Preformed and de novo DSA are associated with T‐cell–mediated rejection in pediatric liver transplant recipients requiring clinically indicated liver biopsy

Despite growing interest about the impact of donor‐specific HLA antibodies (DSA) in LT limited data are available for pediatric recipients. Our aim was to perform a retrospective single‐center chart review of children (0‐16 years) having undergone LT between January 1, 2005 and December 31, 2017, to characterize DSA, to identify factors associated with the development of de novo DSA, and to analyze potential associations with the diagnosis of TCMR. Information on patient‐ and donor‐characteristics and LB reports were analyzed retrospectively. Serum obtained before LT and at LB was analyzed for presence of recipient HLA antibody using Luminex^® technology. MFI > 1000 was considered positive. In 63 pediatric LT recipients with a median follow‐up of 72 months, the overall prevalence of de novo DSA was 60.3%. Most were directed against class II antigens (33/38, 86.8%). Preformed DSA were present in 30% of patients. Twenty‐eight (28/63) patients (44.4%) presented at least one episode of TCMR, mostly (12/28, 43%) moderate (Banff 6‐7). De novo DSA were significantly more frequent in patients with TCMR than in patients without (75% vs 48.6%, P = .03), and patients with preformed and de novo DSA had a significantly higher rate of TCMR than patients without any DSA (66.7% vs 20%, P = .02). Neither preformed DSA nor de novo DSA were associated with frequency or severity of TCMR. Recipients with lower weight at LT developed de novo DSA more frequently (P = .04). De novo DSA were highly prevalent in pediatric LT recipients. Although associated with the development of TCMR, they did not appear to impact the frequency or severity of TCMR or graft survival. Instead, de novo DSA may suggest a state of insufficient IS.     

Late T cell–mediated rejection may contribute to poor outcomes in adolescents and young adults with liver transplantation

Although poor long‐term graft survival in LT in AYA is recognized, detailed epidemiological data are still lacking. L‐TCMR may have poor outcomes. This study aimed to provide a detailed, epidemiological assessment of the association between AYA age and rejection. L‐TCMR was defined in this study as TCMR with central vein or perivenular inflammation occurring later than 3 months after LT. A total of 342 patients who survived for at least 3 months after LT between 2005 and 2015 were enrolled. The AYA group (10‐24 years) was compared with the C group (less than 10 years), and the incidence and outcomes of L‐TCMR were analyzed. In total, 342 patients had LT; 38 of these were AYA with the mean follow‐up period of 6.7 years. A total of 304 patients in C group had a mean follow‐up period of 6.3 years (P = .28). The incidence of L‐TCMR in AYA group was significantly higher than in C group (15.8% vs 4.6%, P = .006). The time to L‐TCMR after LT was significantly shorter in AYA group (P = .01). Neither patient survival nor the incidence of non‐adherence differed significantly between the groups (P = .18 and P = .89). The number of additional immunosuppressants after L‐TCMR was significantly higher in the AYA group (P = .04). A high incidence of L‐TCMR was observed in AYA group irrespective of non‐adherence. AYA patients with L‐TCMR should be followed carefully due to the poor results of post‐treatment biopsy and the need for intensive immunosuppressive therapy.     

Acute antibody‐mediated rejection in ABO‐compatible pediatric liver transplant recipients: case series and review of the literature

Acute AMR is well reported following ABO‐incompatible LTx. However, it remains uncommon in ABO‐compatible LTx. It typically presents with graft dysfunction ≤2 weeks post‐LTx and is often associated with graft loss. We report the clinical presentation, treatment regimen, and outcome of six pediatric LTx recipients diagnosed with early acute AMR based on (i) clinical signs of graft dysfunction, (ii) histopathology indicative of acute injury ± C4d staining, and (iii) presence of HLA DSA. All patients developed elevated ALT and GGT ≤ 45 days post‐LTx. All showed HLA class I (n=4) and/or II (n=6) DSA (peak MFI 6153–11 910). Four had de novo DSA, and two had preformed DSA. Five were initially diagnosed with ACR refractory to steroid therapy. Four exhibited resolution of graft dysfunction with AMR therapy. Two had refractory AMR—one was re‐transplanted; the other was treated with eculizumab and showed improvement in graft function but later died due to a tracheostomy complication. Our case series suggests that AMR following ABO‐compatible LTx may be under‐diagnosed. The presentation can be variable, and treatment should be individualized. Eculizumab may be an option for refractory AMR. Ultimately, future multicenter studies are needed to better define diagnostic criteria, characterize optimal treatment, and assess long‐term outcomes following liver AMR.     

