Kidney Transplantation Research Articles

Association of InVivo Kidney Stiffness Measured by Multifrequency MR Elastography and Long-Term Renal Function in Transplant Recipients and Living Donors.

Kidney transplant (KTx) function assessment is important in treatment planning, while conventional MRI markers lack sensitivity for KTx function. Mechanical kidney properties may serve as MRI markers for renal allograft function. To determine if multifrequency MR elastography (MRE) is associated with KTx function. Prospective, longitudinal. Twelve kidney donors (51 ± 9 years, 8 females) and 12 allograft recipients (48 ± 17 years, 2 females). 1.5 T, MRE, and diffusion-weighted MRI based on spin-echo echo-planar imaging and T2-weighted MRI volumetry. Kidney donors were imaged pre- and post-KTx, while allograft recipients were imaged post-KTx. Renal function was assessed using creatinine levels (at 1 week, 1 month, and 3 years post-KTx in recipients) and glomerular filtration rate (GFR; donors pre-KTx) based on Tc-99m-MAG3 scintigraphy. Kidney volumes were measured by MRI segmentations, and ADC, shear-wave speed (SWS), and loss-angle maps were reconstructed. The correlations between MR parameters, GFR, and creatinine level (minimum value over study period) were investigated. Wilcoxon tests and Pearson correlation coefficients (R). A p < 0.05 was considered statistically significant. No significant lateral differences in renal volume (153 ± 34 cm3, p = 0.34) or SWS (2.5 ± 0.4 m/s, p = 0.20) were found pre-KTx. Volume and SWS increased significantly post-KTx in reference kidneys (volume: +13%, SWS: +11%) and in transplants in recipients (volume: +20%, SWS: +32%). SWS, but not volume (p = 0.75), correlated positively with GFR in donors pre-KTx (R = 0.67) while both SWS (R = ‑0.62) and volume (R = -0.77) negatively correlated with creatinine levels post-KTx. ADC was sensitive to KTx-associated changes in renal function in donors (3% ± 5%) but not recipients (p = 0.88). MRE provides valuable information on renal function and could serve as a baseline for longitudinal monitoring of kidney transplants. Parenchymal stiffening post-KTx had significantly larger effect sizes in denervated allografts than in reference donor kidneys with intact autoregulation of renal blood flow. 2. Stage 2.

Clinical and prognostic characteristics of bilateral Wilms tumor: a multi-center institutional retrospective cohort study experience from China.

This multi-center analysis of data from China reviews the management and long-term outcomes of patients with bilateral Wilms tumors (BWT), and explores prognostic risk factors. We retrospectively analyzed a cohort of pediatric patients with synchronous BWT treated at 18 pediatric oncology centers in China between 2006 and 2023. The overallsurvival (OS) and event-freesurvival (EFS) rates were calculated using Kaplan-Meier methodology. Prognostic risk factors were determined using univariable and multivariable analysis. A total of 167 patients with BWT and a median age at diagnosis of 13months (range 0-78months) were included in the study. Neoadjuvant chemotherapy was administered to 149 index cases; tumor biopsy was performed before initiating chemotherapy in 70 patients. One hundred and three children underwent bilateral nephron-sparingsurgery (NSS) and two hundred fifty-two of the three hundred one kidneys underwent NSS. The four-year OS and EFS rates in the study cohort were 86.5% and 77.8%. After a median follow-up of 50months, four patients developed renal failure requiring dialysis and a single patient received a kidney transplant 26months postoperatively. Regarding prognostic factors, the results of the multifactor analysis indicate that distant metastasis and positive surgical margins have negative impacts on OS and distant metastasis had a negative effect on EFS. Distant metastasis and positive surgical margins affect the long-term prognosis of BWT. Video Abstract (MP4 19393 KB).

