Search Results (2,493)

There is a bidirectional relationship between chronic kidney disease (CKD) and an altered gut microbiome, with gut-derived uremic toxins contributing to cardiovascular-kidney-metabolic effects. In this review, we summarize the interplay between diet, the intestinal microbiota and systemic sequelae including CKD progression, cardiovascular morbidity and cognitive decline. We discuss the current state of knowledge regarding microbiota-modulating therapies that have the potential to delay CKD complications such as plant-dominant diets, oral adsorbents, prebiotics/probiotics, fecal microbiota transplantation and exercise. Full article

Background/Objectives: Mycophenolic acid (MPA) monitoring may improve organ transplant outcomes, yet clinical implementation is hindered by the complex pharmacokinetics of MPA and a lack of clarity regarding the influence of specific patient factors on drug exposure. While the area under the curve (AUC) is the gold standard for MPA monitoring, it is not easily validated or implemented in routine practice. This pilot project aimed to identify key clinical and biochemical covariates driving pharmacokinetic variability in a renal transplant population. Methods: This prospective study analyzed 103 samples from 66 kidney transplant recipients. To estimate total drug exposure (AUC), a limited sampling strategy was used with plasma samples collected at trough, and then 30 and 120 min post-dose. We performed linear univariate and multivariate regressions to evaluate the impact of patient characteristics (age, sex, body mass index (BMI)) and biochemical measurements (P-albumin, P-creatinine, estimated glomerular filtration rate (eGFR), B-tacrolimus) on MPA-AUC, peak concentrations (C_max) and trough levels. Results: At 750 mg twice daily, the median MPA-AUC was 43.5 mg·h/L (IQR: 34.5–53.5). After adjusting for dose, P-albumin and age were independent predictors of AUC: P-albumin levels were positively associated with AUC (β = 1.849, p < 0.001), while age showed a modest negative association (β = −0.282). BMI was significantly and inversely associated with trough concentrations (β = −0.137, p = 0.011), indicating that higher BMI is linked to lower trough concentrations. Male sex was associated with significantly lower AUC and C_max compared to females. Notably, eGFR and B-tacrolimus levels did not significantly influence MPA exposure in this cohort. Conclusions: The covariates BMI, sex, age, and P-albumin significantly influence MPA-AUC. LSS-based AUC monitoring, using 30–60 mg·h/L as a target and with consideration of a few patient-specific factors, could be a pragmatic and feasible approach to improve MMF dosing strategies in kidney transplant recipients. Full article

Background and Clinical Significance: COVID-19 may worsen in patients receiving immunosuppressants. Furthermore, drug–drug interactions and concomitant use of anti-inflammatory drugs complicate treatment. We report the clinical course of severe COVID-19 pneumonia in a 74-year-old Japanese male kidney transplant recipient. Case Presentation: The patient had been taking tacrolimus (TAC) (2.5 mg/day), mycophenolate mofetil (1000 mg/day), and prednisone (5 mg/day) since his kidney transplant 7 years earlier. Twenty days before admission, he tested positive for SARS-CoV-2 antigen and was administered molnupiravir for 5 days. At admission, real-time PCR testing of a nasopharyngeal specimen revealed high viral loads, with Ct values of 22.2 and 27.9 for the E and N2 genes, respectively. An oxygen flow rate of 15 L/min was required to maintain arterial oxygen saturation above 90%. TAC was continued, and antibiotics, steroids, anti-interleukin-6 receptor antibodies, intravenous immunoglobulin, and ensitrelvir (ESV) were administered. With invasive positive-pressure ventilation, positive end-expiratory pressure (PEEP), and prone positioning, the arterial oxygen tension/inspired oxygen tension (P/F) improved from 61.3 to 386 within 7 h. The patient was extubated 30 h after admission. The TAC dose was adjusted from 2.5 mg/day to 1 mg/day to achieve the target trough level. The patient was discharged on hospital day 8. PCR testing at discharge showed a decrease in viral load. Conclusions: This study provides insights into the treatment of COVID-19 in patients receiving immunosuppressants. Combination therapy of ESV and TAC was feasible in kidney transplant recipients with dose adjustment. The use of other anti-inflammatory drugs should also be considered. Full article

