Similar incidence of graft glomerulonephritis in recipients with definitively diagnosed glomerulonephritis and those with unknown etiology: a retrospective observational study.

OBJECTIVE: In China, most of the patients who underwent kidney transplants have unknown causes of end-stage renal disease (uESRD). However, little is known regarding the incidence of graft glomerulonephritis (GN) and graft survival in kidney transplant recipients (KTRs) with uESRD. METHODS: In this retrospective cohort study, 473 of the 565 KTRs who underwent kidney transplantation (KTx) from 2015 to 2020 were included. We mainly observed the occurrence of graft GN between uESRD group and definitively diagnosed GN group, and repeatedly compared after propensity score matching (PSM). RESULTS: The median follow-up was 50 months in 473 KTRs, and about 75% of KTRs of native kidney disease of unknown etiology. The total cumulative incidence of graft GN was 17%, and no difference was observed between the definitively diagnosed GN group and the uESRD group (p = 0.76). Further, PSM analysis also showed no difference in the incidence of graft GN between the 2 groups. Multivariable analysis disclosed males (p = 0.001), younger age (p = 0.03), and anti-endothelial cell anti-body (AECA) positive pre-KTx (p = 0.001) were independent risk factors for graft GN. CONCLUSIONS: The incidence of graft GN was similar between uESRD and definitively diagnosed GN group. The allograft survival was also similar between two groups.

Successful management of concurrent COVID-19 and Pneumocystis Jirovecii Pneumonia in kidney transplant recipients: a case series.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant recipients. Recent years have witnessed a rising incidence of PCP in this vulnerable population, leading to graft loss and increased mortality. Immunosuppression, which is essential in transplant recipients, heightens susceptibility to viral and opportunistic infections, magnifying the clinical challenge. Concurrently, the global impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been profound. Kidney transplant recipients have faced severe outcomes when infected with SARS-CoV-2, often requiring intensive care. Co-infection with COVID-19 and PCP in this context represents a complex clinical scenario that requires precise management strategies, involving a delicate balance between immunosuppression and immune activation. Although there have been case reports on management of COVID-19 and PCP in kidney transplant recipients, guidance on how to tackle these infections when they occur concurrently remains limited. CASE PRESENTATIONS: We have encountered four kidney transplant recipients with concurrent COVID-19 and PCP infection. These patients received comprehensive treatment that included adjustment of their maintenance immunosuppressive regimen, anti-pneumocystis therapy, treatment for COVID-19 and other infections, and symptomatic and supportive care. After this multifaceted treatment strategy, all of these patients improved significantly and had favorable outcomes. CONCLUSIONS: We have successfully managed four kidney transplant recipients co-infected with COVID-19 and PCP. While PCP is a known complication of immunosuppressive therapy, its incidence in patients with COVID-19 highlights the complexity of dual infections. Our findings suggest that tailored immunosuppressive regimens, coupled with antiviral and antimicrobial therapies, can lead to clinical improvement in such cases. Further research is needed to refine risk assessment and therapeutic strategies, which will ultimately enhance the care of this vulnerable population.

Perfusion and oxygenation in allografts with transplant renal artery stenosis: Evaluation with functional magnetic resonance imaging.

BACKGROUND: Transplant renal artery stenosis (TRAS) has been shown to reduce kidney perfusion leading to post-operative hypertension. We aimed to measure the perfusion and oxygenation changes in TRAS with arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging, respectively. METHODS: In this single-center prospective study, a total of seven patients with TRAS and seven age- and sex-matched normal kidney transplant recipients underwent both ASL and BOLD imaging. Moreover, measurements of ASL and BOLD were also performed in five patients after successful angioplasty for TRAS. RESULTS: Allograft cortical perfusion as measured by ASL in the TRAS group was significantly decreased as compared with normal control group (129.9 ± 46.6 ml/100 g vs. 202.4 ± 47.7 ml/100 g, P = .01). Interestingly, allograft oxygenation as indicated by R2* derived from BOLD in both the cortex (16.42 ± 1.90 Hz vs. 18.25 ± 4.34 Hz, P = .33) and the medulla (30.34 ± 2.35 Hz vs. 30.43 ± 6.85 Hz, P = .97) showed no statistical difference between the TRAS and normal control group. In addition, both cortical and medullary oxygenation remained unchanged despite significantly improved cortical perfusion in those undergone successful angioplasty. CONCLUSION: Cortical and medullary oxygenation were preserved in the presence of reduced allograft perfusion in clinically significant TRAS. Prospective larger studies are needed to conclusively establish perfusion and oxygenation changes in TRAS.

