scholarly journals FC 129CHANGES IN PERIPHERAL NK CELLS IN KIDNEY TRANSPLANT RECIPIENTS WITH AND WITHOUT HLA DSA

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Laura Llinas ◽  
Dolores Redondo Pachon ◽  
Dàlia Raïch Regué ◽  
Maria Jose Perez-Saez ◽  
Sara Sanz ◽  
...  

Abstract Background and Aims Antibody-mediated rejection (ABMR) is a frequent cause of renal allograft loss. There is increasing evidence of the role of Natural Killer (NK) cells in the establishment of ABMR damage. Our group described that patients with donor-specific antibodies (DSA) and ABMR present higher proportions of NKG2A+ NK cell subset in peripheral blood than those without HLA DSA or HLA antibodies. Method We selected 177 kidney transplant recipients (KT) with renal biopsies 2011-2017: 77 with ABMR (DSA+: 53, DSA-: 24) and 100 without ABMR (DSA+: 15, DSA-: 85). We assessed graft survival with a median time of follow-up since the renal biopsy of 53 months. In 138 KT we evaluated the peripheral blood NK cell immunophenotyping and its value as a prognostic biomarker. Results Graft survival was worse in ABMR-KT at the end of follow-up (p<0.001) independently of DSA detection (p=0.63). Regarding NK cell immunophenotyping, we observed a lower proportion and absolute NK cell count in ABMR+DSA+-KT and ABMR+DSA--KT compared with ABMR-DSA--KT (p=0.027, p=0.017). ABMR+DSA+-KT showed higher proportion of NKG2A+ NK cells compared with ABMR-DSA--KT (p=0.007). All ABMR+ patients, independently of DSA detection, presented lower absolute NKG2A- NK cell count in comparison with ABMR-DSA--KT (p=0.001, p=0.017). Finally, a proportion of NKG2A- <30% was associated with lower graft survival 36 months after graft biopsy with ABMR (p=0.067) (Figure). Conclusion Graft survival is worse in ABMR+ compared with ABMR- KT independently of DSA detection. Kidney transplant recipients with ABMR show reduced peripheral absolute numbers of NK cells and NKG2A- NK cells regardless of undetectable DSA. This NK cell phenotype associated with a worse medium-term graft survival in cases with ABMR.

2021 ◽  
Author(s):  
Nicolle Litjens ◽  
Annemiek Peeters ◽  
Judith Kal-van Gestel ◽  
Mariska Klepper ◽  
Michiel Betjes

Abstract Natural killer (NK) cells express the Fc-receptor CD16 (FCGR3A) and could therefore mediate renal endothelial cell damage in cases of chronic-active antibody mediated rejection (c-aABMR). The V/V-genotype of the FCGR3A 158 F/V polymorphism is associated with increased CD16 expression and cytotoxicity by NK cells. This study evaluated whether this genotype is associated with the diagnosis of c-aABMR and renal allograft loss.The distribution of the FGCR3A 158 F/V-genotypes was not different for c-aABMR cases (N=133) compared to control kidney transplant recipients (N=116, p=0.65). The V-allele was associated with increased median fluorescence intensity (MFI) of CD16 by NK cells (MFI 3.5x104 versus 1.3x104 for V/V and F/F-genotype, P<0.001). Increased expression of CD16 correlated with CD16-dependent degranulation of NK cells (R=0.4; P=0.02). Moreover, the V/V-genotype was significantly associated with a higher glomerulitis score and an independent risk factor (HR 1.98; P=0.04) for decreased allograft survival. Death-censored graft survival in c-aABMR cases at 3 years follow-up was 33% for the FCGR3A 158 V/V-genotype versus 62% for the F/F-genotype. In conclusion, the FCGR3A V/V-genotype increases CD16-mediated NK cell cytotoxicity and is associated with a higher glomerulitis score and decreased graft survival in cases with c-aABMR.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hey Rim Jung ◽  
Mi Joung Kim ◽  
Yu-Mee Wee ◽  
Jee Yeon Kim ◽  
Monica Young Choi ◽  
...  

Abstract Little is known about the characteristics and clinical implications of specific subsets of intragraft natural killer (NK) cells in kidney transplant recipients. We analyzed 39 for-cause renal transplant biopsies performed at our center from May 2015 to July 2017. According to histopathologic reports, 8 patients (20.5%) had no rejection (NR), 11 (28.2%) had T cell-mediated rejections (TCMR) only, and 20 (51.3%) had antibody-mediated rejection (ABMR). NK cells were defined as CD3–CD56+ lymphocytes that are positive for CD57, CD49b, NKG2A, or KIR. The density of NK cells was significantly higher in the ABMR group (2.57 ± 2.58/mm2) than in the NR (0.12 ± 0.22/mm2) or the TCMR (0.25 ± 0.34/mm2) group (P = 0.002). Notably, CD56+CD57+ infiltrates (2.16 ± 1.89) were the most frequently observed compared with CD56+CD49b+ (0.05 ± 0.13), CD56+NKG2A+ (0.21 ± 0.69), and CD56+KIR+ (0.15 ± 0.42) cells in the ABMR group (P < 0.001). Death-censored graft failure was significantly higher in patients with NK cell infiltration than those without (Log-rank test, P = 0.025). In conclusion, CD56+CD57+ infiltrates are a major subset of NK cells in kidney transplant recipients with ABMR and NK cell infiltration is significantly associated with graft failure post-transplant.