Symptom reduction in kidney transplant patients from 20-minute mindful breathing: a randomized controlled trial

BackgroundMany kidney transplant recipients continue to be affected by multiple symptoms even after their transplant. Mindfulness may be helpful to alleviate some of the symptoms.ObjectivesOur current study aimed to determine the efficacy of a single session of 20-minute mindful breathing in alleviating multiple symptoms in kidney transplant patients.MethodsAdult kidney transplant patients with at least one symptom scoring ≥ 4/10 based on the Edmonton Symptom Assessment Scale (ESAS) were recruited from November 2020 to May 2021. Participants were randomly assigned to either 20-minute mindful breathing or control.ResultsSixty participants were recruited and randomly assigned to intervention (N = 30) or control (N = 30). There was statistically significant greater reduction of the total ESAS score in the intervention group compared with the control group (mean difference = -4.833, confidence interval = -7.837, -1.830, t = -3.251, p = 0002).ConclusionOur results provided evidence that 20-minute mindful breathing could reduce multiple symptoms rapidly in kidney transplant recipients.

Predictive factors for the success of subureteric injection in renal transplant patients with vesicoureteral reflux

BackgroundPredicting the success of endoscopic treatment of VUR in transplant patients may not only protect both the physician and the patient from unnecessary investigations and treatment but may also prolong the life of the graft by preventing possible loss of time.MethodsThis retrospective study included 116 patients with vesicoureteral reflux following kidney transplantation between 2014–2022. Demographic data, preoperative and intraoperative clinical aspects, and postoperative 6th-month success rates were evaluated.ResultsThe success rate of the injection treatment in the 6th month was 41.4%. As the patient age decreased, the success rate of the injection decreased (p = 0.025). While no significant relationship was observed between the preoperative reflux grade, injected volume of the bulking agent, and success (p = 0.109 and 0.222, respectively), a significant decrease in success was observed with an increase in UDR (p < 0.001) in group comparison. Regression analyses demonstrated that pre-injection visual assessment and post-injection orifice mound view influenced the success rate (p < 0.001 and p < 0.001, respectively).ConclusionsIntraoperative visual assessment of the orifice is a reliable indicator for predicting the success of subureteric injection. It not only provides patients with trustworthy postoperative information but also saves clinicians time by anticipating the next surgical stage, ultimately contributing to the prolongation of graft life.

A Meta-analysis of Graft Survival, Patient Survival, and Delayed Graft Function in First-Time and Repeat Kidney Transplants.

Previous evidence showed that while first-time kidney transplants typically yield better outcomes, repeat and subsequent transplants were associated with increased risks of graft failure and adverse patient outcomes, yet conflicting findings exist. The aim of this meta-analysis is to compare graft survival and delayed graft function (DGF) outcomes in first-time kidney transplants (KT), repeat kidney transplants (regrafts), and subsequent KT. Relevant studies were identified through comprehensive searches in PubMed, Web of Science, Cochrane Library, MEDLINE (Ovid) and Scopus until 8 October 2024. Primary outcomes include graft survival, and DGF compared to repeat, and subsequent kidney transplants. The meta-analysis included a total of 16 studies. Analysis on long-term graft survival revealed that patients who underwent a first KT had significantly better graft survival compared to those who received a second transplant (86.7% vs. 77.6%; OR 1.40, 95% CI 1.14-1.71, p = 0.001). At 5 years post-transplant, first KT recipients continued to demonstrate superior graft survival (OR 1.41, 95% CI 1.13-1.77, p = 0.003), although this difference diminished by 10 years, with no significant disparity observed (OR 1.26, 95% CI 0.88-1.81, p = 0.20). Graft survival at 5 years was also significantly higher in second KT recipients compared to those undergoing a third transplant (OR 2.66, 95% CI 1.86-3.80, p < 0.00001). Patient survival outcomes were largely comparable between first and second KT groups, with no statistically significant differences in overall survival (OR 1.25, 95% CI 0.87-1.81, p = 0.23). At specific time points, the 5-year survival rate showed a borderline non-significant trend favoring first KT recipients (OR 1.63, 95% CI 0.97-2.73, p = 0.06), while the 10-year survival rate showed no difference (OR 0.94, 95% CI 0.67-1.32, p = 0.71). Survival rates between second and subsequent retransplants (e.g., third or fourth KT) showed no significant variation, including at 5 years (p = 0.37 and p = 0.90, respectively). DGF rates did not differ significantly between first and second KT recipients (p = 0.11). These findings underscore the superior graft survival associated with first and second kidney transplants compared to subsequent retransplants, particularly in the early post-transplant period, while highlighting the lack of significant differences in overall patient survival across groups; however, variability in outcomes due to study heterogeneity and patient-specific factors warrants cautious interpretation and tailored clinical approaches.

