Infected Kidney Transplant Research Articles

Infections in kidney transplantation

Infections in kidney transplantation

IGRA-based INH regimen for prevention of active tuberculosis after kidney transplantation: A single-centre retrospective study

ObjectivesTo evaluate the effectiveness and safety of Interferon-gamma release Assay (IGRA)-based isoniazid (INH) prophylaxis strategy to prevent tuberculosis (TB) infection in kidney transplantation (KT) with a risk of TB occurrence. MethodsAdult KT recipients (KTRs) between June 2014 and July 2021 were retrospectively enrolled. The development of active TB after KT was evaluated. ResultsOf 925 KTRs, 111 (12.0%) developed active TB. Among the 501 KTRs at a risk of TB occurrence, 70 (14.0%) patients developed active TB, while 41 (9.7%) of 424 patients without risk factors developed active TB (P = 0.05). Two hundred thirty-nine KTRs received IGRA test with 62 (25.9%) were positive. None of IGRA positive patients (0/40) receiving INH prophylaxis developed active TB, whereas 8 out of 22 patients who had positive IGRA results without INH prophylaxis developed active TB (0 vs. 36.4%, P < 0.01). Of note, for those in risk group but with negative IGRA result, no active TB was found even without INH prophylaxis. Although alanine aminotransferase and aspartate aminotransferase in INH prevention group were higher than those before treatment, they did not exceed three-fold of limit of reference range. ConclusionsIGRA-based INH treatment is an effective and safe protocol to prevent the development of active TB in KTRs.

Comprehensive immune profiling of SARS-CoV-2 infected kidney transplant patients.

The immune responses of kidney transplant recipients against SARS-CoV-2 remains under studied. In this prospective pilot study, we performed comprehensive immune profiling using cellular, proteomic, and serologic assays on a cohort of 9 kidney transplant recipients and 12 non-transplant individuals diagnosed with COVID-19. Our data show that in addition to having reduced SARS-CoV-2 specific antibody levels, kidney transplant recipients exhibited significant cellular differences including a decrease in naïve-but increase in effector T cells, a high number of CD28+ CD4 effector memory T cells, and increased CD8 T memory stem cells compared with non-transplant patients. Furthermore, transplant patients had lower concentrations of serum cytokine MIP-1β as well as a less diverse T cell receptor repertoire. Overall, our results show that compared to non-transplant patients, kidney transplant recipients with SARS-CoV-2 infection exhibit an immunophenotype that is reminiscent of the immune signature observed in patients with severe COVID-19.

Protective Effect of Subcutaneous Drains on Wound Infections in Kidney Transplantation

Wound infections following kidney transplantation are common, with a reported incidence of 5%-19%. In the first few days after surgery, these patients receive extremely high doses of immunosuppression and high volumes of intravenous fluids, and they represent a specific subgroup of surgical patients that may benefit from using prophylactic subcutaneous drains. We analyzed a nonrandomized series of 112 consecutive kidney transplants between January 2017 and December 2019: those who received a subcutaneous drain in addition to the standard retroperitoneal drain (SQ drain group) vs those with a retroperitoneal drain alone (standard group). The SQ drain group had a significantly higher median BMI (31.2 vs 25.8, P < .0001) and a trend towards more patients having diabetes and receiving thymoglobulin on induction. Nonetheless, 1/36 (3%) of patients in the SQ drain group had a documented wound infection requiring packing compared to the standard group 13/73 (17%) (P = .032). When multivariate regression analysis accounted for the potential confounders BMI, thymoglobulin use, and diabetes, the protective effect of the SQ drain was more significant (P = .001). An SQ drain may be a simple and inexpensive method to reduce the rate of wound complications in kidney transplant recipients; prospective studies are warranted.

Impaired CD4+ Cytotoxic T Lymphocyte Activity in Polyomavirus BK Infected Kidney Transplant Recipients.

