Renal Allograft Dysfunction Research Articles

Defining the Etiology of Renal Allograft Dysfunction Using Banff 2019 Classification: Correlation with Post-Transplant Duration and Creatinine Levels-A Comprehensive Analysis of 200 Renal Biopsies at a Tertiary Care Medical Center Hospital.

Chronic kidney disease is a growing global health issue, contributing significantly to morbidity and mortality. The incidence of end-stage renal disease (ESRD) is approximately 100 per million population. Renal transplantation remains the cornerstone treatment for ESRD, with a projected 20-year survival rate of 60%. We aim to define the etiology of renal allograft dysfunction using the Banff 2019 classification by analyzing 200 renal allograft biopsies in correlation with creatinine levels across post-transplant time frames. 200 renal allograft biopsies are analyzed using the recent Banff 2019 classification with creatinine levels and post-transplant duration correlation. The study included 150 (75%) male patients and 50 (25%) female patients, with the majority 78 (39%) representing the age group of 16-30 years. 36 (18%) biopsies were within 3-month post-transplant, while 92 (46%) were 2-year post-transplant. According to the Banff 2019 classification, 92 (46.0%) transplant rejection biopsies were identified, with most 54 (27%) exhibiting antibody-mediated rejection (Category 2), including 40 (20%) active acute antibody-mediated rejection (ABMR) and 14 (7.0%) chronic active ABMR. T-cell-mediated rejection (TCMR; Category 4) represented 12 (6%) biopsies, including 10 (5%) acute TCMR and 2 (1%) chronic active TCMR. Category 5, the miscellaneous group, represented 100 (50%) biopsies, out of which 32 (16%) exhibited calcineurin inhibitor (CNI) toxicity, 38 (19%) acute tubular necrosis, and 8 (4%) thrombotic microangiopathy. A notable variation in the dysfunction distribution across different post-transplant time frames indicated a temporal evolution in the underlying causes of allograft dysfunction. Specific Banff categories showed a robust association with renal dysfunction, potentially contributing to the elevation of creatinine levels and renal function deterioration. Our study highlights the intricate pathophysiology of renal allograft dysfunction. Most biopsies were attributed to ABMR whereas one-third of biopsies exhibited mixed lesions (ABMR and TCMR or ABMR and calcineurin inhibitor toxicity (CNIT)). Additionally, this study suggests that renal allograft rejection remains a significant contributor to graft dysfunction. A complex interplay between histological findings, Banff classification, and renal function is noted. A significant difference in the distribution of dysfunction across post-transplant time frames is noted suggesting a temporal evolution in the etiology of allograft dysfunction. Certain Banff categories demonstrate a stronger association with renal dysfunction that may influence creatinine level increase and renal function deterioration. In correspondence to the recent Banff 2019 guidelines for diagnosing ABMR, we emphasize the role of C4d staining on immunofluorescence or immunohistochemistry in allograft biopsies as imperative for timely diagnosis and immunosuppressant therapy adjustment, ultimately enhancing graft survival. Further research is needed to elucidate the underlying mechanisms driving renal dysfunction in different Banff categories, ultimately informing personalized management strategies for patients with renal allograft dysfunction. In line with the Banff 2019 guidelines for diagnosing ABMR, this study highlights the critical role of C4d staining through immunofluorescence or immunohistochemistry in allograft biopsies for early diagnosis and timely adjustment of immunosuppressive therapy, ultimately improving graft survival.

P.525: Transplant renal artery stenosis: A potentially treatable cause of hypertension and renal allograft dysfunction.

P.525: Transplant renal artery stenosis: A potentially treatable cause of hypertension and renal allograft dysfunction.

Ultrasound super-resolution imaging for the assessment of renal allograft dysfunction: A pilot study

BackgroundThe purpose of this study was to examine the feasibility and practical application of ultrasound (US) super-resolution imaging (SRI) in evaluating microvasculature and measuring renal allograft function. MethodsSixteen consecutive patients who received kidney transplants were prospectively enrolled. The patients were assigned as: normal allograft function (n = 6), and allograft malfunction (n = 10). Localizing each potential contrast signal resulted in super-resolution images (SRI). SRI was utilized to assess micro-vessel density (MVD) and microvascular flow rate, whereas contrast-enhanced (CE) US images were statistically processed to get the time to peak (TTP) and peak intensity. Logistic regression was utilized to evaluate their relationship. ResultsUS SRI may be utilized effectively on allografts to show microvasculature with significantly higher resolution than typical color Doppler flow and CEUS pictures. In the multivariate analysis, MVD and TTP were significant US markers of renal allograft failure (p = 0.031 and p = 0.045). The combination of MVD and TTP produced an AUC of 0.783 (p < 0.05) for allograft dysfunction. ConclusionsSRI can accurately portray the microvasculature of renal allografts, while MVD and TTP are appropriate US markers for assessing renal allograft failure.