Insights Into Peritoneal Dialysis Outcomes: An Approach Using Competing Risks Analysis.

Peritoneal dialysis (PD) outcomes analysis presents challenges due to heterogeneous outcomes. Our study aims to evaluate mortality, transition to hemodialysis (HD), and kidney transplant (KT) rates and investigate potential baseline patient characteristics influencing these outcomes. We conducted an observational retrospective registry-based single-center cohort study involving 722 incident adult PD patients admitted between 1985 and 2022. Follow-up duration extended from PD initiation to the first occurrence of death (n = 143), transfer to HD (n = 313), or KT (n = 202). Utilizing competitive risks analysis, we calculated cumulative incidence (CI) functions and applied a Fine and Gray model to baseline variables to understand their impact. The majority of patients were female (n = 401; 55.54%), with an average age of 49.64 ± 15.80 years. Transfer to HD had the highest probability (CI of 0.38 at 60 months), followed by KT (CI of 0.27 at 60 months) and death (CI of 0.19 at 60 months). Diabetes correlated solely with death (HR 1.71 (0.18); p = 0.004). PD-first was associated with a lower risk of HD transfer (HR 0.76 (0.13); p = 0.036) and positively influenced KT (HR 1.73 (0.16); p < 0.01). Vascular access as the reason for PD selection was associated with death (HR 2.16 (0.19); p < 0.001). The main risk for PD patients is transitioning to HD, unaffected by baseline patient characteristics. PD-first option positively influences KT access, and mortality rates remain low and unaffected by this option, ensuring the safety of the technique. Vascular access-related PD initiations correlate with increased mortality, potentially due to comorbidities.

Senescence-induced p21high macrophages contributed to CD8+ T cells-related immune hyporesponsiveness in kidney transplantation via Zfp36/IL-27 axis

Recipients’ age has emerged as a key factor that impacts on acute renal allograft rejection and graft survival. Age-related functional and structural changes in the immune system have been observed, yet the precise influence of aged immunity on kidney transplant remains unclear. In an initial retrospective analysis of clinical data gathered from two major centers in China and Germany, we found a correlation between aging and mitigated rejection outcomes in kidney recipients. To study the mechanism, we performed kidney transplantation on mice and observed attenuated allograft rejection in senescent recipients. Single-cell transcriptome analysis of allograft kidneys indicated a protective role of p21high macrophages in aged mice. Supernatant collected from p21high macrophage primary culture inhibited the cytotoxic function and proliferation of CD8+ T cells. Zfp36 is highly expressed in senescent p21high macrophages. To determine its role in renal allograft rejection, we studied mice with Zfp36 conditionally deleted in macrophages (Zfp36-cKO). These mice developed exacerbated allograft rejection with enhanced IL-27 production and CD8+ T cell hyperactivation. Inhibition of IL-27 with neutralizing antibody or deletion of IL-27 receptor on CD8+ T cells reversed acute renal allograft rejection in Zfp36-cKO mice. Moreover, in vitro silencing Zfp36 with siRNA led to impaired degradation of IL-27 p28 mRNA and a subsequent increase of IL-27 in p21high macrophages. In conclusion, senescent macrophages protect renal allograft rejection by suppressing CD8+ T cells via a Zfp36/IL-27-dependent mechanism. These findings may provide innovative therapeutic strategies for addressing kidney allograft rejection.

SETDB1 recruits CBX3 to regulate the SIRT4/PTEN axis, inhibiting autophagy and promoting ischemia-reperfusion-induced kidney injury.

