Background: Opportunistic infections remain a significant cause of morbidity and mortality after kidney transplantation. This retrospective cohort study aimed to assess the incidence and predictors of post-transplant DNA virus infections (CMV, EBV, BKV and JCV infections) in kidney transplant recipients (KTR) at a single tertiary centre and evaluate their impact on graft outcomes. Methods: KTR transplanted between 2000 and 2021 were evaluated. Multivariate logistic regression analysis and Cox proportional hazard analyses were used to identify factors associated with DNA virus infections and their impact on allograft outcomes respectively. A sub-analysis of individual viral infections was also conducted to describe the pattern, timing, interventions, and outcomes of individual infections. Results: Data from 962 recipients were evaluated (Mean age 47.3 ± 15 years, 62% male, 81% white). 30% of recipients (288/962) had infection(s) by one or more of the DNA viruses. Individually, CMV, EBV, BKV and JCV viruses were diagnosed in 13.8%. 11.3%, 8.9% and 4.4% of recipients respectively. Factors associated with increased risk of post-transplant DNA virus infection included recipient female gender, higher number of HLA mismatch, lower baseline estimated glomerular filtration rate (eGFR), CMV seropositive donor, maintenance with cyclosporin (rather than tacrolimus) and higher number of maintenance immunosuppressive medications. The slope of eGFR decline was steeper in recipients with a history of DNA virus infection irrespective of the virus type. Further, GFR declined faster with an increasing number of different viral infections. Death-censored graft loss adjusted for age, gender, total HLA mismatch, baseline eGFR and acute rejection was significantly higher in recipients with a history of DNA virus infection than those without infection (adjusted hazard ratio (aHR, 1.74, 95% CI, 1.08–2.80)). In contrast, dialysis-free survival did not differ between the two groups of recipients (aHR, 1.13, 95% CI, 0.88–1.47). Conclusion: Post-transplant DNA viral infection is associated with a higher risk of allograft loss. Careful management of immunosuppression and close surveillance of at-risk recipients may improve graft outcomes.

BACKGROUND AND AIMS Improvement in short to medium term kidney transplant outcomes and increasingly successful transplantation older patients have led to increasing occurrence of long-term complications of transplantation. Amongst these complications, cancer has become an important cause of mortality following kidney transplantation necessitating the need to better understand the risk factors for the development of de novo malignancy. This study aimed to evaluate the prevalence and the risk factors of de-novo malignancy in a single UK tertiary nephrology centre. METHOD This retrospective cohort study included all kidney transplant recipients (KTR) at our centre, that underwent kidney transplantation between 2000 and 2020 and followed up at our centre. The incidence and types of malignancies excluding non-melanoma skin cancer (NMSC) were analysed. The characteristics of KTR with post-transplant malignancy (excluding NMSC) were compared to those without post-transplant malignancy. Univariate and multivariate logistic regression analyses were conducted to identify the risk predictors of post-transplant cancers. Graft survival and dialysis free survival and death with functioning graft were assessed using Kaplan-Mayer analysis and Cox-regression. RESULTS We analysed the records of 962 KTR (mean age = 47 ± 15 years), followed-up over a median period of 16 years. About 365 (38%) were women, and 783(81%) were Caucasian. 268(32%) had a pre-emptive transplant and 277(29%) had a live donor transplant. Post-transplant malignancy was diagnosed in 84(9%) KTR. KTR with post-transplant cancers were likely to be older (53 ± 14 versus 47 ± 15 years; P = 0.004), on long-term steroid maintenance therapy (64% versus 47%; P = 0.004) and have a history of post-transplant DNA virus infection (40% versus 29%; P = 0.029). Conversely, those with cancers are less likely to be on mycophenolic acid (MPA) therapy (65% versus 78%; P = 0.023). The most common cancers diagnosed were genitourinary cancers (27%) followed by gastrointestinal (24%) and haematological cancers (24%). Respiratory, neurological and others accounted for 10%, 2.4% and 11% of the diagnosed cancers. In multivariate logistic regression analysis, increasing risk of post-transplant cancer was associated with older age at transplantation [OR: 1.81 (1.3–2.5; P < 0.001)], male gender [OR 2.3 (1.3–8.3; P = 0.01)], corticosteroid maintenance [OR 2.3 (1.1–5.2: P = 0.03)], Tobacco smoking [OR: 3.33 (1.2–8.9: P = 0.01)], higher Baseline estimated glomerular filtration rate (eGFR), [OR: 1.2 (1.0–1.4; P = 0.02)], and post-transplant DNA-virus infection [OR: 2.3 (1.0–5.1; P = 0.02)] (Figure 1). There was no difference in the death censored graft survival between the cancer group and the no-cancer group (log-rank, P = 0.51). However, those with cancers had a significantly worse dialysis free survival (log-rank; P = 0.04) and significantly higher death with functioning graft (log-rank; P = 0.02). In the multivariate Cox regression, adjusted for several confounders, dialysis free survival did not differ significantly between the cancer and non-cancer groups (adjusted hazard ratio; aHR: 1.6; P = 0.10). However, age (aHR: 1.16; P = 0.01), male gender (aHR: 1.6; P = 0.01), cardiovascular disease (CVD) (HR: 1.6; P = 0.01) and acute rejection (aHR: 1.7; P = 0.02) were predictors of lower dialysis free survival. CONCLUSION Post-transplant cancers occurred in 9% of our cohort during a median follow-up of 16years. Genitourinary cancers were the most commonly occurring cancers. Older age, male gender, corticosteroid maintenance, smoking and DNA virus infections were the risk factors of malignancy. There was no significant difference in dialysis free survival between the cancer group and the no cancer groups. Lower dialysis free survival was predicted by age, gender, CVD and a history of acute rejection.

