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Objective This systematic review and meta-analysis aims to investigate the prevalence of cervical high-risk human papillomavirus (hrHPV) among kidney transplant recipients (KTRs) and, furthermore to compare it to that in immunocompetent controls. Methods A systematic literature search was conducted in PubMed, EMBASE, and Cochrane Library databases from January 2000 to February 2023, to identify studies investigating the prevalence of cervical hrHPV in KTRs. Pooled cervical hrHPV prevalences, odds ratios (ORs) comparing KTRs to controls and corresponding confidence intervals (CIs) were estimated using random effects logistic regression models. Heterogeneity between studies was assessed through the I2 statistic, and the significance was evaluated by the Cochrane's Q test. Results Altogether, 16 studies covering >1200 KTRs were included. The prevalence of cervical hrHPV in KTRs was 27.7% (95% CI 21.3–35.1) with substantial interstudy heterogeneity. Stratification indicated a higher prevalence in recent years (2019–2023) and in Asia (39% (95% CI 11.2–61.4)). The prevalence of HPV16 and HPV18 in KTRs was 8.0% (95% CI 3.9–15.9) and 1.7% (95% CI 0.8–3.7), respectively. Comparing hrHPV prevalence in KTRs and controls based on six studies including >500 KTRs and 1000 controls, the OR for hrHPV was 2.0 (95% CI 1.1–3.6). Conclusions This meta-analysis establishes an increased cervical hrHPV prevalence in KTRs compared to controls. The increased risk may be associated with immunosuppressive therapy post-transplantation. Further research is needed to explore the potential benefits of HPV vaccination, including potential revaccination strategies in KTRs., Objective: This systematic review and meta-analysis aims to investigate the prevalence of cervical high-risk human papillomavirus (hrHPV) among kidney transplant recipients (KTRs) and, furthermore to compare it to that in immunocompetent controls. Methods: A systematic literature search was conducted in PubMed, EMBASE, and Cochrane Library databases from January 2000 to February 2023, to identify studies investigating the prevalence of cervical hrHPV in KTRs. Pooled cervical hrHPV prevalences, odds ratios (ORs) comparing KTRs to controls and corresponding confidence intervals (CIs) were estimated using random effects logistic regression models. Heterogeneity between studies was assessed through the I2 statistic, and the significance was evaluated by the Cochrane's Q test. Results: Altogether, 16 studies covering >1200 KTRs were included. The prevalence of cervical hrHPV in KTRs was 27.7% (95% CI 21.3–35.1) with substantial interstudy heterogeneity. Stratification indicated a higher prevalence in recent years (2019–2023) and in Asia (39% (95% CI 11.2–61.4)). The prevalence of HPV16 and HPV18 in KTRs was 8.0% (95% CI 3.9–15.9) and 1.7% (95% CI 0.8–3.7), respectively. Comparing hrHPV prevalence in KTRs and controls based on six studies including >500 KTRs and 1000 controls, the OR for hrHPV was 2.0 (95% CI 1.1–3.6). Conclusions: This meta-analysis establishes an increased cervical hrHPV prevalence in KTRs compared to controls. The increased risk may be associated with immunosuppressive therapy post-transplantation. Further research is needed to explore the potential benefits of HPV vaccination, including potential revaccination strategies in KTRs.

Infection with BK polyomavirus (BKPyV) is a common opportunistic infection after kidney transplantation (KT) and may affect graft function. We aimed to determine the incidence, risk factors, and clinical outcomes of BKPyV DNAemia in a prospective cohort of 601 KT recipients transplanted from 2012 to 2020. BKPyV PCR on plasma was performed at days 60, 90, 180, 270, and 360 post-KT. Any BKPyV DNAemia was defined as a single BKPyV DNA of ≥1000 copies/mL. Severe BKPyV DNAemia was defined as two consecutive BKPyV DNA of ≥10,000 copies/mL. Cumulative incidences were investigated using the Aalen–Johansen estimator, and the risk factors were investigated in Cox proportional hazard models. The incidence of any BKPyV DNAemia and severe BKPyV DNAemia was 21% (18–25) and 13% (10–16) at one year post-KT, respectively. Recipient age > 50 years (aHR, 1.72; 95% CI 1.00–2.94; p = 0.049), male sex (aHR, 1.96; 95% CI 1.17–3.29; p = 0.011), living donors (aHR, 1.65; 95% CI 1.03–2.74; p = 0.045), and >3 HLA-ABDR mismatches (aHR, 1.72; 95% CI 1.01–2.94; p = 0.046) increased the risk of severe BKPyV DNAemia. Any BKPyV DNAemia was associated with an increased risk of graft function decline (aHR, 2.26; 95% CI 1.00–5.12; p = 0.049), and severe BKPyV DNAemia was associated with an increased risk of graft loss (aHR, 3.18; 95% CI 1.06–9.58; p = 0.039). These findings highlight the importance of BKPyV monitoring post-KT.