Early and late assessment of renal allograft dysfunction using intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI): a prospective study.

To evaluate the ability of the Intravoxel Incoherent Motion (IVIM) and monoexponentially ADC in renal allograft function in the early and late phases of transplantation, and to predict their effectiveness in discrimination of the graft pathology. This is a prospective study included participants scanned with quantitative diffusion and perfusion sequences on a 3-T MR scanner (Philips, Ingenia); the ADC and IVIM parameters; were calculated. Correlations and regression analysis with the eGFR, transplantation periods, and pathology were assessed. This study included 105 renal allograft recipients (85 males, and 20 females with mean age = 32.4 ± 11.9years and age range = 22-61years). There was a significant positive correlation between the whole parameters of the ADC and IVIM with eGFR however, the cortical parameters showed higher significant correlation coefficients (p < 0.001). Regression analysis revealed the most significant model can predict eGFR groups included cortical pseudo diffusion (D*) and cortical ADC (p < 0.001). In graft dysfunction eGFR was 61.5ml/min and normal graft was 64ml/min. This model demonstrates a high performance of an AUC 96% [0.93-0.97]. In the late transplantation, there is a higher correlation with D* compared to ADC, p-values = 0.001. IVIM and ADC Values are significant biomarkers for renal allograft function assessment, cortical ADC, and D* had the highest performance even in situations with mild impairment that is not affect the eGFR yet as cases of proteinuria with normal eGFR. Furthermore, D* is superior to ADC in the late assessment of the renal transplant.

Oxidized ATP Suppresses B Lymphocyte Activity to Attenuate Antibody-mediated Rejection of Kidney Allografts in Mice

Background. Antibody-mediated rejection (AMR) is a major cause of renal allograft dysfunction and loss. Targeting B cells and/or donor-specific antibody removal using plasma exchange and anti-CD20 antibodies are increasingly used in clinical practice, but the efficacy remains limited. Recent studies suggest that targeting purinergic P2X7 receptor/ATP axis can have profound immune regulatory effects in transplant models, but the mechanisms involved remain incompletely defined. Methods. Purified B cells were isolated from the spleen of Balb/C mice and cultured with oxidized ATP at different concentrations. Proliferation and differentiation of B cells were examined. Effects of oxidized ATP were examined in a presensitized animal model where kidney allograft rejection mimics aspects of clinical AMR. Histopathology was assessed at the time of rejection or on day 5 after kidney transplantation. Infiltrating immune cells in renal allografts were detected by flow cytometry. Results. Oxidized ATP inhibited B-cell activation and proliferation in vitro, significantly attenuated histological signs of graft injury and prolonged kidney allograft survival. Mechanistically, oxidized ATP inhibited antibody secretion by activated B cells in response to lipopolysaccharide stimulation and markedly suppressed the production of donor-specific antibody in kidney allograft recipients. Oxidized ATP also reduced graft infiltration by other inflammatory cells. Conclusions. These findings provide evidence for the involvement of the purinergic P2X7 receptor pathway in AMR and suggest that targeting this pathways may have important clinical implications.

New-onset diabetes after kidney transplantation: Assessing urinary Wilm's tumor-1 protein to predict renal allograft dysfunction

PurposeNew-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). Materials and methodsKTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. ResultsThe NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 ​mL/min/1.73 ​m2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. ConclusionThe increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.