Ischemia-reperfusion (I/R) injury is a significant factor in the development of acute kidney injury (AKI), particularly in clinical scenarios, such as kidney transplantation, cardiac surgery, and severe hypotension. Autophagy, a critical process that eliminates damaged cellular components, has been shown to mitigate I/R injury by reducing oxidative stress and enhancing cell survival. However, when autophagy is disrupted, it can exacerbate kidney damage. Elucidating the role of autophagy in I/R injury is essential for uncovering the molecular mechanisms driving AKI and could facilitate the development of autophagy-based therapies. Protein expression levels were analyzed through western blot, immunohistochemistry (IHC), and immunofluorescence (IF) staining techniques. Interactions between SIRT4, SETDB1, and CBX3 were explored using chromatin immunoprecipitation (ChIP), sequential ChIP (ChIP-reChIP), and co-immunoprecipitation (Co-IP) assays. The association between SIRT4 and PTEN was also examined via Co-IP. Transmission electron microscopy (TEM) was employed to visualize autophagosomes. Furthermore, an invivo rat model of I/R injury was developed for validation of the findings. Sirtuin 4 (SIRT4) expression was reduced, and autophagy was impaired during I/R injury. Moreover, SIRT4 interacted with phosphatase and tensin homolog (PTEN) to regulate its expression. Furthermore, SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) mediated histone H3 lysine 9 trimethylation (H3K9me3) modifications and recruited chromobox protein homolog 3 (CBX3) to the SIRT4 promoter, leading to the repression of SIRT4 expression in kidney proximal tubular cells. Importantly, SETDB1 knockdown upregulated SIRT4, decreased PTEN expression, promoted autophagy, and protected rats against I/R injury invivo. SETDB1 recruits CBX3 to regulate the SIRT4/PTEN axis, inhibiting autophagy and promoting I/R-induced kidney injury. These results suggest that targeting the SETDB1-SIRT4 axis could offer a novel therapeutic strategy to mitigate renal damage in I/R-induced AKI.

Trichosporon species bloodstream infections in a tertiary care hospital in the western region of Saudi Arabia: a 7-year retrospective chart review from 2016 to 2022.

Despite advances in medical mycology, invasive Trichosporon spp infections continue to be associated with high mortality rates. Limited data exist on the risk factors and outcomes of Trichosporon fungemia, particularly in our region. Therefore, this study aims to describe the risk factors, patient characteristics, antifungal susceptibility, and outcome of Trichosporon bloodstream infections at a tertiary care hospital in Saudi Arabia. This was a single-center retrospective chart review that included adult patients≥16 years with positive blood cultures for Trichosporon spp from January-2016 to December-2022. Descriptive statistics are presented using the mean for continuous variables and the number (percentage) for categorical variables. Ten patients with Trichosporon spp isolated from blood cultures were eligible for inclusion in this study. The mean age was 58.1 years (range 17-83), with 70% male patients. Additionally, 40% had diabetes mellitus, and 40% had underlying malignancy. Trichosporon asahii was the predominant species in 90% of isolates. All patients had recent broad-spectrum antibiotic use, 80% were exposed to corticosteroids, and all had central venous catheters (CVC). One kidney transplant had an early recurrence of Trichosporon spp fungemia. Four patients were cured of the infection, two were treated with voriconazole monotherapy, and two were treated with a combination of liposomal amphotericin B plus Voriconazole. 30-day all-cause mortality was 60%, with three deaths occurring before identification of the isolates. In conclusion, our study reported a predominance of Trichosporon asahii and a mortality rate of 60% in patients with Trichosporon fungemia. Challenges include delayed diagnosis, high mortality, and antifungal resistance, underscoring the need for further research to enhance treatment strategies and patient outcomes.

The role of epithelial cell injury in kidney transplant outcomes - a cross-sectional study.

We defined injury-induced transcriptome states in 4502 kidney transplant biopsies taken 1 day to 45 years post-transplant using genome-wide microarrays. Injury was measured by injury-induced gene sets and classifiers previously developed in transplants. In principal component analysis, PC1 correlated with both acute and chronic kidney injury and related inflammation, and PC2 with time post-transplant. PC3 was a novel dimension that correlated with epithelial remodeling pathways. Both PC1 and PC3 correlated with reduced survival, PC1 effects strongly increasing with time whereas PC3 effects being time-independent. In this model, we studied the expression of genes annotated in native kidneys in epithelial cells with failed repair: 12 "New" gene sets previously defined in single nucleus RNA sequencing of native kidneys with AKI (Genome Med.14(1):103). The "New4" gene sets reflecting epithelial-mesenchymal transition (EMT) correlated with injury PC1, lower eGFR, higher donor age, and future failure as strongly as any gene sets previously derived in transplants, independent of nephron segment of origin and graft rejection. These results suggest that there are two distinct dimensions in kidney transplant response to injury: PC1, AKI-induced changes, failed repair, and inflammation; and PC3, a response involving epithelial remodeling without inflammation. Increasing kidney age amplifies PC1 and particularly PC3.

