Search Results (312)

BK virus is a common childhood infection that is largely asymptomatic in the general population. However, increased cellular immune dysfunction in kidney transplant recipients is associated with an increased risk of BK virus reactivation. Modern immunosuppression regimens have resulted in a reduction in transplant rejection events but increased risk of BK nephropathy. It is now considered a leading cause of allograft loss within the first year of transplantation. Despite advances in screening, it remains both a diagnostic and therapeutic challenge. This review aims to provide an up-to-date summary of the latest clinical research in the diagnosis and treatment of BK virus in kidney transplant recipients. It will also provide a concise overview of emerging diagnostic techniques and new therapies under investigation. Full article

Background/Objectives: Rapid, objective phenotyping of donor kidneys is needed to support peri-implant decisions. Label-free Fourier-transform infrared (FTIR) spectroscopy of static cold-storage Celsior^® perfusion fluid can discriminate kidneys recovered from donation after circulatory death (DCD) versus donation after brain death (DBD). Methods: Preservation solution from isolated kidney allografts (n = 10; 5 DCD/5 DBD) matched on demographics was analyzed in the Amide I and fingerprint regions. Several spectral preprocessing steps were applied, and feature extraction was based on the Fast Correlation-Based Filter. Support vector machines and Naïve Bayes were evaluated. Unsupervised structure was assessed based on cosine distance, multidimensional scaling, and hierarchical clustering. Two-dimensional correlation spectroscopy (2D-COS) was used to examine band co-variation. Results: Donor cohorts were well balanced, except for higher terminal serum creatinine in DCD. Quality metrics were comparable, indicating no systematic technical bias. In Amide I, derivatives improved classification, but performance remained modest (e.g., second derivative with feature selection yielded an area under the curve (AUC) of 0.88 and an accuracy of 0.90 for support vector machines; Naïve Bayes reached an AUC of 0.92 with an accuracy of 0.70). The fingerprint window was most informative. Naïve Bayes with second derivative plus feature selection identified bands at ~1202, ~1203, ~1342, and ~1413 cm⁻¹ and achieved an AUC of 1.00 and an accuracy of 1.00. Unsupervised analyses showed coherent grouping in the fingerprint region, and 2D correlation maps indicated coordinated multi-band changes. Conclusions: Performance in this 10-sample pilot should be interpreted cautiously, as perfect leave-one-out cross-validation (LOOCV) estimates are vulnerable to overfitting. The findings are preliminary and hypothesis-generating, and they require confirmation in larger, multicenter cohorts with a pre-registered analysis pipeline and external validation. Full article

Motility disorders, particularly gastroparesis, are prevalent complications following solid organ transplantation, significantly impacting quality of life, nutritional status, graft survival, and mortality. This comprehensive review synthesises evidence from PubMed, Scopus, and Embase databases on pathophysiology, clinical manifestations, diagnosis, management, and prognostic factors across transplant types. Mechanisms include vagal nerve injury (highest in lung transplants, prevalence 40–91%), immunosuppressive effects (e.g., tacrolimus accelerates motility; mycophenolate impairs it), surgical trauma, microbiome dysbiosis (reduced Firmicutes/Bacteroidetes ratio), and metabolic factors like post-transplant diabetes (OR 5.17 in kidney recipients). Pediatric and thoracic recipients face the highest risks, with lung transplant gastroparesis conferring a 2.7-fold increased mortality/retransplantation hazard (p < 0.05). Diagnosis relies on gastric emptying scintigraphy (gold standard, sensitivity 85–95%) and wireless motility capsules (100% sensitivity for delay), while management encompasses prokinetics (60–80% response), endoscopic G-POEM (85% success), gastric electrical stimulation (100% quality-of-life improvement in series), and nutritional support. Prognostic factors include younger age (better intervention response), aetiology (anatomical worse than metabolic), and early therapy success. Outcomes vary: lung recipients experience severe impacts on chronic allograft dysfunction (83% oesophageal motility abnormalities correlate with 66–67% rejection). Future directions emphasise microbiome therapies, AI predictive models (AUC 0.85), and wearables for continuous monitoring. Multidisciplinary approaches are essential to balance immunosuppression with GI management, addressing ethical dilemmas like drug interactions and access disparities. Ultimately, early screening and personalised interventions can mitigate complications, enhancing long-term transplant success. Full article

