Search Results (456)

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) remains a major contributor to late allograft dysfunction in kidney transplant recipients. Although detailed mechanisms remain incompletely understood, our previous metabolomic studies revealed disruptions in carnitine-related and redox pathways, suggesting impaired mitochondrial β-oxidation of fatty acids. To further characterize metabolic alterations associated with this condition, we conducted an untargeted lipidomic analysis of renal tissues using a murine model of TAC nephrotoxicity. TAC (1 mg/kg/day) or saline was subcutaneously administered to male ICR mice for 28 days, and kidney tissues were harvested for comprehensive lipidomic profiling. Lipidomic analysis was performed with liquid chromatography–tandem mass spectrometry (p < 0.05, n = 5/group). Triacylglycerols (TGs) were the predominant lipid class identified. TAC-treated mice exhibited reduced levels of unsaturated TG species with low carbon numbers, whereas TGs with higher carbon numbers and various degrees of unsaturation were increased. All detected TGs containing docosahexaenoic acid (DHA) showed an increasing trend in TAC-treated kidneys. Although accumulation of polyunsaturated TGs has been previously observed in chronic kidney disease, the preferential increase in DHA-containing TGs appears to be a unique feature of TAC-induced nephrotoxicity. These results suggest that DHA-enriched TGs may serve as a metabolic signature of TAC nephrotoxicity and offer new insights into its pathophysiology. Full article

Background: Several epidemiological studies have indicated that metabolic syndrome (MetS) after renal transplantation is caused by an accumulation of non-immunological risks of renal transplantation, and affects the prognosis of the kidney and the patient by increasing the risk of arteriosclerosis and cardiovascular complications. The incidence of MetS in Japanese renal transplant recipients is 14.9 to 23.8%, but its effects on cardiovascular events and kidney prognosis are not clear. Here, we report the results of a longitudinal study on MetS in renal transplant recipients. Methods: A retrospective cohort study was conducted in 104 stable renal transplant recipients who attended our outpatient department from January 2006 to June 2007 and were diagnosed with MetS at least 6 months after renal transplantation until 31 December 2020, or did not have MetS. The impact of MetS on composite vascular events was examined using multivariate Cox proportional hazards analysis. Results: The hazard ratios for the impact of MetS on composite vascular events diagnosed by NCEP Japan, NCEP Original, NCEP Asia, and IDF criteria on composite vascular events were 2.78 (95% CI: 1.15 to 6.75, p = 0.024), 2.65 (95% CI: 1.04 to 6.80, p = 0.042), 2.37 (95% CI: 0.93 to 6.01, p = 0.070), and 1.91 (95% CI: 0.77 to 4.75, p = 0.164), respectively. P for interaction was used to test the influence of each indicator, but was not statistically significant. Conclusions: MetS is a robust risk factor for graft loss and development of cardiovascular events in Japanese renal transplant recipients, even during long-term follow-up. This finding emphasizes the importance of monitoring and managing MetS in this population to improve long-term outcomes. Full article

Background: Kidney transplantation from a living donor is considered the most beneficial form of treatment for end-stage renal failure, which, in addition to providing patients with better treatment results, significantly improves their quality of life. Understanding factors that influence the willingness to donate kidneys to strangers is critical in promoting and expanding the living donor pool. When considering the decision to become an altruistic kidney donor, individuals must evaluate multiple factors, including the identity of the recipient and their own perceived level of safety. This study aimed to assess the willingness of dialysis center employees to act as living kidney donors for a stranger. Methods: We conducted a cross-sectional study from February 2023 to June 2024 among dialysis specialists across Poland. The study involved 1093 people (doctors and nurses). The study used our survey questionnaire and standardized tools. Results: Nurses (vs. physicians) and those who advocated the regulation of unspecified living kidney donation in Poland, did not believe in the risk of organ trafficking, and would donate a kidney to a husband/wife or friend and accept kidney transplantation from a husband/wife were more likely to donate a kidney to a stranger. Furthermore, respondents who accepted a loved one’s decision to donate a kidney to a stranger were significantly more willing to donate a kidney to such a person themselves. Perceived self-efficacy was positively associated with the willingness to donate a kidney to a stranger. Conclusions: Less than half of healthcare professionals supported unspecific living organ donation in Poland, and nurses were more willing to donate than physicians. The factors supporting the decision generally included knowledge about organ donation and transplantation, a lack of fear of organ trafficking, and attitudes towards donation. Full article