The association between activation of the ERK1/2-NF-κB signaling pathway by TIMP2 expression and chronic renal allograft dysfunction in the CRAD rat model

PurposeThe tissue inhibitor of metalloproteinase 2 (TIMP2), a natural inhibitor of matrix metalloproteinase (MMP), regulates inflammation, fibrosis, and cell proliferation. Chronic renal allograft dysfunction (CRAD) is a primary factor affecting the long-term survival of renal allografts. We assessed whether up-regulation of TIMP2 expression may affect the ERK1/2-NF-κB signaling pathway and CRAD development. MethodsLewis rats received orthotopic F344 kidney allografts to establish the classical CRAD model. The treatment group was injected with a lentivirus encoding a TIMP2-targeting small hairpin (sh)RNA (LTS) at 5 × 108 TU/ml monthly after kidney transplantation. A second CRAD group was injected with a lentivirus TIMP2-control vector (LTC). After 12 weeks, blood, urine, and kidney tissue were harvested to evaluate renal function and pathological examinations. Hematoxylin and eosin staining, Masson staining, and Periodic acid–Schiff staining were performed for renal histopathological evaluation according to the Banff criteria. TIMP2, phospho (p)-ERK1/2, p-p65 (NF-κB) expression levels were measured via immunohistochemical and Western blot analyses. ResultsCompared to the F344 and Lewis control groups, the expression of TIMP2, p-ERK1/2, and p-p65 were significantly higher in the CRAD and CRAD+LTC renal tissues (p < 0.05). There were also increased levels of serum creatinine, nitrogen, and 24 h urinary protein in these two groups (p < 0.05). Typical histopathological changes of CRAD were observed in the CRAD and CRAD+LTC groups. Administration of LTS effectively decreased the expression of TIMP2, p-ERK1/2, and p-P65, and reduced interstitial fibrosis and macrophage infiltration in the treatment group (p < 0.05). Additionally, MCP1 and ICAM-1, which are downstream cytokines of the NF-κB pathway, were also inhibited in the renal rat kidney from the LTS group (p < 0.05). Furthermore, renal function was well preserved in the LTS group compared to the CRAD group and CRAD+LTC group. ConclusionA decrease of TIMP2 can alleviate the progression of inflammation in CRAD via inhibition of the ERK1/2-NF-κB signaling pathway.

Functional MRI evaluation of blood oxygen dependent (BOLD) in renal allograft dysfunction: a prospective study.

Blood oxygen level dependent-magnetic resonance imaging (BOLD-MRI) is a non-invasive functional imaging technique that can be used to assess renal allograft dysfunction. To evaluate the diagnostic performance of BOLD-MRI using a 3-T scanner in discriminating causes of renal allograft dysfunction in the post-transplant period. This prospective study was conducted on 112 live donor-renal allograft recipients: 53 with normal graft function, as controls; 18 with biopsy-proven acute rejection (AR); and 41 with biopsy-proven acute tubular necrosis (ATN). Multiple fast-field echo sequences were performed to obtain T2*-weighted images. Cortical R2* (CR2*) level, medullary R2* (MR2*) level, and medullary over cortical R2* ratio (MCR) were measured in all participants. The mean MR2* level was significantly lower in the AR group (20.8 ± 2.8/s) compared to the normal group (24 ± 2.4/s, P <0.001) and ATN group (27.4 ± 1.7/s, P <0.001). The MCR was higher in ATN group (1.47 ± 0.18) compared to the AR group (1.18 ± 0.17) and normal functioning group (1.34 ± 0.2). Both MR2* (area under the curve [AUC] = 0.837, P <0.001) and MCR (AUC = 0.727, P = 0.003) can accurately discriminate ATN from AR, however CR2* (AUC = 0.590, P = 0.237) showed no significant difference between both groups. In early post-transplant renal dysfunction, BOLD-MRI is a valuable non-invasive diagnostic technique that can differentiate between AR and ATN by measuring changes in intra-renal tissue oxygenation.

Prediction of acute rejection in renal allografts using shear-wave dispersion slope.

