Search Results (1,058)

Regenerative medicine shows significant potential in treating kidney diseases through the application of various types of stem and progenitor cells, including mesenchymal stem cells (MSCs), renal stem/progenitor cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Stem cells possess the unique ability to repair injured organs and improve impaired functions, making them a key element in the research of therapies for kidney tissue repair and organ regeneration. In kidney transplantation, reperfusion injury can cause tissue destruction, leading to an initially low glomerular filtration rate and long-term impact on function by creating irreversible interstitial fibrosis. MSCs have proven useful in repairing early tissue injury in animal models of kidney, lung, heart, and intestine transplantation. The use of stem cell therapies in solid organ transplantation raises the question of whether autologous or allogeneic cells should be preferred. Adipose-derived stem cells (ASCs), characterized by the lack of HLA Class II molecules and low expression of HLA Class I and co-stimulatory signals, are considered immune-privileged. However, the actual risk of graft rejection associated with allogeneic ASCs remains unclear. It has been demonstrated that donor-derived ASCs can promote the development of Treg cells in vitro, and some degree of tolerance induction has been observed in vivo. Nevertheless, a study comparing the efficacy of autologous and allogeneic ASCs in a rat model with a total MHC mismatch for kidney transplantation showed that donor-derived administration of ASCs did not improve the grafts’ survival and was associated with increased mortality through an immunologically mediated mechanism. Given the lack of data, autologous ASCs appear to be a safer option in this research context. The aim of this review was to examine the differences between autologous and allogeneic ASCs in the context of their application in kidney transplantation therapies, considering potential immune reactions and therapeutic efficacy. Some have argued that ASCs harvested from end-stage renal disease (ESRD) patients may have lower regenerative potential due to the toxic effects of uremia, potentially limiting their use in transplantation settings. However, evidence suggests that the beneficial properties of ASCs are not affected by uremia or dialysis. Indeed, some investigators have demonstrated that ASCs harvested from chronic kidney disease (CKD) patients exhibit normal characteristics and function, maintaining consistent proliferative capacity and genetic stability over time, even after prolonged exposure to uremic serum Furthermore, no differences were observed in the response of ASCs to immune activation or their inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells between patients with normal or impaired renal function. This review presents the current achievements in stem cell research aimed at treating kidney diseases, highlighting significant progress and ongoing efforts in the development of stem cell-based therapies. Despite the encouraging results, further research is needed to overcome the current limitations and fully realize the potential of these innovative treatments. Advances in this field are crucial for developing effective therapies that can address the complex challenges associated with kidney damage and failure. Full article

Introduction: Early post-transplant hyperglycemia (EPTH) is an independent risk factor for hospital readmissions, acute rejection, infections and developing post-transplant diabetes mellitus (PTDM). Close glycemic control is prudent in the early post-transplant period. The management of EPTH was evaluated among a cohort of kidney transplant recipients, who either received routine care (RC) or dedicated endocrine care (DEC). Methods: A retrospective analysis was conducted on kidney transplant recipients from 2019 to 2023. The impact of DEC on post-transplant glycemic control was investigated. Hospitalized patients receiving post-transplant insulin therapy were included. DEC involved at least twice-daily blood glucose (BG) assessment by an endocrinologist, while the RC received usual care. A mixed-model analysis was employed to assess differences in BG trajectories between DEC and RC over an eight-day period. Additionally, various glycemic control metrics were compared, including glucose variability, time-in-range for target BG, rates of hypoglycemia and response to hyperglycemia. Results: The cohort comprised 113 patients. In the DEC group, 91% had pre-transplant DM compared to 15% in the RC group (p < 0.001). Patients under DEC had higher baseline BG and glycated hemoglobin compared to those under RC (p < 0.001, for both). The DEC group displayed a lower trajectory of BG over time compared to the RC group (p = 0.002). Patients under DEC were more likely to receive insulin if BG measured above 200 mg/dL (66% vs. 46%) and displayed less below-range BG (<110 mg/dL) compared to those under RC (12.9% vs. 23.6%, p < 0.001). Conclusions: Management of EPTH by DEC improves glycemic outcomes in renal transplant recipients. Full article

