Philip A. Clayton

Recent Peritonitis Associates with Mortality among Patients Treated with Peritoneal Dialysis

Peritonitis is a major complication of peritoneal dialysis, but the relationship between peritonitis and mortality among these patients is not well understood. In this case-crossover study, we included the 1316 patients who received peritoneal dialysis in Australia and New Zealand from May 2004 through December 2009 and either died on peritoneal dialysis or within 30 days of transfer to hemodialysis. Each patient served as his or her own control. The mean age was 70 years, and the mean time receiving peritoneal dialysis was 3 years. In total, there were 1446 reported episodes of peritonitis with 27% of patients having ≥ 2 episodes. Compared with the rest of the year, there were significantly increased odds of peritonitis during the 120 days before death, although the magnitude of this association was much greater during the 30 days before death. Compared with a 30-day window 6 months before death, the odds for peritonitis was six-fold higher during the 30 days immediately before death (odds ratio, 6.2; 95% confidence interval, 4.4-8.7). In conclusion, peritonitis significantly associates with mortality in peritoneal dialysis patients. The increased odds extend up to 120 days after an episode of peritonitis but the magnitude is greater during the initial 30 days.

Steroids and recurrent IgA nephropathy after kidney transplantation.

We studied the impact of steroid use on kidney graft loss due to recurrent IgA nephropathy (IgAN). We used data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) to conduct a survival analysis of adult recipients of a first kidney transplant for IgAN who received a graft between 1988 and 2007. Predictors of graft loss due to recurrent IgAN were analyzed in a competing risk survival analysis with steroid use modeled as a time‐varying covariate. Fifteen hundred twenty‐one recipients with kidney failure due to biopsy‐proven IgAN received a first kidney transplant during the study period. Four hundred and twenty‐eight recipients experienced graft loss, of which 54 losses (12.6%) were attributed to recurrent IgAN. The overall 10‐year cumulative incidence of graft loss from recurrent IgAN was 4.3% (95% CI 3.1–5.8). Prevalence of steroid use was 92% at baseline, 84% at 1 year and 64% at 5 years. After adjusting for age, sex, HLA mismatch, dialysis duration and transplant era, steroid use was strongly associated with a reduced risk of recurrence (subhazard ratio 0.50, 95% CI 0.30–0.84). These results suggest that the risk of graft loss from recurrent disease should be considered when tailoring immunosuppression for patients with IgAN.

Increases in renal replacement therapy in Australia and New Zealand: Understanding trends in diabetic nephropathy

Aim:  The incidence of end‐stage kidney disease (ESKD) has been increasing worldwide, with increasing numbers of older people, people with diabetic nephropathy and indigenous people. We investigated the incidence of renal replacement therapy (RRT) in Australia and New Zealand (NZ) to better understand the causes of these effects.

Outcomes of Kidney Transplantation From Older Living Donors

Background The disparity between donor kidney availability and demand has increased utilization of kidneys from older living donors (OLD). We compared graft and patient outcomes of patients on maintenance dialysis after transplantation with OLD kidneys to those receiving younger live donor (YLD) kidneys and deceased donor (DD) kidneys. Methods Using Australia and New Zealand Dialysis and Transplant Registry, primary live and deceased donor renal transplant recipients aged 18 years or older between 1997 and 2009 were stratified into six groups: standard criteria deceased donor kidneys with total ischemic time of less than 12 hours (SCD, <12), SCD of 12 or greater, expanded criteria donor (ECD) less than 12, ECD of 12 or greater, YLD (LD, <60 years), and OLD kidneys (LD, ≥60 years). Preemptive and multiple-organ transplants were excluded. Results Of the 6,317 renal transplant recipients, 346 (5.5%) received OLD kidneys. Compared with kidneys from SCD of less than 12 hours, OLD kidneys were associated with a greater risk of death-censored graft failure (DCGF; adjusted HR 2.00; 95% confidence interval, 1.32–3.03) and inferior 5-year graft function (estimated glomerular filtration rate of 45 mL/min vs. 56 mL/min), although no increase in 5-year mortality (HR, 1.18; 95% confidence interval, 0.80–1.76). Outcomes for OLD kidneys were also inferior to YLD recipients, although modestly superior to ECD kidneys. Chronic allograft nephropathy was more commonly reported as the cause of DCGF among recipients of OLD kidneys than other donor types. Conclusion Patient survival was equal, but graft outcomes for recipients of OLD kidneys were inferior to those obtained with YLD and SCD kidneys. This study suggests that OLD kidneys should be utilized cautiously, cognizant of the fact that younger recipients may have a life expectancy in excess of the life of the transplanted kidney.