To evaluate the role of shear-wave dispersion slope for predicting renal allograft dysfunction. We retrospectively reviewed 128 kidney transplant recipients (median age, 55years [interquartile range, 43-62years]; male, 68) who underwent biopsy for allograft evaluation from November 2022 to February 2023. Cortex and renal sinus fat stiffness and shear-wave dispersion slope were obtained at shear-wave elastography (SWE). Cortex-to-sinus stiffness ratio (SR) and dispersion slope ratio (DSR)-related clinical and pathologic factors were evaluated using multivariable linear regression analysis. We conducted univariate and multivariate analyses for multiparametric ultrasound (US) parameters for identifying acute rejection and calculated the area under the receiver operating curve (AUC) values. Of 128 patients, 31 (24.2%) demonstrated acute rejection. The SR value did not differ between patient groups (1.21 vs. 1.20, p = 0.47). Patients with acute rejection demonstrated a higher DSR than those without rejection (1.4 vs. 1.21, p < 0.01). Interstitial fibrosis and tubular atrophy grade (IFTA; coefficient, 0.11/grade; p = 0.04) and renal transplant and biopsy interval (coefficient, 0.00007/day; p = 0.03) were SR determinant factors, whereas only IFTA grade (coefficient, 0.10/grade; p = 0.01) for DSR. Multivariate analysis revealed mean resistive index (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.02-1.14, p = 0.01) and DSR value (OR 16.0, 95% CI 3.0-85.8, p = 0.001) as independent factors for predicting acute rejection. An AUC of 0.74 for detecting acute rejection was achieved by combining the resistive index and DSR value. Shear-wave dispersion slope obtained at SWE may help identify renal allograft dysfunction. Acute rejection in renal allografts is a major cause of allograft failure, but noninvasive diagnosis is a challenge. Shear-wave dispersion slope can identify acute rejection non-invasively. • The interstitial fibrosis and tubular atrophy grade was a determinant factor for stiffness ratio and shear-wave dispersion slope ratio between cortex and renal sinus fat. • Shear-wave dispersion slope ratio between cortex and renal sinus fat could identify acute rejection in renal allografts. • A shear-wave dispersion slope has a potential to reduce unnecessary renal biopsy for evaluating renal allografts.

Abstract 26 — Clinical Characteristics of Familial Mediterranean: Fever in Hemodialysis Patients

Introduction Familial Mediterranean fever (FMF) is an inherited genetic disorder characterized by recurrent episodes of fever, serositis, arthritis, and skin rash. Uncontrolled disease can lead to amyloid A disposition, nephrotic syndrome and progressive renal failure. Recurrence of AA amyloidosis post kidney transplantation has been reported. Long-term colchicine therapy will reduce the FMF attacks and risk of AA amyloidosis. Although there is high prevalence of FMF in MENA region, the data of end stage renal disease (ESRD) in FMF is limited. We report our center experience. Method A retrospective chart review study was conducted at Tawam Hospital over 12 years (January 2010 to January 2023). We included adult ESRD on hemodialysis with FMF disease and studied their management outcomes. Descriptive analysis was used. Results 1900 ESRD patients were on hemodialysis during study period, and only two patients were diagnosed with FMF and renal amyloidosis. Case 1: A 60-year-old male patient from Syria who is known to have FMF and polycystic kidney disease leading to ESRD. He underwent successful LRD kidney transplantation in 2009. He was on mycophenolic acid: 540 mg, BID, prednisolone: 5 mg, tacrolimus: 1 mg am, 0.5 mg and colchicine 0.5 mg BID. He developed progressive renal allograft dysfunction with evidence of nephrotic syndrome. The renal biopsy revealed recurrence of AA amyloidosis due to FMF in kidney allograft in 2018. He had decline in renal function over years was initiated on hemodialysis on 2022. He developed two attacks of FMF peritonitis while on hemodialysis that responded well to steroid/colchicine therapy. Case 2: 48 years old male, from Egypt, known to have irritable bowel syndrome. He presented to our hospital with bilateral lower limb edema, and progressive shortness of breath for one month. Investigations revealed heavy proteinuria (8.98 g/g Creat) and acute kidney injury. Serology and autoimmune workup were negative. Kidney biopsy showed renal amyloidosis, and chronic tubulointerstitial nephritis with severe interstitial fibrosis (60%). History taken again and was positive for FMF in his uncle. Genetic study and clinical confirmed the diagnosis of FMF. He was started on colchicine, but developed ESRD within 8 months and initiated on hemodialysis. He had attacks of FMF. Conclusion Renal amyloidosis in FMF patient leads to progressive renal failure despite colchicine therapy. In our dialysis cohort over 12 years, only two FMF patients were identified. Colchicine therapy is required in ESRD-FMF in order to managed FMF attacks and prevent other organ AA amyloidosis.

