Renal Transplant Recipients Research Articles

Fearsome four- Fungal infections in renal transplant recipients

To study the clinical presentation, diagnostic methods, treatment and outcomes of Invasive Aspergillosis Cryptococcal infection, Mucormycosis and Histoplasmosis in renal transplant recipients. : We performed a retrospective analysis of renal transplant recipients with four major fungal infections from January 2000 until December 2022 at a tertiary care centre in Southern India. This study was approved by the institutional ethical committee. We have identified these cases from the electronic records of the microbiology department and renal transplant outpatient clinic. A total of 1970 patients underwent renal transplantation at this institute during study period. A total of 25 patients were diagnosed as having invasive Aspergillosis - 20 patients had pneumonia, three had right maxillary sinusitis, one each had left chronic suppurative otitis media, and skull base osteomyelitis). There were 20 patients with cryptococcal infection of which eight had disseminated infection, seven had meningitis, four had cutaneous cryptococcosis and one had pulmonary cryptococcosis. Mucormycosis was diagnosed in 14 patients, twelve of which had pulmonary mucormycosis, one had oculo-cerebral mucormycosis and one patient had acute invasive fungal maxillarysinusitis. Histoplasmosis was diagnosed in four patients, two of whom had disseminated histoplasmosis and two had cutaneous histoplasmosis. In this study, mortality was highest with mucormycosis (57%) followed by 33.3% with invasive Aspergillosis and 20% with Cryptococci infection. Currently, there is no standard serological test available for the routine identification of invasive fungal infections in patients. Initial cultures may yield negative results due to slow fungal growth and variations in colony appearance. Therefore, it is essential to pursue aggressive sampling methods when fungal infection is suspected. Invasive procedures such as bronchoscopic lavage and abscess aspiration play a crucial role in reaching a diagnosis. In summary, maintaining a high level of suspicion and employing thorough investigations in post-renal transplant recipients are vital for early diagnosis, prompt treatment initiation, prevention of disease spread, and reduction of mortality risk.

Robotic Hysterectomy in Renal Recipient Lady with Very Large Fibroid Uterus

With time, proficiency in minimally invasive surgeries has been increasing, especially with the advent of robotic surgery. In this study, we present the case of a renal transplant recipient with a large uterine fibroid. She underwent a robotic hysterectomy with a multidisciplinary peri-operative management, considering her immunocompromised status.

Risk factors for SARS-CoV-2 pneumonia among renal transplant recipients in Omicron pandemic—a prospective cohort study

BackgroundThe coronavirus disease (COVID-19) pandemic is a global health emergency, and SARS-CoV-2 pneumonia poses significant challenges to health systems worldwide. Renal transplant recipients (RTRs) are a special group and are more vulnerable to viral pneumonia. However, few studies have elucidated the risk factors of SARS-CoV-2 pneumonia in RTRs infected with COVID-19. This study aimed to build a risk prediction model for SARS-CoV-2 pneumonia among RTRs based on demographic and clinical information.MethodsWe conducted a prospective cohort study among 383 RTRs (age ≥ 18 years) diagnosed with COVID-19 from December 21, 2022, to March 26, 2023. Patients’ demographic and clinical information was collected through a questionnaire survey combined with electronic medical records. A stepwise logistic regression model was established to test the predictors of SARS-CoV-2 pneumonia. We assessed the diagnostic performance of the model by calculating the area under the curve (AUC) of the receiver operating characteristic (ROC) and calibration using the Hosmer–Lemeshow (HL) goodness-of-fit test.ResultsOur study showed that the incidence of SARS-CoV-2 pneumonia among RTRs was 31.1%. Older age (OR = 2.08–3.37,95%CI:1.05–7.23), shorter post-transplantation duration (OR = 0.92,95% CI: 0.87,0.99), higher post-transplant Charlson Comorbidity Index (CCI) (OR = 1.84, 95%CI: 1.14,2.98), pulmonary infection history (OR = 3.44, 95%CI: 1.459, 8.099, P = 0.005), fatigue (OR = 2.11, 95%CI: 1.14, 3.90), cough (OR = 2.03, 95%CI: 1.08, 3.81), and lower estimated glomerular filtration rate (eGFR) at COVID-19 diagnosis (OR = 0.98, 95%CI:0.97,0.99) predicted a higher risk for SARS-CoV-2 pneumonia. The model showed good diagnostic performance with Chi-Square = 10.832 (P > 0.05) and AUC = 0.839 (P < 0.001).ConclusionsOur study showed a high incidence of SARS-CoV-2 pneumonia among RTRs, and we built a risk prediction model for SARS-CoV-2 pneumonia based on patients’ demographic and clinical characteristics. The model can help identify RTRs infected with COVID-19 at high risk of SARS-CoV-2 pneumonia to inform timely, targeted, and effective prevention and intervention efforts.