[Erectile function of renal failure patients after hemodialysis or kidney transplantation: A comparative study].

OBJECTIVE: To study the changes in the erectile function of the male patients with renal failure after hemodialysis (HD) or kidney transplantation (KT) and explore the causes of these changes. METHODS: From January 2015 to January 2021, 160 male patients with renal failure complaining of ED underwent HD (n = 80) or KT (n = 80) in the General Hospital of Eastern Theater Command. The patients were aged 25－45 (31.7 ± 4.8) years, 32 ± 4.5 years in the HD group and 31.4 ± 5.1 years in the KT group. We recorded the levels of serum T, E2, FSH and LH and the scores on IIEF-5, Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) of the patients, and compared them between the two groups. RESULTS: Compared with the patients in the HD group, those in the KT group showed a significantly higher T level (ï¼»7.45 ± 3.54ï¼½ vs ï¼»17.75 ± 7.32ï¼½ nmol/L, P < 0.01) and a lower E2 level (ï¼»151.37 ± 20.89ï¼½ vs ï¼»94.17 ± 40.79ï¼½ pmol/L, P < 0.01), but no statistically significant difference from the former group in the levels of FSH (ï¼»8.12 ± 5.12ï¼½ vs ï¼»8.97 ± 2.36ï¼½ IU/L, P > 0.05) and LH (ï¼»5.16 ± 3.87ï¼½ vs ï¼»4.69 ± 2.18ï¼½ IU/L, P > 0.05). There were fewer cases of severe ED in the KT than in the HD group (3.75% vs 16.25%, P < 0.05). Different degrees of anxiety and depression were observed in both groups, with fewer severe cases of anxiety (6.25% vs 30.00%, P < 0.05) and depression (6.25% vs 31.25%, P < 0.05) and more mild cases of anxiety (68.75% vs 47.50%, P < 0.05) and depression (70.00% vs 48.75%, P < 0.05) in the KT than in the HD group, but no statistically significant difference in the incidence of moderate anxiety (25.00% vs 22.50%, P > 0.05) and depression (23.75% vs 20.00%, P > 0.05) between the KT and HD groups. CONCLUSION: For male patients with renal failure, kidney transplantation can evidently improve erectile function, while hemodialysis has a poorer effect. The altered hormone levels, anxiety and depression of the patients are important causes of the changes in their erectile function.

Conversion from mycophenolate mofetil to mizoribine in the early stages of BK polyomavirus infection could improve kidney allograft prognosis: a single-center study from China.

BACKGROUND: Some studies have suggested mizoribine (MZR) could inhibit the replication of BK polyomavirus (BKPyV). The purpose of this study was to explore whether conversion from mycophenolate mofetil (MMF) to MZR in the early stages of BKPyV infection can improve kidney allograft prognosis. METHODS: Twenty-one kidney transplant recipients with BKPyV viruria/viremia and ten with BK polyomavirus-associated allograft nephropathy (BKPyVAN) received MZR conversion therapy were retrospectively identified. The clearance rate of urine and blood BKPyV DNA, change of serum creatinine (SCr), uric acid (UA), hemoglobin (HB), white blood cell (WBC), lymphocyte ratio, platelet (PLT), routine urinalysis, panel reactive antibody (PRA), and gastrointestinal disorders during follow-up of the 2 groups were evaluated and compared. RESULTS: After MZR conversion therapy, the clearance rate of urine and blood viral load in BKPyV viruria/viremia group were 85.7 and 100 %, while that in BKPyVAN were 40 and 87.5 %, respectively. Stable SCr were observed in all cases of BKPyV viruria/viremia group, while that of BKPyVAN was only 40 % (P < 0.001) and one even progressed to end-stage renal disease. The results of routine urinalysis in the two groups showed no significant changes before and after MZR conversion therapy. However, in BKPyV viruria/viremia group, four cases developed acute rejection and one had positive PRA-II but no donor specific antibody, requiring conversion back to MMF. Hyperuricemia was the common adverse effect of MZR. CONCLUSIONS: Conversion from MMF to MZR could help clear BKPyV infection. As compared to BKPyVAN, patients who underwent initiation of MZR conversion therapy in the early stages of BKPyV infection maintained stable allograft function. Prospective studies with larger sample size are needed to ascertain this preliminary finding.

