Anna Francis

Long-Term Outcome of Kidney Transplantation in Recipients with Focal Segmental Glomerulosclerosis

BACKGROUND AND OBJECTIVES FSGS can recur after kidney transplantation and is associated with poor graft outcomes. We aimed to assess the incidence of FSGS recurrence post-transplant and determine the effect of graft source on recurrence and graft survival in patients with biopsy-proven FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using the Australian and New Zealand Dialysis and Transplant Registry, we assessed incidence of FSGS, the influence of donor type on the risk of FSGS recurrence, and graft loss in recipients with ESRD caused by primary FSGS using Kaplan-Meier and logistic regression analyses. RESULTS Between 1992 and 2011, 736 first kidney transplants were performed in 666 adults and 70 children (≤20 years old) with biopsy-proven primary FSGS. FSGS recurred in 76 (10.3%) patients. Younger age (P<0.001), nonwhite ethnicity (P=0.02), and having a live donor (P=0.02) were independent risk factors associated with recurrence. Median graft survival was significantly better for live donor compared with deceased donor grafts (14.8 versus 12.1 years; P<0.01). Disease recurrence predicted poor graft outcomes, with 52% (95% confidence interval, 40% to 63%) 5-year graft survival in the recurrence group compared with 83% (95% confidence interval, 79% to 86%) in the group without recurrent disease (P<0.001). CONCLUSIONS FSGS recurrence after kidney transplantation was more common in live donor kidneys. Despite this, graft survival in live donor recipients was significantly better for both children and adults with FSGS. We propose that live donor transplantation should not be avoided in patients with FSGS.

Incidence and predictors of cancer following kidney transplantation in childhood

Cancer risk is increased substantially in adult kidney transplant recipients, but the long‐term risk of cancer in childhood recipients is unclear. Using the Australian and New Zealand Dialysis and Transplant Registry, the authors compared overall and site‐specific incidences of cancer after transplantation in childhood recipients with population‐based data by using standardized incidence ratios (SIRs). Among 1734 childhood recipients (median age 14 years, 57% male, 85% white), 289 (16.7%) developed cancer (196 nonmelanoma skin cancers, 143 nonskin cancers) over a median follow‐up of 13.4 years. The 25‐year cumulative incidences of any cancer were 27% (95% confidence intervals 24–30%), 20% (17–23%) for nonmelanoma skin cancer, and 14% (12–17%) for nonskin cancer (including melanoma). The SIR for nonskin cancer was 8.23 (95% CI 6.92–9.73), with the highest risk for posttransplant lymphoproliferative disease (SIR 45.80, 95% CI 32.71–62.44) and cervical cancer (29.4, 95% CI 17.5–46.5). Increasing age at transplantation (adjusted hazard ratio [aHR] per year 1.10, 95% CI 1.06–1.14), white race (aHR 3.36, 95% CI 1.61–6.79), and having a functioning transplant (aHR 2.27, 95% CI 1.47–3.71) were risk factors for cancer. Cancer risk, particularly for virus‐related cancers, is increased substantially after kidney transplantation during childhood.

Incidence and predictors of post-transplant lymphoproliferative disease after kidney transplantation during adulthood and childhood: a registry study