Association of IL-1β rs16944 and IL-1RN rs2234663 gene polymorphisms with graft function in renal transplant recipients

BackgroundAfter renal transplantation, renal graft function affects both patient and graft survival. There is growing evidence of the genetic association between interleukin-1β (IL-1β) or its receptor antagonist (IL-1RN) and graft function in renal transplantation. The objective of this study is to investigate the role of the recipient IL-1β and IL-1RN gene polymorphisms and their haplotypes on renal graft outcome.MethodsUsing PCR, IL-1β (− 511C/T) and IL-1RN (86 bp VNTR) gene polymorphisms were determined in 31 renal allograft recipients; eight cases with stable allograft function and 23 cases with early renal dysfunction as well as 26 age- and gender-matched healthy controls.ResultsA statistically significant difference in IL-1 β (− 511C/T) gene polymorphisms and IL-1RN/IL-1β haplotypes was observed on comparing renal allograft recipients with stable allograft function and those with early renal allograft dysfunction. However, the difference in the frequency distribution of IL-1RN gene polymorphisms, between these two groups, did not reach statistical significance. Also, no statistically significant difference was observed in comparing these two gene polymorphisms and their haplotypes between renal allograft recipients and healthy controls.ConclusionThe IL-1β − 511 CT/TT polymorphic genotypes and IL-1RN/IL-1β polymorphic haplotypes are associated with early renal allograft dysfunction. These are observational data that can be repeated in larger studies. If the results obtained are consistent, this might open doors to personalized medicine where clinicians can take necessary measures to identify the renal transplant recipients’ genotypes at risk of mounting an increased inflammatory response and hence administer the appropriate immunosuppressive protocol.

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). Prospective. Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). 1.5 T/T2-weighted imaging and DTI. The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 μmol/L vs. 82.3 ± 20.9 μmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. 2 TECHNICAL EFFICACY: Stage 2.

Prospective quantitative study: Doppler ultrasound in the evaluation of chronic renal allograft disease and correlation with histopathological finding.

Renal allograft biopsy is the gold standard for diagnosing chronic allograft nephropathy, but noninvasive methods are needed to avoid unnecessary biopsies. Doppler ultrasonography, particularly the resistive index (RI), correlates with renal allograft dysfunction. This study aims to assess the relationship between renal sonographic parameters and biochemical parameters in diagnosing graft interstitial fibrosis. The study evaluated 60 renal allograft recipients for sonographic renal morphological features and Doppler indices. The estimated glomerular filtration rate (eGFR) was calculated, and cortical fibrosis after the biopsy was determined using the Banff score. Continuous variables like mean and SD were calculated, and categorical variables were reported using frequencies and proportions. Associations were examined using independent sample t-tests, χ 2tests, and multivariate regression analysis. The mean eGFR was 75.23±25.45ml/min/1.73m2. A significant correlation of eGFR with RI (r=0.341, P=0.008) was seen. A significant difference in mean RI (F=10.167; df=2,57; P<0.001) was seen among the histological grades of fibrosis. Among the histological grades of fibrosis, significant differences in RI among mild and moderate (S.E. 0.033, P=0.043), mild and severe (S.E. 0.026, P=0.001) as well as moderate and severe (S.E. 0.036, P=0.029) was seen. Doppler was able to noninvasively predict allograft fibrosis and could be used as a complementary imaging tool during the follow-up of renal allograft patients. Future research is needed to improve evidence, diagnostic criteria, guidelines, and long-term impact.

Molecular immune monitoring in kidney transplant rejection: a state-of-the-art review.

Although current regimens of immunosuppressive drugs are effective in renal transplant recipients, long-term renal allograft outcomes remain suboptimal. For many years, the diagnosis of renal allograft rejection and of several causes of renal allograft dysfunction, such as chronic subclinical inflammation and infection, was mostly based on renal allograft biopsy, which is not only invasive but also possibly performed too late for proper management. In addition, certain allograft dysfunctions are difficult to differentiate from renal histology due to their similar pathogenesis and immune responses. As such, non-invasive assays and biomarkers may be more beneficial than conventional renal biopsy for enhancing graft survival and optimizing immunosuppressive drug regimens during long-term care. This paper discusses recent biomarker candidates, including donor-derived cell-free DNA, transcriptomics, microRNAs, exosomes (or other extracellular vesicles), urine chemokines, and nucleosomes, that show high potential for clinical use in determining the prognosis of long-term outcomes of kidney transplantation, along with their limitations.