Proenkephalin (PENK): a functional biomarker in chronic kidney diseases - hope or just a new bystander?

Proenkephalin has recently emerged as a promising biomarker of kidney function which improves the early detection of acute kidney injury (AKI) compared to creatinine-based methods. Plasma Proenkephalin concentrations have shown a correlation with glomerular filtration rate (GFR) as assessed by gold standard methods. Previous studies have demonstrated its association with adverse clinical outcomes in various settings, including sepsis, heart failure, kidney transplantation, and chronic kidney disease (CKD). Additionally, in healthy individuals, elevated Proenkephalin concentrations have been linked to a decline in GFR and an increased risk of developing CKD. While evidence suggests that Proenkephalin may be a more accurate tool for assessing glomerular filtration and detecting AKI, recent research has primarily focused on subjects with preserved kidney function, leaving its value in CKD patients less explored. Given the heterogeneity and high risk of rapid renal deterioration in patients with chronically impaired kidney function, a reliable biomarker should retain its ability to reflect kidney function in both CKD and AKI settings. This review summarizes the current evidence on Proenkephalin in patients with chronic kidney diseases.

Feasibility, Acceptability, and Effectiveness of a Smartphone App to Increase Pretransplant Vaccine Rates: Usability Study.

Vaccine-preventable infections result in significant morbidity, mortality, and costs in pediatric transplant recipients. Despite intensive medical care in the pretransplant period, less than 20% of children are up to date for age-appropriate vaccines at the time of transplant. Mobile health apps have the potential to improve pretransplant vaccine rates. This paper aimed to perform phase 2 beta testing of the smartphone app, Immunize PediatricTransplant, to determine (1) if it was effective in achieving up-to-date vaccine status by the time of transplant in a cohort of children awaiting transplants and (2) if the app was feasible and acceptable to parent and transplant provider users. We recruited 25 dyads of parents and providers of a child awaiting a liver, kidney, or heart transplant at Children's Hospital Colorado, Ann and Robert H. Lurie Children's Hospital, and the Children's Hospital of Philadelphia. Parents and providers filled out an entry questionnaire before app use to gather baseline information. A research team member entered the child's vaccine records into the app. The parent and provider downloaded and used the app until the transplant to view vaccine records, read vaccine education, communicate with team members, and receive overdue vaccine reminders. After the transplant (or on April 1, 2024, the conclusion of the study), the parent and provider filled out an exit questionnaire to explore feasibility and acceptability of the app. The child's vaccine records were reviewed to determine if the child was up to date on vaccines at the time of transplant. Twenty-five parent and provider dyads were enrolled; 56% (14/25) had a child awaiting a liver transplant, 28% (7/25) had a child awaiting a kidney transplant, and 16% (4/25) had a child awaiting a heart transplant. At the conclusion of the study, 96% (24/25) of the children were up to date on vaccines. Of the 36 parents and providers who filled out an exit questionnaire, 97% (n=35) agreed or strongly agreed that they felt knowledgeable about pretransplant vaccine use and 86% (n=31) agreed or strongly agreed that communication around vaccines was good after using the app. Further, 91% (20/22) of parents and 79% (11/14) of providers recommended the app to future parents and providers of transplant candidates. Parents and providers suggested that in the future the app should connect directly to the electronic medical record or state vaccine registries to obtain vaccine data. The overwhelming majority of children whose parents and providers used the Immunize PediatricTransplant app were up to date on vaccines at the time of transplant. The majority of app users felt the app was feasible and acceptable. In future iterations of the app and subsequent clinical trials, we will explore whether application programming interfaces might be used to extract vaccine data from the electronic medical record. If implemented broadly, this app has the potential to improve pretransplant vaccine rates, resulting in fewer posttransplant infections and improved posttransplant outcomes.