Background Differences in the epidemiology of post-transplant lymphoproliferative disease (PTLD) between adult and paediatric kidney transplant recipients remain unclear. Methods Using the Australian and New Zealand Dialysis and Transplant Registry (1963-2015), the cumulative incidences of PTLD in children (age <20 years) and adults were calculated using a competing risk of death model and compared with age-matched population-based data using standardized incidence ratios (SIRs). Risk factors for PTLD were assessed using Cox proportional hazards regression. Results Among 23 477 patients (92% adult, 60% male), 505 developed PTLD, with 50 (10%) occurring in childhood recipients. The 25-year cumulative incidence of PTLD was 3.3% [95% confidence interval (CI) 2.9-3.6] for adult recipients and 3.6% (95% CI 2.7-4.8) for childhood recipients. Childhood recipients had a 30-fold increased risk of lymphoma compared with the age-matched general population [SIR 29.5 (95% CI 21.9-38.8)], higher than adult recipients [SIR 8.4 (95% CI 7.7-9.2)]. Epstein-Barr virus (EBV)-negative recipient serology [adjusted hazard ratio (aHR) 3.33 (95% CI 2.21-5.01), P < 0.001], year of transplantation [aHR 0.93 for each year after the year 2000 (95% CI 0.88-0.99), P = 0.02], induction with an agent other than anti-CD25 monoclonal antibody [aHR 2.07 (95% CI 1.16-3.70), P = 0.01] and having diabetes [aHR 3.49 (95% CI 2.26-5.38), P < 0.001] were independently associated with PTLD. Conclusions Lymphoma occurs at similar rates in adult and paediatric recipients, but has been decreasing since the year 2000. EBV-negative patients and those with diabetes or induction agent other than anti-CD25 monoclonal antibody are at substantially increased risk of PTLD.

Treatment of recurrent focal segmental glomerulosclerosis post-kidney transplantation in Australian and New Zealand children: A retrospective cohort study

Disease recurrence affects around a third of renal transplants for children with FSGS and is associated with poor graft outcomes. Unfortunately, there are no large trials guiding treatment for recurrent FSGS. We aimed to describe current therapies and treatment response for recurrent FSGS in 4 centres in Australia and New Zealand. Data were collected on children (age <18 years) with recurrent FSGS (1990‐2015). We reviewed patient charts to obtain clinical information. Ethics approval was obtained from the relevant boards. Complete records were available on 24 patients (62% female, 54% Caucasian). Median time to first recurrence was 4 days (IQR 2‐5 days). There were 14 separate treatment regimens, involving an average of 2 agents. The most common therapies were plasma exchange (20/24 patients, 83%), cyclosporin (15/24, 63%), and methylprednisolone (9/24, 38%). Full remission was achieved in 15 (63%), partial remission in 2 (8%), and no remission in 7 (29%) patients. Of the patients with no remission, 5 lost their graft to recurrent disease and 1 to concurrent acute vascular rejection. The plethora of different treatment regimens reflects the poor evidence guiding management for recurrent FSGS. More research is needed to improve outcomes.

Honey in the Prevention and Treatment of Infection in the CKD Population: A Narrative Review

Infection is a major cause of morbidity and mortality at all stages of chronic kidney disease (CKD). Multiresistant organisms are becoming increasingly common, particularly in the CKD population. Unfortunately, the rapid evolution of antibiotic resistance has not been mirrored by innovation in new antibiotic agents. Novel treatments are therefore urgently needed. Honey has garnered much interest due to its broad-spectrum antibacterial properties based on extensive experimental data. Unlike conventional antibiotics, honey has an added advantage as it appears to avoid inducing antimicrobial resistance in bacteria. This review discusses the potential mechanisms of action and role of honey in infection management in the general population, epidemiology and special challenges of infections in CKD populations, and the clinical trial evidence pertaining to the safety and efficacy of honey for the prevention and treatment of infections in CKD population.

Outcome of Primary Focal Segmental Glomerulosclerosis in Australian and New Zealand Pediatric Renal Transplant Recipients

Abstracts for the IPNA Congress, 30 August 3 September 2013, Shanghai, Chinas for the IPNA Congress, 30 August 3 September 2013, Shanghai, China

The impact of donor/recipient age difference and HLA mismatch on graft outcome in pediatric kidney transplantation

Understanding the relationship between the factors that influence long‐term kidney transplant survival remains a key priority for pediatric nephrologists. We assessed the relative impact of donor/recipient age difference and HLA matching on long‐term graft outcomes.