#6833 ARE KT RECIPIENTS TAKING THEIR IMMUNOSUPPRESSANT MEDICATION? PRELIMINARY EVIDENCE FROM A SUPER-SPECIALIZED TRANSPLANT CENTRE IN SUB-SAHARAN AFRICA

Abstract Background and Aims Immunosuppressant non-adherence is a leading cause of preventable renal allograft dysfunction, rejection and graft loss. The barriers to immunosuppressant adherence as well as associated risk factors of non-adherence vary across studies in different locations. This study aimed to investigate the prevalence of immunosuppressant non-adherence among adult kidney transplant recipients and identify barriers to adherence in a renal transplant cohort. Method A cross sectional survey was conducted using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS), the Immunosuppressant Therapy Barrier Scale and the Beliefs about Medicines Questionnaire. Adherence was defined according to the BAASIS, with barriers to adherence and beliefs about medicines compared between the two groups. Participants were recruited from the out-patient clinic at Zenith Medical and Kidney centre. An advert for the study was placed in consultation rooms and patients were approached to join the study when they attend appointments. IBM SPSS Statistics for Windows, Version 23 (Armonk, NY: IBM Corp) was used for data analysis. Results The rate of non-adherence was 50.7% out of 67 kidney transplant recipients attending outpatient clinic. There were statistically significant associations between non-adherence and occupation (P = 0.049). Participants who are on MMF were more adherent than those on sirolimus (97.0% vs 79.4% and 0.0% vs 8.8%) and this difference is statistically significant (P = .038). Also, participants who have had one or more post-transplant hospital admission are more non-adherent when compared with those that have never been admitted (P = .022) The only significant barrier to adherence was when patients travelled out of town (P &amp;lt; 0.005). Adherence was not associated with patients’ belief about their medicines. Conclusion Interventions aimed at ensuring constant access to immunosuppressant drugs and those based on habit forming may significantly improve adherence in this cohort.

Identification and verification of hub genes associated with ferroptosis in ischemia and reperfusion injury during renal transplantation

Ferroptosis is involved in ischemia and reperfusion injury (IRI) of transplanted kidney. Understanding the molecular mechanisms of ferroptosis is essential to elucidate the pathogenesis of IRI. 1307 differentially expressed genes (DEGs) were obtained by GSE90861 retrieved from the GEO database. 29 ferroptosis-related DEGs were obtained from the intersection with FerrDb database, which were subjected to enrichment analysis and cytoHubba plugin for selecting the top three (IL6, ATF3 and JUN) as hub genes. Next, ROC analysis of hub genes showed good diagnostic prospects in both GSE90861 and GSE126805. Given the close link between ferroptosis and immunity, immunological analysis of CIBERSORTx revealed that the proportions of 10 cell types out of 22 immune cells in the transplanted kidney significantly changed after reperfusion. To study the relationship between IRI and ferroptosis, 15 male C57BL/6j mice were randomly divided into three groups: control (C), ischemia and reperfusion (IR), and IR + Fer-1 (IF) groups. The IRI mouse model not only developed significant histological damage changes, but also exhibited mitochondrial damage, iron accumulation, increased MDA, and decreased GSH. The ferroptosis inhibitor, Fer-1, ameliorated renal IRI, as demonstrated by rise of GPX4 and decline of TFRC, PTGS2 and ACSL4. In addition, hub genes were further confirmed by significant increase in IRI mouse model the same as the GEO database. In brief, ferroptosis-related hub genes (IL-6, ATF3 and JUN) screened were closely relevant to immune response and might be diagnostic biomarkers and therapeutic targets for IRI during renal transplantation, which could prevent renal allograft dysfunction.

Value of conventional ultrasound and contrast-enhanced ultrasound for the assessment of renal allograft dysfunction and prognosis.

Ultrasound (US) is the primary imaging modality for the assessment of transplanted kidneys. This study aims to investigate the ability of conventional US and contrast-enhanced US (CEUS) in assessing renal allograft function and prognosis. A total of 78 consecutive renal allograft recipients were enrolled. Patients were classified as normal allograft function (n=41) and allograft dysfunction (n=37) groups. All patients underwent US and parameters were measured. The independent-samples t-test or Mann-Whitney U test, logistic regression analysis, Kaplan-Meier survival plots, and Cox regression analysis were used. In multivariable analysis, cortical echo intensity (EI) and cortical peak intensity (PI) were determinant US parameters for renal allograft dysfunction (p=.024 and p=.003, respectively). The combination of cortical EI and PI showed an area under the receiver operating characteristic curve (AUROC) of .785 (p<.001). Of 78 patients (median follow-up: 20mo), 16 (20.5%) exhibited composite end points. Cortical PI had a general prediction accuracy with an AUROC of .691, sensitivity of 87.5%, and specificity of 46.8% at the threshold of 22.08dB in predicting prognosis (p=.019). The combination of estimated-glomerular filtration rate (e-GFR) and PI in predicting prognosis showed an AUROC of .845 with a cut-off value of .836, sensitivity of 84.0%, and specificity of 67.3% (p<.001). This study indicates that cortical EI and PI are useful US parameters for evaluating renal allograft function and e-GFR combined with PI may provide a more accurate predictor of survival.

