Acute kidney injury (AKI) in paediatric kidney transplant recipients is common. Infection including urinary tract infection (UTI) and rejection are the most common causes in children. Surgical complications often cause AKI early post-transplant, whereas BK polyomavirus nephropathy rarely occurs in the first month post-transplant. Understanding kidney physiology helps to appreciate the sensitivity of the allograft to AKI, more so than native kidneys. Although the cause of AKI is often multi-factorial, there may be an underlying process that is treatable. Eliciting the aetiology, in this regard, is of paramount importance. Pre-renal and post-renal causes of allograft dysfunction are important to distinguish from intrinsic kidney disease. Clinical information and examination of fluid balance, urine dipstick testing, blood tests, bladder and kidney transplant ultrasound, and kidney transplant biopsy remain vital assessment tools in narrowing the differential diagnosis. A careful prescribed and recreational drug history is always warranted as many drugs including supplements are nephrotoxic. Additional causes such as allograft rejection, recurrent disease, and calcineurin inhibitor toxicity need to be considered in cases of allograft dysfunction, which would not affect the native kidneys. Early detection and assessment of AKI is crucial in promoting recovery. Significant progress has been made in specific pathologies over the last 20 years, which has improved kidney allograft survival rates considerably. Research into identifying AKI biomarkers to assist early diagnosis, before the serum creatinine rises, is ongoing.

Background & ObjectivePresence of lupus nephritis is associated with a shorter time to death in systemic lupus erythematosus. The aim of this study was to determine the frequency of peritubular capillaritis (ptc) and its relationship with both active and chronic lesions in lupus nephritis.Material-MethodsSpecimens from 57 patients were re-evaluated. The degree of inflammation within the peritubular capillaries in each biopsy was assessed according to the Banff classification, and ptc scoring was performed. Additionally, patients were grouped based on high/low activity and chronicity index scores.ResultsForty-five (78.9%) of the patients were female, with a mean age of 27.43 years. Ptc was identified in 45 (78.9%) patients, with ptc scores of 1, 2, and 3 observed in 20 (35.08%), 20 (35.08%), and 5 (8.7%) patients, respectively. Severe ptc (scores 2 or 3) was more commonly detected in patients with elevated serum creatinine (>1.20 mg/dL) compared to those with normal creatinine levels (92.3% vs 29.5%, p < 0.001). The severity of ptc was higher in Class 4 patients than in Class 3 patients (68.2% vs 21.7%, p = 0.005). The rate of high ptc scores was greater in patients with an activity index of 6 or above compared to those with an activity index below 6 (62.5% vs 30.3%, p = 0.032). No significant correlation was found between the chronicity index and ptc.ConclusionsThe findings of this study suggest that ptc is a frequently observed pathological feature in patients with lupus nephritis. Furthermore, the severity of ptc appears to be positively associated with elevated serum creatinine levels, and higher ptc scores are more commonly detected in cases with a high activity index.

Antibody-mediated rejection remains a leading cause of graft loss during kidney transplantation. Ischemia reperfusion injury (IRI) has been reported to promote T cell proliferation, leading to B cell activation and subsequent production of donor-specific antibodies, which target antigens on the vascular endothelium. We hypothesize that a novel therapeutic strategy targeting highly toxic reactive oxygen species could mitigate oxidative stress and immune responses associated with IRI. Our previous study demonstrated that oral administration of a silicon (Si)-based agent consistently generates substantial amounts of hydrogen, effectively suppressing IRI-induced oxidative stress and acute kidney injury in a rat renal clamp model. Here, we investigated the effect of the Si-based agent on immune responses in an allogeneic kidney transplant setting. Using both short-term and long-term evaluation models, we found that the Si-based agent suppressed oxidative stress and acquired immunity activation. Furthermore, early suppression of donor-specific antibody production and amelioration of chronic antibody-mediated rejection were observed. These findings indicate that the Si-based agent offers protective effects on graft function and survival, highlighting its potential clinical application to improve outcomes for kidney transplant recipients.

Given our desire to reduce kidney transplant waiting times by utilizing more difficult-to-place ("higher-risk") DD kidneys, we wanted to better understand post-transplant renal function among 1119 adult DD recipients consecutively transplanted during 2016-2019. Stepwise linear regression of eGFR (CKD-EPI formula) at 3-, 6-, and 12-months post-transplant (considered as biomarkers for longer-term outcomes), respectively, was performed to determine the significant multivariable baseline predictors, using a type I error ≤ 0.01 to avoid spurious/weak associations. Three unfavorable characteristics were selected as highly significant in all three models: Older DonorAge (yr) (p < 0.000001), Longer StaticColdStorage Time (hr) (p < 0.000001), and Higher RecipientBMI (p ≤ 0.00003). Other significantly unfavorable characteristics included: Shorter DonorHeight (cm) (p ≤ 0.00001), Higher Natural Logarithm {Initial DonorCreatinine} (p ≤ 0.001), Longer MachinePerfusion Time (p ≤ 0.003), Greater DR Mismatches (p = 0.01), DonorHypertension (p ≤ 0.004), Recipient HIV+ (p ≤ 0.006), DCD Kidney (p = 0.002), Cerebrovascular DonorDeath (p = 0.01), and DonorDiabetes (p = 0.01). Variables not selected into any model included DonorAKI Stage (p ≥ 0.24), Any DonorAKI (p ≥ 0.04), and five KDRI components: two DonorAge splines at 18 years (p ≥ 0.52) and 50 years (p ≥ 0.28), BlackDonor (p ≥ 0.08), DonorHCV+ (p ≥ 0.06), and DonorWeight spline at 80 kg (p ≥ 0.03), indicating that DonorAKI and the weaker KDRI components have little, if any, prognostic impact on renal function during the first 12 months post-transplant. Additionally, biochemical determinations with skewed distributions such as DonorCreatinine are more accurately represented by natural logarithmic transformed values. In conclusion, one practical takeaway is that donor AKI may be ignored when evaluating DD risk.