Background: The management of end-stage renal disease (ESRD) is undergoing a paradigm shift, with increasing emphasis on kidney transplantation as a preferred treatment modality for elderly patients (≥65 years), who constitute a substantial portion of new ESRD cases. Transplantation offers markedly superior survival and quality of life (QoL) advantages compared to dialysis for this demographic. Nevertheless, key determinants such as frailty, physical functionality, and cognitive function have emerged as critical predictors of post-transplant success. Despite their relevance, standardized methodologies for evaluating these parameters in transplantation candidacy remain absent. This systematic review examines the influence of frailty, physical functionality, and cognitive function on outcomes in elderly kidney transplant recipients. Methods: Adhering to PRISMA guidelines, a rigorous literature search was conducted across PubMed, CINAHL, Embase, PsycINFO, and the Web of Science for studies published up to October 31, 2024. Relevant studies focused on elderly transplant candidates and examined correlations between frailty, physical functionality, or cognitive function and post-transplant outcomes. The Newcastle–Ottawa Scale was employed to evaluate studies quality. Results: Seven studies met the inclusion criteria. Five explored physical functionality, demonstrating that better pre-transplant physical performance predicts enhanced survival. Two studies addressed frailty, utilizing the Fried frailty phenotype, and linked frailty to elevated mortality and diminished QoL recovery. Notably, no studies explored cognitive function in elderly kidney transplant candidates or recipients and its association with post-transplant outcomes, exposing a salient gap in the literature. The included studies’ varied methodologies, reliance on single time-point assessments, and exclusive focus on kidney transplant recipients restrict both comparability among studies and the generalizability of findings to the broader end-stage renal disease (ESRD) population. Conclusions: These findings underscore the profound impact of physical functionality and frailty on transplant outcomes in the growing elderly kidney transplant population, illuminating the necessity for standardized assessment protocols and targeted pre-transplant interventions. The critical gap in cognitive function research underscores a vital direction for future investigation. This research received no external funding. This review is registered with PROSPERO under registration ID CRD42025645838. Full article

The indications for immune checkpoint inhibitor (ICI) use in cancer treatment continue to expand. This is attributable to their proven anticancer activity in addition to their tolerability and favorable toxicity profile as compared to conventional chemotherapeutic agents. ICIs work by blocking the inhibitory signals between tumor cells and T-cells, thereby enhancing the T-cell cytotoxic activity to inhibit tumor growth. Because of their immune-stimulating effect, ICIs are linked to adverse renal outcomes in both native and transplanted kidneys. The risk of kidney allograft rejection in the setting of ICI use has been reported to be around 40%, leading to an increased risk of graft loss. In this report, we review the literature examining outcomes in kidney transplant recipients receiving ICIs for various oncologic indications. Full article

Background/Objectives: Renal transplantation (RT) represents the optimal treatment for end-stage renal disease (ESRD), offering improved quality of life and restored fertility in women post-transplant. While post-transplant pregnancies are possible, they can lead to complications including pre-eclampsia, graft dysfunction, and other adverse outcomes. This study evaluates existing literature to assess pregnancy’s impact on kidney transplantation outcomes, specifically long-term graft function and survival. Methods: We conducted a systematic review of English-language literature from January 2000 to September 2023 across multiple databases, following PRISMA guidelines. We established inclusion criteria focusing on graft function and adverse events. Two independent reviewers performed data extraction, and we assessed risk of bias using the ROBINS-I tool. Results: From 4917 articles, we included 26 studies encompassing 1202 pregnancies in 902 kidney transplant recipients. Mean maternal age was 30.8 years, with an average interval of 52 months between transplant and pregnancy. Pre-pregnancy hypertension occurred in 54.2% of cases, and pre-eclampsia developed in 25.7%. The live birth rate reached 70.5%, while miscarriage, stillbirth, and neonatal death rates were 11.3%, 2.7%, and 2.5%, respectively. We noticed graft dysfunction during pregnancy in 20.2% of cases. Though kidney function often deteriorated temporarily, most patients recovered post-delivery. Discussion: Post-transplant pregnancies remain viable but high-risk, with elevated rates of obstetric complications. Our findings highlight the need for standardized data collection and reporting to better understand and manage pregnancy’s impact on graft outcomes. Conclusions: With appropriate management, pregnancy in kidney transplant recipients is feasible, though it carries elevated risks of obstetric complications. We recommend further multicenter studies with standardized data collection to improve understanding and outcomes. Full article