A clinical study of using ROC to compare the efficiency of ASL and BOLD in diagnosis of renal allograft function.

This retrospective study aims to evaluate the effectiveness of renal transplantation function by comparing arterial spin labeling (ASL) and blood oxygen level dependent (BOLD) imaging with the receiver operating characteristic (ROC) curve. According to the estimated glomerular filtration rate (eGFR) values, 42 patients with normal kidney grafts (the normal kidney graft group, eGFR <60 mL/min/1.73 m2) and 93 patients with injured grafts (the kidney graft injury group, eGFR <60 mL/min/1.73 m2) were included in the present study. Renal blood flow (RBF) and the effective transverse relaxation rate (R2*) were calculated by comparing ASL and BOLD imaging. The ROC curve and the youden index were used to evaluate the diagnostic performance of ASL, BOLD, and the combination of them. The results showed that all the clinical features of the patients, except for gender, differed significantly between the 2 groups (P<0.05). The mean RBF value of the renal transplant injury group (104.33±54.76 mL/100 g/min) was significantly lower than that of the normal group (191.84±63.96 mL/100 g/min, P<0.01). The mean medullary R2* value of the renal transplant injury group (27.91±3.35 1/s) was significantly higher than that of the normal group (25.22±2.94 1/s, P<0.01). Negative correlations were found between R2* and eGFR (r=-0.44), and RBF and R2* (r=-0.54; both P<0.01). The ROC analysis showed that both RBF and R2* reflected injured renal function [area under the curves (AUC) =0.86 and 0.72, respectively]. In addition, the AUC of RBF and R2* combined was 0.86, which was comparable to that of RBF alone (P=0.95), while combining R2* and RBF improved the diagnostic performance of R2* alone (AUC =0.86 versus 0.72, respectively; P<0.01). The youden index analysis showed that the diagnostic accuracy of ASL was 80.00%, better than 71.85% of BOLD; the sensitivity and specificity of ASL in diagnosing renal allograft dysfunction were 79.57% and 80.95%, superior to 77.42% and 59.52% of BOLD. Our results showed that the non-invasive assessment of ASL in clinical kidney transplant function is a more promising imaging technique than BOLD.

Subcapsular hematoma in postrenal transplant patients: A report of three cases

Subcapsular hematomas are not uncommon after renal transplantation but they rarely cause parenchymal compression or graft dysfunction. They occur following trauma during kidney retrieval or benching, and appear soon after reperfusing the graft kidney. Significant subcapsular hematoma may present with flank pain and tenderness, hypertension, increased drain output and decreased urine output. Duplex ultrasonography and computed tomography help in diagnosis. Early recognition and surgical intervention are important to restore graft function. We report successful outcome after hematoma evacuation in three patients with post-transplant subcapsular hematomas that caused renal allograft dysfunction.

IRF1/ZNF350/GPX4-mediated ferroptosis of renal tubular epithelial cells promote chronic renal allograft interstitial fibrosis.

Renal interstitial fibrosis and tubular atrophy are essential pathological characteristics of chronic renal allograft dysfunction (CAD). Herein, we revealed that ferroptosis of renal tubular epithelial cells (RTECs) might contribute to renal tubular injury in CAD. Mechanistically, TNF-α induced ferroptosis by inhibiting GPX4 transcription through upregulating IRF1 in RTECs. IRF1 could bind with ZNF350 to form a transcription factor complex, which directly binds to the GPX4 promoter region to inhibit GPX4 transcription. Ferroptotic RTECs might secrete profibrotic factors, including PDGF-BB and IL-6, to activate neighboring fibroblasts to transform into myofibroblasts or induce EMT in adjacent RTECs. In conclusion, our results confirmed a novel role of ferroptosis in renal tubular injury and interstitial fibrosis, thereby providing insights into the pathogenesis of chronic renal allograft interstitial fibrosis during CAD.