Cadmium induces epithelial-mesenchymal transition and migration of renal cancer cells by increasing PGE2 through a cAMP/PKA-COX2 dependent mechanism.

Environmental or occupational exposure of Cadmium (Cd) is concerned to be a threat to human health. The kidney is main target of Cd accumulation, which increases the risk of renal cell carcinoma (RCC). In addition, low content of Cd had been determined in kidney cancer, however, the roles of presence of Cd in renal tumors progression are still unclear. The present study is proposed to determine the effect of low-dose Cd exposure on the renal cancer cells and aimed to clarify the underlying mechanisms. The cell viability, cytotoxicity, and the migratory effect of low-dose Cd on the renal cancer cells were detected. Moreover, the roles of reactive oxygen species (ROS), Ca2+, and cyclic AMP (cAMP)/protein kinase A (PKA)-cyclooxygenase2 (COX2) signaling, as well as COX2 catalytic product prostaglandin E2 (PGE2) on cell migration and invasion were identified. Our results suggested that low dose Cd exposure promoted migration of renal cancer Caki-1 cells, which was not dependent on Cd-induced ROS and intracellular Ca2+ levels. Cd exposure induced cAMP/PKA-COX2, which mediated cell migration and invasion, and decreased expressions of epithelial-mesenchymal transition (EMT) marker, E-cadherin, but increased expressions of N-cadherin and Vimentin. Moreover, Cd-induced secretion of PGE2 feedback on activation of cAMP/PKA-COX2 signaling, also promoted EMT, migration and invasion of renal cancer Caki-1 cells. This study might contribute to understanding of the mechanism of Cd-induce progression of renal cancer and future studies on the prevention and therapy of renal cell carcinomas.

Coronavirus disease 2019 in renal transplant recipients: Report of two cases.

Coronavirus disease 2019 (COVID-19) has been a pandemic worldwide. The data about COVID-19 in renal transplant recipient are deficiency. Herein, we report two COVID-19 cases in renal transplant recipients. Both cases were discharged following a treatment regimen including discontinued immunosuppressant and low-dose methylprednisolone-based therapy. There were no signs of rejection during the treatment. These successfully treated cases can provide helpful information about the management of COVID-19 in renal transplant recipients.

Calcimimetic compound NPS R-467 protects against chronic cadmium-induced mouse kidney injury by restoring autophagy process.

In the kidney, disturbance of calcium homeostasis can cause renal hemodynamic changes, leading to glomerulonephritis, tubular damage and renal vascular disease, and thus promotes the development of chronic kidney disease (CKD). Cadmium (Cd) is a toxic heavy metals proved to induce disturbances of calcium homeostasis and nephrotoxicity. Calcium sensing receptor (CaSR) is abundantly expressed in the kidney and plays an important role in maintaining body calcium homeostasis. Our previous study suggested that the activation of CaSR could act as a protective pathway to reduce Cd-induced cytotoxicity in renal proximal tubular cells. However, its application in animal models, its treatment efficacy and underlying mechanisms are still unclear. Therefore, an in vivo animal model (ICR male mouse, n = 5) subjected to Cd-induced nephrotoxicity was used in this study. In the present study, the results indicated that long-term (4 weeks) but not short-term (7 days) Cd exposure induced kidney injury, including induced glomerular atrophy, renal proximal tubule damage, increased malondialdehyde (MDA) level, elevated urine protein quantity, and upregulated kidney injury molecule 1 (KIM-1). It was further observed that chronic Cd exposure induced inhibition of autophagy flux, which triggered kidney apoptosis and injury. However, NPS R-467 restored Cd-inhibited autophagy flux and reduced Cd-induced kidney apoptosis and injury. Finding from this study indicated that activation of CaSR in prevention from nephrotoxicity and kidney injury caused by Cd, which might be helpful for the treatment of clinical CKD.

Conservative Management of Catastrophic Antiphospholipid Syndrome-Related Skin Necrosis: A Case Report.