Kidney transplant recipients remain at high risk of cardiovascular events and premature death. Whether chronic histological changes in protocol allograft biopsies provide prognostic information for patient outcomes beyond graft survival remains uncertain. In this prospective study of 458 kidney transplant recipients with biopsies performed at 3 and 12 months and followed up to 8 years, we assessed the association between vascular and interstitial lesions and major adverse cardiovascular events (MACEs) or all-cause mortality. Fifty-eight patients (12.7%) died and 49 (10.7%) experienced MACEs during follow-up. The most notable finding was that progression of hyaline arteriolar thickening (aah) between 3 and 12 months independently predicted all-cause mortality, even after adjustment for estimated glomerular filtration rate, diabetes, and previous cardiovascular disease. In addition, vascular fibrous intimal thickening at 12 months was also independently associated with mortality, while associations of baseline vascular or interstitial lesions were attenuated after full multivariable adjustment. These results suggest that progressive aah reflects an ongoing recipient-related vascular process rather than donor-derived injury. Monitoring this dynamic histological change in repeated biopsies performed for protocol or for cause may provide transplant nephrologists with an early signal of increased mortality risk. Full article

Background: Renal allograft biopsy is essential in the follow-up of pediatric kidney transplant recipients, but the optimal sedation strategy remains uncertain. Methods: We retrospectively reviewed 711 ultrasound-guided biopsies in 251 children and adolescents (2009–2024), comparing oral conscious sedation with midazolam to deep intravenous (IV) sedation with propofol, midazolam, and ketamine. Outcomes included tissue yield, diagnostic success, complications, and cost-effectiveness. Results: IV sedation was used in 77.1% of procedures and was associated with longer cortical cores (median 1.8 vs. 1.5 cm, p < 0.001) and more glomeruli (16 vs. 8, p < 0.001), improving tissue yield and consequently increasing diagnostic success from 75% to 88.5% (p < 0.001; OR 2.6). Biopsy-related complications occurred in 12.9% of cases, with no difference between groups. Sedation-related complications, all mild or moderate, occurred only with IV sedation (4.9%). The improved tissue yield reduced the cost per successful diagnosis (EUR 1243 vs. EUR 1467), making IV sedation the dominant strategy. Conclusions: IV sedation enhances the diagnostic quality and cost-effectiveness of pediatric kidney allograft biopsies without increasing overall risk, though prospective studies should also assess patient anxiety and comfort. Full article

Renal involvement is an important complication of multiple myeloma (MM) and is related not only to worse clinical outcomes but also to lower quality of life, particularly when progressing to end-stage renal disease. Traditionally, MM patients were not considered eligible for kidney transplant; however, these paradigms are changing. The new era of MM therapies brought proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and, most recently, cellular therapies, leading to longer survival and sustained hematological responses. Knowledge of cytogenetic abnormalities has helped risk stratification. These advances result in the identification of patients who achieve durable remission and may benefit from kidney transplant programs as an option for renal replacement therapy. Reported 5-year allograft survival ranges from 50 to 66%, progression-free survival is 44%, and overall survival is 61%, depending on pre-transplant remission depth. This review summarizes updated available evidence regarding kidney transplants in MM, proposes evidence-based eligibility criteria for kidney transplantation in this population, and outlines therapeutic strategies for long-term follow-up. In conclusion, kidney transplantation may be a feasible option for carefully selected MM patients achieving deep and sustained remission, though prospective data are still needed. Full article

Matrix metalloproteinase type 9 (MMP-9), which cleaves collagen type IV in basal membranes, has been associated with the progression of chronic kidney disease. The objective of the present study was to evaluate the characteristics of donors, recipients, induction therapies, and allograft function on MMP-9 transcripts from mononuclear cells in kidney transplant recipients. Transcripts were determined in peripheral blood mononuclear cells from 67 incident renal transplant recipients eight days post-transplant using quantitative real-time PCR and quantified using the ΔΔCq method. Median MMP-9 transcripts were 6.1 (IQR, 1.5 to 66.5, N = 4) in AB0-incompatible donor transplants; 3.2 (IQR, 2.0 to 16.9, N = 17) in living donor transplants; and 4.2 (IQR, 2.3 to 9.2, N = 46) in deceased donor transplants (p = 0.8). Importantly, renal transplant recipients who were treated with thymoglobulin had significantly higher median MMP-9 transcripts compared to all other induction therapies (14.5; IQR, 2.8 to 31.9, N = 10; vs. 3.5, IQR, 2.2 to 8.8, N = 57; p = 0.01). Median MMP-9 transcript levels were similar in recipients with delayed allograft function and immediate allograft function (8.86; IQR, 5.29 to 11.57, N = 7; vs. 3.4; IQR, 2.35 to 9.49, N = 60; p = 0.245). Induction therapy with thymoglobulin causes significantly higher MMP-9 transcripts in peripheral blood mononuclear cells, probably indicating an increased inflammatory response. Full article

