Risk factors and prognosis of late acute rejection in Chinese kidney transplant recipients.

AIM: Accumulating literature indicates that late acute rejection (LAR) after kidney transplantation portends an unfavourable prognosis. There are no data on the incidence of LAR in Asian subjects, or its risk factors and associated clinical outcomes. METHODS: We conducted a retrospective single-centre case-+control study to investigate the incidence, risk factors and prognosis of LAR in Chinese kidney transplant recipients. Subjects with or without LAR were matched for age, gender, era of transplantation, allograft type, and maintenance immunosuppression regimen. RESULTS: Thirty-two episodes of LAR occurred within an observation period of 12 years giving an incidence rate of 0.46 episodes per 1000 patient-years. Acute rejection within the first year after transplantation was associated with an increased risk of LAR (OR 3.59, P = 0.041). In patients receiving maintenance immunosuppression regimen with steroid, cyclosporin A (CsA) and mycophenolate or an m-TOR inhibitor, patients with LAR showed lower trough CsA levels prior to and at the time of rejection compared to Controls (86.0 ± 26.1 vs. 105.6 ± 13.3 µg/L, P = 0.049; and 75.7 ± 35.7 vs. 106.0 ± 20.5 µg/L, P = 0.032, respectively). Trough CsA level below 80 µg/L was associated with the development of LAR (OR 10.82, P = 0.032). Patients with LAR showed an inferior allograft survival (P < 0.001) while patient survival rates were similar (P = 0.122). CONCLUSIONS: Late acute rejection is uncommon in Chinese kidney transplant recipients but is associated with reduced allograft survival. Risk factors include acute rejection in the first post-transplant year and trough CsA level below 80 µg/L in patients on CsA-based maintenance immunosuppression. Minimization of immunosuppression in apparently stable kidney transplant recipients must be exercised with caution.

Rapid reduction of viruria and stabilization of allograft function by fusidic acid in a renal transplant recipient with JC virus-associated nephropathy.

JC virus (JCV)-associated nephropathy has been increasingly recognized as a cause of allograft dysfunction with graft loss in renal transplant recipients. Like many other opportunistic viral infections in transplant recipients, there are currently limited therapeutic options for this condition. Fusidic acid has previously been reported to exhibit antiviral activity against JCV in in vitro assays. We report the first in vivo study to document the rapid reduction of JC viruria and stabilization of allograft function by oral fusidic acid (fusidate sodium) in a deceased donor renal transplant recipient with JCV-associated nephropathy and acute allograft dysfunction which did not improve initially to surgical relief of hydronephrosis and reduction of immunosuppressants. Rapid reduction of JC viruria detected by quantitative PCR and stabilization of renal function were observed. Fusidic acid has several practical advantages in this clinical setting, including a low EC50 against JCV, high plasma C max, long half-life, availability of both oral and intravenous formulations, excellent oral bioavailability, good patient tolerability, and lack of serious drug interactions with other drugs taken by renal transplant recipients. Further mechanistic and clinical studies are necessary to evaluate this treatment option for JCV-associated nephropathy.

Palliative care in kidney transplant recipients with graft failure.

Kidney transplantation is the best renal replacement therapy for patients with end stage kidney disease. It provides longer patient survival and better quality of life than dialysis. The clinical course after kidney transplantation could be complex and variable. Patients may develop various complications or even kidney graft failure. Symptom burden related to uraemia in patients with graft failure, and the side-effects of immunosuppression, cause psychological distress and adversely affect the quality of life of patients. Treatment decisions in patients with graft failure can be challenging to patients and their caregivers. Renal palliative care is an emerging field, but its adoption remains relatively low among kidney transplant recipients with progressive graft failure. In this context, timely consideration and referral for palliative care can improve symptom burden, reduce stress in patients and their caregivers, and facilitate treatment goal setting and advanced care planning. Common barriers to bring palliative care to suitable patients include: (I) misconception in patients, caregivers and healthcare providers that palliative care means abandonment of life sustaining treatment; (II) over-optimistic prognostic assessment and over-aggressive management approach; (III) insufficient awareness and training in palliative care of healthcare professionals; (IV) inadequate access to and insufficient resources in palliative care. Enhanced training and awareness, and further studies, would be needed to optimize the decision process and delineate the benefit of palliative care, and to guide evidence-based practice in the transplant population.

Immunogenicity and Safety of COVID-19 Vaccines in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis.

Background: Systematic data on the efficacy and safety of COVID-19 vaccine in patients on renal replacement therapy (RRT) remains limited. We conducted a meta-analysis on the efficacy and safety of COVID-19 vaccine in patients on RRT. Methods: Eligible studies were identified by systematic literature search in four electronic databases. Twenty-seven studies (4,264 patients) were included for meta-analysis. 99% patients received mRNA vaccine. Results: Patients on RRT showed inferior seropositivity after two-dosed COVID-19 vaccine, 44% lower than the general population. Kidney transplant recipients (KTRs) had significantly lower seropositivity than patients on haemodialysis (HD) or peritoneal dialysis (PD) (26.1 vs. 84.3% and 92.4% respectively, p < 0.001 for both). Compared with healthy controls, KTRs, HD and PD patients were 80% (95% CI: 62-99%), 18% (95% CI: 9-27%) and 11% (95% CI: 1-21%) less likely to develop antibodies after vaccination (p < 0.001, <0.001 and 0.39 respectively). In KTRs, every 1% increase in using mycophenolate was associated with 0.92% reduction in seropositivity (95% CI: -1.68, -0.17, p = 0.021) at population level. The overall adverse event rate attributed to vaccination was 2.1%. Most events were mild. Conclusion: Patients on RRT, particularly KTRs, had significantly reduced antibody response after two-dosed COVID-19 vaccination. Vaccination is generally well tolerated. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021261879.