Catastrophic antiphospholipid syndrome is an extremely rare autoimmune disease with complex and diverse clinical manifestations. Cutaneous necrosis is one of its rare clinical features. However, interventions for this manifestation are not standardized and lack evidence, which increases treatment difficulty. Here, study authors report the successful care and follow-up of a 46-year-old female patient with nephrotic syndrome and catastrophic antiphospholipid syndrome complicated by full-thickness cutaneous necrosis of the dorsum of the right hand that lasted more than 4 months and 1 month prior to wound treatment, respectively. Study authors set up an interprofessional team, including a nephrologist, a vascular surgeon, and two specialist wound care nurses to provide holistic wound care and treat her complex systemic conditions. After 84 days of treatment, which involved removing necrotic tissue with autolytic wound debridement, reducing inflammation with hydrofiber dressings containing silver, and promoting re-epithelialization with hydrocolloid paste and systemic medications, the wound healed successfully. Authors followed up with the patient at 1, 4, 6, 11, and 19 months after healing. The quality of scar was monitored, and the function of her right hand recovered normally.

Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort.

BACKGROUND: Transplant glomerulopathy (TG) represents a major cause of long-term allograft failure and is the leading cause of overall post-transplant proteinuria. The extent to which histopathologic features predicts prognostication is uncertain. METHODS: A single-center retrospective cohort with biopsy-proven TG was investigated. Renal biopsies were scored according to Banff 2017. The primary outcome was death-censored graft failure defined as return to dialysis or estimated glomerular filtration rate (eGFR) decreased to <15 mL/min/1.73 m2. The prognostic significance of clinical and histopathologic parameters was determined using Cox proportional hazards models. RESULTS: Data from 180 cases were available for analysis with a median follow-up of 5.0 (2.6-8.2) years. In multivariable models, ci + ct score (HR 3.1; 95% CI 2.0-4.9), cg score (HR 1.7; 95% CI 1.1-2.8), eGFR (HR 2.1; 95% CI 1.4-3.2) and proteinuria (HR 2.4; 95% CI 1.6-3.7) were independent predictors of the primary outcome. Mesangial Immunoglobulin A deposition did not significantly affect allograft survival. The only significant pathologic factors for the severity of proteinuria were cg and g + ptc (adjusted R2 = 0.46) as determined by multivariable stepwise linear regression analysis. CONCLUSIONS: Severe ci + ct and cg at biopsy were predictors of unfavorable allograft prognosis in TG patients even after taking into consideration clinical characteristics. Histologic severity of cg and g + ptc was significantly associated with clinical proteinuria.

The immunophenotyping of different stages of BK virus allograft nephropathy.

Objectives: To investigate the immunohistochemical features of different stages of BK virus allograft nephropathy (BKVN) and further elucidate the underlying immunological mechanism involved in the evolution of BKVN. Methods: Fifty-two renal transplant recipients with biopsy proven BKVN were retrospectively selected. According to the third edition of the American Society of Transplantation Infection guidelines, 10 patients were categorized as having mild BKVN (stage A), 25 were moderate (stage B) and 17 were severe (stage C). The differential infiltrations of CD3+ (T lymphocytes), CD4+ (helper T lymphocytes), CD8+ (cytotoxic T lymphocytes), CD20+ (B lymphocytes), CD68+ (macrophages) and CD138+ (plasma cells) cells and the expression of interleukin-2 receptor (IL-2R) and human leukocyte antigen DR (HLA-DR) were compared among the three groups. Results: CD3+, CD4+, CD8+, CD20+, CD138+ and CD68+ cells infiltrations, IL-2R and HLA-DR expression were positive in the BKVN patients. Moreover, with increasing stages of BKVN, the numbers of positively stained inflammatory cells and the expression of IL-2R were significantly increased in the severe group compared to the mild group, whereas no statistically significant differences were observed with regard to HLA-DR expression. Eosinophil and neutrophil infiltration could also be observed in moderate to advanced BKVN. Conclusion: Renal allograft damage caused by BKVN involved T lymphocyte-, B lymphocyte- and mononuclear macrophage-mediated immune responses. Inflammatory cell infiltrations in the renal allograft were probably the driving force for BKVN progression. Additionally, eosinophils and neutrophils may be involved in the pathophysiological mechanism of BKVN.

Proteinuria, Estimated Glomerular Filtration Rate and Urinary Retinol-Binding Protein as Clinical Predictors of Long-Term Allograft Outcomes in Transplant Glomerulopathy.