Background and Objectives: Non-invasive imaging biomarkers for the early detection of chronic kidney allograft injury are needed to improve long-term transplant outcomes. T1 mapping by magnetic resonance imaging (MRI) has emerged as a promising method to assess renal structure and function. This study aimed to determine the potential of MRI as a diagnostic tool for evaluating graft function and structural changes in kidney grafts 1 year after transplantation. Materials and Methods: Thirty-four kidney transplant recipients were prospectively recruited, with 27 completing the follow-up at one year. Renal MRI at 3T was performed to acquire T1, T2, and apparent diffusion coefficient (ADC) maps. Clinical parameters, including estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio (PCR), and histological IF/TA scores, were collected. MRI parameters were compared across the groups stratified by clinical and histological markers. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. Results: At 1 year, T1 corticomedullary differentiation (CMD) values were significantly higher in patients with elevated ACR (≥3 mg/mmol), PCR (≥15 mg/mmol), and mild to moderate or severe IF/TA, reflecting a reduction in the corticomedullary gradient. T1 CMD demonstrated moderate-to-good diagnostic performance in detecting ACR (AUC 0.791), PCR (AUC 0.730), and IF/TA (AUC 0.839). No significant differences were observed in T2 or ADC values across these groups. T1 CMD also showed a significant positive correlation with ACR but not with eGFR, suggesting a closer association with structural rather than functional deterioration. Conclusions: T1 mapping, particularly T1 CMD, shows promise as a non-invasive imaging biomarker for detecting chronic allograft injury and monitoring renal function 1 year after kidney transplantation. Full article

Introduction: Renal artery stenosis can significantly impact long-term graft survival rates following kidney transplant. Early recognition and management can improve the longevity of the kidney allograft. We aimed to evaluate the clinical role of duplex ultrasound in the diagnosis of renal artery stenosis (RAS). We also wanted to evaluate the current incidence of renal artery stenosis at our institute. Methods: A retrospective, consecutive series of 367 patients who underwent renal transplantation between 1 January 2020 and 30 December 2024 was conducted. We collected data regarding the recipients’ age, body mass index, and comorbidities. All patients diagnosed with renal artery stenosis were identified. The incidence of kidney transplant artery stenosis and presentation were recorded. All general physical parameters and laboratory data were collected and analyzed. Results: A total of 28 patients had initial suspicion of renal artery stenosis, documented via initial dedicated duplex ultrasound of the transplanted kidney. The initial mean systolic BP at initial US was 151 (99–213) mmHg, and mean creatinine was 2.43 (1.28–6.38) mg/dL. However, on repeat duplex ultrasound, three patients showed no features of renal artery stenosis and had no physical parameters consistent with RAS. A total of 25 patients diagnosed with RAS on initial duplex ultrasound underwent angiography. Twenty-four patients were confirmed with RAS on angiography, while one patient had a normal angiogram. Among patients diagnosed with TRAS, the mean resistive index was 0.71 ± 0.17 at the upper pole, 0.73 ± 0.19 at the mid pole, and 0.71 ± 0.21 at the lower pole. The mean peak systolic velocity was 462.57 ± 166.28 cm/s. Conclusions: Duplex ultrasound is an important initial tool for diagnosing transplant renal artery stenosis. An increase in peak systolic velocity was observed in our cohort; however, resistive indices were largely within acceptable limits. Management should be guided by clinical parameters (e.g., elevated systolic BP and rising creatinine) alongside imaging findings. Full article

Background: Kidney transplantation is the treatment of choice for pediatric patients with end-stage kidney disease. However, transplantation in children weighing < 15 kg remains challenging due to limited donor availability and higher surgical and medical risks. We report our 35-year single-center experience in this population, focusing on perioperative and long-term outcomes. Methods: We retrospectively analyzed kidney transplants performed from 1987 to 2023 in children weighing < 15 kg. Data on demographics, donor type, complications, immunosuppression, and outcomes at 2, 5, and 10 years (including survival, graft function, rejection, infections, and urological issues) were collected. Outcomes were compared between deceased and living donors and between recipients weighing < 10 kg and ≥10 kg. Results: Ninety-six transplants were included (mean age 3.3 years; mean weight 11.1 kg), 80 from deceased and 16 from living donors. Most patients (69.8%) had been treated with peritoneal dialysis. Median follow-up was 120 months. Patient survival was 95.8%; graft survival was 78.1%. Eight grafts (8.3%) were lost to renal vein thrombosis, all in deceased-donor recipients (p = 0.60). Preserved renal function (eGFR > 60 mL/min/1.73 m²) declined from 80.4% at 2 years to 66.0% at 5 years and 18.0% at 10 years. Graft survival at 10 years was significantly lower in children < 10 kg vs. ≥10 kg (49.6% vs. 80.3%, p = 0.003). CAKUT was associated with higher urological complication rates (p = 0.017). No significant differences emerged between living and deceased donor groups. Conclusions: Transplantation in children < 15 kg is feasible with good outcomes, but those <10 kg present lower graft survival at 10 years. Multidisciplinary assessment and center experience are key to optimizing results. Full article