448 Surviving the Double Edge: Squamous Cell Carcinoma in a Renal Transplant Recipient

448 Surviving the Double Edge: Squamous Cell Carcinoma in a Renal Transplant Recipient

Effect of Parathyroidectomy After Renal Transplantation on Grafted Kidney Function Within One Year: A Meta-Analysis

Objective: Secondary hyperparathyroidism (sHPT) is a common symptom of chronic kidney disease (CKD), and at the time of transplantation, more than two-thirds of patients with end-stage renal disease have secondary hyperparathyroidism. After kidney transplantation, parathyroid function is normalized in some kidney transplant recipients, but up to 50% of kidney transplant recipients develop tertiary hyperparathyroidism (tHPT) one year after kidney transplantation. The effect of parathyroidectomy on the grafts is currently unclear, so we conducted a meta-analysis of these studies to assess the changes in graft function one year after parathyroidectomy after kidney transplantation to investigate the resection in renal transplant recipients. Methods: A thorough exploration was conducted across Embase, PubMed, Web of Science, and the Cochrane Library databases to gather pertinent literature spanning from January 1, 2000, to December 31, 2023. The search criteria encompassed terms such as "kidney transplantation," "parathyroidectomy," and "hyperparathyroidism." Results: Twelve studies were scrutinized to assess alterations in graft functionality at 1, 3, 6, and 12 months post-parathyroidectomy. The meta-analysis unveiled a notable decline in overall glomerular filtration rate and a concurrent elevation in serum creatinine one year post-parathyroidectomy, signifying an impairment in graft function compared to the preoperative phase. Significant heterogeneity was observed among the studies. Conclusion: Following parathyroidectomy in renal transplant recipients one year post-surgery, calcium and parathyroid hormone levels normalized. Nonetheless, there was evident impairment in graft function and an elevated risk of graft loss. Hence, the safety of parathyroidectomy in patients with secondary hyperparathyroidism post-renal transplantation necessitates meticulous consideration.

Clinical characteristics and outcomes of invasive pulmonary aspergillosis in renal transplant recipients: A single-center experience

ObjectiveThis study aimed to explore the clinical features, early diagnostic methods, and therapeutic approaches for invasive pulmonary aspergillosis (IPA) in patients after renal transplantation (RT). MethodsWe retrospectively examined 22 patients who were diagnosed with IPA post-RT and treated at our institution between 2005 and 2024. ResultsPatients had an average age of 46.4 ± 9.4 years, with a predominance of men (72.7 %). The incidence of IPA after RT was 1.29 %. The median time of IPA onset after transplantation was 12 months. Fever was the predominant symptom (72.7 %), followed by cough and expectoration (31.8 %) and hemoptysis (13.6 %). Frequent computed tomography findings included consolidations (68.2 %) and cavities (45.5 %) with halo signs, multiple nodules, and air crescent signs. Neutropenia was noted in five patients, including one case of agranulocytosis. Impaired renal function was observed in 59.1 % of the cases. Serum 1,3-β-D-glucan and galactomannan (GM) assays were positive in 45.5 % of patients, with bronchoalveolar lavage fluid GM tests confirming IPA in 83.3 % of those tested. Next-generation sequencing confirmed Aspergillus infection in 11 patients. Ultimately, 68.2 % of the patients recovered, whereas 31.8 % succumbed to the infection, with the deceased demonstrating a significantly high rate of complications. ConclusionsPatients with IPA had high mortality rates. The symptoms of IPA after RT are usually nonspecific, making diagnosis very difficult. Bronchoalveolar lavage fluid GM testing and next-generation sequencing proved relatively helpful as detection methods for IPA. Antifungal treatments should be initiated as soon as possible to avoid complications.

