Carla Burballa

Impact of Recurrent Acute Kidney Injury on Patient Outcomes

Background/Aims: Recurrent acute kidney injury (AKI) is common among patients after a first hospitalized AKI. However, little is known about the prognosis of recurrent AKI episodes in chronic kidney disease (CKD) development, cardiovascular events and mortality. Methods: A retrospective study included patients admitted to our Hospital from 2000 to 2010. AKI was defined according to the Acute Dialysis Quality Initiative criteria. In the follow-up period after the first AKI episode, clinical, laboratory data and the number of repeated AKI episodes, etiology and severity were recorded. Results: Among the 359 AKI survivor patients included, 250 new AKI episodes were observed in 122 patients (34%). Variables independently associated to new episodes were: type 2 DM [OR 1.2, 95%CI 1.2-3.8, p=0.001], ischemic heart disease [OR 1.9; 95%CI 1.1-3.6, p=0.012], and SCr at the first AKI event>2,6 mg/dl [OR 1.2; 95%CI 1.03-1.42, p=0.02]. Development of CKD during four years follow-up was more frequent in patients with recurrent AKI, HR [2.2 (95% CI: 1.09-4.3, p=0.003)] and 44% of recurrent AKI patients who developed CKD occurred during the first 6 months after the initial event. Cardiovascular events were more frequent among patients with recurrent AKI patients than in those with one AKI episode (47.2% vs 24%, p=0.001). Mortality at 4 years was higher in the patient subgroup with several episodes of AKI as compared with those with a single episode [HR: 4.5 (95% CI 2.7-7.5) p<0.001]. Conclusion: Episodes of recurrent AKI have a high potential to be associated with relevant complications such as cardiovascular events, mortality and CKD development.

KDPI Score: A comparison with classical ECD/SCD classification in predicting outcomes

Background Kidney donor shortage requires an expansion in selection criteria and objective tools to minimize discarded organs. Easy donor pretransplant variables such as age, standard/expanded criteria donors (SCD/ECD) and Kidney Donor Profile Index (KDPI), have demonstrated correlations with patient and graft outcomes. We aimed to establish the accuracy of the three models to determine the prognostic value on kidney transplantation (KT) major outcomes. Methods Retrospective study in deceased donor KT at our institution. Unadjusted Cox and Kaplan-Meier survival, and multivariate Cox analysis were fitted to analyze the impact of the three predictor scores donor age, SCD/ECD and KDPI on outcomes. Results KT included. Donor age 53.6±15.2y; 41.9% ECD; mean KDPI 69.4±23.4%. Median follow-up 51.9m. Unadjusted Cox and Kaplan-Meier showed that the three prognostic variables (donor age, ECD status and KDPI) were related with increased risk of patient death, graft failure and death-censored graft failure. However, in the multivariate analysis only KDPI was related with higher risk of graft failure (HR 1.03 each 1% [1.01-1.05]; p=0.014). Multivariate models for graft failure were calculated including donor age as a continuous variable, donor age >60y, ECD definition, KDPI (continuous variable) or different KDPI cut-offs (Figure). Figure. No caption available. Conclusions SCD/ECD classification did not provide significant prognostic outcome information. KDPI was linearly related with higher risk of graft failure, providing a better assessment. More studies are needed before using KDPI as a tool to discard or accept kidneys for transplantation.

Detection of HLA Donor-Specific Antibodies with Screening and/or Specificity Kits and Antibody-Mediated Rejection in Kidney Transplant Recipients