Background: Pregnancy following liver and kidney transplantation is rare. The presence of a rare genetic disorder and advanced chronic kidney disease (CKD) further complicates clinical management, for which evidence-based guidelines are limited. Case presentation: A 29-year-old woman with Alagille syndrome underwent combined liver and kidney transplantation in early childhood. She had stage 4 CKD, and her baseline creatinine was around 250 umol/L. Her pregnancy was unplanned and diagnosed at 19+1 weeks of gestation. After the diagnosis of pregnancy, immunosuppressive therapy was promptly adjusted, and potentially teratogenic medications were discontinued. At 21+1 weeks’ gestation, creatinine and urea levels rose despite multidisciplinary management, and she started renal replacement therapy. Despite ongoing multidisciplinary care, the pregnancy was complicated by placental abruption at 24+5 weeks, requiring a preterm cesarean section. A live-born female infant weighing 590 g was delivered. Discussion: The coexistence of CKD, long-term immunosuppression, and high obstetric risk requires early multidisciplinary assessment and individualized management. Currently, standardized protocols for monitoring and treatment are lacking in this rare population, making clinical decision-making particularly challenging, especially regarding CKD progression. Conclusion: Pregnancy in women with combined liver and kidney transplantation and advanced CKD carries a high risk of severe renal and obstetric complications. Preconception counseling and early referral to multidisciplinary teams may help improve management in similar rare clinical scenarios. Full article

Background/Objectives: Hepatitis B virus (HBV) transmission risk from donors with resolved HBV infection remains a concern in kidney transplantation, because covalently closed circular deoxyribonucleic acid (DNA) may persist despite serological recovery. In this study, we evaluated the transmission risk from anti-hepatitis B core antibody (anti-HBc)-positive, hepatitis B surface antigen (HBsAg)-negative, and HBV-DNA-negative living donors to anti-HBc-negative recipients. Methods: We retrospectively reviewed living-donor kidney transplantations performed at our institution (June 2011–December 2024). Among 277 transplantations, 26 met the inclusion criteria. All recipients had received HBV vaccination prior to transplantation. Serological markers, including HBsAg, anti-HBc, anti-hepatitis B surface antibody (anti-HBs), and HBV-DNA, were monitored before and after transplantation. Results: Five recipients (19.2%) achieved anti-HBs seroconversion after vaccination pre-transplantation, but all lost protective antibody levels before or shortly after transplantation. Five recipients (19.2%) showed transient post-transplantation anti-HBs positivity; three cases were considered vaccine-related, and two were possibly transplant-related. None of the patients developed liver enzyme elevation, clinical hepatitis, HBsAg positivity, or anti-HBc seroconversion. Among the four recipients tested for HBV-DNA, all results remained undetectable throughout follow-up. None of the recipients maintained protective anti-HBs levels pre- or post-transplantation, despite universal vaccination. Two recipients (7.7%) developed delayed anti-HBs positivity without anti-HBc seroconversion, HBsAg positivity, or detectable HBV-DNA, suggesting possible subclinical HBV antigen exposure from the allograft. Conclusions: Kidney transplantation from donors with resolved HBV infection was not associated with clinically evident HBV infection, although transient serological changes were observed. Optimized vaccination strategies and structured post-transplant monitoring may enhance the safety of transplantations involving such donors. Full article