Fosravuconazole L-lysine ethanolate (F-RVCZ) is a prodrug of ravuconazole and a triazole antifungal drug used for the treatment of onychomycosis. It has been reported in previous studies that the kidney injury caused by F-RVCZ is 1% or less.

Serum creatinine levels were compared, and glomerular filtration rate and urine protein were estimated before and after starting the administration of F-RVCZ, as well as after the end of the administration period. The cause of kidney injury was investigated using renal pathology, and risk factors were also investigated.

F-RVCZ was administered to 46 patients. Ten of these patients were excluded because three were maintenance dialysis patients and seven were not measured for serum creatinine. Remaining 36 patients were included in the analyses. Kidney injury occurred in 27.8% of patients treated with F-RVCZ; this condition persisted in 10% of patients after the end of the administration period. No changes were observed in the urinalysis after the administration of F-RVCZ. A kidney biopsy was performed in one patient, but no lesions were found that could be the cause of kidney injury. Patients who developed kidney injury were significantly more likely to be receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (odds ratio 18.9, 95% confidential interval: 1.69-210, p = 0.0169).

Kidney injury is caused by F-RVCZ more frequently than previously reported, but the mechanism remains unclear.

We recently discovered 2 urinary exosomal mRNA signatures to identify and differentiate T-cell-mediated rejection (TCMR) from antibody-mediated rejection (ABMR) in kidney transplant recipients. Here, we developed Exosome Transplant Rejection Urine (ExoTRU), a urinetest based on a 4-gene signature from the previous discovery cohort, showed its clinical utility in a new cohort of kidney transplant recipients undergoing clinically indicated biopsies, and validated it through a separate laboratory in an independent-cohort of patients.

A workflow suited for clinical laboratories was developed, allowing for smaller urine volumes and widely standardized qPCR instrumentation. A total of 226 urine samples from 214 patients were paired with clinically indicated biopsies. Urinary exosomal mRNAs levels were evaluated for previously defined targets.

Four mRNAs (IL32, B2M, CXCL11, and PGK1) performed well in distinguishing biopsies with rejection or significant inflammation from those without inflammation, achieving 94% sensitivity, 62% positive predictive value, and 52% specificity. Patients who tested positive by the signature but negative by biopsy were nearly twice as likely to experience adverse outcomes in the 5-year follow-up period, including subsequent rejection, thereby showing the limitations of kidney biopsies and the prognostic potential of molecular signatures. The evaluation of an independent validation cohort showed similar performance, achieving an area under the curve (AUC) of 0.838. Another 6-gene signature distinguished TCMR from ABMR, with an AUC of 0.756.

Exosomal mRNA gene signatures identified patients with different stages and classes of rejection, including early stage and significant inflammation, enabling improved decision-making and patient management and reducing unnecessary biopsies by 45%. This represents a potential tool for risk stratification based on poor outcomes in patients with positive signatures.

Acute allograft rejection in patients undergoing renal transplantation is diagnosed through histopathological analysis of renal graft biopsies, which can be used to quantify elementary lesions. However, quantification of elementary lesions requires considerable expertise, time, and effort. Using a 2-stage classification strategy, we sought to examine the effectiveness of deep learning in detecting and classifying glomeruli into 4 groups, namely normal, abnormal, sclerotic, and glomerulitis, as a potential biopsy triage system focused on transplant rejection. We used the U-Net model to build a glomeruli detection model using 137 kidney biopsy slides obtained from 80 kidney transplant patients. The median age of the patients was 52 (19-74) years, with 65% being men and 35% women. MobileNetV2 and VGG16 models were compared using a 2-stage classification strategy. In the first classification step, the models classified glomeruli into sclerotic and nonsclerotic glomeruli. In the second classification step, the nonsclerotic glomeruli from the first step were classified as normal, abnormal, or glomerulitis. The U-Net model achieved satisfactory detection (Dice coefficient = 0.90), and the MobileNetV2 model was the best for the 2 classification steps, with F1 scores of 0.85, 0.91, 0.98, and 0.92 for normal, abnormal, sclerotic, and glomerulitis, respectively. The 2-stage classification strategy identifies sclerotic glomeruli and abnormal glomeruli relative to permeable glomeruli and quantifies glomerulitis with significant accuracy while avoiding bias from abnormal glomeruli that do not have glomerulitis, providing valuable diagnostic information.

Non-invasive assessment of renal fibrosis in patients with chronic kidney disease (CKD) remains a clinical challenge. This study aims to integrate radiomics and clinical factors to develop an end-to-end pipeline for predicting interstitial fibrosis (IF) in CKD patients.

This retrospective study included 80 patients with CKD, with 53 patients in training set and 27 patients in test set. All patients underwent renal computed tomography (CT) scans and biopsy. Patients were classified into two groups based on their renal IF grade: mild-moderate and severe. Radiomics features were extracted from the automatically segmented right renal region on CT images, and univariate analysis along with multiple Least Absolute Shrinkage and Selection Operator (LASSO) was employed to construct the radiomics signature. Subsequently, logistic regression models were developed to create the radiomics model and the combined model. The predictive performance of both models was evaluated through discrimination, calibration, and decision curve analysis (DCA), and a nomogram was constructed for the model demonstrating superior performance.

The combined model significantly outperformed the radiomics model, achieving a cross-validated AUC of 0.935±0.041 in the training set, compared to 0.804±0.024 for the radiomics model. In the test set, the combined model outperformed the radiomics model, with an AUC of 0.918 [95% CI 0.799-1] vs. 0.764 [95% CI 0.549-0.979], p=0.031 (DeLong test, Statistic: -2.152). Calibration curves and DCA indicated that the combined model demonstrated good calibration and better clinical net benefit.

This end-to-end workflow could serve as a potential non-invasive tool to predict renal IF grade (mild-moderate vs. severe) in CKD patients.

