Influence of pretransplant class I and II non-donor-specific anti-HLA immunization on immunologic outcome and graft survival in kidney transplant recipients.

BACKGROUND: Anti-HLA immunization determined by Panel Reactive Antibody (PRA) is known to have a negative impact on patient and graft survival. The predictive value of peak PRA (pPRA) on immunologic outcome, however, and the individual effects of anti-HLA class I and II antibodies remain uncertain. METHODS: The influence of HLA immunization on immunologic outcome parameters and graft survival was investigated in 1150 adult patients without pretransplant donor-specific antibodies (DSA) and in a subgroup of elderly kidney recipients aged ≥ 65 (n = 264). Anti-HLA immunization was defined as a pPRA > 0%. We investigated the influence of class I and II pPRA by dividing all kidney recipients into four pPRA groups (0%, 1-20%, 21-80%, >80%). RESULTS: Patients with non-donor-specific pretransplant anti-HLA immunization were at a higher risk for developing de novo DSA (49.9% vs. 18.7% p < 0.001), antibody mediated rejections (ABMR) (15.7% vs. 5.1%; p < 0.001), had a poorer death censored graft survival (69.2% vs. 86.2%; p < 0.001) and a higher decline of the calculated GFR. In elderly patients anti-HLA immunization only had a significant influence on the development of DSA (40.5% vs. 27.4%; p = 0.004). A multivariate model adjusted for all relevant factors revealed only class I but not class II pretransplant HLA immunization as a significant independent risk factor for de novo DSA, ABMR and death censored graft loss (HR 2.76, p < 0.001, HR 4.16, p < 0.001 and HR 2.07, p < 0.001, respectively). CONCLUSION: Mainly non-donor-specific pretransplant HLA class I immunization is an independent risk factor for the development of de novo DSA, ABMR and graft loss.

Validation of the Living Kidney Donor Profile Index in a European cohort and comparison of long-term outcomes with US results.

BACKGROUND: Recently, a risk index for living donor kidney (LDK) transplantation [living kidney donor profile index (LKDPI)] was proposed to compare LDKs with each other and with deceased donor kidneys (DDKs). Until now, the LKDPI has not been validated externally. METHODS: This long-term retrospective analysis included 1305 consecutive adult kidney transplant recipients who were transplanted 2000-16 in our centre. The Kidney Donor Profile Index (KDPI) was calculated in 889 DDKs and the LKDPI in 416 LDKs. Outcome was followed over a median of 6.5 years. RESULTS: The median LKDPI was 17 and the median KDPI was 69, with a high proportion of donor kidneys with a very high KDPI (40% KDPI ≥ 80). Categorization of LDK into LKDPI quartiles (LKDPI -45-3, 3-17, 17-33, 33-90) revealed a significant difference in death-censored graft survival. Comparing corresponding subgroups of the LKDPI and KDPI (LKDPI/KDPI 0-20 or 20-40) showed comparable graft survival. A multivariate analysis adjusting for relevant recipient factors revealed the KDPI [hazard ratio (HR) 1.21; P < 0.001) and LKDPI (HR 1.15; P = 0.049) as significant independent predictors of graft loss. Time-to-event receiver operating characteristic analyses for graft survival demonstrated lower predictive discrimination of the LKDPI [area under the curve (AUC) 0.55] compared with the KDPI (AUC 0.66). The 10-year graft survival of LDK recipients was inferior in the USA compared with our centre (79% versus 84%). CONCLUSIONS: These results provide external validation of the LKDPI to predict death-censored graft survival and confirm comparability of the LKDPI with the KDPI to discriminate post-transplant outcome.

Assessment of the Kidney Donor Profile Index in a European cohort.

Background: Recently, transplant societies have had to change their allocation policies to counter global organ shortages. However, strategies differ significantly and long-term outcomes and cross-regional applicability remain to be evaluated. Methods: Therefore, we retrospectively analysed the Kidney Donor Profile Index (KDPI) of 987 adult kidney transplants at our centre using data from the Organ Procurement and Transplantation Network (OPTN) as a reference. Results: In our cohort, the median KDPI was 66%, with a higher proportion of >85% KDPI kidneys compared with the US cohort (32.3% versus 9.2%). Among elderly patients (≥65 years of age), 62% received >95% KDPI kidneys, which were primarily allocated within the Eurotransplant Senior Program (ESP). After 10 years, the rate of death-censored graft survival was 70.5%. Recipients of >85% KDPI kidneys were significantly older, demonstrating higher mortality, poorer graft survival and lower estimated glomerular filtration rate. Patients receiving ≥99% KDPI kidneys had a satisfactory 5-year death-censored graft survival (72.9%). The 5-year survival rate of patients living with a functioning graft exceeded the matched OPTN data in the whole KDPI range, despite a higher proportion of elderly recipients. Multivariate analysis revealed KDPI as an independent risk factor for graft loss (hazard ratio 1.14/10%, P < 0.001), although C-statistics of 0.62 indicated limited discriminative ability for individuals. Conclusion: The analysis demonstrated KDPI as a potentially useful tool for donor quality assessment in a European cohort. Most importantly, our analysis revealed acceptable outcomes even for very high KDPI kidneys.