IGG3 anti‐HLA donor‐specific antibodies and graft function in pediatric kidney transplant recipients

Anti‐HLA DSAs are associated with ABMR and graft loss in KT recipients, yet the influence of DSA IgG subclass on outcomes in pediatric KT recipients is not completely understood. We performed a single‐center retrospective chart review of pediatric KT recipients with anti‐HLA DSAs, aiming to study the association between specific DSA IgG subclasses and graft outcomes, including ABMR and significant graft dysfunction (graft loss or 50% decrease in eGFR). Thirty‐six patients (mean age 15.4y) with DSAs initially detected 1 month‐14.3 years post‐transplantation were followed for a median of 2.8 years. Rates of IgG1, 2, 3, and 4 subclass detection were 92%, 33%, 58%, and 25%, respectively. Twenty‐two patients (61%) had clinical ABMR, whereas 19% had subclinical ABMR, and 13 (36%) experienced significant graft dysfunction. Patients with IgG3+ DSAs had a higher risk of graft dysfunction compared with IgG3‐ patients (52% vs 13%, P = .03). In a multiple Cox proportional regression analysis, the presence of IgG3+ DSA was independently associated with significant graft dysfunction (HR 10.45, 95% CI 1.97‐55.55, P = .006). In conclusion, IgG3 subclass DSAs are associated with graft dysfunction and may be useful for risk stratification and treatment decisions in DSA‐positive pediatric KT recipients.     

Persistent C4d and antibody‐mediated rejection in pediatric renal transplant patients

Pediatric renal transplant recipient survival continues to improve, but ABMR remains a significant contributor to graft loss. ABMR prognostic factors to guide treatment are lacking. C4d staining on biopsies, diagnostic of ABMR, is associated with graft failure. Persistent C4d+ on follow‐up biopsies has unknown significance, but could be associated with worse outcomes. We evaluated a retrospective cohort of 17 pediatric renal transplant patients diagnosed with ABMR. Primary outcome at 12 months was a composite of ≥50% reduction in eGFR, transplant glomerulopathy, or graft failure. Secondary outcome was the UPCR at 12 months. We used logistic and linear regression modeling to determine whether persistent C4d+ on follow‐up biopsy was associated with the outcomes. Forty‐one percent reached the primary outcome at 12 months. Persistent C4d+ on follow‐up biopsy occurred in 41% and was not significantly associated with the primary outcome, but was significantly associated with the secondary outcome (estimate 0.22, 95% CI 0.19‐0.25, P < .001), after controlling for confounding factors. Persistent C4d+ on follow‐up biopsies was associated with a higher UPCR at 12 months. Patients who remain C4d+ on follow‐up biopsy may benefit from more aggressive or prolonged ABMR treatment.     

Evolution of renal function and urinary biomarker indicators of inflammation on serial kidney biopsies in pediatric kidney transplant recipients with and without rejection

Urinary CXCL10 and metabolites are biomarkers independently associated with TCMR. We sought to test whether these biomarkers fluctuate in association with histological severity of TCMR over short time frames. Forty‐nine pairs of renal biopsies obtained 1‐3 months apart from 40 pediatric renal transplant recipients were each scored for TCMR acuity score (i + t; Banff criteria). Urinary CXCL10:Cr and TCMR MDS were obtained at each biopsy and were tested for association with changes between biopsies in acuity, estimated GFR (ΔeGFR), and 12‐month ΔeGFR. Sequential biopsies were obtained 1.8 ± 0.8 months apart. Biopsy 1 was usually obtained under protocol (75%), and 62% percent had evidence of TCMR. Using each biopsy pair for comparison, ΔeGFR did not predict change in acuity. By contrast, change in acuity was significantly correlated with change in urinary CXCL10:Cr (ρ 0.45, P  = .003) and MDS (ρ 0.29, P  = .04) between biopsies. The 12‐month ΔeGFR was not predicted by TCMR acuity or CXCL10:Cr at Biopsy 2; however, an inverse correlation was seen with urinary MDS (ρ ?0.35; P  = .02). Changes in eGFR correlate poorly with evolving TCMR acuity on histology. Urinary biomarkers may be superior for non‐invasive monitoring of rejection, including histological response to therapy, and may be prognostic for medium‐term function.     