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) is a serious issue for long-term graft survival in kidney transplantation. However, the pathophysiology of TAC nephrotoxicity remains unclear. In this study, we analyzed whole blood samples from mice that developed TAC nephrotoxicity in order to discover its mechanism. Mice were divided into a TAC group and a control group (n = 5 per group). The TAC group received TAC subcutaneously (1 mg/kg/day for 28 days), while the control group received normal saline instead. After the administration period, whole blood was collected and metabolomic analysis was performed, revealing significant changes in 56 metabolites. The major metabolic changes were related to uremic toxins, vascular damage, and NAD+. NAD+ levels were significantly lower in the TAC group, and ADP-ribose, nicotinamide, and nicotinamide N-oxide, which are degradation products of NAD+, were significantly higher, suggesting impairment of the NAD+ salvage pathway. NAD+ deficiency suggests cellular aging and mitochondrial dysfunction, which may induce vascular damage and chronic kidney disease. Our study demonstrated a correlation between low NAD+ levels and the pathophysiology of TAC nephrotoxicity.

Acute rejection (AR) is a significant complication in liver transplantation, impacting graft function and patient survival. Kupffer cells (KCs), liver-specific macrophages, can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes, both of which critically influence AR outcomes. Angiopoietin-like 4 (ANGPTL4), a secretory protein, is recognized for its function in regulating inflammation and macrophage polarization. This study investigates the effects of ANGPTL4 on KC polarization through cellular interactions between hepatocytes (HCs) and KCs. Using a rat orthotopic liver transplantation model, we observed reduced ANGPTL4 expression during AR, whereas increased ANGPTL4 levels were linked to immune tolerance. Administration of ANGPTL4 recombinant protein improved liver function, suppressed inflammation, and promoted M2 polarization of KCs. Co-culture experiments demonstrated that hepatocyte-derived ANGPTL4 significantly modulates KC polarization and inflammatory responses, mainly by inhibiting the NF-κB signaling pathway. The results emphasize the promise of ANGPTL4 as a therapeutic target to reduce AR and improve liver transplant outcomes by influencing hepatocyte-KC interactions.

BK viremia (BKPyV-DNAemia) and nephropathy (BKPyVAN) are significant causes of morbidity and mortality in kidney transplant recipients (KTRs). Vitamin D supports immune function, yet low 25-hydroxyvitamin D [25(OH)D] is common among KTRs. The association between serum 25(OH)D, measured 61 days to 2 years post-transplant, and subsequent incident BKPyV-DNAemia and BKPyVAN was examined in KTRs without previous BKPyV-DNAemia or BKPyVAN, respectively. Out of 3308 KTRs, 399 (12%) were vitamin D deficient [25(OH)D ≤ 20 ng/mL], and 916 (27.7%) were insufficient [25(OH)D 21-29 ng/mL]. A total of 184 KTRs developed BKPyV-DNAemia and 44 developed BKPyVAN. The incidence rate (/100 person-years) for BKPyV-DNAemia was 2.88 in the 25(OH)D sufficient group, 2.22 in the insufficient group, and 2.37 in the deficient group. The incidence rate (/100 person-years) for BKPyVAN was 0.30 in the 25(OH)D sufficient group, 0.75 in the insufficient group, and 1.28 in the deficient group. Vitamin D deficiency (adjusted hazard ratio [aHR] compared to 25(OH)D sufficiency: 3.92; 95% CI: 1.66-9.23) and insufficiency (aHR: 2.22; 95% CI: 1.11-4.45) remained significantly associated with the incidence of BKPyVAN after adjustment for baseline characteristics. Low serum 25(OH)D was associated with an increased risk of BKPyVAN but not BKPyV-DNAemia.

De novo donor-specific HLA antibody (dnDSA) are associated with poor outcomes. Whether this observation applies to both HLA class I and II dnDSA remains unclear.

We studied 1236 consecutive kidney recipients who had routine anti-HLA antibody surveillance post-transplant.

During the screening period, 55/1236 (4.4%) patients developed dnDSA: 18 (33%) HLA-I only, 33 (60%) HLA-II only, and 4 (7%) both classes. Thirty patients experienced graft loss at a median of 39 months after dnDSA detection: 9/18 (50%) HLA-I only, 17/33 (52%) HLA-II only, and 4/4 (100%) both classes. A control group was created by matching patients with dnDSA to patients who did not develop DSA and had a functioning graft at the time of dnDSA detection in their respective cases. Compared with these controls, the risk estimates of graft loss were similar between patients with HLA-I only and HLA-II only dnDSA (aHR [95% CI] 2.7 [1.1-6.6], p=0.04 and 3.1 [1.5-6.6], p<0.01 respectively). Additionally, the risk of graft loss decreased with increasing CNI trough levels following dnDSA detection (aHR 0.7 [0.6-0.9] for each increase in 1 ng/mL, p=0.02).

The prognosis of patients with dnDSA is similar regardless of the HLA class specificity. Lower calcineurin inhibitor levels predict graft loss in such patients.

Robot-assisted kidney transplantation (RAKT) is increasingly being adopted worldwide. Despite this growing interest, there remains a notable gap in the literature, especially concerning its effectiveness in immunologically high-risk patients compared to conventional open kidney transplantation (OKT). This study investigates the viability and success of RAKT in comparison with OKT, particularly for recipients with ABO incompatibility (ABOi).

This retrospective, single-center study included 239 living-donor transplants between October 2020 and February 2023, with 210 patients undergoing ABOi-OKT and 29 undergoing ABOi-RAKT. A composite of biopsy-proven acute rejection (BPAR), graft failure, and the development of de novo donor-specific antibodies was analyzed through univariate and multivariate models. Propensity score matching (PSM) was utilized to ensure a balanced comparison between the two groups. Following PSM, a total of 131 cases in the OKT group and 26 cases in the RAKT group were analyzed.