BACKGROUND/AIMS: We aimed to explore the associations between clinical parameters and long-term allograft outcomes in transplant glomerulopathy (TG) in a large retrospective cohort with long follow-up. METHODS: Clinical and laboratory data at biopsy from 180 cases of TG with an estimated glomerular filtration rate (eGFR)> 15ml/min/1.73m2 from January 2004 to December 2016 at our center were retrospectively analyzed. The main outcome of this study was initiation of replacement therapy or an eGFR declined to < 15 ml/min/1.73m2. RESULTS: During a median follow-up of 5 years (interquartile range 2.6-8.2 years), 117 cases (65.0%) achieved the combined event. Kaplan-Meier method yielded the 1-year and 5-year cumulative renal allograft survival rates after a histopathologic diagnosis of TG were 84% (95% confidence interval [CI] 81-87%) and 33% (95% CI 27-39%) respectively. In univariate analysis, allograft outcome differed significantly by eGFR, proteinuria, blood hemoglobin level, urinary retinol-binding protein (urRBP) and urinary N-acetyl-ß-D-glucosaminidase (urNAG) level at the time of biopsy. Multivariate Cox analysis revealed that a higher level of eGFR was the most powerful predictor of allograft survival. Compared with those with eGFR≥60, the hazard ratio (HR) increased from 4.50 (95% CI: 1.03-19.71, p=0.0462) for patients with eGFR between 30 and 59 ml/min/1.73m2 to 9.14 (95% CI 1.97-42.45, P=0.0047) when eGFR decreased to 15 to 29 ml/min/1.73m2. Additionally, proteinuria and higher urRBP values (≥2.85mg/dl) were found to confer much worse survival rates for TG patients in multivariate Cox analysis. Male sex (HR 0.48, P=0.02) and HCV infection (HR 1.78, P=0.0499) were also found to be independent risk factors for worse allograft survival. CONCLUSION: Five clinical features-impaired renal function, higher proteinuria, higher urRBP level, male sex and HCV infection-are independent predictors of an unfavorable renal allograft outcome. urRBP is a simple and useful parameter that can add invaluable information for the clinical follow-up of patients with TG.

Clinicopathological analysis of proliferative glomerulonephritis with monoclonal IgG deposits in 5 renal allografts.

BACKGROUND: We present a case series of 5 patients with proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) of renal allografts to better define its natural history, presenting characteristics, pathological features and treatment outcome. RESULTS: These 5 patients presented 5 to 19 months post-kidney transplantation for complaints of serum creatinine (Scr) elevation, proteinuria or hematuria. Membranoproliferative glomerulonephritis (MPGN) pattern was the most frequently observed histological manifestation. Immunofluorescence showed monoclonal IgG3κin 3 patients and IgG3λ in the other 2 cases. Immunofluorescence staining helped to establish PGNMID in the absence of conspicuous microscopic changes in one case. Rituximab and bortezomib were effective in alleviating proteinuria in all 4 treated patients and decreasing Scr in 2 cases. Plasmapheresis treatment in another patient was not effective in preventing Scr elevation. At last-follow-up, 2 patients were in dialysis and 2 had improved kidney function with almost normal Scr and no proteinuria. The remaining one patient died of pulmonary infections. CONCLUSIONS: We conclude that PGNMID occurs early after kidney transplant. PGNMID should be included in the differential diagnoses of recurrent MPGN in renal allografts. Rituximab and bortezomib are helpful to decrease proteinuria and Scr in a subset of patients. Larger studies are needed to conclusively establish best treatment strategies for PGNMID in renal allografts.

Risk factors for BK virus infection in living-donor renal transplant recipients: a single-center study from China.

OBJECTIVES: BK virus (BKV) infection has become one of the main complications in renal transplant recipients (RTRs) with the arrival of newer potent immunosuppressive agents. However, reports on the epidemiology of BKV infection and risk factors in Chinese population after renal transplantation are scarce. METHODS: From June 2015 to July 2016, living-donor renal transplant recipients (LDRTRs) who routinely received the quantitative BKV DNA testing of urine and plasma samples using quantitative real-time polymerase chain reaction (PCR) for the first time after transplantation were selected, while dialysis patients and healthy living donors during that period served as controls. Potential variables were compared and analyzed using logistic regression model multivariate analysis to assess the BKV infection related factors in LDRTRs. RESULTS: Among the 52 LDRTRs identified, BKV DNA was detected in 16 urine samples (30.8%), significantly higher than that of dialysis patients (6.3%) and healthy living donors (4.2%) (p < .001). Nevertheless, no statistically significant difference wax noted between the latter two groups in urine samples (p = .842). Meanwhile, BKV DNA detection in blood samples was all negative in the three groups. Univariate analysis shown tacrolimus (Tac) trough level and lymphocyte percentage were associated with BKV infection in LDRTRs. Multivariate regression analysis also showed Tac trough level (HR, 1.644; p = .03), lymphocyte percentage (HR, 0.878; p = .026) were associated with BKV infection in LDRTRs. CONCLUSIONS: In Chinese population, the incidence of BKV infection increased significantly after living-donor renal transplantation. Significantly increased Tac trough level and decreased lymphocyte percentage might be the risk factors for BKV infection in LDRTRs.