Background Detection of HLA donor-specific antibodies (DSA) with solid phase multiplex-bead arrays has been significant but imperfectly associated with antibody-mediated rejection (AMR) in kidney transplant (KT) recipients. Nowadays to assess the presence of DSA, Luminex panels manufactured kits are used for screening and single antigen beads (SAB) for determining the specificity. The high cost of SAB limits their general use. In many laboratories SAB are only used if screening is positive. We aimed to evaluate if SAB only performed when screening is positive (strategy1) fails to identify relevant DSA detected by direct SAB (strategy2). Methods Kidney transplant recipients with post-transplant biopsies (2011-2015) and serum for DSA evaluation were recruited. We compared validity of both strategies in DSA detection. Results 118 KT recipients with one biopsy each; 16 normal biopsies (N), 53 with AMR and 49 with Interstitial Fibrosis and Tubular Atrophy (IFTA). Figure 1 shows the prevalence of DSA in the groups with both strategies. There were no differences in sensitivity (60.3% vs. 77.3%, p=0.08) or specificity (92.3% vs. 87.7%; p=0.44) between strategy 1 and 2. Significant differences were found in positive (86.5% vs. 83.6%; p=0.01) and negative (74% vs. 82.6%; p=0.02) predictive values. Figure. No caption available. Strategy 2 detected DSA in 15 cases missed by screening. Among them, 1 had N biopsy, 4 IFTA and 10 AMR (with 3 graft-losses). Conclusions The evaluation of anti-HLA antibodies with direct SAB increased the detection of DSA in 17% cases of AMR and 17% without AMR missed by using SAB after screening+. It seems advisable to use directly SAB for DSA studies in case of possible AMR. Further studies are needed to assess cost-benefit analysis.

Antibody-Mediated Rejection With and Without HLA Donor-Specific Antibodies in Kidney-Transplantation

Background Correlation between antibody-mediated damage (AMR) and HLA donor-specific antibodies (DSA) is strong but imperfect in kidney transplant (KT) recipients. We reviewed histopathology and HLA DSA in AMR patients and compared them with those with only interstitial fibrosis and tubular atrophy (IFTA) or no abnormalities. Methods Retrospective assessment of patients with biopsies (Banff’13) and serum samples (pre- and postransplant) tested for HLA antibodies. Results A total of 118 patients were studied. The diagnoses were normal biopsy (n=16), AMR (n=53) and IFTA (n=49). Death-censored graft survival was worse in patients with AMR than with IFTA or normal biopsies. Pre-transplant DSA were more frequent in AMR cases than IFTA or normal ones (46.3%, 20.5 and 6.3%, p=0.003). Differences were mostly due to pre-transplant DSA combined I&II (22 vs 2.3 and 0%, p=0.004) but not to isolated DSA class I or II. At biopsy, 75.5% AMR patients had HLA DSA (7.5% class I, 54.7% II and 13.2% combined I&II), but also 14.6% of IFTA and 6.3% of normals. Twelve AMR patients (22.6%) had no DSA pre-transplant or peri-biopsy. AMR patients with and without DSA were similar at baseline, except that more DSA+AMR patients were sensitized pretransplant and less well DR-matched, with no differences in graft function or immunosuppression. Patients with AMR with or without DSA showed similar microvascular inflammation and chronic changes. Conclusions 20% of patients with AMR do not show circulating HLA DSA. These patients are more frequently HLA unsensitized pre-transplant, without other differences at transplantation, in their biopsies or at follow-up. Figure. No caption available. Figure. No caption available.

Usefulness of the KDPI in Spain: A comparison with donor age and definition of standard/expanded criteria donor

INTRODUCTION Kidney donor shortage requires expanding donor selection criteria, as well as use of objective tools to minimize the percentage of discarded organs. Some donor pre-transplant variables such as age, standard/expanded criteria donor (SCD/ECD) definition and calculation of the Kidney Donor Profile Index (KDPI), have demonstrated correlations with patient and graft outcomes. We aimed to establish the accuracy of the three models to determine the prognostic value of kidney transplantation (KT) major outcomes. MATERIAL AND METHODS We performed a retrospective study in deceased donor KTs at our institution. Unadjusted Cox and Kaplan-Meier survival, and multivariate Cox analyses were fitted to analyze the impact of donor age, SCD/ECD and KDPI on outcomes. RESULTS 389 KTs were included. Mean donor age was 53.6±15.2 years; 163 (41.9%) came from ECD; mean KDPI was 69.4±23.4%. Median follow-up was 51.9 months. The unadjusted Cox and Kaplan-Meier showed that the three prognostic variables of interest were related to increased risk of patient death, graft failure and death-censored graft failure. However, in the multivariate analysis only KDPI was related to a higher risk of graft failure (HR 1.03 [95% CI 1.01-1.05]; p=0.014). CONCLUSIONS SCD/ECD classification did not provide significant prognostic information about patient and graft outcomes. KDPI was linearly related to a higher risk of graft failure, providing a better assessment. More studies are needed before using KDPI as a tool to discard or accept kidneys for transplantation.