After PSM, the mean recipient age was 48.56 years for OKT and 47.96 years for RAKT. Both groups had comparable one-year (RAKT: 92.4%, OKT: 93.1%) and two-year BPAR-free survival rates (RAKT: 92.4%, OKT: 91.9%). Mean estimated glomerular filtration rate values were similar at 12 months post-transplant (RAKT: 62.15 ml/min/1.73 m², OKT: 64.53 ml/min/1.73 m²). Operative times were significantly longer for RAKT (291.42 vs. 150.81 min, p < 0.001), while cold ischemic time was also longer for RAKT (119.77 vs. 47.22 min, p < 0.001). Hospital stays were shorter for RAKT (median 6 vs. 8 days, p < 0.001). There was no significant difference in the composite outcome of BPAR, graft failure, and de novo donor-specific antibodies between the two groups (HR 0.858, 95% CI: 0.180-4.096, p = 0.848).

RAKT is a safe and effective alternative to OKT in ABOi patients, demonstrating similar perioperative outcomes, graft survival rates, and renal function. The application of ropensity score matching analysis strengthens the reliability of these findings, confirming RAKT's viability for high-risk kidney transplant recipients.

The clinical trial associated with this study was registered on 2024-02-24 with the Clinical Trial Number NCT06287008|| https://www.

gov/ ).

Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls.

In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection.

We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment.

In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).

The effects of COVID-19 on the immune profile of kidney transplant recipients are unknown. Immunosuppression adjustment during the illness can increase the risk for de novo donor-specific anti-HLA antibodies (DSA) and acute rejection episodes. This single-center retrospective study includes adult kidney transplant recipients diagnosed with COVID-19 between March 2020 and December 2022, screened for anti-HLA antibodies (AbHLA) pre-transplant and after COVID-19. Analyzed data comprised demographics, immunosuppressive therapy before and during the illness, hospitalization rate, and AbHLA specificity. Two hundred sixty-seven transplant recipients were included and divided according to the pre-transplant AbHLA profile: absent [PRA- (n = 206, 77%)], non-DSA (N = 46, 17%), and DSA+ (n = 15, 6%). The DSA+ group was younger (40.5 ± 16.5; PRA- 50.3 ± 13.4; non-DSA 49.3 ± 11.7 years; p = 0.02). The hospitalization rate was higher in groups with preformed AbHLA (DSA+ n = 8, 53%; non-DSA = 24, 52%; PRA- n = 54, 26%; p < 0.01). Immunosuppression was maintained in 222 (83%), withdrawn in 33 (12%), and reduced in 11 (4%) cases without difference among groups. Twenty-two (8%) cases of de novo DSA were observed after COVID-19 [PRA-, n = 16 (73%) and non-DSA, n = 6 (27%)]. In the DSA+ group, the AbHLA profile remained stable. There were 6 (2%) cases of post-COVID-19 antibody-mediated rejection (DSA+ n = 4, 66%; non-DSA n = 1, 17%, PRA- n = 1, 17%) without T cell-mediated rejection cases. Post-COVID-19 de novo DSA was more frequent in groups without pre-transplant AbHLA, not having association with changes in immunosuppressive therapy.

The optimal dose of rabbit anti-thymocyte globulin (r-ATG) in renal transplantation is still under debate. We previously reported that a low-dose r-ATG induction of 3 mg/kg can be used safely and effectively in low-risk kidney transplants with good results in the first year after transplantation compared to basiliximab induction.

The purpose of this study is to evaluate the long-term impact of this trial of low-dose r-ATG versus basiliximab on post-transplant outcomes (patient and graft survival, biopsy-proven acute rejection incidence [BPAR], infectious complications, and side effects).

Observational study (three-year follow-up) of a 12-month single-center, open-label RCT in de novo kidney allograft recipients assigned to receive either thymoglobulin or basiliximab before transplantation.

Patients in the basiliximab group (BG) underwent more kidney transplant biopsies than patients in the low-dose r-ATG group (TG) (50 vs. 31.8%, p = 0.07). Although the 12-month cumulative incidence of BPAR was lower in BG, by the end of the three-year follow-up period this incidence was higher (22%) than in the low-dose TG (15%) (p = ns). Steroids were withdrawn more frequently in the TG group and sirolimus was most frequently indicated. Graft function and graft survival were higher in the low-dose TG than in the BG at three-year follow-up but not statistically significant. Patient survival was similar between groups (>90%).

These three-year follow-up data confirm the efficacy and favorable safety aspects of the low-dose r-ATG (3 mg/kg) in low-risk kidney transplantation.

Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described.

We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies.

Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States. Participants were most often nephrologists (52%), followed by surgeons (46%), and other staff (4%). Pancreas allograft biopsies were performed mostly by interventional radiologists (74%), followed by surgeons (11%), nephrologists (8%), and gastroenterologists (1%). Limitations in the radiologist's or biopsy performer's comfort level or expertise to safely perform a biopsy, or to obtain sufficient/adequate samples were the two most common challenges with pancreas transplant biopsies. Pancreas transplant biopsies were read by local pathologists at a majority (86%) of centers. Challenges reported with pancreas biopsy interpretation included poor reliability, lack of reporting of C4d staining, lack of reporting of rejection grading, and inconclusive interpretation of the biopsy. Staff at a third of responding programs (34%) stated that they rarely or never perform pancreas allograft biopsies and treat presumed rejection empirically.

This national survey identified significant variation in clinical practices related to pancreas allograft biopsies and potential barriers to pancreas transplant utilization across the United States. Consideration of strategies to improve program experience with percutaneous pancreas biopsy and to support optimal management of pancreas allograft rejection informed by histology is warranted.

Persistent chronic hypotension affects 5-10% of dialysis patients. It seems to be reversible after receiving a functioning graft, but data regarding its influence on transplant outcomes are scarce. We analyze the evolution of patients with chronic hypotension in dialysis who undergo kidney transplantation at our center.