BACKGROUND AND AIMS Although improvement in histocompatibility matching, immunosuppressive therapy and antimicrobial treatment have led to improved long-term allograft survival, cardiovascular diseases (CVD) remain the major cause of morbidity and mortality in kidney transplant recipients (KTR). In addition to the accumulated risks due to chronic kidney disease and dialysis, kidney transplantation conveys its own unique risk factors for CVD. These include the metabolic effects of immunosuppressive treatments such as post-transplant hyperglycaemia, dyslipidaemia and hypertension as well as the effects of suboptimal kidney function including volume overload, anaemia, mineral bone disease and left ventricular hypertrophy. The predictors of cardiovascular diseases in KTR, however, have not been clearly defined. This study aimed to first ascertain the incidence of post-transplant CVD in those KTR without a prior confirmed history of CVD, then identify the predictors of CVD transplant associated CVD risk factors and finally evaluate the impact of CVD on graft and patient survival in this era of modern immunosuppressive medications. METHOD We evaluated 962 KTR transplanted between 2000 and 2020 and followed in a single centre. About 328 KTR with a history of pre transplant CVD were excluded. CVD was defined as a composite of Ischaemic heart disease, myocardial infarction, heart failure, stroke or peripheral vascular disease. Logistic regression analyses were performed to identify the risk predictors of post-transplant CVD. Kaplan–Meier plots and multivariate Cox proportional hazards regression analysis were used to identify and characterize predictors of dialysis free survival. RESULTS Among 634 KTR included in the analysis (mean age: 45 ± 15 years), CVD was reported in 101 KTR (16%) during a median follow-up of 95.9 months. About 274(43%) were females, 531(84%) were Caucasians. KTR with post-transplant CVD were likely to be older (50 ± 13 versus 44 ± 15 years; P  < 0.001), had spent more time on dialysis [median (IQR) 21 (1–51) versus 11 (0–3) months; P = 0.004] and received cyclosporin maintenance (18% versus 7%; P = 0.01). Incidence of post-transplant CVD was independently predicted by older age [OR: 1.40 (1.15–1.70: P = 0.001)], tacrolimus therapy [OR: 0.81 (0.71–0.93), P = 0.002], mean haemoglobin concentration [OR: 0.86 (0.75–1.00), P = 0.049] and average C-reactive protein (CRP) level [OR: 1.13 (1.02–1.25), P = 0.02] (Figure 1). The median dialysis free survival was significantly lower in KTR who developed post-transplant CVD (14.7 versus 20 years, P = 0.009). In the multivariate Cox regression analysis, the factors associated with worse dialysis free survival in our cohort (survival with a functioning graft) were older age at transplantation [hazard ratio (HR): 1.03; P  < 0.001), a history of post-transplant CVD (HR: 1.68; P = 0.006), higher post-transplant parathormone levels (HR: 1.02; P < 0.001), higher mean urine protein creatinine ratio (uPCR) (HR: 1.003: P < 0.001), a greater annual rise in uPCR (HR: 1.002; P  < 0.001) and a history of acute rejection (HR: 1.56; P = 0.03). Statin treatment was associated with better dialysis free survival outcome (HR: 0.60; P = 0.01). CONCLUSION The incidence of post-transplant CVD in KTR with no history of pre-transplant CVD was 16%. Age at transplantation and average CRP were independent predictors of post-transplant CVD whereas treatment with Tacrolimus was associated with a lower risk of CVD. Statin therapy was associated with better dialysis free survival whereas a higher PTH was linked to poor survival. It was interesting to note that diabetes was not independently associated with the risk and outcome of post-transplant CVD in our cohort.