Late acute rejection: Incidence,risk factors,and effect on graft survival and function

Long‐term graft survival and function has not kept pace with short‐term success in kidney transplant (Tx) recipients. LAR ≥6 months post‐Tx may contribute to lack of improvement; risk factors for LAR are not well known. Of 64 Tx recipients followed over six yr, 23 (35.9%) had LAR (LAR group) and 41 had no LAR (no LAR group). Of all variables, significant risk factors for LAR included DGF, (43.4% LAR vs. 14.6% in no LAR group, p = 0.0096); de novo DSA (65.2% vs. 26.8%, p = 0.003); mean COV% of TAC (41.8% vs. 34.6%, p = 0.03); and non‐adherence (34.8% vs. 7.3%, p = 0.0043). DGF and DSA remained statistically significant (p = 0.002 and 0.003, respectively); COV% TAC had borderline significance (p = 0.057), and non‐adherence was not significant on multivariate regression analysis. Patients with LAR had inferior graft survival and function, whereas graft function was stable in the no LAR group over a mean follow‐up of 31.2 months. Patients with de novo DSA and DGF should be considered at risk of LAR; an early diagnosis and treatment of LAR may improve graft survival and function.     

Donor‐specific antibodies in a pediatric kidney transplant population—Prevalence and association with antiproliferative drug dosing

Prevalence and implications of anti‐HLA class I and class II antibodies are beginning to be better characterized in pediatric kidney transplant recipients. dnDSA formation is predictive of AMR and downstream diminished graft function and survival. However, risk factors for the development of dnDSA are not well defined in this patient population. After introducing DSA surveillance into our pediatric kidney transplant program, we are reporting the prevalence of class I and class II DSA in 67 otherwise stable recipients. Secondary end‐points included risk factors for DSA development and assessment of graft function. Significantly, lower median daily MMF doses were observed in patients with DSAs compared to patients without DSAs (371 vs 617 mg/m²/d, respectively; P = 0.035). Class II DSA formation was more common, with a prevalence of 17.9%, as compared to 10.4% for class I DSA. Estimated glomerular filtration rate was also decreased in patients with positive DSA vs those with negative titers (71, SD 25 vs 78, SD 29 mL/min/1.73 m², respectively; P = 0.034). We conclude that reduced‐dose MMF is associated with dnDSA and DSA is associated with diminished graft function in stable pediatric kidney transplant recipients.     

Clinical and histopathologic features of antibody‐mediated rejection among pediatric renal transplant recipients with preformed vs de novo donor‐specific antibodies

Preformed and de novo donor specific antibodies (pDSA and dnDSA) are risk factors for ABMR. This study compares the effects of pDSA vs dnDSA in pediatric kidney transplant recipients. Sixteen pediatric patients with biopsy‐proven ABMR were evaluated. Strong DSA (MFI >10 000) was recorded at transplant, rejection, and follow‐up. DSAs with the highest MFI were termed iDSAs. Allograft biopsies were scored according to Banff 2013 criteria. Seven of 16 (44%) patients had pDSA at transplant; 9 (56%) developed dnDSA. Patients with pDSA developed ABMR earlier (median = 63 vs 1344 days, P = .017), while patients with dnDSA were more likely to have strong Class II iDSA (100% vs 28%, P = .009). Viral infection or non‐adherence was more common in patients developing dnDSA (88.8% vs 28.6%, P < .01). Pathology in those with pDSAs demonstrated worse transplant glomerulitis (g score 1.57 ± 0.98 vs 0.56 ± 0.73, P = .031); however, those with dnDSAs exhibited higher C4d+ ABMR (P = .013). Patients developing dnDSAs showed ABMR later post‐transplant with predominance of HLA‐Class II iDSAs. Inadequate immunosuppression likely contributes to dnDSA formation. Patients with no DSA who have unprotocolized decreases in immunosuppression should be screened for dnDSA as it could lead to early intervention and potentially better outcomes.     

Non‐invasive staging of chronic kidney allograft damage using urine metabolomic profiling