A retrospective observational study was conducted. Sixty-six patients with chronic hypotension (defined as systolic blood pressure ≤ 100 mm Hg at the time of transplantation) were identified. A control group of 66 non-hypotensive patients was assigned. The evolution of both groups was compared.

Hypotensive patients had higher rates of primary non-function (18.2% vs. 6.1%; P = 0.03) mainly due to venous thrombosis of the allograft, worse renal function at the end of follow-up (eGFR of 35 mL/min/1.73 m2 vs 48 mL/min/1.73 m2, P = 0.001) but there was no statistical difference in graft survival after censoring for primary non-function. After multivariable adjustment, chronic hypotension remained an independent predictor factor for graft failure (adjusted HR of 2.85; 95% CI: 1.24-6.57; P = 0.014). Use of vasoactive drugs and anticoagulation in hypotensive patients was associated with 7.1% of venous graft thrombosis compared to 17.3% in those with no intervention (P = 0.68). Receiving a functioning graft implied blood pressure normalization in patients with chronic hypotension.

Chronic hypotension in dialysis has a negative impact on short-term kidney transplant outcomes but a lower impact on long-term results. It is reversible after receiving a functioning graft. Identifying this subgroup of patients seems crucial to implement measures aimed at improving transplant results.

Antibodies to angiotensin II type 1 receptor (AT1R-Abs) are among the most well-studied non-HLA antibodies in renal transplantation. These antibodies have been shown to be common in pediatric kidney transplantation and associated with antibody-mediated rejection (AMR), vascular inflammation, development of human leukocyte donor-specific antibodies (HLA DSA), and allograft loss. As AT1R-Ab testing becomes more readily accessible, evidence to guide clinical practice for testing and treating AT1R-Ab positivity in pediatric kidney transplant recipients remains limited. This review discusses the clinical complexities of evaluating AT1R-Abs given the current available evidence.

Kidneys are among the most structurally complex organs in the body. Their architecture is critical to ensure proper function and is often impacted by diseases such as diabetes and hypertension. Understanding the spatial interplay between the different structures of the nephron and renal vasculature is crucial. Recent efforts have demonstrated the value of three-dimensional (3D) imaging in revealing new insights into the various components of the kidney; however, these studies used antibodies or autofluorescence to detect structures and so were limited in their ability to compare the many subtle structures of the kidney at once. Here, through 3D reconstruction of fetal rhesus macaque kidneys at cellular resolution, we demonstrate the power of deep learning in exhaustively labelling seventeen microstructures of the kidney. Using these tissue maps, we interrogate the spatial distribution and spatial correlation of the glomeruli, renal arteries, and the nephron. This work demonstrates the power of deep learning applied to 3D tissue images to improve our ability to compare many microanatomical structures at once, paving the way for further works investigating renal pathologies.

Renal pathology is a relatively recent entry in nephrology. While diseases of the kidney are old, their study began in the 19th century with the report of Richard Bright of the lesions of end-stage kidney disease. Its easy diagnosis from albuminuria soon elevated Bright's nephritis into a leading cause of death. The transformative events in the care of these cases were renal replacement therapy that converted a fatal into a chronic disease, and kidney biopsy that allowed study of the course and pathogenesis of kidney disease. Apart from its fundamental contributions to clinical nephrology, biopsy of renal allografts became an integral component of the evaluation and care of kidney transplant recipients. The Banff transplant pathology conferences launched in 1991 led to developing the classification of allograft pathology into an essential element in the evaluation, treatment, and care of allograft recipients with spirit of discovery. That success came at the cost of increasing complexity leading to the recent realization that it may need the refinement of its consensus-based system into a more evidence-based system with graded statements that are easily accessible to the other disciplines involved in the care of transplanted patients. Collaboration with other medical disciplines, allowing public comment on meeting reports, and incorporation of generative artificial intelligence (AI) are important elements of a successful future. The increased pace of innovation brought about by AI will likely allow us to solve the organ shortage soon and require new classifications for xenotransplantation pathology, tissue engineering pathology, and bioartificial organ pathology.

Urine CXCL10 is a promising biomarker for posttransplant renal allograft monitoring but is currently not widely used for clinical management.

Large retrospective studies and data from a prospective randomized trial as well as a prospective cohort study demonstrate that low urine CXCL10 levels are associated with a low risk of rejection and can exclude BK polyomavirus replication with high certainty. Urine CXCL10 can either be used as part of a multiparameter based risk assessment tool, or as an individual biomarker taking relevant confounders into account. A novel Luminex-based CXCL10 assay has been validated in a multicenter study, and proved to be robust, reproducible, and accurate.

Urine CXCL10 is a well characterized inflammation biomarker, which can be used to guide performance of surveillance biopsies. Wide implementation into clinical practice depends on the availability of inexpensive, thoroughly validated assays with approval from regulatory authorities.

Rejection remains the most important factor limiting the survival of transplanted kidneys. Although a pathological biopsy of the transplanted kidney is the gold standard for diagnosing rejection, its limitations prevent it from being used as a routine monitoring method. Recently, peripheral blood lymphocyte subpopulation testing has become an important means of assessing the body's immune system, however, its application value and strategy in the field of kidney transplantation need further exploration. Additionally, the development and utilization of routine test parameters are also important methods for exploring diagnostic strategies and predictive models for kidney transplant diseases. This study aims to explore the correlation between peripheral blood lymphocyte subpopulations and T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), as well as their diagnostic value, in conjunction with routine blood tests.

A total of 154 kidney transplant recipients, who met the inclusion and exclusion criteria and were treated at the Second Xiangya Hospital of Central South University from January to December, 2021, were selected as the study subjects. They were assigned into a stable group, a TCMR group, and an ABMR group, based on the occurrence and type of rejection. The basic and clinical data of these recipients were retrospectively analyzed and compared among the 3 groups. The transplant kidney function, routine blood tests, and peripheral blood lymphocyte subpopulation data of the TCMR group and the ABMR group before rejection treatment were compared with those of the stable group.

