Demographic and clinical characteristics have been presented in Table 1. 56 patients (56%) received living donations (LD), and 44 (44%) had deceased donations (DD). 17 (30.4%) of the LD were AB0-incompatible transplantations. 64 recipients (64%), the majority, were male. The mean age of the recipients at the time of KTx was 49.3 years (SD = 15.62).
Patients’ outcome data have been presented in Table 2.
In patients who received LD, pre-transplant suPAR levels were significantly lower compared to those receiving DD (suPAR 6,839 (4,887, 10,183) pg/ml, vs. 9,117 (6,891, 12,211) pg/ml, p=0.008, Figure 1).
Dialysis vintage and cold ischemic time were significantly shorter in LD than DD recipients (19.7 months vs. 77.5 months, p < 0.001; 2.47 hours vs. 9.96 hours, p < 0.001).
It was found that kidney function improved one year after KTx to a mean eGFR of 57.3 ± 20.1 ml/min/1.73 m2 (Table 1). Although LD recipients showed a tendency toward a higher eGFR compared to DD recipients (60.0 ± 20.3 ml/min/1.73 m2 vs. 53.9 ± 19.5 ml/min/1.73 m2, p = 0.075), the difference was not statistically significant. In contrast, suPAR levels significantly declined in LD and DD recipients after KTx (8,095 (5,818, 11,192) pg/ml before KTx vs. 4,376 (2,757, 5,612) pg/ml one year after KTx; Fig. 2), (n = 100, p < 0.001).
One year after KTx, the suPAR levels of recipients aligned without any detectable difference between those who had LD and DD (LD 4,332 (2,914, 5,567) pg/ml vs. DD 4,413 (2,575, 6,049) pg/ml, n=100, p=0.879, Fig. 3).
Dialysis vintage tended to be associated with suPAR levels prior to KTx (n = 100, p = 0.067,). Upon a closer analysis, it was seen that preemptive recipients who never underwent dialysis had significantly lower suPAR levels (suPAR 5,249 (2,302, 7,806) pg/ml, n = 8) compared to patients on any mode of dialysis before transplantation (suPAR 8,392 (6,011, 11,503) pg/ml, n = 92) (p = 0.006) (see Figure 4 A). The suPAR levels of patients on hemodialysis (suPAR 8,322 pg/ml (5,956, 11,475), n = 71) and patients treated with peritoneal dialysis (8,075 (6,936, 12,492) pg/ml, n = 12) were comparable (p = 0.928) (see Fig. 4 A). One year after KTx, the suPAR levels of patients on any mode of dialysis prior to transplant compared with preemptively transplanted patients became equal (Fig. 4 B).
The suPAR levels in patients one year after KTx were not correlated to the eGFR at the same time (p=0.24, r= -0.119). However, it was associated with the development of the eGFR between the second and fourth year after KTx. Higher suPAR levels one year after KTx could be associated with a higher eGFR-loss in the following three years (Figure 5, n = 82 (18 patients lost of follow-up), p = 0.021, r = -0.255).
In our study, a correlation between the suPAR levels and the incidence or the number of biopsy-proven allograft rejections could not be detected.
We found that only four patients experienced terminal graft failures by the time of the follow-up. Moreover, two patients died during the course of the study, and two patients died without losing their graft before. Due to these small number of events, we did not perform survival analyses with these endpoints.
Instead, we took a loss of renal function in terms of more than 30% of eGFR loss from year one as an endpoint , . eGFR-loss >30% was stated, when it was constant for at least one month and did not increase subsequently. Our patient collective was divided into two groups based on a cut-off for suPAR below and above 6,212 pg/ml by calculating the Youden-index for a ROC-curve according to suPAR measured after one year. (n = 82 vs. n = 18). Patients with allograft loss were defined as eGFR-loss >30%, patients who died with unimpaired allograft function were handled as negative for eGFR-loss > 30%. The Kaplan-Meier analysis and Log-rank test showed a significant ten-month reduced time to eGFR-loss > 30% for patients with suPAR levels above 6,212 pg/ml (33.5 vs. 61.9 months, Figure 6).
The suPAR levels after one year as an independent risk factor for eGFR-loss > 30% subsequently
To evaluate whether suPAR after one year is independently associated with accelerated eGFR-loss survival, apart from other known risk factors, we performed a multivariable Cox-regression analysis that included several known risk factors causing inferior allograft survival (Table 3).
Besides the well-known risk factors for kidney allograft failure such as age at the time of KTx (p = 0.012, HR 1.052), previous KTx (p = 0.036, HR 0.214), and the occurrence of acute rejection episodes (p = 0.033, HR 0.265), the Cox-regression analysis confirmed suPAR one year after transplantation as an independent risk factor for eGFR-loss > 30% (p = 0.001, HR 1.000).