Regional Nerve Blocks Used in Renal Transplantation and Donor Nephrectomy: A Narrative Review.

Perioperative opioid-related adverse drug events have been associated with increased length of hospitalization, higher costs, and increased patient mortality. Consequently, alternative means of analgesia, which may mitigate these risks, are important to explore. Peripheral nerve blocks (PNBs), including transversus abdominis block (TAPB), quadratus lumborum block (QLB), and erector spinae plane block (ESPB), have been used to reduce opioid requirements after renal transplant and donor nephrectomy. TAPB is most frequently studied; however, few studies compare approaches. PubMed was queried on July 13th 2022 and again on April 14th 2024 for studies on the use of regional analgesia for kidney transplantation and donor nephrectomy. This review surveys 29 publications that empirically investigated use of a PNB alone or as part of enhanced recovery after surgery (ERAS) protocols for patients undergoing renal transplant or donor nephrectomy, summarizing the evidence for each PNB. We found that TAPB was the most studied technique, and that few studies compared analgesic techniques. Overall, this body of research supports the use of TAPB to reduce pain and opioid requirements in the postoperative period after renal transplantation. Fewer studies support the use of TAPB following donor nephrectomy or the use of other PNBs for either procedure. Future studies may further investigate the use of TAPB after donor nephrectomy, compare various PNBs to TAPB, and investigate long-term outcomes.

Replacing Mycophenolate Mofetil by Everolimus in Kidney Transplant Recipients to Increase Vaccine Immunogenicity: Results of a Randomized Controlled Trial.

Vaccine immunogenicity is reduced in kidney transplant recipients (KTRs), especially in those using mycophenolate mofetil (MMF). Whether replacement of MMF by everolimus improves vaccine immunogenicity is unknown. KTRs were randomized 1:1 to continue MMF or switch to everolimus. Participants received one coronavirus disease 2019 (COVID-19) booster vaccination and two herpes zoster (HZ) vaccinations at 6, 10 and 14 weeks postrandomization. Primary outcome was the neutralizing antibody response 28 days after COVID-19 vaccination. Secondary outcomes included antibody and T-cell responses 28 days after COVID-19 and HZ vaccination, and safety. In 110 KTRs, COVID-19 vaccination resulted in comparable Omicron XBB.1.5 neutralizing antibody titers in the everolimus versus MMF group (308 [74.4-1314] vs 327 [115-897]; P = .83), whereas severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike-specific T-cell responses were slightly lower with everolimus (118 [32.1-243] vs 228 [113-381] spot-forming cells [SFCs]/106 peripheral blood mononuclear cells [PBMCs]; P = .02). HZ vaccination led to higher varicella zoster virus (VZV) glycoprotein E (gE)-specific immunoglobulin G titers with everolimus (2192 [888-4523] vs 1101 [440-2078] 50% endpoint titer; P = .004), while VZV gE-specific T-cell responses were similar (85.0 [27.5-155] vs 115 [50.0-258] SFCs/106 PBMCs; P = .24). Besides known side effects, everolimus led to more bacterial infections (27.3% vs 11.1%; P = .03). Six weeks' replacement of MMF by everolimus in KTRs does not improve COVID-19 booster vaccine immunogenicity, whereas 10 weeks' replacement enhances humoral HZ vaccine immunogenicity. While replacing MMF by everolimus may improve vaccine responses, its timing and potential risks require careful consideration.

Risk of aspiration during general anaesthesia in patients on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Implications for patients on the kidney transplant waiting list

Risk of aspiration during general anaesthesia in patients on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Implications for patients on the kidney transplant waiting list

Kidney failure care for migrants: a European survey.