The stable, TCMR group, and ABMR group showed no statistically significant differences in immunosuppressive maintenance regimens or sources of transplanted kidneys (all P>0.05). However, the post-transplant duration was significantly longer in the ABMR group compared with the stable group (P<0.001) and the TCMR group (P<0.05). Regarding kidney function, serum creatinine levels in the ABMR group were higher than in the stable group and the TCMR group (both P<0.01), with the TCMR group also showing higher levels than the stable group (P<0.01). Both TCMR and ABMR groups had significantly higher blood urea nitrogen levels than the stable group (P<0.01), with no statistically significant difference between TCMR and ABMR groups (P>0.05). The estimated glomerular filtration rate (eGFR) was lower in both TCMR and ABMR groups compared with the stable group (both P<0.01). In routine blood tests, the ABMR group had lower hemoglobin, red blood cell count, and platelet count than the stable group (all P<0.05). The TCMR group had higher neutrophil percentage (P<0.05) and count (P<0.05) than the stable group, and the ABMR group had a higher neutrophil percentage than the stable group (P<0.05). The eosinophil percentage and count in the TCMR group were lower than in the stable and ABMR groups (all P<0.05). Both TCMR and ABMR groups had lower basophil percentage and count, as well as lower lymphocyte percentage and count, compared with the stable group (all P<0.05). There were no significant differences in monocyte percentage and count among the 3 groups (all P>0.05). In lymphocyte subpopulations, the TCMR and ABMR groups had lower counts of CD45+ cells and T cells compared with the stable group (all P<0.05). The TCMR group also had lower counts of CD4+ T cells, NK cells, and B cells than the stable group (all P<0.05). There were no significant differences in the T cell percentage, CD4+ T cell percentage, CD8+ T cell percentage and their counts, CD4+/CD8+ T cell ratio, NK cell percentage, and B cell percentage among the stable, TCMR, and ABMR groups (all P>0.05).

The occurrence of rejection leads to impaired transplant kidney function, accompanied by characteristic changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations in kidney transplant recipients. The different characteristics of changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations during TCMR and ABMR may help predict and diagnose rejection and differentiate between TCMR and ABMR.

Kidney transplantation is considered the most effective treatment for end-stage renal failure. Recent studies have shown that the significance of the immune microenvironment after kidney transplantation in determining prognosis of patients. Therefore, this study aimed to conduct a bibliometric analysis to provide an overview of the knowledge structure and research trends regarding the immune microenvironment and survival in kidney transplantation.

Our search included relevant publications from 2013 to 2023 retrieved from the Web of Science core repository and finally included 865 articles. To perform the bibliometric analysis, we utilized tools such as VOSviewer, CiteSpace, and the R package "bibliometrix". The analysis focused on various aspects, including country, author, year, topic, reference, and keyword clustering.

Based on the inclusion criteria, a total of 865 articles were found, with a trend of steady increase. China and the United States were the countries with the most publications. Nanjing Medical University was the most productive institution. High-frequency keywords were clustered into 6 areas, including kidney transplantation, transforming growth factor β, macrophage, antibody-mediated rejection, necrosis factor alpha, and dysfunction. Antibody mediated rejection (2019-2023) was the main area of research in recent years.

This groundbreaking bibliometric study comprehensively summarizes the research trends and advances related to the immune microenvironment and survival after kidney transplantation. It identifies recent frontiers of research and highlights promising directions for future studies, potentially offering fresh perspectives to scholars in the field.

Ultrasound shear wave elastography (SWE) methods are being used to differentiate healthy versus diseased tissue on the basis of their viscoelastic mechanical properties. Tissue viscoelasticity is often studied by analyzing shear wave phase velocity dispersion curves, which is the variation of phase velocity with frequency or wavelength. Recently, a unique approach using a generalized Stockwell transformation (GST-SFK) was proposed for the calculation of dispersion curves in viscoelastic media over expanded frequency band. In this work, the method's robustness was evaluated on data from five custom-made viscoelastic tissue-mimicking phantoms and sixty in vivo renal transplants. For each phantom, 15 shear wave motion data acquisitions were taken, while 10-13 acquisitions were acquired for renal transplants measured in the renal cortex. For each data-set mean and standard deviation (SD) of estimated phase velocity dispersion curves were studied. In addition, the viscoelastic parameters of the Zener model were examined, which were preceded by a convergence analysis. For viscoelastic phantoms scanned with a research ultrasound scanner, and for the in vivo renal transplants scanned with a clinical scanner, the decisive advantage of the GST-SFK method over the standard two-dimensional Fourier transform (2D-FT) method was shown. The GST-SFK method provided dispersion curve estimates with lower SD over a wider frequency band in comparison to the 2D-FT method. These advantages are relevant to the analysis of the mechanical properties of tissues in clinical practice to discriminate healthy from diseased tissue.

The XVI-th Banff Meeting for Allograft Pathology was held at Banff, Alberta, Canada, from 19th to 23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30th anniversary of the first Banff Classification, premeeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis. In a postmeeting survey, agreement was reached on the delineation of the following phenotypes: (1) "Probable antibody-mediated rejection (AMR)," which represents donor-specific antibodies (DSA)-positive cases with some histologic features of AMR but below current thresholds for a definitive AMR diagnosis; and (2) "Microvascular inflammation, DSA-negative and C4d-negative," a phenotype of unclear cause requiring further study, which represents cases with microvascular inflammation not explained by DSA. Although biopsy-based transcript diagnostics are considered promising and remain an integral part of the Banff Classification (limited to diagnosis of AMR), further work needs to be done to agree on the exact classifiers, thresholds, and clinical context of use.