We aimed to determine the influence of donors’ vascular function on renal function in recipients and to evaluate the role of Orai1 calcium channels as a potential marker. A prospective collaborative multicenter study was designed. Blood, aorta (HA), mesenteric arteries (HMAs) and corpus cavernosum (HCC) specimens were obtained from organ donors at the kidney procurement procedure (n = 60). Evolution (up to 2 years) of renal function measured as serum creatinine (SCr) and glomerular filtration rate (GFR) was evaluated in respective recipients (n = 64). Vascular responses were determined in HA, HMA and HCC from donors. Tumor necrosis factor-α, asymmetric dimethyl arginine and Orai1 were measured in plasma. Orai1 protein expression was also evaluated in each donor’s aorta. Endothelium-dependent vasodilation (HMA, HCC) and adrenergic contraction (HA) in donors determined renal function in recipients, 12 months post-transplantation. Donors in the best quartile of vascular function predicted lower SCr and higher GFR in kidney recipients for 12/24 months. Plasma Orai1 in donors was negatively correlated with vascular function and predicted renal function at 3–6 months post-transplantation. Donor Orai1 vascular content was associated with reduced vascular function and with poorer recipient renal function for 1-year post-transplantation. Systemic vascular function of kidney donors determines recipients’ renal function at short/mid-term. Donors’ vascular function and recipients’ renal function are negatively associated with donors’ Orai1 vascular expression, being a potential biomarker of renal outcomes. Full article

Asymptomatic bacteriuria (ASB) is a very frequent condition in kidney transplant recipients (KTRs). Guidelines advise against screening and treatment of ASB beyond the first month after renal transplantation. Here, we report the case of a 40-year-old female KTR with untreated ASB complicated with allograft pyelonephritis with urosepsis and acute kidney injury. The reported case highlights that ASB remains a grey area in the management of KTRs (after the first month), and there is a need for new ad hoc studies to identify which patients should be screened and eventually treated. Until new findings are available, it is suggested not to treat KTRs with ASB; however, if ASB is detected, stricter monitoring and non-antibiotic prophylaxis are necessary to favor prevention or prompt therapy of severe urinary tract infections. Full article

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 KTRs transplanted from 2005 to 2024. Data on patient characteristics and outcomes were collected. Propensity score matching (PSM) compared 34 localized RCC cases in KTRs with 34 non-transplant RCC cases. The statistical analyses used Kaplan–Meier estimates, the log-rank test, and the Cox regression. Results: The RCC incidence was 0.64 per 1000 person-years, with a standardized incidence ratio of 4.40 (95% CI: 3.33–5.80). In the KTR cohort, clear cell RCC was present in 42%, and papillary RCC was present in 42%. RCC developed predominantly in native kidneys (92%). UICC stage I was present in 74%. The treatment for the non-metastatic RCC was nephrectomy in the majority of cases (91%). For the metastatic RCC, 71% received a tyrosine kinase inhibitor (TKI). In the KTR cohort, the 3- and 5-year overall survival (OS) rates were 85% and 72%, respectively, with a median OS of 199 months; the synchronous metastasized (M1) patients had a median OS of 14 months. Rejection, age, advanced UICC stage, higher pT stage, clinical positive lymph nodes, M1, and higher grade were significantly associated with poor OS. The 5-year OS (96% vs. 84%, p = 0.72) and MFS (92% vs. 93%, p = 0.61) were comparable in the PSM cohort between the KTRs and the non-KTRs in the localized RCC. Conclusions: KTRs have a higher risk of RCC and present at a localized stage with comparable OS rates to non-transplant RCC patients. Adverse tumor characteristics, including synchronous metastases, significantly affect the prognosis, highlighting the need for surveillance and individualized treatment, particularly for metastatic RCC. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) have significantly improved the management of diabetes mellitus (DM). In the general population, these drugs have additional benefits, such as weight loss, improvement of liver steatosis, and a cardiorenal protective effect. However, data regarding the effects of GLP-1RAs or SGLT-2Is in the treatment of posttransplant diabetes mellitus (PTDM), obesity, and their potential cardiorenal protective effects in liver transplant (LT) recipients remain limited. PTDM increases the risk of developing graft steatosis, experiencing major cardiovascular events (MACEs), and developing chronic kidney disease and reduces long-term survival in LT recipients. The aim of this systematic review was to evaluate the efficacy and safety of GLP-1RAs and SGLT-2Is in the treatment of PTDM in LT recipients. Methods: Twelve retrospective studies (five specifically conducted in LT recipients and seven in mixed solid organ transplant cohorts, including LT recipients) that collectively enrolled 402 LT recipients treated with GLP-1RAs and/or SGLT-2Is for PTDM were selected. Results: GLP-1Ras and SGLT-2Is reduced serum glycated hemoglobin levels, body weight, and insulin requirements in LT recipients. Some studies reported benefits in reducing graft steatosis, improving renal function, and in reducing the occurrence of MACEs. Common adverse events included gastrointestinal symptoms, which rarely required treatment discontinuation. Conclusions: GLP-1RAs and SGLT-2Is represent promising treatment options for PTDM in LT recipients, offering metabolic benefits with manageable side effects. However, further prospective studies are needed to establish the long-term safety and efficacy, as well as the favorable impact on patient survival, of these drugs in LT recipients. Full article