The management of migrants with kidney failure and no medical insurance raises complex medical, social, financial, and ethical issues. The survey aimed to investigate (i) current practices in managing these patients, and (ii) the perspective of European nephrologists on ethical dilemmas and optimal care. The survey was piloted by the ISN Western Europe Regional Board, with members of the Young Nephrologists' Platform (YNP) of the European Renal Association (ERA), and disseminated to European nephrologists in the ISN and YNP networks. Responses were collected anonymously via SurveyMonkey. A total of 378 responses were collected from 29 European countries. Most (57%) managed fewer than 3 migrant patients with kidney failure per week, while 10% managed more than 11. Most respondents indicated that access to dialysis was unrestricted (59%), although only 25% said migrant patients were systematically eligible for kidney transplantation. Many nephrologists (38%) were unaware of the directives of governmental bodies or hospital protocols regarding migrant patients. The most common obstacles to patient management included language non concordance (64%), uncertainty about the future (56%), and lack of knowledge of medical history (49%). Two-thirds felt managing migrant patients was a moral duty, though 52% reported stress within the clinical caregiving team. Despite strong commitment from European nephrologists, a fragmented legal framework, remaining barriers, and uneven case distribution hinder optimal care for migrant patients with kidney disease.

Romosozumab for managing severe osteoporosis in patients undergoing kidney transplantation: A retrospective case series

Abstract Recipients of kidney grafts often develop severe osteoporosis. However, no consensus has emerged on the most appropriate medications for managing osteoporosis in these recipients. In this study, we investigated the efficacy of romosozumab as an additional treatment option for managing severe osteoporosis in kidney transplant recipients. Our retrospective observational study included 12 such recipients who were treated with romosozumab for 12 months—8 newly initiated on romosozumab and 4 treated with romosozumab after initial treatment with other agents. Endpoints were side effects, new fractures, blood tests, and changes in bone mineral density. Pearson correlation coefficients were used to assess associations of the percent change in bone mineral density after 1 year of treatment with age, dialysis duration, and time (years) since transplantation. During treatment with romosozumab, the patients did not develop severe hypocalcemia or experience marked deterioration of kidney function at 1 year post-treatment. Metabolic markers of bone formation and resorption were similar to those in the general population with osteoporosis. The average changes in bone mineral density at the spine and total hip were 15.18% and 8.83%, respectively, indicating a favorable increase. Further, the change in spine bone mineral density was inversely correlated with age and time since transplantation. Treatment of osteoporosis with romosozumab was observed to be safe for kidney transplant recipients and had a favorable therapeutic effect on both spine and hip bone mineral density.

Targeting the complement lectin pathway with a highly specific MASP-2 inhibitor protects against renal ischemia–reperfusion injury

Renal ischemia-reperfusion injury (IRI) is a common complication in several clinical scenarios including kidney transplantation. Mannan-binding lectin-associated serine proteinase (MASP)-2 is essential for activation of the complement lectin pathway, which has been implicated in the pathogenesis of renal IRI and therefore represents a potential therapeutic target. We developed a new, affinity-enhanced MASP-2 inhibitor, EVO24, by directed evolution of the D2 domain of human tissue factor pathway inhibitor. EVO24 was fused with a human IgG1-Fc to create the homodimer EVO24L, which potently and selectively inhibited the lectin pathway in human and mouse serum in vitro. EVO24L was tested in a mouse model of unilateral warm renal IRI. EVO24L administered before and after ischemia significantly protected against IRI, with improved renal function as well as reduced tubular injury and inflammatory cell infiltration at 24 h compared to vehicle-treated mice. Immunofluorescence analyses showed reduced deposition of complement components (C3d, C4d, and C9) and reduced expression of VCAM-1, indicating a decrease in complement activation and endothelial cell activation. Additionally, EVO24L treatment lowered plasma levels of complement C5a, hyaluronan (a marker of endothelial glycocalyx shedding), and the proinflammatory cytokines IL-6 and TNF-α. Our findings indicate that EVO24L inhibits acute inflammatory responses in renal IRI by blocking the lectin pathway, confirming the important role of this pathway in acute ischemic kidney injury and warranting further investigation of EVO24L in clinical settings.

Medical Therapy versus Bariatric Surgery in Kidney Transplant Candidates.

Medical Therapy versus Bariatric Surgery in Kidney Transplant Candidates.

Infectious Diarrhea in Kidney Transplant Recipients

Infectious Diarrhea in Kidney Transplant Recipients