Pregnancy Outcomes for Kidney Transplant Recipients

Pregnancy outcomes in a transplant population have not been well documented. Data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the National Perinatal Epidemiology and Statistics Unit (NPESU) were analyzed. We described pregnancy outcomes within the transplant population and compared these to outcomes for the general population. Six hundred ninety‐two pregnancies in 447 transplant recipients were reported between 1971 and 2010 (ANZDATA); a corresponding 5 269 645 pregnancies were reported nationally in Australia between 1991 and 2010 (NPESU). At pregnancy transplant mothers had a median age of 31 years (interquartile range [IQR]: 27, 34), a median creatinine of 106 µmol/L (IQR: 88, 1103 µmol/L) and a functioning transplant for a median of 5 years (IQR: 3, 9). The mean gestational age at birth was 35 ± 5 weeks in transplant recipients, significantly shorter than the national average of 39 weeks (p < 0.0001). Mean live birth weight for transplant recipients was 873 g lower than the national average (2485 ± 783 g vs. 3358 ± 2 g); a significant difference remained after controlling for gestational age. There was lower perinatal survival rate in babies born to transplant recipients, 94% compared with 99% nationally (p < 0.001). Although transplant pregnancies are generally successful, outcomes differ from the general population, indicating these remain high‐risk pregnancies despite good allograft function.

Transplantation rates for living- but not deceased-donor kidneys vary with socioeconomic status in Australia.

Socioeconomic disadvantage has been linked to reduced access to kidney transplantation. To understand and address potential barriers to transplantation, we used the Australia and New Zealand Dialysis and Transplant Registry and examined primary kidney-only transplantation among adult non-Indigenous patients who commenced chronic renal replacement therapy in Australia during 2000-2010. Socioeconomic status was derived from residential postcodes using standard indices. Among the 21,190 patients who commenced renal replacement therapy, 4105 received a kidney transplant (2058 from living donors (660 preemptive) or 2047 from deceased donors) by the end of 2010. Compared with the most socioeconomic disadvantaged quartile, patients from the most advantaged quartile were more likely to receive a preemptive transplant (relative rate 1.93), and more likely to receive a living-donor kidney (adjusted subhazard ratio 1.34) after commencing dialysis. Socioeconomic status was not associated with deceased-donor transplantation. Thus, the association between socioeconomic status and living- but not deceased-donor transplantation suggests that potential donors (rather than recipients) from disadvantaged areas may face barriers to donation. Although the deceased-donor organ allocation process appears essentially equitable, it differs between Australian states.

Mycophenolate versus azathioprine for kidney transplantation: a 15-year follow-up of a randomized trial.

Background The use of mycophenolate mofetil (MMF) is associated with less acute rejection than azathioprine (AZA) early after kidney transplantation. However, the long-term impact of MMF versus AZA is less well studied. Methods The Tricontinental Mycophenolate Mofetil Renal Transplantation Study was a double-blind randomized placebo-controlled trial of MMF versus AZA, together with cyclosporine and steroids, first reported in 1996. We analyzed the long-term outcomes of the Australian cohort of patients enrolled in this study using follow-up data from the Australia and New Zealand Dialysis and Transplant Registry. Patient and graft survival, cancer incidence, and estimated kidney function were compared on an intention-to-treat basis. Results A total of 133 Australian patients participated in the study: 45 were randomized to AZA, 44 were randomized to MMF 2 g/d, and 44 were randomized to MMF 3 g/d. Baseline characteristics were similar between the groups. Median follow-up was 13.8 years, during which there were 97 graft failures, 75 deaths, and 1 lost to follow-up. There were no statistically significant differences between the groups in long-term patient or graft survival, cancer incidence, or kidney function. Death-censored graft survival was best in the group with 3 g/d MMF and worst in the group with 2 g/d MMF. By 5 years, 42% of the MMF group had switched permanently to AZA, whereas crossover from AZA to MMF was rare. Conclusions This long-term examination, although limited by small numbers, found little evidence for the superiority of MMF over AZA.

Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death independent of initial immunosuppression in renal transplant recipients

Human leukocyte antigen (HLA) mismatches have been shown to adversely affect renal allograft outcomes and remain an important component of the allocation of deceased donor (DD) kidneys. The ongoing importance of HLA mismatches on transplant outcomes in the era of more potent immunosuppression remains debatable. Using Australia and New Zealand Dialysis and Transplant Registry, live and DD renal transplant recipients between 1998 and 2009 were examined. The association between the number of HLA mismatches and HLA‐loci mismatches and outcomes were examined. Of the 8036 renal transplant recipients, 59% had between 2 and 4 HLA mismatches. Compared with 0 HLA mismatch, increasing HLA mismatches were associated with a higher risk of graft failure and patient death in the adjusted models. HLA mismatches were associated with an incremental risk of rejection although the relative risk was higher for live donor kidney transplants. Increasing HLA‐AB and HLA‐DR mismatches were associated with a greater risk of acute rejection, graft failure, death‐censored graft failure, and/or death. There was no consistent association between initial immunosuppressive regimen and outcomes. Our results corroborate and extend the previous registry analyses demonstrating that HLA mismatches are associated with poorer transplant outcomes independent of immunosuppression and transplant era.

Socio-economic status and incidence of renal replacement therapy: a registry study of Australian patients

BACKGROUND Socio-economic disadvantage has been linked to higher incidence of end-stage kidney disease in developed countries. Associations between socio-economic status (SES) and incidence of renal replacement therapy (RRT) have not been explored for different kidney diseases, genders or age groups in a country with universal access to healthcare. METHODS We investigated the incidence of non-indigenous patients commencing RRT in Australia in 2000-09, using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Patient postcodes were grouped into deciles using a standard SES index. We analysed incidence by five groups of kidney diseases, age groups, gender and geographic remoteness. RESULTS Incidence of RRT decreased with increasing area advantage. Differences were most evident for the most disadvantaged areas [markedly increased burden; incident rate ratio (IRR) 1.27; 95% confidence interval (CI) 1.18-1.38] and most advantaged decile (decreased burden, IRR 0.76; 95% CI 0.72-0.81), compared with decile 5. Patients with diabetic nephropathy showed the greatest disparities: residents of the most disadvantaged decile were 2.38 (95% CI 2.09-2.71) times more at risk than the most advantaged decile. Congenital and genetic kidney diseases showed lesser gradients-the most disadvantaged decile was 1.28 times (95% CI 0.98-1.68) more at risk. SES was not associated with incidence for patients older than 69 years. DISCUSSION These SES gradients existed, despite all Australians having access to healthcare. Diseases associated with lifestyle show the greatest gradients with SES.

Daily Variation in Death in Patients Treated by Long-term Dialysis: Comparison of In-Center Hemodialysis to Peritoneal and Home Hemodialysis

BACKGROUND There has been little study to date of daily variation in cardiac death in dialysis patients and whether such variation differs according to dialysis modality and session frequency. STUDY DESIGN Observational cohort study using ANZDATA (Australia and New Zealand Dialysis and Transplant) Registry data. SETTING & PARTICIPANTS All adult patients with end-stage kidney failure treated by dialysis in Australia and New Zealand who died between 1999 and 2008. PREDICTORS Timing of death (day of week), dialysis modality, hemodialysis (HD) session frequency, and demographic, clinical, and facility variables. OUTCOMES & MEASUREMENTS Cardiac and noncardiac mortality. RESULTS 14,636 adult dialysis patients died during the study period (HD, n = 10,338; peritoneal dialysis [PD], n = 4,298). Cardiac death accounted for 40% of deaths and was significantly more likely to occur on Mondays in in-center HD patients receiving 3 or fewer dialysis sessions per week (n = 9,503; adjusted OR, 1.26; 95% CI, 1.14-1.40; P < 0.001 compared with the mean odds of cardiac death for all days of the week). This daily variation in cardiac death was not seen in PD patients, in-center HD patients receiving more than 3 sessions per week (n = 251), or home HD patients (n = 573). Subgroup analyses showed that deaths related to hyperkalemia and myocardial infarction also were associated with daily variation in risk in HD patients. This pattern was not seen for vascular, infective, malignant, dialysis therapy withdrawal, or other deaths. LIMITATIONS Limited covariate adjustment. Residual confounding and coding bias could not be excluded. Possible type 2 statistical error due to limited sample size of home HD and enhanced-frequency HD cohorts. CONCLUSIONS Daily variation in the pattern of cardiac deaths was observed in HD patients receiving 3 or fewer dialysis sessions per week, but not in PD, home HD, and HD patients receiving more than 3 sessions per week.