The reactivation of polyomavirus BK (BKPyV) contributes to increased morbidity and mortality rates of transplant patients, especially kidney transplant recipients (KTRs). CD4+ T cells are important immune cells active during BKPyV infection in KTRs. This research tried to examine the phenotype of CD4+ T cells in the stage of BKPyV activation in KTRs.The re cipients were separated into 2 groups of BKPyV-active and nonactive KTRs (10 patients in each group) and were compared with 10 healthy control subjects. The viral load was evaluated by Taq-man quantitative real-time PCR. The frequency of different CD4+ T cell subsets was determined by analyzing markers such as CD45RO, CCR7, CD27, CD107a, perforin, and granzyme B using flow cytometry. The gene expression levels of transcription factors, including TBX21, GATA3, STAT3, and STAT6, contributing to CD4+ T cell activation, were also assessed. A significantly higher proportion in CCR7+CD27+CD45RO-CD4+ T cell (naive Tcell) subsets was detected in BKPyV-active KTRs compared to nonactive ones. A significant increase was detected in the frequency of CD107a+, perforin+, and granzyme B+ CD4+ T cells in the BKPyV-active group compared to the nonactive group. In CD4+ T cells of KTRs, the mRNA expression of TBX21 and GATA3 was significantly increased in KTRs without BKPyV reactivation compared to BKPyV-active ones. This investigation focused on the CD4+ T cell as an immunodominant T cell type with potential cytotoxicity. Based on these results, BKPyV may have a direct influence on the repertoire of CD4+ T cell subsets. Particularly, cytotoxic CD4+ T cells need further investigation to be considered as a therapeutic approach for BKPyV infection.

Experience in the treatment of a primary infected kidney transplant

Introduction. Infectious complications contribute to a significant decrease in graft and recipient survival rates. The article describes a case report of transplantation of the primary infected kidney transplant. Material and methods. A 33-year-old patient with type 1 diabetes mellitus and end-stage renal disease underwent kidney transplantation. The deceased donor was a 46-year-old man with a confirmed brain death as a result of acute cerebrovascular accident. Results. The early postoperative period was complicated by the development of primary infection of kidney transplant. Despite the ongoing treatment aimed at preserving the transplant, we had to remove it in order to prevent the development of further complications. Conclusion. Kidney transplantation improves the quality of life of patients with end-stage renal disease. In case of uncontrolled course of the infectious process after primary infected graft transplantation, it is necessary to perform transplantectomy in a timely manner in order to save the recipient’s life, since the graft itself is the source of infection.

Hypoalbuminemia is a risk factor for invasive fungal infections and poor outcomes in infected kidney transplant recipients.

Invasive fungal infections (IFI), are estimated to occur in 2%-14% of kidney transplant recipients (KTRs) in the current era of immune suppression and are associated with high mortality rates. We hypothesized that hypoalbuminemia in KTRs is a risk factor for IFI and would be associated with poor outcomes. In this study, using data from a prospective cohort registry, we describe the frequency of IFI due to Blastomycosis, Coccidioidomycosis, Histoplasmosis, Aspergillosis, and Cryptococcus in KTRs with serum albumin levels measured 3-6months before diagnosis. Controls were selected based on incidence density sampling. KTRs were divided into three groups based on the pre-IFI serum albumin level: normal (≥4g/dL), mild (3-4g/dL), or severe (<3g/dL) hypoalbuminemia. Outcomes of interest were uncensored graft failure after IFI and overall mortality. A total of 113 KTRs with IFI were compared with 348 controls. The incidence rate of IFI among individuals with normal, mild, and severe hypoalbuminemia was 3.6, 8.7, and 29.3 per 100 person-years, respectively. After adjustment for multiple variables, the trend for risk of uncensored graft failure following IFI was greater in KTRS with mild (HR=2.1; 95% CI, .75-6.1) and severe (HR=4.47; 95% CI, 1.56-12.8) hypoalbuminemia (P-trend<.001) compared to those with normal serum albumin. Similarly, mortality was higher in severe hypoalbuminemia (HR=1.9; 95% CI, .67-5.6) compared to normal serum albumin (P-trend<.001). Hypoalbuminemia precedes the diagnosis of IFI in KTRs, and is associated with poor outcomes following IFI. Hypoalbuminemia may be a useful predictor of IFI in KTRs and could be incorporated into screening algorithms.