BACKGROUND: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Considerable clinical research has focused on improving graft survival and an increasing number of kidney recipients die with a functioning graft. There is a need to improve patient survival and to better understand the individualized risk of comorbidities and complications. Here, we developed a method to stratify recipients into similar subgroups based on previous comorbidities and subsequently identify complications and for a subpopulation, laboratory test values associated with survival.METHODS: First, we identified significant disease patterns based on all hospital diagnoses from the Danish National Patient Registry for 5752 kidney transplant recipients from 1977 to 2018. Using hierarchical clustering, these longitudinal patterns of diseases segregate into 3 main clusters of glomerulonephritis, hypertension, and diabetes. As some recipients are diagnosed with diseases from >1 cluster, recipients are further stratified into 5 more fine-grained trajectory subgroups for which survival, stratified complication patterns as well as laboratory test values are analyzed.RESULTS: The study replicated known associations indicating that diabetes and low levels of albumin are associated with worse survival when investigating all recipients. However, stratification of recipients by trajectory subgroup showed additional associations. For recipients with glomerulonephritis, higher levels of basophils are significantly associated with poor survival, and these patients are more often diagnosed with bacterial infections. Additional associations were also found.CONCLUSIONS: This study demonstrates that disease trajectories can confirm known comorbidities and furthermore stratify kidney transplant recipients into clinical subgroups in which we can characterize stratified risk factors. We hope to motivate future studies to stratify recipients into more f

RATIONALE & OBJECTIVE: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs. STUDY DESIGN: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial. SETTING & PARTICIPANTS: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion. INTERVENTION: Continuation with a CNI-based regimen or switch to belatacept for 12 months. OUTCOMES: Comparison of the change in the estimated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness. RESULTS: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pressure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss. LIMITATIONS: The heterogeneous baseline estimated glomerular filtration rate and time from transplantation to trial enrollment in the participants. A limited study duration of 1 year. CONCLUSIONS: We found no effects on the calculated CV risk by switching to the belatacept treatment. Participants in the belatacept group had not only l

Background Recurrent urinary tract infections (rUTIs) are common after renal transplantation (RTx), and the impact on graft and patient survival remains controversial. Objective In this study, we investigate the incidence and risk factors for rUTIs in a cohort of RTx recipients and evaluate the effect on graft and patient survival. Design, setting, and participants A retrospective cohort of adult patients who underwent RTx at Rigshospitalet, Denmark, between 2014 and 2021 was evaluated in this study. Outcome measurements and statistical analysis Risk factors for rUTIs were explored with a multivariable cause-specific Cox proportional hazard analysis. The Kaplan-Meier estimate was used to assess overall survival. Results and limitations A total of 571 RTx recipients were included. The median age was 52 yr (interquartile range: 42–62 yr). Of the cases, 62% were deceased donor RTx. A total of 103 recipients experienced rUTIs. We found increasing age (hazard ratio [HR]: 1.02 per year increase, 95% confidence interval [95% CI]: 1.00–1.04, p = 0.02), female gender (HR: 2.1, 95% CI: 1.4–3.3, p < 0.001), history of lower urinary tract symptoms (HR: 2.3, 95% CI: 1.4–3.5, p = 0.001), and a UTI within 30 d of surgery (HR: 3.5, 95% CI: 2.1–5.9, p < 0.001) were associated with rUTIs. No influence of rUTIs on overall or graft survival was observed. Conclusions One in six patients experience rUTIs after RTx. Pre- and postoperative variables affect the risk of rUTIs, but none are easily modifiable. In this cohort, rUTIs did not affect the graft function or survival. The etiology of rUTIs remains poorly understood, and there is a continuous need to study how rUTIs can be reduced and treated optimally., BACKGROUND: Recurrent urinary tract infections (rUTIs) are common after renal transplantation (RTx), and the impact on graft and patient survival remains controversial.OBJECTIVE: In this study, we investigate the incidence and risk factors for rUTIs in a cohort of RTx recipients and evaluate the effect on graft and patient survival.DESIGN SETTING AND PARTICIPANTS: A retrospective cohort of adult patients who underwent RTx at Rigshospitalet, Denmark, between 2014 and 2021 was evaluated in this study.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Risk factors for rUTIs were explored with a multivariable cause-specific Cox proportional hazard analysis. The Kaplan-Meier estimate was used to assess overall survival.RESULTS AND LIMITATIONS: A total of 571 RTx recipients were included. The median age was 52 yr (interquartile range: 42-62 yr). Of the cases, 62% were deceased donor RTx. A total of 103 recipients experienced rUTIs. We found increasing age (hazard ratio [HR]: 1.02 per year increase, 95% confidence interval [95% CI]: 1.00-1.04, p = 0.02), female gender (HR: 2.1, 95% CI: 1.4-3.3, p < 0.001), history of lower urinary tract symptoms (HR: 2.3, 95% CI: 1.4-3.5, p = 0.001), and a UTI within 30 d of surgery (HR: 3.5, 95% CI: 2.1-5.9, p < 0.001) were associated with rUTIs. No influence of rUTIs on overall or graft survival was observed.CONCLUSIONS: One in six patients experience rUTIs after RTx. Pre- and postoperative variables affect the risk of rUTIs, but none are easily modifiable. In this cohort, rUTIs did not affect the graft function or survival. The etiology of rUTIs remains poorly understood, and there is a continuous need to study how rUTIs can be reduced and treated optimally.PATIENT SUMMARY: In this study, we looked at the risk factors for recurrent urinary tract infections in patients after kidney transplantation. We conclude that 21.5% of patients experience recurrent urinary tract infections 5 years after