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a frequent and severe complication of open-heart surgery. Although oxidative/inflammatory mechanisms are known to contribute to its pathophysiology, the circulating factors involved are poorly understood. In this preliminary investigation, we evaluated the effects of plasma from patients undergoing cardiac surgery on endothelial and renal tubular cells at anesthesia induction (T0) and 48 h after surgery (T1). Plasma levels of thiobarbituric acid-reactive substances (TBARSs), glutathione (GSH), and nitric oxide (NO) were measured in parallel. At T0, patient plasma showed increased TBARSs and reduced GSH and NO levels, consistent with oxidative imbalance, and induced cellular injury. In both cell types, plasma exposure reduced cell viability and mitochondrial membrane potential, while it increased oxidant release. Endothelial cells also showed decreased NO production, whereas renal tubular displayed increased apoptotic markers and reduced anti-aging factors. At T1, these alterations were further aggravated only in patients who developed CSA-AKI, whose plasma caused more severe endothelial and tubular damage. These findings support the presence of circulating injurious factors in cardiac surgery patient plasma that may contribute to CSA-AKI pathogenesis and help identify patients at risk before irreversible kidney damage develops. Full article

Annually, there are more than two million deaths from liver disease. This is driven by organ inflammation and scarring, leading to a decline in function and regeneration. Frequently, this can develop into decompensated liver disease, resulting in the loss of physiological balance and toxin build-up within the body, with an increased risk of patient mortality. Currently, there are no approved medicines for the long-term treatment of liver cirrhosis. The only successful treatment option for end-stage liver disease patients is donor organ transplantation. However, patient requirement outstrips the number of donated organs. To address this bottleneck, researchers around the world have developed cell-based prototype systems to restore failing liver function, with some in clinical trials. Although significant progress has been made, no mainstream commercial liver assist products are available for routine clinical use. In this study we developed a stem cell-derived vascularized liver tissue implant prototype from pluripotent cells. The liver tissue was produced from a stem cell line that is banked at clinical grade, and displayed stable and mature liver function over a 6-week period in vitro. This included decreasing levels of the fetal marker, alpha-fetoprotein, when the serum albumin increased. This was further supported by stable alpha-1-antitrypsin secretion and cytochrome P450 function. Following the establishment of stable liver tissue, it was delivered as a cell product or attached to an electrospun polycaprolactone scaffold, to form a tissue implant. Next, cellular material was quality-controlled, and subsequently shipped to a contract research organization for external in vivo validation. The transplanted liver tissue functioned when implanted into the kidney capsule and subcutaneously, remaining functional for up to two weeks in vivo. Full article

Oxidative stress and inflammation are key drivers of kidney injury and disease progression. In this context, the role of sialic acids emerged as a critical regulatory layer linking redox imbalance, immune activation, and tissue damage. Sialic acids are terminal negatively charged residues that regulate complement activity, immune cell signaling, and the structural integrity of the glomerular filtration barrier. Alterations in sialylation, resulting from impaired biosynthesis or increased sialidase activity, disrupt immune homeostasis, enhance inflammatory responses, and promote complement-mediated injury. In the kidney, these mechanisms contribute to podocyte dysfunction, glomerular inflammation, and fibrosis and are implicated in glomerulopathies, transplantation, and plasma cell dyscrasias. Emerging evidence also highlights the therapeutic potential of targeting sialic acid metabolism through inhibition of desialylation or restoration of sialylation pathways. Overall, sialic acids represent dynamic modulators at the intersection of oxidative stress and immunity, offering novel opportunities for biomarker development and mechanism-based therapies in kidney disease. Full article