The relation of NCCR variations and host transcription factors gene regulation in BK polyomavirus infected kidney transplant patients

BackgroundBK polyomavirus (BKPyV) infection in immunocompromised patients can led to polyomavirus-associated nephropathy (BKPyVAN) especially after kidney transplantation. The polyomavirus genome contains enhancer elements that are important transcription activators. In this study, the association between viral and host gene expression and NCCR variations was evaluated in kidney transplant recipients (KTRs) with BKPyV active, and BKPyV in-active infection. Methods and ResultsBlood samples were collected from selected KTRs who divided to patients with active and in-active BKPyV infection. Transcriptional control region (TCR) anatomy was compared to the genomic sequence of archetype BKPyV strain WW using nested PCR method and sequencing. The expression level of some transcription factor genes was evaluated using in-house Real-time PCR (SYBR Green) technique. Most changes were observed after TCR anatomy detection in the Q and P blocks. The expression level of VP1 and LT-Ag viral genes were significantly higher in patients with active infection compared with non-infected ones. Transcription factor genes SP1, NF1, SMAD, NFκB, P53, PEA3, ETS1, AP2, NFAT and AP1 were significantly higher in BKPyV active group in comparison in-active and control groups. The analyses revealed that viral load level and mutations frequency has significant correlation. ConclusionsBased on the results, increasing of NCCR variations were associated with higher viral load of BKPyV especially in Q block. Host transcriptional factors and viral genes all had higher express level in active BKPyV patients versus no in-active ones. Detection of the relation between NCCR variation and BKPyV severity in KTRs need to be confirmed in further complicated studies.

An outpatient model of care for COVID-19 infected kidney transplant patients - The hospital-at-home.

The COVID-19 pandemic is protracted and episodic surges from viral variants continue to place significant strain on healthcare systems. COVID-19 vaccines, antiviral therapy and monoclonal antibodies have significantly reduced COVID-19 associated morbidity and mortality. Concurrently, telemedicine has gained acceptance as a model of care and a tool for remote monitoring. These advances allow us to safely transit our inpatient-based care for COVID-19 infected kidney transplant recipients (KTRs) to a hospital-at-home (HaH) model of care. KTRs with PCR-proven COVID-19 infection were triaged by teleconsult and laboratory tests. Suitable patients were enrolled into the HaH. Remote monitoring via teleconsults were conducted daily until patients were de-isolated based on a time-based criterion. Monoclonal antibodies were administered in a dedicated clinic where indicated. Eighty-one KTRs with COVID-19 were enrolled into the HaH between February and June 2022, 70 (86.4%) completed HaH recovery without complications. Eleven (13.6%) patients required inpatient hospitalization for medical issues (n=8) and weekend monoclonal antibody infusion (n=3). Patients requiring inpatient hospitalization had longer transplant vintage (15 years vs. 10 years, p=.03), anaemia (haemoglobin 11.6g/dL vs. 13.1g/dL, p=.01), lower eGFR (39.8 vs. 62.9mL/min/1.73 m2 , p < .05) and lower RBD levels (<50 AU/mL vs. 1435 AU/mL, p=.02). HaH saved 753 inpatient patient-days with no deaths observed. Hospital admission rates from the HaH programme was 13.6%. Patients who required inpatient care had direct access admission without utilization of emergency department resources. Selected KTRs with COVID-19 infection can be safely managed in a HaH programme; alleviating strain on inpatient and emergency healthcare resources.

National survey of prevention and management of CMV infection in pediatric kidney transplantation in comparison to clinical practice guidelines.

Cytomegalovirus (CMV) is one of the most frequent opportunistic infections in kidney transplant (KT) recipients and is a risk factor for patient and graft survival after KT. Center-to-center variation, optimal prevention and treatment strategies in pediatric KT are currently unknown. This survey aimed to assess current CMV prevention and treatment strategies used among French pediatric KT centers. A web-based survey was sent to all 13 French pediatric kidney transplantation centers. Twelve (92%) centers responded to the survey. All centers used prophylaxis for the donor-positive/recipient-negative (D+/R-) group. For R + patients, 54% used prophylaxis, 37% used a pre-emptive strategy. In the low-risk group, D-/R-, 50% used a pre-emptive approach and 50% had no specific prevention strategy. The antiviral used by all centers for prophylaxis was valganciclovir (VGCV). The duration of prophylaxis varied from 3 to 7 months and the duration of viral load monitoring varied from 6 months to indefinitely. No center used a hybrid/sequential approach. For the treatment of CMV DNAemia, VGCV or intravenous GCV were used. Therapeutic drug monitoring of VGCV was performed in 5 centers (42%). Five centers reported drug resistance. Eight centers (67%) administered VGCV during the treatment of acute graft rejection. There is uniformity in CMV management in some areas among pediatric KT centers in France but not in others which remain diverse and are not up to date with current guidelines, suggesting unnecessary variation which could be reduced with better evidence to inform practice.