Pathology reports contain key information about the patient's diagnosis as well as important gross and microscopic findings. These information-rich clinical reports offer an invaluable resource for clinical studies, but data extraction and analysis from such unstructured texts is often manual and tedious. While neural information retrieval systems (typically implemented as deep learning methods for natural language processing) are automatic and flexible, they typically require a large domain-specific text corpus for training, making them infeasible for many medical subdomains. Thus, an automated data extraction method for pathology reports that does not require a large training corpus would be of significant value and utility.

To develop a language model-based neural information retrieval system that can be trained on small datasets and validate it by training it on renal transplant-pathology reports to extract relevant information for two predefined questions: (1) "What kind of rejection does the patient show?"; (2) "What is the grade of interstitial fibrosis and tubular atrophy (IFTA)?"

Kidney BERT was developed by pre-training Clinical BERT on 3.4K renal transplant pathology reports and 1.5M words. Then, exKidneyBERT was developed by extending Clinical BERT's tokenizer with six technical keywords and repeating the pre-training procedure. This extended the model's vocabulary. All three models were fine-tuned with information retrieval heads.

The model with extended vocabulary, exKidneyBERT, outperformed Clinical BERT and Kidney BERT in both questions. For rejection, exKidneyBERT achieved an 83.3% overlap ratio for antibody-mediated rejection (ABMR) and 79.2% for T-cell mediated rejection (TCMR). For IFTA, exKidneyBERT had a 95.8% exact match rate.

ExKidneyBERT is a high-performing model for extracting information from renal pathology reports. Additional pre-training of BERT language models on specialized small domains does not necessarily improve performance. Extending the BERT tokenizer's vocabulary library is essential for specialized domains to improve performance, especially when pre-training on small corpora.

The process of immunization following vaccination in humans bears similarities to that of immunization with allografts. Whereas vaccination aims to elicit a rapid response, in the transplant recipient, immunosuppressants slow the immunization to alloantigens. The induction of CD4+CXCR5+ T follicular helper (Tfh) cells has been shown to correlate with the success of vaccine immunization.

We studied a cohort of 65 transplant recipients who underwent histological evaluation concurrent with PBMC isolation and follow-up sampling to investigate the phenotypic profiles in the blood and allotissue and analyze their association with clinical events.

The proportion of circulating Tfh cells was heterogeneous over time. Patients in whom this compartment increased had lower CCR7-PD1+CD4+CXCR5+ T cells during follow-up. These patients exhibited more alloreactive CD4+ T cells using HLA-DR-specific tetramers and a greater proportion of detectable circulating plasmablasts than the controls. Examination of baseline biopsies revealed that expansion of the circulating Tfh compartment did not follow prior intragraft leukocyte infiltration. However, multicolor immunofluorescence microscopy of the grafts showed a greater proportion of CXCR5+ T cells than in the controls. CD4+CXCR5+ cells were predominantly PD1+ and were in close contact with B cells in situ. Despite clinical stability at baseline, circulating Tfh expansion was associated with a higher risk of a composite of anti-HLA donor-specific antibodies, rejection, lower graft function, or graft loss.

In otherwise stable patients post-transplant, circulating Tfh expansion can identify ongoing alloreactivity, detectable before allograft injury. Tfh expansion is relevant clinically because it predicts poor graft prognosis. These findings have implications for immune surveillance.

Interstitial fibrosis and tubular atrophy (IF/TA), a histologic feature of kidney allograft destruction, is linked to decreased allograft survival. The role of lipid metabolism is well-acknowledged in the area of chronic kidney diseases; however, its role in kidney allograft fibrosis is still unclarified. In this study, how lipid metabolism contributes to kidney allografts fibrosis was examined.

A comprehensive bioinformatic comparison between IF/TA and normal kidney allograft in the Gene Expression Omnibus (GEO) database was conducted. Further validations through transcriptome profiling or pathological staining of human recipient biopsy samples and in rat models of kidney transplantation were performed. Additionally, the effects of enhanced lipid metabolism on changes in the fibrotic phenotype induced by TGF-β1 were examined in HK-2 cell.

In-depth analysis of the GEO dataset revealed a notable downregulation of lipid metabolism pathways in human kidney allografts with IF/TA. This decrease was associated with increased level of allograft rejection, inflammatory responses, and epithelial mesenchymal transition (EMT). Pathway enrichment analysis showed the downregulation in mitochondrial LC-fatty acid beta-oxidation, fatty acid beta-oxidation (FAO), and fatty acid biosynthesis. Dysregulated fatty acid metabolism was also observed in biopsy samples from human kidney transplants and in fibrotic rat kidney allografts. Notably, the areas affected by IF/TA had increased immune cell infiltration, during which increased EMT biomarkers and reduced CPT1A expression, a key FAO enzyme, were shown by immunohistochemistry. Moreover, under TGF-β1 induction, activating CPT1A with the compound C75 effectively inhibited migration and EMT process in HK-2 cells.

This study reveal a critical correlation between dysregulated lipid metabolism and kidney allograft fibrosis. Enhancing lipid metabolism with CPT1A agonists could be a therapeutic approach to mitigate kidney allografts fibrosis.

Microvascular injury resulting from activation and exocytosis are early signs of tissue damage caused by allografting. However, humoral anti-graft reactions are not easily detectable in transplant biopsies. The aim of this study was to establish a bioassay to recapitulate this process in a prospective approach.

The study was executed by using our previously established protocol to isolate and freeze the donors' microvascular endothelial cells (MVEC) at the transplantation (34 living-related donors and 26 cadaver donors); and to collect sera from the recipients before the transplantation, one-, three- and six-months after transplantation. The activation and exocytosis of the MVEC were determined by incubating the donors' cultures with the recipients' sera. We determined if there was any endothelial activation by quantifying the releases of monocyte chemotactic protein-1 (MCP-1) and interleukin 8 (IL-8) in supernatants and the expressions of membrane intercellular adhesion molecule-1 (CD54) and intercellular adhesion molecule-1 (CD106) by flow cytometry. Endothelial exocytosis was determined by quantifying soluble E-selectin (CD62E) and cytoplasmic von Willebrand Factor (vWF) in supernatants. Endothelial activation or exocytosis was considered positive when the fold change (≧1.5) of post-transplantation to pre-transplantation was reached. We also monitored serum PRA and cytokines using Luminex multiple-plex and cytometric bead-based assay respectively.