Background/Objectives: The course of treatment for renal artery stenosis following renal transplantation depends on the severity of the condition. Mild cases are typically managed medically, while more significant stenosis with flow limitation and graft dysfunction requires percutaneous intervention. Surgical treatment is generally reserved as a last resort. This study aimed to evaluate the outcomes of interventional radiology in managing renal artery stenosis at our transplant center. Methods: The electronic medical records of patients who underwent renal transplantation at our center between January 2020 and December 2024 were reviewed to identify cases of renal artery stenosis and their subsequent management through interventional radiology. Sociodemographic and clinical data were collected for both recipients and donors. Data analysis was performed using SPSS version 26. Results: Out of the total 368 patients who received renal allograft at our center from January 2020 to December 2024, 25 patients were confirmed with duplex ultrasound to have renal artery stenosis. The majority of affected patients were African American, had Class I Obesity and presented with cardiovascular co-morbidities. The mean time from transplant to the diagnosis of RAS was 4.25 (SD ± 3.81) months. The mean serum creatinine level at presentation was 2.54 (SD ± 1.21 mg/dL). All 25 patients underwent digital subtraction angiography, and 24 patients were confirmed to have renal artery stenosis requiring further intervention. The creatinine levels at one week, three months and one year post-intervention were 2.12 (SD ± 1.00), 1.83 (SD ± 0.63) and 2.15 (SD ± 1.68) mg/dL, respectively. Conclusions: Percutaneous interventional treatment for renal artery stenosis is associated with improvements in hemodynamic parameters and the stabilization of allograft function. Follow-up is needed to monitor for the potential occurrence of restenosis. Full article

Cryptococcosis, an opportunistic fungal infection predominantly caused by Cryptococcus neoformans, is the third most common invasive fungal disease in solid organ transplant recipients. While well-characterized in adult kidney transplant (KT) patients, pediatric data remain sparse. This article compares clinical presentation, immune response, renal involvement, and management strategies of cryptococcosis between adult and pediatric KT recipients. In adults, the disease typically presents as cryptococcal meningitis or pulmonary infection, often complicated by delayed diagnosis and high mortality. In contrast, children frequently exhibit non-specific respiratory symptoms or disseminated disease, reflecting immune immaturity and increased susceptibility to hematogenous spread. Key immunopathological differences include impaired Th1 type responses, macrophage dysfunction, and variable complement activity across age groups. Management involves similar antifungal regimens such as liposomal amphotericin B, flucytosine, and fluconazole, but requires weight-based dosing and careful toxicity monitoring in pediatric patients. Early diagnosis through serum cryptococcal antigen screening, appropriate adjustment of immunosuppressive therapy, and coordinated multidisciplinary care are essential. The findings underscore the need for pediatric specific research and clinical vigilance, emphasizing tailored antifungal dosing and individualized immune management to improve outcomes in this vulnerable population. Full article