Application of Metagenomic Next-Generation Sequencing in the Treatment Guidance of Infection in Kidney Transplantation

Application of Metagenomic Next-Generation Sequencing in the Treatment Guidance of Infection in Kidney Transplantation

BK Polyomavirus (BKPyV) and Cytomegalovirus (CMV) Infections in Kidney Transplantation (KT) From Hepatitis C Positive (HCV) Viremic Donors to Uninfected Recipients

BK Polyomavirus (BKPyV) and Cytomegalovirus (CMV) Infections in Kidney Transplantation (KT) From Hepatitis C Positive (HCV) Viremic Donors to Uninfected Recipients

401.6: Circulating Plasma Proteomics Analysis of CMV Infection in Kidney Transplantation.

401.6: Circulating Plasma Proteomics Analysis of CMV Infection in Kidney Transplantation.

Safety, Efficacy, and Relapse of Nirmatrelvir-Ritonavir in Kidney Transplant Recipients Infected With SARS-CoV-2

IntroductionThe efficacy of nirmatrelvir-ritonavir (NR; Paxlovid, Pfizer, New York, NY) to decrease the risk of progression to severe COVID-19 in high-risk patients has been demonstrated. However, evidence in infected kidney transplant recipients (KTRs) is lacking. Moreover, NR has significant and potentially harmful interactions with calcineurin inhibitors (CNIs).MethodsIn this single-center retrospective study, we included all KTRs treated with NR from April 28 to June 3, 2022. A standard management strategy of CNI dose adaptation (discontinuation of tacrolimus 12 hours before the start of NR and administration of 20% of the cyclosporine dose) and laboratory follow-up was applied.ResultsA total of 14 patients were included. Compared with day-0 (day before NR initiation), day-7 plasma creatinine concentrations and SARS-CoV-2 viral loads were similar (P = 0.866) and decreased (P = 0.002), respectively. CNI trough concentrations at the end of the treatment were satisfactory, nonetheless, with high individual variability. After a median follow-up time of 34 days, no death or viral pneumonia were observed. Nevertheless, 2 patients experienced early SARS-CoV-2 infection relapses (at day-10 and day-21) associated with an increase in SARS-CoV-2 viral loads.ConclusionNR can be used in KTRs but requires a strict protocol of drug adaptation. We observed 2 cases of early relapse after NR treatment that need further investigations.

Effect of nirmatrelvir/ritonavir on calcineurin inhibitor levels: Early experience in four SARS-CoV-2 infected kidney transplant recipients

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Parvovirus B19 infection in kidney transplant recipients: A prospective study in a teaching hospital in Shanghai, China

BackgroundThere is a lack of epidemiological studies on the course and clinical characteristics of Parvovirus B19 (B19V) infections in kidney transplant (KT) recipients. This study was undertaken to provide recommendations for clinical B19V infection diagnosis and treatment. MethodsSerum samples of KT recipients were regularly collected and tested for B19V-DNA copies, B19V-IgG/IgM levels, as well as hematological parameters and functions of kidney and liver. The course of B19V infection was described according to the results of serology and DNA testing, and the clinical and epidemiological data were combined for analysis. Results75% B19V infections occurred within 2 weeks after KT(n = 9). The infection rate of B19V in KT recipients was high, namely 10.17% (n = 12). The number of 10 patients IgM antibodies against B19V (IgM+) and theDNA B19V (DNA+), whereas 2 patients were IgM negative (IgM-) but DNA+. The B19V infected KT patients showed several symptoms, including anemia (100%), reduction of platelets (8.33%), and damage to liver (75%) and kidney function (16.67%) Patients with progressive anemia in the first two weeks after KT, which combined with the decrease of reticulocytes, are more likely to have B19V infection. Associations of four main therapeutic risk factors for B19V infections in KT patients have been analyzed. B19V infection was associated with use of basiliximab (OR = 1.19; 95%- CI: 1.08–1.32; P = 0.003) and use of thymoglobulins (OR = 0.84; 95%-CI: 0.76–0.93; P = 0.003). ConclusionsDoctors should be alert to B19V infection, especially in the immunodeficient patients within the first two weeks after transplantation.