Poor outcomes of proliferative glomerulonephritis with monoclonal IgG deposits in renal allografts: a retrospective multicenter study.

BACKGROUND: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) in renal allografts is a rare, renal-limited disease. No study has reported the long-term outcomes and prognostic features of PGNMID in renal allografts in the Chinese population. METHODS: We retrospectively included transplant patients diagnosed with PGNMID who underwent renal allograft biopsy at three transplant centers from April 2012 to July 2020. We observed the clinicopathologic features, explored the long-term graft survival, and investigated the characteristics associated with the prognosis. RESULTS: A total of 13 transplant patients with PGNMID were included, out of 3821 biopsies. The mean follow-up time was 55 months since kidney transplantation (KTx). At diagnosis, all patients presented with proteinuria (100%) and most of them with hematuria (92%). IgG3κ (69%) was the main immunofluorescence (IF) subtype. The median graft survival of the total cohort was 17 months from diagnosis and 49 months from kidney transplantation. During follow-up, 9 patients needed dialysis and 2 out of 9 patients who progressed to dialysis died of infection. Primary membranoproliferative glomerulonephritis (MPGN) (P = 0.014) and MPGN pattern at diagnostic biopsy (P < 0.001) were associated with a higher risk of graft loss. CONCLUSIONS: The long-term outcome of allograft PGNMID was relatively poor in the Chinese population. Primary MPGN and MPGN pattern in renal allograft were associated with  poor outcomes.

Evaluation of vascular lesions using circulating endothelial cells in renal transplant patients.

OBJECTIVE: To investigate the correlation between circulating endothelial cells (CECs) and vascular lesions in renal allografts. METHODOLOGY: Sixty-two renal transplant patients were divided into four groups according to biopsy data. CECs were isolated from peripheral blood with anti-CD136-coated immunomagnetic Dynabeads and counted by microscopy during biopsy. CEC numbers were compared in each group, as well as the correlation between CECs and C4d and vascular changes in different groups. RESULT: CECs counts were higher in the acute rejection (AR) with endarteritis group than in the normal group (p < 0.01), acute tubular necrosis (ATN) group (p < 0.01) and chronic allograft nephropathy (CAN) group (p < 0.01), there were no difference among ATN, normal and CAN) group (p = 0.587). There was no difference among the normal group without hyaline, normal group with hyaline and CAN with hyaline group. An increasing CECs count was related to C4d-positive AR (p = 0.008; κ score = 0.519) and infiltration of inflammatory cells (p = 0.002, κ score = 0.573) in proximal tubule cells (PTCs). The CECs count decreased after intensive therapy in five patients (p = 0.001). CONCLUSION: Elevation of the CEC count in blood was related to endarteritis. Elevation of CEC count was related to C4d deposition and infiltration of inflammatory cells in PTCs.

Predominance of intraglomerular T-bet or GATA3 may determine mechanism of transplant rejection.

The transcription factors T-bet and GATA3 determine the differentiation of helper T cells into Th1 or Th2 cells, respectively. An altered ratio of their relative expression promotes the pathogenesis of certain immunological diseases, but whether this may also contribute to the pathogenesis of antibody-mediated rejection (ABMR) versus T cell-mediated rejection (TCMR) is unknown. Here, we characterized the intragraft expression of T-bet and GATA3 and determined the correlation of their levels with the presence of typical lesions of ABMR and TCMR. We found a predominant intraglomerular expression of T-bet in patients with ABMR, which was distinct from that in patients with TCMR. In ABMR, interstitial T-bet expression was typically located in peritubular capillaries, although the overall quantity of interstitial T-bet was less than that observed in TCMR. The expression of intraglomerular T-bet correlated with infiltration of CD4+ and CD8+ lymphocytes, which express T-bet, as well as intraglomerular CD68+ monocyte/macrophages, which do not express T-bet. The predominance of intraglomerular T-bet expression relative to GATA3 expression associated with poor response to treatment with bolus steroid. In summary, predominance of intraglomerular T-bet expression correlates with antibody-mediated rejection and resistance to steroid treatment.