Nowadays, there have truly been spectacular advances in surgical techniques, the preservation of organs for transplants, the optimal and efficient selection of both donors and recipients, a more efficient diagnosis and prediction of possible complications of transplants, and important progress in the advances of pharmacological immunosuppression protocols and procedures. In this sense, survival rates after transplantation of various organs have been progressively increasing, especially in the case of lung transplants, whose average survival rate is usually lower than that of other types of solid organ transplants. Thus, detecting acute and subclinical rejection and chronic allograft rejection of any implant is important. This is important in all transplants, such as heart and lung transplants. In this last type of transplant, particularly, and due to the chronic dysfunction of the lung allograft, it is key to detect rejection early and on time, since it can reach close to half of the transplant patient population. Therefore, practical diagnostic tools are needed to visualize the level of allograft damage using genomic methods such as those that measure donor-derived cell-free DNA, where its amount increases in the plasma component of the transplant after tissue injury or due to allograft infection. This biomarker has become a key element with light and hope, but with some shadows of caution due to its use as a panacea. Our research team has experience in solid organ transplantation in quantifying this parameter in the progression of the lesion of the implanted allograft, and our experience and comparison with the published literature will be presented in the following review, discussing validated and non-validated results. Full article

Recurrence of the original glomerular disease (GN) poses a significant threat to kidney transplant function and longevity. The probability and severity of this recurrence vary, with C3 glomerulopathy and certain forms of FSGS exhibiting particularly high rates. Kidney transplant GN recurrence risk hinges on the characteristics of the initial GN, recipient/donor genetics, recipient age, donor type, end-stage kidney disease (ESRD) progression rate, and proteinuria levels. Standard immunosuppression has limited efficacy in preventing primary disease recurrence; however, agent selection and induction therapy can influence the risk for specific GNs. Diagnosing recurrent GN involves a comprehensive approach, including clinical evaluation, laboratory tests (such as proteinuria, hematuria, and specific biomarkers like anti-PLA2R for membranous nephropathy or complement for C3G), and, critically, an allograft biopsy analyzed with light, immunofluorescence, and electron microscopy. Treatment strategies are evolving towards targeted therapies, such as rituximab for antibody-mediated GN and complement inhibitors for C3G, moving away from broad immunosuppression. This narrative literature review provides practical monitoring algorithms for post-transplant settings, synthesizing information on the incidence, predictors, diagnostic strategies, and therapeutic options for various glomerular disease subtypes. The methodology involved searching MEDLINE, Embase, and Cochrane databases from 1996 to 2025, prioritizing systematic reviews, cohort studies, registries, and interventional reports. Eligibility criteria included adult transplant recipients and English-language reports on recurrent glomerular disease outcomes, excluding most single-patient case reports. Limitations include potential selection bias, omission of relevant studies, and the absence of a formal risk-of-bias assessment or meta-analysis. The evidence base is heterogeneous, with inconsistent outcome reporting and scarce randomized controlled trials. Future efforts should focus on developing predictive biomarkers, standardizing diagnostic and response criteria, conducting multicenter prospective cohorts and pragmatic trials, and creating shared registries with harmonized data. Full article

End-stage kidney disease is preferably treated by kidney transplantation. The function of the allograft often determines kidney-controlled processes and requires long-term monitoring. Kidneys are organs with a very high metabolic rate, and, thus, a metabolomics approach is suitable to observe systemic metabolic changes that are related to graft adaptation. To understand these ongoing changes in post-transplant pediatric patients, we applied a targeted liquid chromatography/tandem mass spectrometry-based metabolomics approach. Time-dependent changes of 140 metabolites in plasma samples prospectively collected from 23 pediatric kidney graft recipients receiving tacrolimus-based immunosuppression were monitored over the first 4 years after transplantation and compared to levels prior to transplantation. Furthermore, by comparing the pre-transplant metabolite levels to those measured in healthy children, we were able to obtain insights into the pathways associated with kidney failure. Arginine biosynthesis, alanine, aspartate, glutamine, and glutamate metabolism, taurine and tryptophan metabolism were the most affected pathways that separate the pediatric patients with and without kidney failure. Accumulation of uremic toxins such as various tryptophan/kynurenine and tryptophan/indole metabolism pathway intermediates, and betaine and methionine cycle metabolites was evident in patients with restricted kidney function. Furthermore, reduced nicotinamide production, insufficient hydroxylation of phenylalanine to tyrosine, lowered cysteine, arginine, glutamine, taurine, and overall amino acid utilization, as well as diminished levels of protective antioxidants such as glutathione and vitamins B6 and C, were all the result of progressive kidney failure leading to transplantation. Importantly, following kidney transplantation and recovery of kidney function, the levels of most of the previously described metabolites normalized toward the levels observed in healthy participants. The here identified metabolic patterns could be used as markers to monitor the progression of pediatric chronic kidney disease patients towards kidney failure, and assuming their direct association with kidney function, they could serve as markers of successful graft adaptation. Full article