Mortality Due to COVID-19 in Renal Transplant Recipients, Related to Variants of SARS-CoV-2 and Vaccination in Mexico

BackgroundSARS-CoV-2 infection in transplant patients has shown greater lethality and vaccination in this group of patients has shown less information. The objective of this study is to show the statistics in Mexico of lethality in kidney recipients infected with COVID-19 in relation to vaccination and variants of the coronavirus.MethodsThis is a bibliographic search of kidney transplant recipient patients since the start of the pandemic in Mexico to determine lethality after SARS-CoV-2 compared to the general population and in relation to patients, the 4 most important infectious peaks in the country due to identified variants, and also before and after vaccination.ResultsThe global lethality is 26.91% from the beginning of the pandemic to April 9, 2022 in kidney recipients in Mexico (130 deaths of 483 infected kidney transplant recipients) compared to the national lethality of 5.60%. Variant B. 1.1.220 represented the highest lethality with 30.43% and the lowest lethality was Omicron with 16.41%. The lethality prior to vaccination was 30.94% and 23.46% after it.ConclusionBoth some variants and vaccination have influenced a lower lethality due to COVID-19 in Mexico in kidney transplant patients; It is important to consider global recommendations, such as a third or fourth dose, a combination of mRNA vaccines and vectors in order to reduce lethality in this group of patients.

Clinical Characteristics and Immunosuppression Management in Kidney Transplant Recipients Infected with Severe Acute Respiratory Syndrome Coronavirus 2 Infection - An Observational Study

Background: COVID-19 infected kidney transplant patients need specialist care in tailoring their immunosuppression drugs alongside routine care. Methods and Materials: This is an observational data from a single center of 12 kidney transplant recipients (KTR) who were hospitalized with COVID-19 from April 2020 to November 2020. The demographics, COVID treatment including immunosuppressive drug regimen were reviewed. Their graft function during the stay, at the time of discharge, and 30 days after discharge was also reviewed. Results: Of 12 patients included, 83% were male patients. The median age was 37 years and the median time since transplant was 42 months. Common comorbidities were diabetes (50%), hypertension (50%), and cardiovascular disease (8%). Ninety-two percent had triple immunosuppressive regimen whereas 8% were in steroid-free protocol. Fifty percent had mild COVID, 8% had moderate disease, and 41% has severe COVID which was managed with institution-specified protocol. Steroids dose was increased in all patients. Antimetabolite was uniformly withdrawn in all patients irrespective of disease severity. Acute kidney injury was noted in 50% of patients which recovered to baseline at discharge. Graft function at 2 weeks and 30 days after discharge was stabilized close to their baseline value. Mortality was 8%. Conclusion: Reduction of immunosuppression, especially the withdrawal of antimetabolites, was found to be safe without graft rejection in KTRs.

A Structured Telemedicine Model in the Management of COVID-19 Infected Kidney Transplant Patients in a Tertiary Care Center in India.

A Structured Telemedicine Model in the Management of COVID-19 Infected Kidney Transplant Patients in a Tertiary Care Center in India.

Risk factors for urinary tract infection in kidney transplantation from brain death donor and its role in graft function.

Urinary tract infection (UTI) is the most common infection complication after kidney transplantation, and the reports of the incidence vary greatly among different centers. This study aims to explore the risk factors for UTI after kidney transplantation with the donation from brain death (DBD) and the impact on graft function, thus to provide theoretical basis for comprehensive prevention and treatment of UTI after kidney transplantation. The clinical and laboratory data of DBD kidney transplantation from January 2017 to December 2018 in Xiangya Hospital, Central South University were collected and retrospectively analyzed. Patients were assigned into an UTI group and a non-UTI group. The base line characteristics, post-transplant complications, and graft function were compared between the 2 groups. Multivariate logistic regression was used to analyze the risk factors for UTI. A total of 212 DBD kidney transplant recipients were enrolled in this study. UTI occurred in 44 (20.75%) patients after transplantation. The female, the time of indwelling catheter, and postoperative urinary fistula were independent risk factors for UTI after DBD kidney transplantation. A total of 19 strains of gram-positive bacteria, 12 strains of gram-negative bacteria , and 10 strains of fungi were isolated from the urine of 44 UTI patients. The UTI after kidney transplantation significantly increased time of hospital stay (P<0.001) and raised the cost for antibiotics (P=0.004). The graft function was much worse in the UTI group compared with the non-UTI group (P<0.001) at 3 months after transplantation. Twenty (45.45%) patients recurred UTI within one year after transplantation. Non-hemodialysis before transplantation and perioperative combination of antibacterial and antifungal drugs were independent risk factors for recurrence of UTI. UTI after DBD kidney transplantation transplantation affects the renal function at 3 months and increases the patient's economic burden.