Chronic kidney allograft damage is characterized by IFTA and GS. We sought to identify urinary metabolite signatures associated with severity of IFTA and GS in pediatric kidney transplant recipients. Urine samples (n = 396) from 60 pediatric transplant recipients were obtained at the time of kidney biopsy and assayed for 133 metabolites by mass spectrometry. Metabolite profiles were quantified via PLS‐DA. We used mixed‐effects regression to identify laboratory and clinical predictors of histopathology. Urine samples (n = 174) without rejection or AKI were divided into training/validation sets (75:25%). Metabolite classifiers trained on IFTA severity and %GS showed strong statistical correlation (r = .73, P < .001 and r = .72; P < .001, respectively) and remained significant on the validation sets. Regression analysis identified additional clinical features that improved prediction: months post‐transplant (GS, IFTA); and proteinuria, GFR, and age (GS only). Addition of clinical variables improved performance of the %GS classifier (AUC = 0.9; 95% CI = 0.85‐0.96) but not for IFTA (AUC = 0.82; 95% CI = 0.71‐0.92). Despite the presence of potentially confounding phenotypes, these findings were further validated in samples withheld for rejection or AKI. We identify urine metabolite classifiers for IFTA and GS, which may prove useful for non‐invasive assessment of histopathological damage.     

Early outcomes comparing induction with antithymocyte globulin vs alemtuzumab in two steroid‐avoidance protocols in pediatric renal transplantation

Steroid avoidance in pediatric kidney transplants was found effective with extended daclizumab induction. Upon discontinuation of daclizumab, lymphocyte‐depleting agents became used, with little comparative data. We assessed outcomes in children undergoing low immunologic‐risk deceased donor (DD) kidney transplants using induction with antithymocyte globulin (ATG) compared to alemtuzumab. We reviewed consecutive DD kidney transplants from January 2015 to September 2017 at two pediatric centers that used different lymphocyte‐depleting agents in steroid‐avoidance protocols: ATG (Center A) and alemtuzumab (Center B), with tacrolimus and MMF as maintenance immunosuppression . Anti‐infective prophylaxis was based on center protocol. Over the first year post‐tx, there were similar rates of infections. EBV and BK viremia were comparable though Center A manifested more low‐grade CMV viremia (A 46% vs B 0%; P = .0009) at median onset 1.8 months, followed by early seroconversion. Reduction of immunosuppression did not differ between groups. DSA at 1 year was similar (A 8% vs 13%) with low rates of BPAR. Need for steroid‐based conversion was low. There were no graft losses and no differences in median eGFR at 30, 90, 180, and 365 days. (a) 1‐year graft outcomes are excellent in steroid‐avoidance regimens using ATG or alemtuzumab induction; (b) conversion to steroid‐based therapy is low; (c) alemtuzumab/high‐dose MMF is associated with lower WBC and more GCSF use; (d) alemtuzumab/higher dose MMF results in more diarrhea and azathioprine conversion than ATG/lower dose MMF; (e) CMV viremia is seen more often with ATG use with infection prophylaxis reduction; however, seroconversion occurs promptly.     

Donor‐specific HLA antibodies and graft function in kidney‐transplanted children – the Vienna cohort

In the pediatric population, little is known on de novo DSA development, its impact on graft function, and association with suboptimal IS. We assessed the prevalence of de novo DSA in the Vienna cohort of 40 renal transplanted children and adolescents and prospectively followed its association with clinical parameters, graft function, and proteinuria for one yr. At the cross‐sectional analysis (median post‐transplant time of five yr), 17% of the patients had developed de novo DSA. All HLA‐Ab were anti‐HLA class II antibodies and persisted in 85% of the cases until the follow‐up screening performed within one yr. Basic clinical and laboratory parameters did not differ between DSA‐negative and DSA‐positive patients at the time of HLA‐Ab screening. Suboptimal IS due to reduced medication or non‐adherence could not be proven in DSA‐positive patients. The changes in eGFR did not differ during the prospective study period, but there was a significantly higher proteinuria in the DSA‐positive patients during the follow‐up. Our data demonstrate an overall prevalence of 17% of de novo DSA in a pediatric renal transplant cohort. During 12 months of prospective follow‐up time, we could demonstrate a significant impact of de novo DSA presence on proteinuria.     

Association of post‐transplant donor‐specific HLA antibody with liver graft fibrosis during long‐term follow‐up after pediatric liver transplantation

The aim of this study was to evaluate the significance of post‐transplant DSA as a predictor of liver fibrosis during long‐term follow‐up after pediatric LT. We evaluated the histological findings in 18 LT recipients who underwent liver biopsy after DSA screening. Liver fibrosis was scored based on the METAVIR fibrosis staging. Patients were divided into 2 groups based on histological findings, and clinical characteristics among patients with liver fibrosis were assessed. Of 18 patients, 7 were included in the fibrosis group. No significant between‐group differences were found regarding peritransplant characteristics, including age, sex, primary disease, ABO incompatibility, and immunosuppressive regimen. Episodes of acute rejection and non‐adherence to immunosuppressive drugs were comparable between both groups. The MFI for anti‐DR DSA and positive rate were significantly higher in the fibrosis group (1655 vs 216; P = .019, 86% vs 27%; P = .012, respectively). MFI for anti‐DQ DSA was higher in the fibrosis group, but non‐significantly (2052 vs 384; P = .46). Post‐transplant anti‐DR DSA is associated with graft fibrosis during long‐term follow‐up. This finding seems useful for the implementation of valid histological examinations of liver grafts for patients with higher MFI, especially for anti‐DR DSA, after pediatric LT.     

