year post‐transplant (p = 0.01). In(AB40) and In(GFAP) showed the same pattern. The AB42/AB40 was not different pre‐KT vs controls (p = 0.58) and did not change following KT. Cognitive function improved post‐KT. Patients with residual kidney function had lower baseline levels of AD blood biomarkers.ConclusionIn severe CKD, blood biomarkers of AD are dependent on kidney function and caution should be used in interpreting them.