RATIONALE & OBJECTIVE: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.STUDY DESIGN: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.SETTING & PARTICIPANTS: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m 2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion. INTERVENTION: Continuation with a CNI-based regimen or switch to belatacept for 12 months.OUTCOMES: Comparison of the change in the estimated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness.RESULTS: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pressure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss.LIMITATIONS: The heterogeneous baseline estimated glomerular filtration rate and time from transplantation to trial enrollment in the participants. A limited study duration of 1 year.CONCLUSIONS: We found no effects on the calculated CV risk by switching to the belatacept treatment. Part

Type 2 diabetes mellitus (T2DM) can be multifactorial where both genetics and environmental factors play a role. We aimed to investigate the use of polygenic risk scores (PRS) in the prediction of pre-transplant T2DM and post-transplant diabetes mellitus (PTDM) among solid organ transplant (SOT) patients. Using non-genetic risk scores alone; and the combination with PRS, separate logistic regression models were built and compared using receiver operator curves. Patients were assessed pre-transplant and in three post-transplant periods: 0-45, 46-365 and >365 days. A higher PRS was significantly associated with increased odds of pre-transplant T2DM. However, no improvement was observed for pre-transplant T2DM prediction when comparing PRS combined with non-genetic risk scores to using non-genetic risk scores alone. This was also true for predictions of PTDM in all three post-transplant periods. This study demonstrated that polygenic risk was only associated with the risk of T2DM among SOT recipients prior to transplant and not for PTDM. Combining PRS with a clinical model of non-genetic risk scores did not significantly improve the predictive ability, indicating its limited clinical utility in identifying patients at high risk for T2DM before transplantation, suggesting that non-genetic or different genetic factors may contribute to PTDM.

Objectives: Posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients has a high mortality and may present early (<2 years) or late (≥2 years) posttransplantation. We investigated the clinical characteristics of early and late PTLD among kidney and liver transplant recipients. Methods: Recipients, transplanted at Rigshospitalet, with PTLD development as adults from January 2010 to August 2020, were included. Clinical characteristics, laboratory parameters, and pathology of early and late PTLD were compared. Results: Thirty-one PTLD cases were detected where 10 (32%) were early and 21 (68%) were late PTLD. EBV DNA in plasma was detected in 78% versus 28% in early and late PTLD (p =.037). None of the recipients with early PTLD and nine recipients with late PTLD (47%) had Ann Arbor stage IV at the time of their diagnosis (p =.006). Cyclophosphamid–Hydroxyrubicin–Oncovin–Prednisolon was used for treatment in 10 (48%) recipients with late PTLD (p = 0.032) only. There was no difference in mortality between the two groups. Conclusions: Recipients with late PTLD had a lower prevalence of detectable EBV DNA in plasma, were diagnosed with more advanced disease, and were more frequently treated with chemotherapy compared to recipients with early PTLD.

Background: We investigated 10-year trends in deceased donor kidney quality expressed as the kidney donor risk index (KDRI) and subsequent effects on survival outcomes in a European transplant population. Methods: Time trends in the crude and standardized KDRI between 2005 and 2015 by recipient age, sex, diabetic status and country were examined in 24 177 adult kidney transplant recipients in seven European countries. We determined 5-year patient and graft survival probabilities and the risk of death and graft loss by transplant cohort (Cohort 1: 2005-06, Cohort 2: 2007-08, Cohort 3: 2009-10) and KDRI quintile. Results: The median crude KDRI increased by 1.3% annually, from 1.31 [interquartile range (IQR) 1.08-1.63] in 2005 to 1.47 (IQR 1.16-1.90) in 2015. This increase, i.e. lower kidney quality, was driven predominantly by increases in donor age, hypertension and donation after circulatory death. With time, the gap between the median standardized KDRI in the youngest (18-44 years) and oldest (>65 years) recipients widened. There was no difference in the median standardized KDRI by recipient sex. The median standardized KDRI was highest in Austria, the Netherlands and the Basque Country (Spain). Within each transplant cohort, the 5-year patient and graft survival probability were higher for the lowest KDRIs. There was no difference in the patient and graft survival outcomes across transplant cohorts, however, over time the survival probabilities for the highest KDRIs improved. Conclusions: The overall quality of deceased donor kidneys transplanted between 2005 and 2015 has decreased and varies between age groups and countries. Overall patient and graft outcomes remain unchanged.