Background/Objectives: Phosphate is a macro-element involved in all cellular energetic processes. As about 90% of the phosphate filtered by the glomerulus is excreted by kidneys, the impairment of renal function and the consequent over-secretion of parathyroid hormone and fibroblast growth factor 23 results in the increase in the serum phosphate levels. The association between phosphate and hemoglobin is controversial, as both direct and indirect relationships have been reported. The present study aims to investigate the relationship between phosphate and hemoglobin in a large prospective, longitudinal cohort including dialysis patients from the Sicilian Registry of Nephrology, Dialysis, and Transplantation. Methods: In this prospective cohort study, we included 6263 hemodialysis patients to achieve a total of 120,462 repeated measurements of serum phosphate and hemoglobin over time. The longitudinal association between phosphate and hemoglobin was analyzed by univariate and multivariate Linear Mixed Models. Results: The mean age was 66 ± 16 years and the median dialysis vintage was 5 months [IQR: 2–16]. Mean and median values of hemoglobin and phosphate were 10.7 g/dL (SD 1.3 g/dL) and 4.6 mg/dL [IQR 3.9–5.5 mg/dL], respectively. The multivariate model, adjusted for potential confounders, confirmed the positive association between serum phosphate and hemoglobin [adjβ = 0.13, 95%CI 0.03–0.23, p = 0.01)]. These results were confirmed in analyses stratified for the use of phosphate binders. Conclusions: In our large cohort of dialysis patients, we found a linear, direct relationship between phosphate and hemoglobin levels. As a reduction in phosphate is associated with a parallel reduction in hemoglobin levels, hypophosphatemia can accentuate anemia in dialysis patients. Our results generate the hypothesis that monitoring serum phosphate in clinical practice might provide a better management of anemia. Full article

Background: A significant loss in bone density and strength occurs during the post-renal-transplant period with higher susceptibility to fracture. The study aims to compare the performance of the Radiofrequency Echographic Multi Spectrometry (REMS) in the bone mineral density assessment with the conventional dual-energy X-ray absorptiometry (DXA) in a cohort of kidney transplant recipients (KTR). Methods: A cohort of 40 patients underwent both DXA and REMS examinations on the lumbar spine and/or proximal femur. The paired t-test was used to compare DXA and REMS measurements; the chi-square test was used to compare the prevalence of osteoporosis/osteopenia. The agreement between the two techniques was assessed through Spearman’s correlation. Results: As expected, most KTR patients were osteopenic or osteoporotic with both REMS and DXA (86.5% and 81% for the femur; 88% and 65% for the lumbar spine p < 0.05). A modest correlation (r = 0.4, p < 0.01) was observed at the lumbar spine between the T-score measured by REMS and DXA. A strong correlation was defined between REMS and DXA in the femoral region (r = 0.7, p < 0.0001). Conclusions: The study demonstrates the exchangeability of the two techniques on the proximal femur in KTR and a higher diagnostic accuracy of REMS at the spine level than DXA. Full article

Objective: In this study, we aimed to determine post-traumatic growth and depression levels in renal transplant recipients and the relationship between these two variables. Design and Methods: The study was conducted with a descriptive, cross-sectional, and correlational design. The data for the study were collected at the organ transplant unit of a research and training hospital located in the west of Turkey. The sample of the study included 122 kidney transplant recipients (n = 122). A Sociodemographic Information Form, the Post-Traumatic Growth (PTG) Inventory, and the Beck Depression Inventory (BDI) were employed to collect data. In the analyses of the data, descriptive statistics, ANOVA, an independent-samples t-test, post hoc tests, and Pearson correlation tests were used. Results: As the ages of the renal transplant recipients increased, their depression scores decreased, while their PTG scores increased. Higher depression levels were identified in the female participants compared to the male participants and in those with a low income compared to other income groups. The lowest PTG levels were found in the recipients who received their kidney transplants from third-degree relatives. Age, gender, economic status, and time of transplant were predictors of depression. The identity of the donor was the most significant predictor of PTG (62% explanation rate). A strong and inverse correlation was found between depression and PTG (p < 0.05). Conclusions: Post-traumatic growth was found to decrease depression. However, while poor economic status led to depression, high economic status did not lead to a significant change in PTG. As education levels increased, PTG decreased, but education status did not have any significant effect on depression. On the other hand, there was a negative correlation between PTG and depression. The results obtained in this study are valuable and important in terms of understanding depression better and determining PTG as a significant factor that could alleviate it. Full article