The reactivation of BK polyomavirus (BKPyV) during severe immunosuppression plays a crucial role in two significant syndromes observed in transplant recipients: BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant patients and BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) in hematopoietic cell transplant (HCT) recipients. This review aims to summarize the current understanding and lingering ambiguity by looking at three primary questions: (1) In cases with BKPyV-related illnesses in transplant patients, which diagnostic methods have the best track record of accuracy and success? (2) Which therapy approaches have the best track records of safety and efficacy in real-world clinical settings? (3) What can immunological research teach us about the development of future tailored treatments? Diagnosis involves the patient’s appearance, ruling out other potential causes, and employing quantitative PCR to identify active viral replication in urine or plasma. BKPyV-HC can vary from self-limited hematuria to potentially fatal bleeding, while BKPyVAN may lead to loss and dysfunction of the allograft. Reducing immunosuppression remains the key aspect of treatment. However, the effectiveness of antivirals (such cidofovir and leflunomide) is not always the same, and supporting measures depend on the syndrome. Researchers are looking into new immunotherapies, such as virus-specific cytotoxic T cells. Due to the intricate viro-immunopathology and lack of defined treatment regimens, future initiatives should focus on prospective studies to establish validated thresholds, enhance management algorithms, and integrate immune surveillance into individualized therapy. Full article

Allograft inflammatory factor-1 (AIF1) is a conserved calcium-binding protein involved in inflammatory and neuro-immune responses and expressed in Pomacea canaliculata (Pc-AIF1) during cephalic tentacle regeneration. Here, we investigated the expression and distribution of Pc-AIF1 in control conditions and during cephalic tentacle regeneration. A transcriptomic analysis of 315 RNA-seq datasets revealed maximal Pc-AIF1 expression in circulating hemocytes and hemocyte-rich tissues. Pc-AIF1 was also highly expressed in neural ganglia. Fluorescence in situ hybridization (FISH) evidenced Pc-AIF1 in circulating hemocytes and in the phagocytic hemocyte aggregates in the posterior kidney. qPCR showed the constitutive expression of Pc-AIF1 in cerebral ganglia. FISH experiments showed Pc-AIF1-positive cells within the cephalic tentacle blastema at 24 h post-amputation (hpa). Even if the amputation left them untouched, both the ipsilateral and contralateral cerebral ganglia increased Pc-AIF1 expression until 48 hpa. Immunocytochemical experiments evidenced positive cells to RCA120 (a microglial marker in mammals) among circulating hemocytes, in the connective tissue surrounding the cerebral ganglia, and within the regenerating tentacles. These findings suggest that Pc-AIF1 is a neuro-immune marker constitutively expressed in hemocyte populations and neural tissues; it is associated with the immediate hemocyte response to wounding and the neuro-immune interplay during the regeneration of sensory organs. Full article