De novo development of circulating anti-endothelial cell antibodies rather than pre-existing antibodies is associated with post-transplant allograft rejection.

Anti-endothelial cell antibodies (AECAs) are thought to be involved in the development of renal allograft rejection. To explore this further, we determine whether AECAs play a role both in predicting the incidence of allograft rejection and long-term outcomes by analysis of serum samples from 226 renal allograft recipients for AECAs pre- and post-transplant. Surprisingly, the presence of pre-existing AECAs was not associated with either an increased risk of rejection or a detrimental impact on recipient/graft survival. Subsequent de novo AECAs, however, were associated with a significantly increased risk of early acute rejection. Moreover, these rejections tended to be more severe with a significantly increased incidence of both steroid-resistant and multiple episodes of acute rejection. The acute rejections associated with de novo AECAs did not correlate with C4d deposition at the time of renal biopsy, but did demonstrate an association with the presence of glomerulitis and peritubular capillary inflammation. Significantly more patients with de novo AECAs developed graft dysfunction. Thus, our prospective study suggests the emergence of de novo AECAs is associated with transplant rejection that may lead to allograft dysfunction.

The role of donor-derived cell-free DNA in the detection of renal allograft injury.

Donor-derived cell-free DNA refers to the cell-free DNA derived from apoptosis or necrosis of allograft tissue, circulating in the body fluids of patients after organ transplantation, and carries health information on the donor tissue. In the past two years, donor-derived cell-free DNA has rapidly become a research hotspot in the field of graft rejection detection after organ transplant. Recent published data have increased our understanding of donor-derived cell-free DNA in the field of kidney transplantation, especially in association with acute rejection. Donor-derived cell-free DNA is predicted to become the next-generation biomarker for the non-invasive detection of allograft rejection. This article reviews the research, involving donor-derived cell-free DNA in ischemia-reperfusion injury, delayed graft function, acute rejection (antibody mediated rejection and T-cell mediated rejection), and BK virus nephropathy. We further discuss the limitations of current research models and suggest directions for future study.

Donor-derived cell-free DNA: An independent biomarker in kidney transplant patients with antibody-mediated rejection.

INTRODUCTION: Antibody-mediated rejection (ABMR) is a major cause of kidney transplant failure which requires donor-specific antibodies (DSA) for a definitive diagnosis. Donor-derived cell-free DNA (ddcfDNA) is an emerging biomarker used to assess kidney allograft injury. However, current data is limited to predict the accuracy of ddcfDNA in ABMR diagnosis. This study was conducted to compare the performance of DSA with plasma ddcfDNA for the diagnosis of ABMR. METHODS: In this retrospective single-center observational study, we enrolled 50 kidney transplant recipients who were diagnosed with the suspicion of rejection between June 2018 and May 2019 at the Jinling Hospital. Plasma ddcfDNA was measured by using a novel target region capture sequencing methodology. A total of 37 patients who were tested with DSA and biopsy were divided into four subgroups (ABMR+/DSA+, ABMR+/DSA-, ABMR-/DSA+, ABMR-/DSA-) for the distribution of ddcfDNA (%) by ABMR and DSA. RESULTS: The median level of ddcfDNA in biopsy showed that the ABMR group (1.66%, IQR 1.34-3.76%) was significantly higher than the median level (0.63%, IQR 0.43-0.74%) in non-ABMR (p < 0.001). With a ddcfDNA cutoff of 0.96%, the AUC was 0.90 (95%CI, 0.86-0.95), which was associated with a sensitivity of 90.5% (95%CI, 69.6-98.8%) and specificity of 96.6% (95%CI, 82.2-100%), a PPV of 95% (95%CI, 73.4-99.2%) and NPV of 93.3% (95%CI, 78.9-98.1%) were also observed. Among the four subgroups, ddcfDNA had no significant difference in both DSA+ group and DSA-group (p > 0.05). In the diagnosis of ABMR, the specificity, sensitivity, PPV and NPV of DSA were 50%, 74.1%, 41.7%, 80%, respectively. CONCLUSIONS: ddcfDNA levels in the blood could highly distinguish (biopsy-supported) ABMR occurrence, irrespective of whether this method is accompanied by DSA or not.