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; the prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, the management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlights the clinical importance, underlying mechanisms and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs. Full article

Hepatitis C virus (HCV) has emerged as a major global health concern and, if left untreated, can lead to significant liver damage, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma (HCC). Approximately 40% of patients with HCV infection experience extrahepatic manifestations, including renal involvement. HCV-related renal disease is of significant importance among patients with chronic kidney disease (CKD), leading to higher morbidity and mortality. The renal damage due to HCV infection primarily results from cryoglobulinemia and glomerulonephritis, with conditions such as membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) being most prevalent. Despite advancements in treatment, including the use of directly acting antiviral agents (DAAs), renal complications remain a significant burden in untreated patients. HCV-positive patients on hemodialysis (HD) or those who have undergone kidney transplantation face increased mortality rates compared to their HCV-negative counterparts. Managing HCV infection before kidney transplantation is crucial to mitigate the risk of HCV-related renal complications. Conversely, kidney transplantation from HCV-infected donors is well established, as post-transplant treatment for HCV is safe and effective, potentially reducing mortality and morbidity for patients on transplant waiting lists. This review aims to provide a comprehensive analysis of the renal manifestations of HCV, emphasizing the importance of early diagnosis and treatment to improve patient outcomes. Full article

Background/Objectives: The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare the presumed differences between various eras over a 17-year timeline. Methods: This is a prospective, observational study on consecutive patients stabilized with VA-ECMO and transplanted with VA-ECMO from July 2007 to December 2023 at a reference center (98 patients). Objective variables were mortality and morbidity from renal failure, venous thromboembolic disease (VTD), primary graft dysfunction (PGD), the need for tracheostomy, severe myopathy, reoperation, post-transplant ECMO, vascular complications, and sepsis/infection. Results: The percentage of patients who reached transplantation without the need for mechanical ventilation has increased over the periods studied. No significant differences were found between the study periods in 30-day mortality (p = 0.822), hospital discharge (p = 0.972), one-year mortality (p = 0.706), or five-year mortality (p = 0.797). Survival rates in these periods were 84%, 75%, 64%, and 61%, respectively. Comorbidities were very frequent, with an average of 3.33 comorbidities per patient. The most frequent were vascular complications (58%), the need for post-transplant ECMO (57%), and myopathy (55%). The development of myopathy and the need for post-transplant ECMO were higher in recent periods (p = 0.004 and p = 0.0001, respectively). Conclusions: VA-ECMO support as a bridge to HT allows hospital discharge for 3 out of 4 transplanted patients. This survival rate has not changed over the years. The comorbidities associated with this device are frequent and significant. Full article

Living donor kidney transplantation (LDKT) currently represents the treatment of choice for patients with end-stage renal failure. LDKT is a serious event with profound psychological, interpersonal, familial, and social implications. Over the last few years, there has been an exponential growth in living donation programs involving genetically and emotionally related donors, as well as people who donate to an unrelated and unknown subject. The implementation of paired exchange programs, Samaritan donation, and preemptive transplantation raise further ethical issues, which are inextricably linked to the unique psychosocial context of both the donor and the recipient. The present narrative review aims to provide an update on the main ethical challenges related to LDKT. We conducted a comprehensive literature search in PubMed/Medline. The results of the most relevant studies were narratively synthesized from a psychosocial perspective around the four principles of biomedical ethics: autonomy, beneficence, non-maleficence, and justice. Finally, we discussed the potential future directions to provide an effective, patient-centered, and ethical psychosocial assessment and follow-up of living donors and recipients that underwent LDKT. Full article