Objective: To evaluate the early oncological outcomes of patients treated with robot-assisted radical prostatectomy for prostate cancer with multiple PIRADS lesions at baseline mpMRI in a tertiary referral center. Methods: Data of consecutive patients undergoing robot-assisted radical prostatectomy between 2020 and 2022 at a high-volume tertiary referral center were prospectively collected. mpMRI data was evaluated by two expert uro-radiologists at our center. All patients received an MRI–ultrasound fusion biopsy. Results: Overall, 286 patients with multiple PIRADS lesions treated with robot-assisted radical prostatectomy at a tertiary referral center were included. Unilateral and bilateral nerve-sparing were achieved in 63 (22.3%) and 124 (43.1%) patients, respectively. Median age was 69 years (IQR: 64–72), while median Charlson Comorbidity Index was 3 (IQR: 2–4). The presence of two PIRADS lesions was found in the 81.8% of cases, while 18.2% presented with three or more. Bilateral lesions were observed in 67.4% of cases. The dominant lesion was PIRADS 4 in 57.3% and PIRADS 5 in 32.3% of cases, with a median diameter of 12 mm (IQR: 10–17). Pathological upstaging to pT3 occurred in 61% of patients. Overall, 9.8% of cases exhibited positive surgical margins (PSMs), most of them single and limited in extent. Postoperative major complications were recorded in 6.3% of patients. At a median follow-up of 18 months (IQR: 6–29), biochemical recurrence (BCR) occurred in 8% of patients. Patients with PIRADS 5 lesions experienced shorter BCR-free survival compared to those with PIRADS 3–4. On multivariable Cox regression, PIRADS 5 independently predicted biochemical recurrence (HR: 2.52; 95% CI: 1.10–5.80; p = 0.029), after adjustment for age, number of lesions, and nerve-sparing status, with the performance of nerve-sparing not associated with an increased risk of recurrence, including in patients with multifocal disease. Conclusions: Nerve-Sparing Robot-Assisted Radical Prostatectomy in patients with multiple PIRADS lesions achieves encouraging short-term oncologic outcomes, with biochemical recurrence-free survival exceeding 84% at 3 years, despite high rates of multifocality and pathological upstaging. Full article

Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis. This prospective single-center, non-randomized, single-arm cohort study enrolled renal transplant recipients with refractory anemia, defined as hemoglobin (Hb) ≤10 g/dL despite receiving the maximum doses of erythropoiesis-stimulating agents for 12 weeks. The studied parameters were Hb, ferritin, iron saturation index, glomerular filtration rate (eGFR), and C-reactive protein (CRP). Follow-up assessments were conducted at 4, 8, and 12 weeks after starting Roxadustat. The primary endpoint was the proportion of patients achieving Hb > 11 g/dL at 12 weeks. Secondary endpoints included changes from baseline in studied parameters and adverse effects. Twenty recipients (11 male, 9 female) with a median age of 69.0 years and a median time post-transplant of 62.5 months were included. Median baseline eGFR was 16.5 mL/min/1.73 m². At 12 weeks, 19 of 20 (95%) achieved Hb > 11 g/dL. Median Hb increased significantly from 9.1 g/dL to 11.5 g/dL, with a median individual change of +2.7 g/dL (IQR 1.7–3.4; p < 0.001). The only non-responder increased Hb from 9.5 to 10.2 g/dL. Ferritin decreased significantly over 12 weeks, whereas no statistically significant changes were observed in transferrin saturation, CRP, or eGFR. No serious adverse events were observed. In this prospective cohort, roxadustat was associated with short-term hemoglobin improvement and high Hb target attainment; however, these findings should be interpreted cautiously given the single-arm design and limited sample size. Full article