Pulmonary malakoplakia due to Prescottella (Rhodococcus) soli in a renal transplant recipient: First reported case

AbstractPrescottella (Rhodococcus) soli is a soil-dwelling organism not previously thought to be pathogenic in humans. We discuss the case of a 78-year-old male renal transplant recipient presenting with respiratory symptoms and multiple pulmonary nodules, found to be pulmonary malakoplakia secondary to infection with Prescottella (Rhodococcus) soli. Treatment was commenced with vancomycin, meropenem and azithromycin for an induction period of two weeks and continued with indefinite oral moxifloxacin and azithromycin with significant clinical improvement. Although rare, Prescottella species, including Prescottella soli, should be considered in the differential diagnosis of pulmonary nodules, particularly in immunocompromised patients. More data is required to inform optimal treatment.

Arbovirus in Solid Organ Transplants: A Narrative Review of the Literature.

The incidence of arbovirus infections has increased in recent decades. Other than dengue, chikungunya, and West Nile viruses, the data on arbovirus in solid organ transplant (SOT) are limited to case reports, and infections in renal transplant recipients account for most of the reported cases. Dengue and West Nile infections seem to be more severe with higher mortality in SOT patients than in the general population. Acute kidney injury is more frequent in patients with dengue and chikungunya although persistent arthralgia with the latter is less frequent. There is no clear relationship between arboviral infection and acute cellular rejection. Pre-transplant screening of donors should be implemented during increased arboviral activity but, despite donor screening and negative donor nucleic acid amplification test (NAT), donor derived infection can occur. NAT may be transiently positive. IgM tests lack specificity, and neutralizing antibody assays are more specific but not readily available. Other tests, such as immunohistochemistry, antigen tests, PCR, metagenomic assays, and viral culture, can also be performed. There are a few vaccines available against some arboviruses, but live vaccines should be avoided. Treatment is largely supportive. More data on arboviral infection in SOT are needed to understand its epidemiology and clinical course.

RNA-binding protein biomarkers NR4A2 and NR4A3 in renal ischemia-reperfusion injury diagnosis.

The diagnosis of renal ischemia and reperfusion injury (RIRI) is crucial for renal transplant recipients. RNA-binding proteins (RBPs) may have an impact on disease development. Therefore, this study explored the biomarkers associated with RBPs in RIRI. The RIRI related datasets, GSE37838 and GSE43974, and 3964 RBPs were employed in this research. The differential expression analysis was implemented for RIRI and control to gain differentially expressed genes in GSE37838. Then, differentially expressed genes were overlapped with RBPs to acquire intersection genes. Further, the machine learning, diagnostic analysis, and expression validation were executed to filtered biomarkers for RIRI. Additionally, pathway enrichment, molecular networks, and drug prediction were proceed. The area under the curve values of NR4A2 and NR4A3 were >0.7, as well as the expression trend was consistent in both datasets, and all of them were remarkably highly expressed in RIRI. Therefore, they were considered as biomarkers of RIRI. Enrichment analyses revealed that they were both associated with neuroactive ligand-receptor interactions, among others. Further, the lncRNA-miRNA-mRNA and transcription factors (TF)-mRNA network was constructed, revealing that they were all regulated by noncoding RNAs and TF, such as SNHG5-hsa-mir-10b-5p-NR4A3, CREB1, TFAP2A, etc. In addition, a large number of biomarker-related drugs were predicted, among which cadmium acetate, potassium chromate (VI), etc were associated with NR4A2 and NR4A3. In this study, we identified biomarkers associated with RBPs in RIRI, explored their associated pathways and drugs, which provided new insights into the clinical diagnosis and treatment of RIRI.

Clinical Outcomes of Clonal Hematopoiesis in Renal Transplant Recipients

Clinical Outcomes of Clonal Hematopoiesis in Renal Transplant Recipients

Skin cancer incidence in Mexican renal transplant recipients: a cohort over 56 years.

Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America. This 56-year (1967-2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long-term incidence of malignant cutaneous neoplasms in Mexican RTRs. Over 56 years, 1642 RTRs (58% male) were studied. Median follow-up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5-7.9), with an incidence density rate of 6.5 (95% CI: 5.4-7.9) per 1000 person-years and a median latency of 9.8 years. Incidence increased with longer transplantation-related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6-9.1) for any skin cancer and 7.5 (95% CI: 3.8-14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer-related mortality rate of 2.7%. Limitations of the study include its single-center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure. Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non-White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs.