Donor‐specific anti‐HLA antibody production following pediatric ABO‐incompatible heart transplantation

ABO‐i heart transplantation can be performed in infants with end‐stage heart failure to increase organ availability. The development of newly detected DSAs is associated with decreased cardiac graft survival, and the effect of ABO‐i transplantation on DSA production is unknown. We examined DSA production and rejection frequency in infant recipients of ABO‐i and ABO‐c heart transplants via a retrospective cohort study of infant heart transplant recipients transplanted at a single pediatric center between January 2004 and November 2014. Patients were included if they were less than 1 year of age at transplant and had a minimum of 6 months follow‐up. DSA positivity was examined under two categories, either the lowest level detectable (MFI > 500) or a level presumed to have clinical relevance in our immunogenetics laboratory (MFI > 5000). Of 52 patients, 36 received ABO‐c transplants and 16 received ABO‐i transplants. Compared to ABO‐c recipients, the ABO‐i group showed a consistent but statistically non‐significant finding of less frequent ndDSA positivity (69.4% ABO‐c vs 43.8% ABO‐i with MFI >500, P = 0.122; 41.7% ABO‐c vs 25% ABO‐i with MFI >5000, P = 0.353). Additionally, ABO‐i patients were less likely to have any form of rejection (12.5% vs 47.2%, P = 0.027) or acute cellular rejection (6.3% vs 38.9%, P = 0.021). Our data suggest that infants receiving ABO‐i heart transplants may be less likely to develop ndDSAs or have rejection compared to same age ABO‐c recipients. Larger multicenter studies are needed to confirm results from this single center study.     

Impacts of donor‐specific anti‐HLA antibodies and antibody‐mediated rejection on outcomes after intestinal transplantation in children

AMR is a risk factor for graft failure after SBTx. We studied impact of DSAs and AMR in 22 children transplanted between 2008 and 2012 (11 isolated SBTx, 10 liver inclusive Tx, and one modified multivisceral Tx). Three patients never developed DSA, but DSAs were found in seven in the pre‐Tx period and de novo post‐Tx in 19 children. Pathology revealed cellular rejection (15/19), with vascular changes and C4d+. Patients were treated with IV immunoglobulins, plasmapheresis, and steroids. Rescue therapy included antithymocyte globulins, rituximab, eculizumab, and bortezomib. Pathology and graft function normalized in 13 patients, graft loss occurred in two, and death in seven. At the end of the follow‐up, 15 children were alive (68%), 13 with functioning graft (59%). Prognosis factors for poor outcome after Tx were the presence of symptoms at AMR suspicion (P +.033). DSAs were often found following SBTx, mostly de novo. Resistant ACR or severe AMR is still difficult to differentiate, with a high need for immunosuppression in both. DSAs may precede development of severe disease and pathology features on the graft: relationship and correlation need to be better investigated with larger groups before and after Tx.     

Post‐transplant blood transfusions and pediatric renal allograft outcomes

The association of blood transfusions with GS after pediatric KTx is unclear. We retrospectively analyzed blood transfusions post‐KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post‐KTx blood transfusion as a time‐dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post‐KTx; 48% >12 months. Transfused and non‐transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non‐transfused recipient patient survival, antibody‐mediated and ACR, and DSA free survival. Transfusions <1 month post‐KTx did not impact DCGS (P=NS). Patients transfused >12 months post‐KTx had significantly lower 12 month eGFR (compared to non‐transfused) and worse subsequent DCGS. Post‐KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS.     