Background: Pulmonary fibrosis (PF) is a chronic, progressive lung disease with limited treatment options. Liuweidihuang pill (LDP), a classical formula for kidney-yin deficiency, has been reported to have anti-inflammatory and anti-oxidative activities, suggesting potential relevance to PF. Purpose: This study evaluated whether LDP attenuates bleomycin-induced PF in mice and whether gut microbiota remodeling may contribute to its protective effects. Methods: Mice received intratracheal bleomycin followed by LDP gavage. Lung pathology was assessed by hematoxylin–eosin (HE) and Masson staining. Inflammatory cytokines, hydroxyproline (HYP), and α-SMA were measured. LDP and LDP-containing serum were profiled by UPLC-MS. The gut microbiota was analyzed using 16S rDNA sequencing. To further explore whether microbiota-related changes were associated with the protective phenotype, fecal microbiota transplantation (FMT) and probiotic VSL#3 intervention were performed. In addition, LDP-containing serum was tested in a TGF-β1-induced EMT model in A549 cells. Results: LDP reduced lung index, inflammatory infiltration, interstitial fibrosis, α-SMA expression, HYP content, and pro-inflammatory cytokine levels in bleomycin-treated mice. These effects were accompanied by gut microbiota remodeling and transcriptomic changes related to inflammation, metabolism, and fibrosis. VSL#3 partially reproduced the protective phenotype, whereas FMT showed limited efficacy. LDP-containing serum had a limited inhibitory effect on EMT inhibited EMT in vitro, suggesting that systemic host responses may contribute to the in vivo effect. Conclusions: LDP attenuated early bleomycin-induced PF and was associated with reduced inflammation and gut microbiota remodeling. These findings suggest a possible role for microbiota–host interactions in LDP-associated protection; however, causal directionality, key active effectors, and protein-level pathway validation remain unresolved. Full article

Purpose: Simultaneous liver–kidney transplantation (SLK) eligible candidates may receive SLK or liver-alone transplant (LA) with access to kidney transplant after initial LA (KAL). We aimed to characterize SLK-eligible recipient outcomes according to treatment approach. Methods: This study utilized 2017–2023 SRTR data to identify SLK-eligible deceased donor liver transplants. Recipients were placed into two groups based on whether SLK was performed; non-SLK patients were sub-stratified into LA and KAL cohorts. After baseline comparisons, 2-year patient and graft survival outcomes were characterized by univariable and multivariable Cox proportional hazard regression and Kaplan–Meier analysis. Results: Among 4879 candidates identified, 3746 (76.8%) underwent SLK, 1023 (21.0%) LA, and 110 (2.3%) KAL. SLK recipients maintained the highest eGFRs at 6 months, 1 year, and 2 years post-transplant (p < 0.01). Compared to SLK recipients, non-SLK recipients had a higher 2-year risk of mortality (aHR 2.46, p < 0.01), all-cause events (aHR 1.91, p < 0.01), and liver graft failure (HR 1.55, p = 0.02). LA conferred a higher 2-year mortality risk (aHR 2.98, p < 0.01) and all-cause event risk (aHR 2.25, p < 0.01), while KAL had comparable mortality risk to SLK (aHR 0.43, p = 0.40). Conclusions: When SLK-eligible candidates undergo transplants, SLK remains the optimal path forward, even when a safety net kidney can be performed. Full article

The endothelial glycocalyx (EG) is a dynamic endothelial surface layer composed of proteoglycans, glycosaminoglycans, glycoproteins, and adsorbed plasma proteins that regulates permeability, mechanotransduction, leukocyte trafficking, coagulation, and nitric oxide signaling. In kidney transplantation (KT), the EG is exposed to cumulative injury from recipient uremia, donor instability, preservation, machine perfusion, reperfusion, rejection, and immunosuppressive toxicity. This narrative review summarizes EG biology in KT, with emphasis on biomolecular findings relevant to ischemia–reperfusion injury, delayed graft function, rejection, and chronic allograft injury. Particular attention is given to syndecan-1, heparan sulfate, heparanase, soluble thrombomodulin, matrix metalloproteinases, angiopoietin-2/Tie2 signaling, selectins, miR-126, extracellular vesicles, and urinary or perfusate-derived readouts. Current evidence is biologically coherent but uneven: human data are largely observational, whereas many therapeutic concepts remain preclinical or exploratory. Glycocalyx-centered phenotyping may eventually improve risk stratification and trial enrichment, but clinical implementation will require standardized sampling, sample-source-aware biomarker panels, prospective validation, and clear separation between mechanistic plausibility and proven clinical utility. Full article