Effects of CYP3A5 Genetic Polymorphisms on the Weight-adjusted through Concentration of Sirolimus in Renal Transplant Recipients: A Systematic Review and Meta-analysis.

Sirolimus, one of the immunosuppressive drugs administered to renal transplant recipients, is metabolized by cytochrome P450 (CYP) 3A5. Accordingly, CYP3A5 polymorphism is a genetic factor affecting sirolimus pharmacokinetics (PK). Therefore, we conducted a systematic review and meta-analysis on the association between sirolimus PK and CYP3A5*3 polymorphism. We searched for studies published up to 13 June 2024 from PubMed, Embase, Cochrane Library, and Web of Science. We reviewed studies on the relationship between CYP3A5*3 polymorphism and weightadjusted trough concentration/dose (C0 /D) ratio and dosage of sirolimus in renal transplant recipients, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We evaluated mean differences (MDs) and 95% confidence intervals (CIs). A total of seven studies were included. The weight-adjusted C0 /D ratio of sirolimus was significantly higher in patients with the CYP3A5*3/*3 rather than CYP3A5*1/*1 or CYP3A5*1/*3 genotype (MD 95.27 ng/mL per mg/kg; 95% CI: 58.06, 132.47; I2 = 74%; p < 0.00001). Also, the weight-adjusted dosage of sirolimus was significantly lower in patients with the CYP3A5*3/*3 rather than CYP3A5*1/*1 or CYP3A5*1/*3 genotype (MD -2.60 × 10-3 mg/kg; 95% CI: -4.52, -0.69; I2 = 44%; p = 0.008). Our meta-analysis showed a significant effect for the CYP3A5*3 genotype on weight-adjusted C0 /D ratio and dosage of sirolimus in adult renal transplant recipients.

Dosing strategy of tacrolimus when co-administered with Wuzhi tablet in renal transplant recipients.

Tacrolimus (TAC) is a first-line immunosuppressant to prevent allograft rejection. Wuzhi tablet is widely used as a TAC-sparing agent in China that could significantly elevate TAC exposure. However, insufficient data support the dose recommendation of TAC when co-administered with Wuzhi. A total of 305 adult renal transplant patients with 2,541 TAC trough concentrations (C0) were enrolled for population pharmacokinetic (PPK) modeling. CYP3A5 polymorphism was genotyped, and corresponding clinical factors were recorded. Nonlinear mixed-effects modeling and Monte Carlo simulation were used for dose recommendation. PK parameters were calculated based on one-compartment model with first-order absorption and elimination. The estimated total clearance (CL/F) and volume of distribution (Vd/F) of TAC were 23.84 L/h and 1,075.96 L, respectively. Wuzhi, CYP3A5 genotype, hematocrit (HCT), and weight were found to have a significant influence on CL/F. CL/F was significantly lower in the individuals who were CYP3A5 non-expressers and received TAC together with Wuzhi. CYP3A5 genotype (expressers or non-expressers), body weight (40-80 kg), and hematocrit (20 - 40%) were selected as the specific clinical scenarios, and the starting dose of TAC ranged from 1.5 to 4.5 mg when co-administered with Wuzhi. We establish a TAC PPK model comprising Wuzhi as a covariate in renal transplant recipients and recommend an initial dose of TAC when co-administered with Wuzhi, which could provide reference for the individualized regimens of TAC.

SGLT2 inhibitor in diabetic and non-diabetic renal transplant recipients

IntroductionSodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular prognosis in patients with CKD, diabetes and heart failure, as well as slowing decline of kidney dysfunction in albuminuric patients. Although safety and efficacy of SGLT2i have not been investigated in kidney transplant recipients (KTRs), their marketing authorization leaves the possibility of their use in these patients in France. MethodsProspective multicentre real-life study including all consecutives KTRs treated with SGLTi. ResultsWe identified 347 KTRs treated with SGLT2i (97 % with dapagliflozin), with an initiation of treatment most often beyond the first year after transplantation (87 %). Importantly, 226 (65.1 %) were diabetic and 245 (70.6 %) were treated with ACE inhibitors or ARBs. We found a low incidence of urinary tract infection (6.6%) and genital mycosis (0.6%), without any serious adverse event. Overall, SGLT2i were stopped in 54 patients (15.6%). The causes of SGLT2i discontinuations were very diverse. The main causes were graft dysfunction (32 %), intercurrent infections (17 %), urinary infections (11%), and digestive symptoms (9%). KTRs with a low estimated GFR, especially those with eGFR < 30 ml/min/1.73m2, presented the highest incidence of SGLT2i discontinuation (p=0.003). SGLT2i were associated with a reduction in proteinuria, found in both diabetic and non-diabetic KTRs. In addition, they had an antihypertensive effect restricted to uncontrolled-hypertensive patients. ConclusionSGLT2i have been used in KTRs since their authorization in France. They were discontinued more frequently in patients with impaired graft function, but the expected side-effects were infrequent and not life-threatening. The short-term antiproteinuric and antihypertensive effects are promising.