Copper is an essential element in the diet of mammals, including humans. It plays an important role in the physiological regulation of various enzymes and is consequently involved in several biological processes such as angiogenesis, oxidative stress regulation, neuromodulation, and erythropoiesis. Copper is essential for facilitating the transfer of iron from cells to the bloodstream, which is necessary for proper absorption of dietary iron and the distribution of iron throughout the body. In particular, patients with end-stage renal failure who require renal replacement therapy are at increased risk for disorders of copper metabolism. Many studies on hemodialysis, peritoneal dialysis, and kidney transplant patients have focused on serum copper levels. Some reported mild deficiency, while others reported elevated levels or even toxicity. In some cases, it has been reported that alterations in copper metabolism lead to an increased risk of cardiovascular disease, malnutrition, anemia, or mielopathy. The aim of this review is to evaluate the role of copper in patients undergoing hemodialysis and its potential clinical implications. Full article

Background: Complement-mediated hemolytic uremic syndrome (CM-HUS), formerly known as atypical HUS, is a rare but potentially fatal thrombotic microangiopathy (TMA) characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and acute kidney injury. It is primarily caused by complement dysregulation. The condition can progress to end-stage renal disease (ESRD), often necessitating kidney transplant. In rare instances, it can develop in post-renal-transplant patients. Methods: Here, we present the cases of two patients with ESRD status post kidney transplant who presented with thrombocytopenia, anemia, and acute kidney injury. In both cases, work-up was suggestive of CM-HUS, and stabilization was achieved with eculizumab. Discussion: The pathogenesis of CM-HUS involves dysregulation of the complement system, and complement inhibitors such as eculizumab can be used for initial management and relapse. The relapse rate following eculizumab treatment can range from 20 to 67%. Patients with a history of kidney transplant are more prone to relapse than those with native kidneys. Re-treatment with complement inhibitors has proven effective in managing relapses, and long-term continuation of complement inhibitor medications is recommended to prevent recurrence. Conclusions: CM-HUS is rare, especially in post-transplant patients, and can be potentially fatal. It is crucial for clinicians to recognize and treat this condition promptly. Management often involves complement inhibitors. The risk of relapse is particularly high in patients with a history of kidney transplant, but long-term continuation of these medications can prevent relapse. Full article

Introduction: Deoxyguanosine Kinase (DGUOK) deficiency is a very rare disorder characterized by liver dysfunction, neurological manifestations, and metabolic disorders secondary to severely reduced mitochondrial DNA content. These patients develop early-onset liver failure, and their liver transplantation (LT) indication remains debatable due to the possibility of neurological involvement. Case Report: We present the case of a 6-month-old female diagnosed with DGUOK deficiency who developed liver failure. At 9 months, she underwent a living-related LT with an initial favorable evolution under immunosuppression therapy with tacrolimus. Four months after LT, she presented two prolonged bacterial and Rotavirus enteritis episodes. She developed classical post-transplant complications (severe renal tubular acidosis type IV, secondary to the high tacrolimus level, and post-transplant lymphoproliferative disease) during these episodes. Her condition deteriorated progressively, with reversible hypotonia and significant weight loss. However, the neurological evaluation did not reveal any signs suggestive of the progression of the underlying disease. A few months later, her clinical features and laboratory parameters improved considerably. Conclusions: This case highlights the unpredictable evolution of children with LT for liver failure due to DGUOK deficiency. Full article

