Returning to dialysis after kidney allograft failure: the experience of the Italian Registry of Paediatric Chronic Dialysis

Frequencies and percentages described patient demographic and clinical characteristics at the time of transplantation for categorical variables and median and interquartile ranges for continuous variables. Chi-square or Fisher’s exact tests were used to evaluate potential differences in the categorical variables’ distribution according to the dialysis modality. Similarly, the Kruskal–Wallis test was used for continuous variables.

The potential predictive factors of the dialysis modality after transplantation that we investigated were gender, primary kidney disease, cause of KAF, dialysis modality before transplantation, number of dialysis cycles, comorbidity, duration of dialysis before transplantation, elapsed time between transplantation and dialysis, age and calendar year at transplantation. Information on all the variables considered was generally complete except for the cause of KAF (40% missing data). Hence, a complete-case analysis was performed excluding the cause of KAF from multivariable regression models. Univariate and multivariable analyses were conducted by logistic regression. Continuous variables were modeled as linear and then as restricted cubic splines with three knots fixed at their distribution tertiles. If there was no evidence of non-linear trends, the model with linear terms was chosen. The potential interactions between the variables included in the model were verified.

Follow-up data were available up to the end of June 2019. Outcomes of interest included patient death, re-transplantation, and change of dialysis modality. All analyses were performed in a competing risk setting [16] with time since transplantation as the primary timescale. Non-parametric cause-specific cumulative incidence function, i.e. the probability of that outcome occurring before either of the two competing events, was estimated for all three competing events. When we compared the dialysis modality, we performed a multivariable cause-specific hazards model, adjusted for potential confounders identified according to our a priori knowledge [17]. This modelling allows estimating the hazard corresponding to the cause-specific cumulative incidence function and, consequently, the hazard ratio (HR) of peritoneal dialysis (PD) vs. haemodialysis (HD) separately for each interest event. The following confounders were identified: gender, primary kidney disease, dialysis modality before transplantation, number of dialysis cycles, comorbidity, duration of dialysis before transplantation, age, and calendar year at transplantation. The proportionality assumption was checked by Schoenfeld residuals. Similarly to the prediction model, continuous variables were shaped first as linear and then as restricted cubic splines with three knots fixed at their distribution tertiles. If there was no evidence of non-linear trends, the model with linear terms was chosen. Potential modifications of the effect of dialysis modality were checked, including interaction terms with the model variables. Stata 13.0 was used for all statistical analyses.

Baseline characteristics of the 118 patients who initiated dialysis after KAF during the study period are summarized in Table 1. The post-transplant dialysis choice was PD in 41 (35%) and HD in 77 (65%) patients, while before kidney transplantation, 74 (62.7%) had been on PD and 44 (37.2%) on HD. Of the 41 patients who underwent PD after KAF, 37 (90.2%) had been treated with PD before transplant, and 4 (9.8%) with HD. Among patients on HD after KAF, the pre-transplant dialysis modality distribution was HD in 40 (51.9%) and PD in 37 patients (48.1%). Primary kidney disease, cause of KAF, and age at dialysis re-initiation were significantly different between the two groups. After KAF, among patients treated with PD, there was a higher prevalence of HUS (9.8 vs. 2.6%) as primary kidney disease, while among patients treated with HD, a higher prevalence of cystic kidney diseases (16.9 vs. 2.4%) was observed. In the transplantation course, patients on PD after KAF were more prone to have had a primary disease recurrence (35 vs. 16%) and a chronic rejection (30 vs. 12%) than HD patients, among whom acute rejection was a more frequent cause of allograft loss. At dialysis re-initiation, compared with HD, patients on PD were younger (median age 11.5 years [IQR 7.3–16.2] vs. 14.6 years for HD [IQR 11.4–17.5]; p = 0.01), and re-started dialysis in earlier calendar years (median calendar year was 2004 [IQR 01–08] for PD patients vs. 2012 [IQR 07–17] for HD; p < 0.001). HD was more frequently adopted in patients with more than 2 dialysis cycles, and its choice depended primarily on patient and family preferences. Subjects who had undergone pre-transplant PD tended to continue in the same modality after KAF. Gender, donor type, the presence of comorbidities, and the length of dialysis pre- and post-transplant were comparable between the two groups.

Univariate and multivariable analyses were conducted to evaluate factors that influenced the type of post-transplant dialysis (Table 2). In the multivariable analysis, the probability of being treated with PD after KAF was higher for patients who underwent PD in the pre-transplant dialysis cycle (OR 8.20; 95%CI 1.82–37.01; p = 0.006) and in the less recent era (OR 0.87 per year increase; 95% CI 0.80–0.94; p = 0.001). Gender, age, primary kidney disease, presence of comorbidity, dialysis vintage, and transplant duration did not affect the choice of dialysis modality.

At the end of follow-up, 6 PD (13.6%) and 3 HD (4.2%) patients died, with a cumulative incidence of mortality slightly higher in PD patients (p = 0.09) (Fig. 1). However, after adjustment for several covariates, patients on PD exhibited an increased but non-significant risk of mortality compared with HD (HR 2.15; 95% CI 0.54–8.6; p = 0.28) (Table 3).

Seven out of 41 PD patients (17%) and 4 out of 77 HD individuals (5%) required a switching in dialysis modality; 19 patients on PD (46%) and 36 on HD (47%) received a re-transplantation. Cumulative incidence for both events at the end of the follow-up was similar. Multivariable analysis risk of re-transplantation and switching modality are shown in Supplementary Table 1.

Overall, 86 (73%) and 55 (46.7%) patients had no complications in the pre- and post-transplant dialysis course, respectively. Sixty complications in 74 PD patients (resulting in 1 episode per 33.4 patient-months) and 19 complications in 44 HD patients (resulting in 1 episode per 49.8 patient-months) were reported in the pre-transplant course. One hundred four complications in 41 PD patients (resulting in 1 episode per 17.4 patient-months) and 90 complications in 77 HD patients (resulting in 1 episode per 31.4 patient-months) were reported in the DAGF course. Rate of complications occurring during the pre- and post-transplant period, based on dialysis modality, are reported in Table 4. DAGF patients on PD had a higher rate of both clinical and dialysis-related complications as compared with those on HD. Among patients who re-started PD after KAF, dialysis-related complications were peritonitis and exit-site infections (9 patients; 45%), peritoneal membrane failure (5; 25%), encapsulating peritoneal sclerosis (3; 15%), hypertension (2; 10%), and mechanical complications (1; 5%). In the HD cohort, dialysis-related complications in the post-transplant course were arteriovenous fistula or catheter malfunction (5; 35.8%), severe fluid overload (3; 21.4%), hypertension (2; 14.3%), catheter exit-site infection (2; 14.3%), intradialytic hypotension (1; 7.1%), and unknown causes (1; 7.1%). A comparison in the type of dialysis-related complications in pre- and post-transplantation period is reported in Supplementary Table 2. In those patients who had dialysis-related complications in the pre-transplant course, the relative risk for complications in the dialysis course after KAF was 1.16 (95% CI 0.53–2.53) for PD and 6.15 (95% 2.57–14.7) for HD.