This retrospective, multi-centre, multi-country registry analysis examined the outcomes of 241 patients with HUS ESKD over 46 years. The principal findings were that HUS ESKD was a rare cause of ESKD (0.4% of cases) and was independently associated with younger age, female gender and European racial origin. HUS ESKD was also independently associated with a higher probability of recovery of dialysis-independent renal function and increased risks of renal allograft failure compared with other causes of ESKD.
Very few studies have comprehensively examined the predictors and outcomes of HUS ESKD, particularly in dialysis populations. One previous investigation by the Forum of ESKD Networks in the United States reported 199 cases of HUS ESKD
. In keeping with the findings of the present study, the Forum observed a preponderance of young, white, female patients. The respective proportions of patients aged under 20 years, whites and females were 30% vs 33%, 91% vs 88% and 63% vs 71%. These findings are likely explained by the fact that HUS typically affects children and younger adults, particularly females
[17, 18]. The effect of ethnicity on HUS risk has not been well studied, although African-Caribbean ancestry has been observed as a risk factor
Survival of HUS ESKD patients on dialysis has also not been previously well described. The Forum of ESKD Networks
 found that the overall survival of HUS patients was 77% at 3 years and somewhat better than that seen in diabetic ESRD controls. However, the authors noted that “this probably reflects in part the lower average age of the patients.” In the present investigation, the 3-year renal replacement therapy survival rates of ESKD patients with HUS and matched controls with other causes of ESKD were 74% and 80%, respectively. Following adjustment for racial origin and comorbidities, patients with HUS ESKD had comparable survival. This also applied to patients treated with dialysis, even after adjusting for the competing risks of renal transplantation and recovery of renal function. The causes of death in the HUS patients were similar to those of other ESKD patients and the limited numbers did not permit useful, multivariable, sub-group analyses.
Although the overall mortality rate of HUS ESKD patients was comparable to that of matched controls, HUS patients were also more likely to experience spontaneous recovery of dialysis-independent renal function. A total of 21 (8.7%) HUS ESKD patients recovered renal function, although 13 (62%) of these patients returned to dialysis after a median period of 0.94 years. There have been previous reports of renal recovery in patients with HUS, even after relatively long periods on dialysis
[19–22]. Nissenson et al.
 observed that 9% of patients with ESKD secondary to HUS were able to discontinue dialysis. Moreover, our group has previously found HUS to be an independent predictor of dialysis-independent renal function recovery in ESKD patients
[23, 24]. The appreciable incidence of renal recovery suggests that caution should be exercised when listing HUS ESKD patients for renal transplantation within the first year following dialysis commencement.
Although the overall rate of renal transplantation was considerably higher in HUS (54%) than in other causes of ESKD (34%), renal allograft outcomes were significantly worse. Compared with non-HUS patients, HUS patients had significantly inferior overall renal allograft survival rates at 1 year (73% vs 91%, respectively), 5 years (62% vs 85%) and 10 years (49% vs 73%). The one-year first renal allograft survival rates in HUS ESKD patients were 69% for deceased donor transplants and 79% for living donor transplants. These findings are appreciably better than those reported for 78 patients by the International Registry of Recurrent and Familial HUS/TTP (32% and 50%, respectively). Part of the apparent disparity in findings may be potentially explained by HUS population heterogeneity, vintage bias and ascertainment bias (since the International HUS/TTP Registry included data provided by selected, interested global renal units as well as that obtained from literature searches, whereas the ANZDATA Registry included all patients with HUS ESKD who ever received renal replacement therapy in Australia and New Zealand since 1963). For patients who did not experience renal allograft failure, possibly reflecting a less severe form of HUS, their overall survival was superior to their non-HUS counterparts.
HUS recurrence occurred in 12% of HUS patients undergoing renal transplantation after a median period of 0.82 years and accounted for 25 of all renal allograft failures in patients with HUS ESKD. These findings were somewhat lower than those of other investigations reporting recurrence rates of 25-50%
[1, 2, 12], but may have related to HUS population heterogeneity (due to inclusion of patients with typical HUS who had a low risk of post-transplant recurrence), classification bias due to difficulties in distinguishing HUS recurrence from antibody-mediated rejection, and possible ascertainment and reporting bias. In keeping with the findings of other studies
, living kidney donation was a significant risk factor for HUS recurrence in the renal allograft.
The strengths of this study included its very large sample size and inclusiveness. We included all HUS patients receiving renal replacement therapy in Australia and New Zealand during the study period, such that a variety of centres were included with varying approaches to the treatment of HUS and ESKD. This greatly enhanced the external validity of our findings. These strengths should be balanced against the study’s limitations, which included limited depth of data collection. ANZDATA does not collect important information, such as distinction between typical (diarrhoea-associated) and atypical HUS (which has an important effect on dialysis and transplant outcomes), date of HUS diagnosis, severity of comorbidities, patient compliance, individual unit management protocols (including plasma exchange and eculizumab therapy), laboratory values (such as platelet counts, serum lactate dehydrogenase concentrations and serum ADAMTS13 measurements) and complement regulatory protein genetic mutation and autoantibody results. Even though we adjusted for a large number of patient characteristics, the possibility of residual confounding could not be excluded. In common with other Registries, ANZDATA is a voluntary Registry and there is no external audit of data accuracy, including the diagnosis of HUS.