We found 41.2% recipients (14 out of 34, ranging from 1.5 to 5.2 folds, p < 0.05) exhibited positive MVEC activation in the first month after transplantation as determined by IL-8 levels; 26.5% recipients (9 out of 34, ranging from 1.5 to 11.8 folds, p < 0.05) by MCP-1 levels. In the group of three months post-transplantation, 70.6% patients were positive (12 out of 17, ranging from 1.8 to 87.1 folds, p < 0.05) by IL-8 increased levels; 24% recipients (4 out of 17, ranging from 1.8 to 50.5 folds, p < 0.05) measured by MCP-1 levels. However, these changes disappeared six months after transplantation. Flow cytometric data showed that a time-dependent of CD54+ and CD106+ expressions existed over the course of six months. Most CD54+ and CD106+ cells were CD31- (platelet-endothelial cell adhesion molecule-1), though CD31+/CD106+ (37.5%, 3 out of 8) and CD31+/CD106+ (25%. 2 out of 8) were seen. When comparing donor MVEC activation to their recipient's proinflammatory cytokine levels or PRA status, we could not draw a conclusion regarding the connections between them. The sera collected from recipients at either one- or three-months after allografting did not significantly induce the release of either soluble CD62E or vWF (p > 0.05), indicating exocytosis was not significantly involved in the acute phase of allografting.

This bioassay enables us to detect the activation and exocytosis of donor MVEC elicited by respective sera from mismatched kidney recipients.

Incomplete resolution of T cell-mediated rejection (TCMR) after treatment may not be detected with serum creatinine monitoring and is associated with donor-specific antibodies and chronic rejection. We evaluate the utility of follow-up biopsies (FUB) to identify and characterize rates of persistent TCMR after treatment in pediatric kidney transplant patients.

Patients from two pediatric transplant centers performing standard of care FUB at 1.5-2 months after treatment for TCMR were included. FUB were evaluated for extent of rejection resolution (complete vs. incomplete) and grade. Clinical data at time of FUB and later were reported, where available.

Fifty-eight patients underwent FUB, at mean of 1.7 months (SD 0.7) post-index biopsy. Rejection grade on index biopsy was Banff borderline (≥i1t1 and

CONCLUSIONS

FUB were effective at detecting persistent rejection, which was common among pediatric transplant patients after standard TCMR treatment. Until more effective rejection treatments or sensitive biomarkers are available, FUB may be effectively utilized to identify patients with ongoing rejection who would benefit from further treatment.

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To probe the correlations of parameters derived from standard DWI and its extending models including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI) with the pathological and functional alterations in CKD.

Seventy-nine CKD patients with renal biopsy and 10 volunteers were performed with DWI, IVIM, diffusion kurtosis tensor imaging (DKTI) scanning. Correlations between imaging results and the pathological damage [glomerulosclerosis index (GSI) and tubulointerstitial fibrosis index (TBI)], as well as eGFR, 24 h urinary protein and Scr) were evaluated.CKD patients were divided into 2 groups: group 1: both GSI and TBI scores <2 points (61 cases); group 2: both GSI and TBI scores ≥2 points (18 cases).

There were significant difference in cortical and medullary MD, and cortical D among 3 groups and between group 1 and 2. Cortical and medullary MD, cortical D, and medullary FA were negatively correlated with GSI score (r = -0.322 to -0.386, P < 0.05). Cortical and medullary MD and D, medullary FA were also negatively correlated with TBI score (r = -0.257 to -0.395, P < 0.05). These parameters were all correlated with eGFR and Scr. Cortical MD and D showed the highest AUC of 0.790 and 0.745 in discriminating mild and moderate-severe glomerulosclerosis and tubular interstitial fibrosis, respectively.

The corrected diffusion-related indices, including cortical and medullary D and MD, as well as medullary FA were superior to ADC, perfusion-related and kurtosis indices for evaluating the severity of renal pathology and function in CKD patients.

Rejection requires cell-cell contact involving immune cells. Inferring the transcriptional programs of cell-cell interactions from single-cell RNA-sequencing (scRNA-seq) data is challenging as spatial information is lost.

We combined a CD45 pos enrichment strategy with Cellular Indexing of Transcriptomes and Epitopes by sequencing based quantification of leukocyte surface proteins to analyze cell-cell interactions in 11 human kidney transplant biopsies encompassing a spectrum of rejection diagnoses. scRNA-seq was performed using the 10X Genomics platform. We applied the sequencing physically interacting cells computational method to deconvolute the transcriptional profiles of heterotypic physically interacting cells.

The 11 human allograft biopsies generated 31 203 high-quality single-cell libraries. Clustering was further refined by combining Cellular Indexing of Transcriptomes and Epitopes by sequencing data from 6 different leukocyte-specific surface proteins. Three of 6 doublet clusters were identified as physically interacting cell complexes; macrophages or dendritic cells bound to B cells or plasma cells; natural killer (NK) or T cells bound to macrophages or dendritic cells and NK or T cells bound to endothelial cells. Myeloid-lymphocyte physically interacting cell complexes expressed activated and proinflammatory genes. Lymphocytes physically interacting with endothelial cells were enriched for NK and CD4 T cells. NK cell-endothelial cell contact caused increased expression of endothelial proinflammatory genes CXCL9 and CXCL10 and NK cell proinflammatory genes CCL3 , CCL4 , and GNLY .

The transcriptional profiles of physically interacting cells from human kidney transplant biopsies can be inferred from scRNA-seq data using the sequencing physically interacting cells method. This approach complements previous methods that estimate cell-cell physical contact from scRNA-seq data.