Cancer risk in patients with diabetic nephropathy: A retrospective cohort study in Hong Kong.

Diabetic nephropathy (DN) is a leading cause of end-stage kidney disease nowadays. Certain cancers are more common in patients with diabetes mellitus. However, there are no data concerning the cancer pattern in patients with DN. The aim of this study is to investigate the site-specific cancer risk and mortality in these patients.A retrospective cohort study of 5643 DN patients between 2000 and 2015 was conducted in 2 large hospitals in Hong Kong. Incidence and mortality of various cancers were compared with those of general population using standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) respectively.With 24,726 person-years follow-up, 250 cancers were diagnosed. Overall cancer incidence was similar between DN patients and the general population (SIR 1.05, 95% confidence interval [CI] 0.92-1.19). However, certain site-specific cancers are increased in DN patients: the highest risk was observed for laryngeal cancer (SIR 3.03, 95% CI 1.11-6.60), followed by cancers of liver (SIR 1.96, 95% CI 1.35-2.76) and colorectum (SIR 1.92, 95% CI 1.53-2.37), but the risk of prostate cancer was lower (SIR 0.48, 95% CI 0.21-0.95) in the males with DN. The SMR of all cancers was 1.17 (95% CI 1.01-1.37). For individual specific site, only colorectal cancer carried a significant higher mortality risk (SMR 2.45, 95% CI 1.82-3.23).Our data suggested that DN is associated with increased incidence of cancers of colorectum, liver, and larynx but decreased incidence of prostate cancer. Moreover, there is increased mortality of colorectal cancer in patients with DN.

Posttransplant lymphoproliferative disorders in kidney transplant recipients: a retrospective cohort analysis over two decades in Hong Kong.

OBJECTIVE: To characterize the posttransplant lymphoproliferative disorders (PTLD) including the Epstein-Barr virus (EBV) status, histological subgroups, site of occurrence and the clinical outcome in the Chinese kidney transplant recipients. METHODS: A retrospective cohort study of 1, 227 adult kidney transplant recipients who were followed up in two transplant centers in Hong Kong over two decades. RESULTS: 23 (1.9%) patients developed PTLD. Median duration from transplant to PTLD was 104 (5-252) months. Six patients (26.1%) had early PTLD and 17 (73.9%) had late PTLD. Ten (43%) developed PTLD >10 years after transplant. All patients in early PTLD group were EBV-positive. In the late PTLD group, 60% were EBV-negative and 40% EBV-positive. More than 90% of cases were monomorphic PTLD with majority being diffuse large B cell lymphoma. Bone marrow was the most common extranodal site. The overall treatment response rate was 52.2 %. None of the patients developed rejection or relapse after PTLD. At a median follow-up of 9 (1-79) months after PTLD, 18 patients died. Patient survival was 48% at 1 year and 30% at 3 years and death-censored allograft survival was 82% at 1year and 73% at 3 years. CONCLUSION: Late PTLD is common. Careful adjustment of immunosuppression, close monitoring of patients, increased awareness and early detection of the disease are essential.

Chronotropic incompetence, echocardiographic abnormalities and exercise intolerance in renal transplant recipients.

BACKGROUND: Chronotropic incompetence (CI) is an independent predictor of cardiovascular events and overall mortality. The prevalence and significance of CI in renal transplant patient has not been examined. METHODS: 38 non-heart failure renal transplant recipients were recruited for a transthoracic echocardiogram and treadmill stress test using the modified Bruce protocol. RESULTS: 15 patients (39.5%) had CI (defined as failure to reach 85% of the maximum age-predicted heart rate, or <8 0% of predicted heart rate reserve). CI patients had higher left ventricular (LV) mass (216.5 ± 56.1 vs. 183.1 ± 40.0 g, p = 0.04), increased septal wall thickness (11.7 ± 1.4 vs. 10.7 ± 1.1 mm, p = 0.03) and posterior wall thickness (10.9 ± 1.9 vs. 9.5 ± 1.7 mm, p = 0.02). At multivariate analysis, CI was associated with elevated serum creatinine [odds ratio (OR) 1.04, p = 0.03] and increased LV mass (OR 1.03, p = 0.03). CI was associated with shorter exercise duration (3.53 ± 2.20 vs. 8.08 ± 2.34 min, p < 0.01) and lower metabolic equivalents (5.40 ± 2.05 vs. 9.82 ± 2.39, p < 0.01). At multivariate analysis, exercise duration was negatively associated with CI (ß = -0.54, p < 0.01). CONCLUSIONS: CI is present in approximately 40% of asymptomatic renal transplant recipients and is associated with reduced exercise tolerance, left ventricular hypertrophy, and worse allograft function .