P232 Unveiling hidden threats: Understanding upper tract urothelial carcinoma in Dutch renal transplant recipients

P232 Unveiling hidden threats: Understanding upper tract urothelial carcinoma in Dutch renal transplant recipients

Clinical Recommendations for Managing Genitourinary Adverse Effects in Patients Treated with SGLT-2 Inhibitors: A Multidisciplinary Expert Consensus.

Background: SGLT-2 inhibitors (SGLT-2is) are considered to be a first-line treatment for common conditions like type 2 diabetes, chronic kidney disease, and heart failure due to their proven ability to reduce cardiovascular and renal morbidity and mortality. Despite these benefits, SGLT-2is are associated with certain adverse effects (AEs), particularly genitourinary (GU) events, which can lead to treatment discontinuation in some patients. Preventing these AEs is essential for maintaining the cardiorenal benefits of SGLT-2is. Methods: A multidisciplinary panel of experts from various medical specialties reviewed the best available evidence on GU AEs associated with SGLT-2i therapy. The panel focused on the prevention and management of genital mycotic infections, urinary tract infections, and lower urinary tract symptoms in both the general population and high-risk groups, such as renal and cardiac transplant recipients. Results: The panel found that permanent discontinuation of SGLT-2is results in a rapid loss of cardiorenal benefits. Preventive strategies, including identifying high-risk patients before initiating therapy, are critical for minimizing GU AEs. Clinical trials show that most GU infections linked to SGLT-2i therapy are mild to moderate in severity and typically respond to standard antimicrobial treatment, without the need for discontinuation. Conclusions: Routine discontinuation of SGLT-2is due to GU AEs is not recommended. Therapy should be resumed as soon as possible, unless severe or persistent conditions contraindicate their use, in order to preserve the significant benefits of SGLT-2is in reducing cardiovascular and renal events.

Heterologous Versus Homologous COVID-19 Boosters: Immune Response Outcomes in Renal Transplant Recipients.

We aimed to investigate the immune responses to homologous and heterologous COVID-19 booster vaccinations in renal transplant recipients (RTRs) and to identify factors affecting these responses. In this prospective multicenter observational study, we measured the antibody kinetics of 90 RTRs using the chemiluminescent microparticle immunoassay method. The mean age of participants was 45.2 ± 11.4 years, with 35.6% being female. On the 42nd day after the first vaccine dose, the median antibody level was 16.7 (IQR 2.5-249.5) AU/mL, and the seropositivity rate was 60% (n = 36). Mycophenolic acid (MFA) (OR: 0.087, 95% CI: 0.024-0.311) and ACE inhibitor use (OR: 0.203, 95% CI: 0.052-0.794) were identified as independent factors affecting seropositivity. Patients who received the Pfizer/BioNTech booster had significantly higher antibody levels compared to those who received the CoronaVac/Sinovac booster (p = 0.021). Additionally, a significantly higher rate of COVID-19 positivity was observed among patients who received the CoronaVac/Sinovac booster (p = 0.031). Heterologous COVID-19 booster vaccination is significantly more effective than homologous inactivated booster vaccination in enhancing immune responses and preventing new infections in RTRs. MFA and ACE inhibitor usage were independent factors affecting seropositivity. Additional COVID-19 vaccine doses are needed in this patient group.