Background/Objectives: Vesicoureteral reflux (VUR) is considered one of the major causes of post-renal transplant febrile urinary tract infections (UTI), leading to impaired renal function and the premature loss of the renal graft. We aimed to evaluate whether surgical VUR correction, such as open redo ureteric reimplantation, could be an option for treatment and provide better outcomes in post-transplant care for patients with UTI compared to their pre-VUR correction clinical state. Methods: Our study presents a retrospective analysis of 10 kidney transplant recipients with febrile UTI at the Renal Transplant Service of a Brazilian public hospital from 2010 to 2020. We selected patients who primarily underwent a surgical correction of post-transplant VUR, which was corrected by extravesical reimplantation without a stent in all patients by the same professional surgeon. Results: From 710 patients who received kidney transplants, 10 patients (1.4%) suffered from febrile UTI post-transplant and underwent surgical correction for VUR. Despite the study’s limitations, such as its retrospective nature and limited sample size, the efficacy of open extravesical ureteral reimplantation in reducing post-operative febrile UTI in renal transplant patients was observed. Conclusions: As febrile UTI can contribute significantly to patient mortality after kidney transplantation and VUR emerges as a major cause of post-transplant febrile UTI, it is essential to treat it and consider the surgical outcome. This study emphasizes the timely detection and effective treatment of VUR via extravesical techniques to reduce febrile UTI occurrences post-transplant and it contributes insights into the role of surgical interventions in addressing VUR-related complications post-kidney transplantation. Full article

Objective: Interstitial fibrosis/tubular atrophy (IFTA) is a common, irreversible, and progressive form of chronic kidney allograft injury, and it is considered a critical predictor of kidney allograft outcomes. The extent of IFTA is estimated through a graft biopsy, while a non-invasive test is lacking. The aim of this study was to evaluate the feasibility and accuracy of an MRI radiomic-based machine learning (ML) algorithm to estimate the degree of IFTA in a cohort of transplanted patients. Approach: Patients who underwent MRI and renal biopsy within a 6-month interval from 1 January 2012 to 1 March 2021 were included. Stable MRI sequences were selected, and renal parenchyma, renal cortex and medulla were segmented. After image filtering and pre-processing, we computed radiomic features that were subsequently selected through a LASSO algorithm for their highest correlation with the outcome and lowest intercorrelation. Selected features and relevant patients’ clinical data were used to produce ML algorithms using 70% of the study cases for feature selection, model training and validation with a 10-fold cross-validation, and 30% for model testing. Performances were evaluated using AUC with 95% confidence interval. Main results: A total of 70 coupled tests (63 patients, 35.4% females, mean age 52.2 years) were included and subdivided into a wider cohort of 50 for training and a smaller cohort of 20 for testing. For IFTA ≥ 25%, the AUCs in test cohort were 0.60, 0.59, and 0.54 for radiomic features only, clinical variables only, and a combined radiomic–clinical model, respectively. For IFTA ≥ 50%, the AUCs in training cohort were 0.89, 0.84, and 0.96, and in the test cohort, they were 0.82, 0.83, and 0.86, for radiomic features only, clinical variables only, and the combined radiomic–clinical model, respectively. Significance: An ML-based MRI radiomic algorithm showed promising discrimination capacity for IFTA > 50%, especially when combined with clinical variables. These results need to be confirmed in larger cohorts. Full article

We recently reported in a rat model of kidney transplantation that the addition of sodium thiosulfate (STS) to organ preservation solution improved renal graft quality and prolonged recipient survival. The present study investigates whether STS pre-treatment would produce a similar effect. In vitro, rat kidney epithelial cells were treated with 150 μM STS before and/or during exposure to hypoxia followed by reoxygenation. In vivo, donor rats were treated with PBS or 2.4 mg/kg STS 30 min before donor kidneys were procured and stored in UW or UW+150 μM STS solution at 4 °C for 24 h. Renal grafts were then transplanted into bilaterally nephrectomised recipient rats which were then sacrificed on post-operative day 3. STS pre-treatment significantly reduced cell death compared to untreated and other treated cells in vitro (p < 0.05), which corresponded with our in vivo result (p < 0.05). However, no significant differences were observed in other parameters of tissue injury. Our results suggest that STS pre-treatment may improve renal graft function after transplantation. Full article