Moving on: transitioning young people with chronic kidney disease to adult care

Advances in the care of children mean that adolescents with chronic kidney disease (CKD) are surviving to adulthood and requiring transition to adult care. The transition phase is well-recognised to be associated with considerable excess morbidity and graft loss, but these outcomes may be avoidable through a structured transition programme. This review will discuss the (1) challenges encountered by patients with CKD, caregivers and clinicians during transition; (2) predictors and outcomes of transition; (3) current guidelines on transition from paediatric to adult renal services; (4) interventions and research directions that may help to improve the care and outcomes for young people with CKD in transition. In spite of the substantial improvement in health gains required for this disadvantaged population, there is to date only limited evidence on the effects of current transition programmes.

Post-transplant lymphoproliferative disease may be an adverse risk factor for patient survival but not graft loss in kidney transplant recipients

Better prognostication of graft and patient outcomes among kidney transplant recipients with post-transplant lymphoproliferative disease (PTLD) in the rituximab era is needed to inform treatment decisions. Therefore, we sought to estimate the excess risks of death and graft loss in kidney transplant recipients with PTLD, and to determine risk factors for death. Using the ANZDATA registry, the risks of mortality and graft loss among recipients with and without PTLD were estimated using survival analysis. A group of 367 patients with PTLD (69% male, 85% white, mean age 43 years) were matched 1 to 4 to 1468 controls (69% male, 88% white, mean age 43 years), and followed for a mean of 16 years. Recipients with PTLD experienced poorer 10-year patient survival (41%, 95% confidence intervals 36-47%) than controls (65%, 63-68%). Excess mortality occurred in the first 2 years post-transplant (hazard ratio 8.5, 6.7-11), but not thereafter (1.0, 0.76-1.3). Cerebral lymphoma (2.0, 1.3-3.1), bone marrow disease (2.0, 1.2-3.3) and year of diagnosis prior to 2000 (2.2, 1.4-3.5; after 2000 reference) were risk factors of death. PTLD did not confer an excess risk of graft loss (1.08, 0.69-1.70). Thus, PTLD is a risk factor for death, particularly in the first two years after diagnosis. Cerebral or bone marrow diseases were associated with increased mortality risk, but overall survival in the rituximab era (post 2000) has improved.

Quality of life of children and adolescents with chronic kidney disease: a cross-sectional study

Objective The aim was to compare quality of life (QoL) among children and adolescents with different stages of chronic kidney disease (CKD) and determine factors associated with changes in QoL. Design Cross-sectional. Setting The Kids with CKD study involved five of eight paediatric nephrology units in Australia and New Zealand. Patients There were 375 children and adolescents (aged 6–18 years) with CKD, on dialysis or transplanted, recruited between 2013 and 2016. Main outcome measures Overall and domain-specific QoL were measured using the Health Utilities Index 3 score, with a scale from −0.36 (worse than dead) to 1 (perfect health). QoL scores were compared between CKD stages using the Mann-Whitney U test. Factors associated with changes in QoL were assessed using multivariable linear and ordinal logistic regression. Results QoL for those with CKD stages 1–2 (n=106, median 0.88, IQR 0.63–0.96) was higher than those on dialysis (n=43, median 0.67, IQR 0.39–0.91, p<0.001), and similar to those with kidney transplants (n=135, median 0.83, IQR 0.59–0.97, p=0.4) or CKD stages 3–5 (n=91, 0.85, IQR 0.60–0.98). Reductions were most frequent in the domains of cognition (50%), pain (42%) and emotion (40%). The risk factors associated with decrements in overall QoL were being on dialysis (decrement of 0.13, 95% CI 0.02 to 0.25, p=0.02), lower family income (decrement of 0.10, 95% CI 0.03 to 0.15, p=0.002) and short stature (decrement of 0.09, 95% CI 0.01 to 0.16, p=0.02). Conclusions The overall QoL and domains such as pain and emotion are substantially worse in children on dialysis compared with earlier stage CKD and those with kidney transplants.