Background: Ischemia-reperfusion injury (IRI) impairs kidney transplants. Diazepam can reduce IRI through peripheral benzodiazepine receptors. We aimed to evaluate the effect of diazepam premedication on the IRI of the rat kidney. Methods: Fourteen days after unilateral nephrectomy, male Sprague-Dawley rats underwent a 45 min sole kidney ischemia. Sixty minutes prior to ischemia, the animals were randomly assigned to a subcutaneous injection of 0.75 mg diazepam (n = 28) or 0.5 mL 0.9% NaCl (n = 31). Results: After 48 h, serum creatinine of diazepam-administered rats was lower and creatinine clearance was higher than in controls (119.8 ± 73.3 vs. 217.5 ± 105.3 µmol/L, p < 0.01 and 0.14 ± 0.07 vs. 0.08 ± 0.05 mL/min/100 g BM, p < 0.01, respectively). Moreover, the former had lower urinary losses of sodium and potassium (fractional excretions of 1.24 ± 1.39% vs. 2.87 ± 3.66%, p = 0.02 and 111.1 ± 95.7% vs. 199.0 ± 143.3%, p < 0.01, respectively). After 7 days, diazepam-treated rats remained superior vs. controls, regarding serum creatinine (53.7 ± 12.7 vs. 77.6 ± 21.3 µmol/L, p < 0.01), creatinine clearance (0.22 ± 0.08 vs. 0.17 ± 0.06 mL/min/100 g BM, p < 0.01), potassium sparing (50.2 ± 31.7% vs. 73.4 ± 38.7% excretion, p < 0.01), and renal edema (1.92 ± 0.45 vs. 2.30 ± 0.61 g of kidney mass, p < 0.01). Furthermore, their 24 h proteinuria was marginally reduced (4.03 ± 2.62 vs. 5.06 ± 2.74 mg, p = 0.06). Conclusions: Administration of diazepam preceding renal ischemia attenuates subsequent kidney injury in rats. Benzodiazepines may be beneficial prior to kidney transplantation. Full article

Background/Objectives: Early transient endocrine dysfunction after simultaneous pancreas-kidney transplantation (SPK) frequently triggers urgent investigations to exclude thrombosis, pancreatitis, or rejection, yet many recipients recover during the index admission. We tested whether pre-transplant day zero (D0) serum Fourier-transform infrared spectroscopy (FTIRS) captures a biochemical fingerprint associated with a Start&Stop trajectory (initial insulin independence followed by transient dysfunction with recovery). Methods: In a single-center retrospective case-control study nested within 104 consecutive SPK recipients with available D0 serum, 12 Start&Stop cases were matched 1:1 to 12 No-Stop controls. Serum FTIR spectra went through structured quality control and standardized preprocessing. A Naïve Bayes classifier with Fast Correlation-Based Filter (FCBF) feature selection was evaluated using leave-one-out cross-validation (LOOCV) and label-permutation analysis. Results: Under LOOCV, the primary FTIRS model (Savitzky-Golay second derivative; 600–900 and 2800–3400 cm⁻¹) achieved excellent discrimination (ROC-AUC 1.00) with accuracy 0.958 and F1 score 0.958. Discrimination collapsed under label permutation (ROC-AUC 0.461), supporting a non-random label-spectrum association. Discriminant information mapped mainly to carbohydrate/glycoprotein-associated bands (~946–1161 cm⁻¹), protein structural contributions near the amide III region (~1300 cm⁻¹), and lipid/protein stretching modes (~2865–3163 cm⁻¹), consistent with a multicomponent systemic biochemical state. Conclusions: In this exploratory matched case-control cohort, pre-transplant D0 serum FTIRS signatures were associated with the subsequent Start&Stop phenotype after SPK. These findings should be interpreted as recipient-side exploratory risk-stratification signals rather than clinically actionable decision tools. Larger multicenter validation in unselected cohorts, with standardized endpoint adjudication, preanalytical control, fully nested model development and inter-instrument harmonization, is required before clinical implementation or population-level risk calibration. Full article