Author(s):  
Michał Ciszek ◽  
Krzysztof Mucha ◽  
Bartosz Foroncewicz ◽  
Dorota Żochowska ◽  
Maciej Kosieradzki ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Carolina Figueiredo ◽  
Rita Leal ◽  
Clara Pardinhas ◽  
Filipe Mira ◽  
Luís Rodrigues ◽  
...  

Abstract Background and Aims Histological findings that meet criteria for borderline changes “suspicious” for acute T cell mediated rejection (BR) as defined by the Banff Classification (2017) are frequently seen. However, its clinical significance, as well as the appropriate clinical management, are still controversial. Our goal was to compare clinical outcomes of kidney transplant recipients with biopsy proven BR versus acute T cell mediated rejection (aTCMR) and the influence of treating BR rejection in graft outcomes. Method A retrospective cohort study was performed in all kidney transplant recipients with biopsy proven BR and aTCMR between January 2012 and December 2018. Data related to donor and recipient demographics, treatment and subsequent evolution of serum creatinine, proteinuria and graft survival were collected. Mean time at follow up was 31.2 ± 29.1 months. Results We included 91 patients with biopsy proven T cell rejection of which 34 (37.4%) had a BR and 57 (62.6%) aTCMR: 39 (68.4%) IA, 9 (15.8%) IB, 7 (28.1%) IIA and 2 (3.5%) IIB. There was no difference between groups (BR vs aTCMR) regarding age (45,5 vs 48,1, p=0,38), sex (male 73% vs 60%, p=0,27) or race (Caucasian 100% vs 93%, p=0.114). For both groups, deceased donor was more frequent (82% vs 95%, p=0.074), and there was no difference in cytotoxic PRA (mean 4.5 ± 9.2 vs 3.7 ± 12.8, p=0.762) or number of compatibilities (mean 2.2 ± 1.2 vs 2.4 ± 1.3, p=0.539). At the time of rejection diagnosis, the mean time of transplant was similar between groups (32.9 ± 43.6 vs 42.3 ± 67.4 months, p=0.467), but estimated glomerular filtration rate (GFR) was significantly higher in patients with BR when compared to aTCMR (32.0 ± 22.5 vs 19.9 ± 13.1 ml/min/1.73m2, p=0.009). We found no significant difference in proteinuria at the time of biopsy between the 2 groups. Treatment with steroids was started in 20 (58.8%) patients with BR and all the patients with aTCMR were treated with steroids with or without thymoglobulin, depending on the Banff class. Fourteen (41.2%) patients with BR were followed closely with no acute interventions. At 1-year post biopsy, graft survival was 70%, and we found no significantly statistical difference between the two groups (79.4% vs 64.3%, p=0.129). In patients with preserved graft, there was no difference in GFR (41.9 ± 17.7 vs 37.7 ± 19.8, p=0.401) at 12 months post biopsy for both groups. When performing Kaplan-Meyer survival curves at follow-up, we also found no difference between BR and aTCMR (57.6 ± 7.1 vs 43.6 ± 5.5 months, p=0.157) (Figure 1). When analyzing the BR group (N=34) and comparing the patients that were treated (N=20) versus the patients with conservative approach (N=14), we found no difference in demographic features, sCr at biopsy (3.0 ± 1.1 vs 2.8 ± 2.1 mg/dl, p=0.696) and time post-transplant (28.1 ± 43.2 vs 39.7 ± 44.8 months, p=0.454). Graft survival at 1-year was 80% for treated patients and 79% for non-treated patients, p=0.919 and GFR for patients with preserved graft was not different between groups (43.9 ± 21.0 vs 39.7 ± 13.5 ml/min/1.73m2, p=0.572). When performing survival curves, we found that treated patients had almost the double time with functioning graft compared to non-treated patients (71.9 ± 8.5 vs 41.3 ± 6.2 months, p=0.104), although not statistically different probably due to the small sample size (figure 2). Conclusion Our study showed that despite having better GFR at time of biopsy, patients with BR (overall and treated) did not present better graft survival nor graft function at 1 year post biopsy or at follow up, compared with aTCMR. We also found a tendency to better graft survival in patients with BR treated with steroids compared with conservative approach. These results reinforce the importance of borderline rejection in graft outcomes and that the decision of whether to treat or not can influence long-term outcomes.