Cost-effectiveness analysis of denosumab versus alendronate for improving bone mineral density in renal transplant recipients: a comparative study

BackgroundDenosumab and alendronate had a positive impact on bone mineral density (BMD) preservation after kidney transplantation. However, the cost-effectiveness of these agents in the context of kidney transplantation remains largely unexplored. We have conducted a cost-effectiveness analysis to compare the cost and the clinical outcomes of adding subcutaneous (SC) 60 mg denosumab every 6 months vs. oral weekly 70 mg Alendronate, to the standard care therapy (vitamin D and calcium) in renal transplant recipients (RTRs). The impact of both drugs on BMD t-score improvement and fracture prevention was investigated. A decision-analysis model from a health care payer perspective was applied.ResultsThe cost-effectiveness analysis has shown that alendronate add-on to the standard therapy was the most cost-effective regimen, in terms of BMD improvement and fracture prevention with an incremental cost-effectiveness ratio (ICER) of $154/patient/year. The one-way sensitivity analyses have delineated the change in cost-effectiveness when alendronate retail unit price was increased by 25% and 50%, or when denosumab retail unit price was decreased by 25% and 50%. The model was sensitive to the uncertainties (95% confidence interval) in the probabilities of fracture prevention and the probabilities of attaining the desired outcome.ConclusionThe model suggests that oral once weekly alendronate add-on regimen to standard therapy seems to be substantially more cost effective than twice yearly SC denosumab in terms of BMD improvement and fracture prevention in RTRs. Longer time horizon models with longer follow-up periods for fracture risks and adverse events are warranted to validate these data.

Virus-specific Th17 Cells Are Induced by Human Cytomegalovirus after Renal Transplantation.

CMV infection and Th17 cells are independently associated with increased risk for late allograft loss after renal transplantation. Although CMV-specific Th17 cells are detectable in animal models and nontransplant clinical populations, evidence linking CMV and Th17 cells after renal transplantation remains unclear. This prospective observational study evaluated a cohort of renal transplant recipients during 12 mo posttransplant to assess the presence of CMV-specific Th17 cells in peripheral blood and their relationship to pretransplant CMV serostatus and CMV DNAemia. CMV-specific Th17 cells were identified among CMV serostatus donor (D)+ and/or recipient (R)+ recipients and expanded during both primary (D+/R-) and reactivated (D+/R+, D-/R+) CMV DNAemia. A subset of CMV-specific Th17 cells coexpressed IFN-γ, indicating a Th1/17 phenotype. These Th17 and Th1/17 cells expressed CCR6, CCR5, activation and terminal differentiation markers (CD95, OX40, HLA-DR, CD57), and a central/effector memory phenotype. CMV-specific Th1/17 cells expressed activating/inhibitory receptors (CD57, 4-1BB, CD160, CTLA-4, PD-1) at higher frequencies than Th17 cells. In contrast, staphylococcal enterotoxin B-induced Th17 cells did not expand during CMV DNAemia, did not differ between CMV serostatus groups over time, expressed CCR6, predominantly coexpressed TNF-α, and had lower expression of activating and inhibitory receptors than pp65-specific Th17 and Th1/17 cells. These data show that CMV-specific Th17 cells expand during episodes of CMV DNAemia among renal transplant recipients, and that these virus-specific Th17 and Th1/17 cells have distinct phenotypes from global circulating Th(1)/17 cells. These results suggest a potential proinflammatory pathway by which CMV-induced Th17 cells may contribute to allograft injury, increasing risk for late allograft loss.

Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. In the last decade, the number of older renal transplant recipients has significantly increased. However, these patients are at a higher risk of developing post-transplant complications. Therefore, identifying the suitable biomarkers to predict which older patients are at risk of complications is crucial. Cellular senescence could provide insights into the increased vulnerability in this population and guide personalized post-transplant care. This preliminary study involved biopsies from 25 patients with renal allograft rejection and 18 patients without rejection, further divided into older (50-65 years) and younger (29-40 years) groups. Biopsies were collected at different time points after transplantation, and rejection was classified according to the histological Banff 07 criteria. Additionally, immunohistochemistry for the markers of cellular senescence, p27kip1 and p16INK4a, was performed. We observed that the number of p27kip1-positive glomeruli was higher in the older patients with rejection compared to the younger patients with rejection, and a similar pattern was found in the patients without rejection. However, the number of p27kip1-positive tubules was higher in the older patients with rejection compared to the younger patients with rejection, as well as compared to both the older and younger patients without rejection. Tubular p16INK4a expression was not significantly different in the older patients with rejection compared to the younger patients with rejection, and the same pattern was observed in the patients without rejection. However, it was increased in the older patients with rejection in comparison to the older patients without rejection. Our preliminary data suggest the strong potential of both p16INK4a and p27kip1 as biomarkers of renal graft rejection, particularly in older renal transplant recipients.