Effect of small donor weight and donor–recipient weight ratio on the outcome of liver transplantation in children

A small donor weight is a risk factor for HAT with potential for graft loss. To test this hypothesis, we evaluated outcomes of pediatric liver transplants utilizing donors <20 kg using the UNOS database from 01/2003 to 01/2012 (n = 1311). All isolated liver transplants with whole organ grafts were included. Recipients were divided into four groups based on donor weight: group 1, donor weight <5 kg (n = 34 [2%]); group 2, 5–10 kg (431 [33%]); group 3, 10–15 kg (560 [43%]); and group 4, 15–20 kg (286 [22%]). Actuarial patient survival for the first year post‐transplant was significantly lower in groups 1 and 2 compared to groups 3 and 4 (p = 0.002), similarly the one‐yr graft function (p < 0.0001). The difference was due to graft loss within the first month for groups 1 and 2. HAT was significantly higher in groups 1 and 2 compared to others (p = 0.0006). Logistic regression analysis demonstrated donor weight as the most predictive factor with analysis of the ROC curve showing a cutoff point at 7.8 kg. The donor–recipient weight ratio did, in none of the models, gain statistical significance.     

Successful treatment of refractory donor lymphocyte infusion‐induced immune‐mediated pancytopenia with rituximab

A 6‐year‐old male with chronic granulomatous disease, who was transplanted with bone marrow and exhibited increasing mixed chimerism, subsequently received two donor lymphocyte infusions (DLI). Two weeks after the second DLI, the patient developed acute graft‐versus‐host disease (GVHD) and progressive pancytopenia that was associated with autoantibody production. Conventional treatment did not improve the pancytopenia. However, administration of Rituximab (RTX) (375 mg/m²/week for four consecutive weeks) resulted in a rapid resolution of the pancytopenia. The patient achieved full donor chimerism without GVHD symptoms. RTX can be valuable for managing immune‐mediated cytopenias that arise after DLI and are refractory to conventional therapies. Pediatr Blood Cancer 2010;54:329–331. © 2009 Wiley‐Liss, Inc.     

Minimum mycophenolic acid levels are associated with donor‐specific antibody formation

Although de novo DSA are associated with inferior graft survival, there are no effective strategies to prevent their formation. Underexposure to MPA (prodrug: MMF) also contributes to rejection rates early after transplantation, but the effect of this phenomenon on the formation of DSA long‐term post‐transplantation is unknown. Data are expressed as mean (standard deviation). All available data from 32 renal transplant recipients (age at transplantation 7.5 [4.5] yr) on tacrolimus and MPA immunosuppression with an average follow‐up of 9.4 (s.d. 4.6) yr were analyzed. DSA were measured using the Luminex assay (>500 MFI was considered DSA‐positive). Tacrolimus and MPA levels were measured with the Abbot Tacro II and EMIT assay, respectively. Among 1964 MPA and 3462 tacrolimus trough levels, the average MPA trough level was 3.2 (1.5) mg/L and the average tacrolimus level was 6.7 (2.8) ng/mL. At last follow‐up, only 5/32 patients had undetectable DSA, with 5/32 having no class I antibodies and 6/32 having no class II antibodies. DSA formation was associated with a lower minimum MPA trough level (0.27 [0.23] vs. 0.47 [0.18] mg) and cystatin C eGFR (48 [21] vs. 70 [23] mL/min/1.73 m²) for class I DSA formers. The average eGFR of patients without class I DSA was 70 (23) mL/min/1.73 m², whereas the average eGFR of patients with class I DSA was 48 (21) mL/min/1.73 m² (p = 0.0071). MPA trough levels <1.3 mg/L long‐term post‐transplantation are associated with the formation of DSA. The association between the formation of DSA and minimum MPA exposure may support a strategy for preventing the formation of DSA.     

Delayed graft function in pediatric deceased donor kidney transplantation: Donor‐related risk factors and impact on two‐yr graft function and survival: A single‐center analysis

There is mounting evidence that the quality of organs from cadaver donors may be influenced by events occurring around the time of brain death. Aim of this present study was to analyze the correlation of DGF with brain‐dead donor variables in a single‐center pediatric population and to evaluate DGF influence on patients‐ and grafts outcome. End‐points of the study were DGF prevalence, DGF donor‐related risk factors, graft function, patient‐ and graft survival rate, respectively, at six, 12, and 24 months FU. The univariate analysis showed that donor age above 15 yr and vascular cause of donor brain death represented risk factors for DGF. The multivariate analysis confirmed as independent risk factors for DGF donor age >15 yr. At six months FU, DGF showed a negative impact on graft function. In conclusion, among all considered brain‐dead donor resuscitation parameters, just non‐traumatic cause of death turned out to be of impact for DGF. Donor age >15 yr represented the only independent risk factor for prolonged DGF in our series of children. At two‐yr FU, DGF showed a transient negative impact on six‐month graft function.