2020 ◽  
Vol 104 (S3) ◽  
pp. S630-S631
Author(s):  
Yenifer Sanchez-Avila ◽  
Nasly Patino-Jaramillo ◽  
Andrea Garcia-Lopez ◽  
Fernando Giron-Luque

Diabetes ◽  
1988 ◽  
Vol 37 (9) ◽  
pp. 1247-1252 ◽  
Author(s):  
J. A. Van der Vliet ◽  
X. Navarro ◽  
W. R. Kennedy ◽  
F. C. Goetz ◽  
J. J. Barbosa ◽  
...  

2021 ◽  
Vol 10 (14) ◽  
pp. 3063
Author(s):  
Napat Leeaphorn ◽  
Charat Thongprayoon ◽  
Pradeep Vaitla ◽  
Panupong Hansrivijit ◽  
Caroline C. Jadlowiec ◽  
...  

Background: Lower patient survival has been observed in sickle cell disease (SCD) patients who go on to receive a kidney transplant. This study aimed to assess the post-transplant outcomes of SCD kidney transplant recipients in the contemporary era. Methods: We used the OPTN/UNOS database to identify first-time kidney transplant recipients from 2010 through 2019. We compared patient and allograft survival between recipients with SCD (n = 105) vs. all other diagnoses (non-SCD, n = 146,325) as the reported cause of end-stage kidney disease. We examined whether post-transplant outcomes improved among SCD in the recent era (2010–2019), compared to the early era (2000–2009). Results: After adjusting for differences in baseline characteristics, SCD was significantly associated with lower patient survival (HR 2.87; 95% CI 1.75–4.68) and death-censored graft survival (HR 1.98; 95% CI 1.30–3.01), compared to non-SCD recipients. The lower patient survival and death-censored graft survival in SCD recipients were consistently observed in comparison to outcomes of recipients with diabetes, glomerular disease, and hypertension as the cause of end-stage kidney disease. There was no significant difference in death censored graft survival (HR 0.99; 95% CI 0.51–1.73, p = 0.98) and patient survival (HR 0.93; 95% CI 0.50–1.74, p = 0.82) of SCD recipients in the recent versus early era. Conclusions: Patient and allograft survival in SCD kidney recipients were worse than recipients with other diagnoses. Overall SCD patient and allograft outcomes in the recent era did not improve from the early era. The findings of our study should not discourage kidney transplantation for ESKD patients with SCD due to a known survival benefit of transplantation compared with remaining on dialysis. Urgent future studies are needed to identify strategies to improve patient and allograft survival in SCD kidney recipients. In addition, it may be reasonable to assign risk adjustment for SCD patients.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1102
Author(s):  
Angelica Rodriguez-Niño ◽  
Diego O. Pastene ◽  
Adrian Post ◽  
M. Yusof Said ◽  
Antonio W. Gomes-Neto ◽  
...  

Carnosine affords protection against oxidative and carbonyl stress, yet high concentrations of the carnosinase-1 enzyme may limit this. We recently reported that high urinary carnosinase-1 is associated with kidney function decline and albuminuria in patients with chronic kidney disease. We prospectively investigated whether urinary carnosinase-1 is associated with a high risk for development of late graft failure in kidney transplant recipients (KTRs). Carnosine and carnosinase-1 were measured in 24 h urine in a longitudinal cohort of 703 stable KTRs and 257 healthy controls. Cox regression was used to analyze the prospective data. Urinary carnosine excretions were significantly decreased in KTRs (26.5 [IQR 21.4–33.3] µmol/24 h versus 34.8 [IQR 25.6–46.8] µmol/24 h; p < 0.001). In KTRs, high urinary carnosinase-1 concentrations were associated with increased risk of undetectable urinary carnosine (OR 1.24, 95%CI [1.06–1.45]; p = 0.007). During median follow-up for 5.3 [4.5–6.0] years, 84 (12%) KTRs developed graft failure. In Cox regression analyses, high urinary carnosinase-1 excretions were associated with increased risk of graft failure (HR 1.73, 95%CI [1.44–2.08]; p < 0.001) independent of potential confounders. Since urinary carnosine is depleted and urinary carnosinase-1 imparts a higher risk for graft failure in KTRs, future studies determining the potential of carnosine supplementation in these patients are warranted.


2003 ◽  
Vol 64 (10) ◽  
pp. S19
Author(s):  
D.S. Rodriguez ◽  
E. Jankowska-Gan ◽  
L.D. Haynes ◽  
G. Leverson ◽  
D. Heisey ◽  
...  

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