Background/Objectives: APOL1 renal-risk variants (RRVs) are of increasing relevance to kidney disease and transplant outcomes. It is currently understood that the presence of RRVs in donors negatively impacts kidney allograft survival in an autosomal recessive pattern of inheritance. Less well known is the interplay between ischemia and alternative allograft preservation methods, such as normothermic machine perfusion (NMP), on APOL1 gene expression. To investigate this, we examined the effects of APOL1 RRVs on APOL1 gene expression in ischemic donor kidneys and compared the differences in cytokine and APOL1 expression patterns between the alternative preservation methods, static cold storage (CS) and NMP. Methods: Non-utilized deceased donor kidney pairs from donors of African ancestry were procured from Mid-America Transplant after being deemed unsuitable for kidney transplant. Samples were collected from each donor kidney pair and DNA was extracted for APOL1 genotyping. APOL1 RRVs G1 (rs73885319) (rs60910145) and G2 (rs71785313) were identified by Sanger sequencing. From each pair, one kidney underwent 6 h NMP (n = 3) and the contralateral kidney 6 h of CS (n = 3) following the initial CS. Renal perfusion and biochemical, and histologic parameters were recorded. NMP was directly compared with CS using paired donor kidneys using NMP with allogeneic red blood cells, followed by assessment of perfusion, biochemical, and histologic parameters, in addition to gene expression. Results: Donor genotyping identified kidney pairs as heterozygous for the G1 RRV (G1/G0), homozygous for the G0 allele (G0/G0), and homozygous for the G2 RRV (G2/G2), respectively. All kidneys were successfully reperfused, with mRNA transcript levels of APOL1-related genes subsequently measured. Significant differences in APOL1 gene expression were observed among all three groups of kidneys. In paired kidneys from baseline to hour 6 of NMP, mRNA expression varied significantly between G1/G0 and G2/G2 homozygous pairs (p = 0.002) as well as between the G0/G0 and G2/G2 pairs (p = 0.002). APOL1 expression shifted by a significantly higher-fold change of 2.4 under NMP conditions in the G2/G2 genotype (p < 0.001). The inflammatory cytokine marker IFN-γ was also significantly upregulated in the G2/G2 genotype kidney, in both CS and NMP groups (p = 0.001). Other related genes such as KIM-1 were upregulated by a change of 3.9-fold in the NMP group for the G2/G2 kidney. Conclusion: Donor kidney pairs with the high-risk APOL1 genotype, especially G2/G2, show increased APOL1 expression and inflammation, particularly under NMP conditions. NMP enables detection of genotype-specific molecular changes in an ischemic reperfusion injury model, supporting its potential to improve donor kidney assessment before transplantation. Full article

Background and Objectives: Kidney transplantation remains the gold-standard treatment for end-stage renal disease (ESRD). For deceased donor transplantation, optimal allograft preservation represents a critical determinant of success. While static cold storage (SCS) has been the historical standard, hypothermic machine perfusion (HMP) has emerged in recent decades as a technologically advanced alternative. However, comparative data from smaller-volume centers utilizing exclusively donation after brain death (DBD) donors remain scarce. Materials and Methods: This retrospective single-center study included 94 patients who received kidney transplants from deceased DBD donors between January 2018 and December 2024. We employed a paired kidney study design where one kidney from each donor was preserved using HMP (LifePort, set at 30/20 mm Hg pressure), while the contralateral kidney was stored in SCS. Parameters compared were creatinine concentration in recipient serum after transplantation, DGF, acute rejection and hospital stay. Results: The HMP group had a significantly longer cold ischemia time (CIT) (18.09 ± 5.91 h, range: 6.5–34.0 h) compared to the SCS group (12.36 ± 5.18 h, range: 4.0–23.0 h; p < 0.005). The DGF rate was significantly lower in the HMP group (4.3%) than the SCS group (25.5%) (p = 0.004). HMP was also associated with a shorter mean hospitalization (11.81 vs. 15.66 days, p = 0.008) and superior early graft function, particularly in kidneys with CIT ≥ 18 h, which showed significantly lower serum creatinine at day 14 (124.48 vs. 164.89 µmol/L, p = 0.036). Conclusions: HMP usage in kidney transplantation decreased the possibility for DGF in DBD donors and shortened the post-op hospitalization time. It is a feasible method for kidney storage before transplantation even in a case of prolonged CIT. Full article

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is common and various tools are proposed to identify patients at risk of AKI. The determination of the Doppler-derived renal resistance index (RRI) is useful for detecting the occurrence of tubular necrosis or allograft rejection. This study questions the value of RRI in identifying CSA-AKI, defined according to the renal risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) classification. Methods: We conducted a prospective, unblinded, observational study in patients undergoing open heart surgery. Clinical and surgical data were collected from the electronic medical files and the Cleveland score was calculated for each patient. Before the surgery and upon admission to the intensive care unit (ICU), blood flow in the renal cortical or arcuate arteries was measured and the RRI was computed. The capability of preoperative serum creatinine, the Cleveland score, and the preoperative and postoperative change in RRI were investigated with the area under the receiver operating characteristic curve (ROC-AUC) to predict the AKI. Results: Within the first five postoperative days, 31.4% developed CSA-AKI. All patients with stage 1 AKI recovered normal creatinine levels before ICU discharge while those with stage 2 or 3 (AKI 2/3) exhibited persistent changes. To discriminate AKI 2/3, the ROC-AUC was less than 0.7 for the preoperative serum creatinine and RRI, 0.879 for the Cleveland score, and 0.710 for the postoperative RRI. The change between the preoperative and postoperative RRI (dRRI) provided a ROC-AUC of 0.825 (sensitivity 72.7% and specificity 96.6%) with an optimal cut-off point at 9.4%. Conclusions: Noninvasive determination of RRI is helpful for detecting PO-AKI and provides additional information to clinical markers. Full article