The natural history of de novo donor-specific HLA antibodies after kidney transplantation

Cuesta, Covadonga López del Moral; Wu, Kaiyin; Naik, Marcel; Osmanodja, Bilgin; Akifova, Aylin; Lachmann, Nils; Stauch, Diana; Hergovits, Sabine; Choi, Mira; Bachmann, Friederike; Halleck, Fabian; Schrezenmeier, Eva; Schmidt, Danilo; Budde, Klemens

doi:10.3389/fmed.2022.943502

Cited by 7 publications

(18 citation statements)

References 60 publications

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“…Except for the deterioration in eGFR before pregnancy, we did not find any other predictors for adverse pregnancy outcomes. The strength of this study is the comparison with a matched control cohort with detailed information regarding baseline characteristics, allograft function parameters with the emphasis on dynamic changes, and a detailed long-term mean follow-up time in both cohorts including regular determinations of HLA antibodies [ 60 ]. Since common clinical indicators were not helpful for risk prediction, the use of current biomarkers such as sFlt-1 and PlGF and the detection and validation of new biomarkers derived from multiple organ and cellular sources need to be explored in future studies [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy after Kidney Transplantation—Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health

Kaatz

Latartara

Bachmann

et al. 2023

JCM

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Women of childbearing age show increased fertility after kidney transplantation. Of concern, preeclampsia, preterm delivery, and allograft dysfunction contribute to maternal and perinatal morbidity and mortality. We performed a retrospective single-center study, including 40 women with post-transplant pregnancies after single or combined pancreas–kidney transplantation between 2003 and 2019. Outcomes of kidney function up to 24 months after the end of pregnancy were compared with a matched-pair cohort of 40 transplanted patients without pregnancies. With a maternal survival rate of 100%, 39 out of 46 pregnancies ended up with a live-born baby. The eGFR slopes to the end of 24 months follow-up showed mean eGFR declines in both groups (−5.4 ± 14.3 mL/min in pregnant versus −7.6 ± 14.1 mL/min in controls). We identified 18 women with adverse pregnancy events, defined as preeclampsia with severe end-organ dysfunction. An impaired hyperfiltration during pregnancy was a significant risk contributor for both adverse pregnancy events (p < 0.05) and deterioration of kidney function (p < 0.01). In addition, a declining renal allograft function in the year before pregnancy was a negative predictor of worsening allograft function after 24 months of follow-up. No increased frequency of de novo donor-specific antibodies after delivery could be detected. Overall, pregnancies in women after kidney transplantation showed good allograft and maternal outcomes.

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Section: Discussionmentioning

confidence: 99%

Pregnancy after Kidney Transplantation—Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health

Kaatz

Latartara

Bachmann

et al. 2023

JCM

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“…Sensitization could be related to a period of underexposure, either due to non-adherence or iatrogenic reduction of immunosuppression [ 22 – 28 ]. Additionally, poor HLA matching [ 28 – 31 ] and previous episodes of T-cell mediated rejection (TCMR) [ 29 , 30 , 32 – 34 ] have been associated with DSA development. Other risk factors pertain to certain recipient characteristics such as age or ethnicity [ 35 , 36 ].…”

Section: Methodsmentioning

confidence: 99%

“…Despite this strong relationship, not all recipients with preformed DSA or dnDSA seem to progress to ABMR or graft failure [ 16 , 29 , 45 ]. Multiple mechanisms have been proposed to explain this variation in effect of HLA-DSA on graft outcomes.…”

Section: Methodsmentioning

confidence: 99%

The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice

van den Broek,

Meziyerh,

Budde

et al. 2023

Transpl Int

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Solid phase immunoassays improved the detection and determination of the antigen-specificity of donor-specific antibodies (DSA) to human leukocyte antigens (HLA). The widespread use of SPI in kidney transplantation also introduced new clinical dilemmas, such as whether patients should be monitored for DSA pre- or post-transplantation. Pretransplant screening through SPI has become standard practice and DSA are readily determined in case of suspected rejection. However, DSA monitoring in recipients with stable graft function has not been universally established as standard of care. This may be related to uncertainty regarding the clinical utility of DSA monitoring as a screening tool. This consensus report aims to appraise the clinical utility of DSA monitoring in recipients without overt signs of graft dysfunction, using the Wilson & Junger criteria for assessing the validity of a screening practice. To assess the evidence on DSA monitoring, the European Society for Organ Transplantation (ESOT) convened a dedicated workgroup, comprised of experts in transplantation nephrology and immunology, to review relevant literature. Guidelines and statements were developed during a consensus conference by Delphi methodology that took place in person in November 2022 in Prague. The findings and recommendations of the workgroup on subclinical DSA monitoring are presented in this article.

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“…The patients received regular follow-up visits with laboratory assessments including plasma creatinine, estimated glomerular filtration rate (eGFR), and albumin-creatinine-ratio (ACR) as standard of care (SOC) at baseline and after one, three, and six months. Additionally, de novo donor-specific antibody (dnDSA) formation was assessed once per year in all patients, as previously described [ 16 , 17 , 18 ]. We assessed main clinical events (acute kidney injury, biopsy-proven rejection episodes, and death) as well.…”

Section: Methodsmentioning

confidence: 99%

Donor-Derived Cell-Free DNA for Kidney Allograft Surveillance after Conversion to Belatacept: Prospective Pilot Study

Osmanodja

Akifova

Oellerich

et al. 2023

JCM

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Donor-derived cell-free DNA (dd-cfDNA) is used as a biomarker for detection of antibody-mediated rejection (ABMR) and other forms of graft injury. Another potential indication is guidance of immunosuppressive therapy when no therapeutic drug monitoring is available. In such situations, detection of patients with overt or subclinical graft injury is important to personalize immunosuppression. We prospectively measured dd-cfDNA in 22 kidney transplant recipients (KTR) over a period of 6 months after conversion to belatacept for clinical indication and assessed routine clinical parameters. Patient and graft survival was 100% after 6 months, and eGFR remained stable (28.7 vs. 31.1 mL/min/1.73 m2, p = 0.60). Out of 22 patients, 2 (9%) developed biopsy-proven rejection—one episode of low-grade TCMR IA and one episode of caABMR. While both episodes were detected by increase in creatinine, the caABMR episode led to increase in absolute dd-cfDNA (168 copies/mL) above the cut-off of 50 copies/mL, while the TCMR episode did show slightly increased relative dd-cfDNA (0.85%) despite normal absolute dd-cfDNA (22 copies/mL). Dd-cfDNA did not differ before and after conversion in a subgroup of 12 KTR with previous calcineurin inhibitor therapy and no rejection (12.5 vs. 25.3 copies/mL, p = 0.34). In this subgroup, 3/12 (25%) patients showed increase of absolute dd-cfDNA above the prespecified cut-off (50 copies/mL) despite improving eGFR. Increase in dd-cfDNA after conversion to belatacept is common and could point towards subclinical allograft injury. To detect subclinical TCMR changes without vascular lesions, additional biomarkers or urinary dd-cfDNA should complement plasma dd-cfDNA. Resolving CNI toxicity is unlikely to be detected by decreased dd-cfDNA levels. In summary, the sole determination of dd-cfDNA has limited utility in the guidance of patients after late conversion to belatacept. Further studies should focus on patients undergoing early conversion and include protocol biopsies at least for patients with increased dd-cfDNA.

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The natural history of de novo donor-specific HLA antibodies after kidney transplantation

Abstract: Budde K (2022) The natural history of de novo donor-specific HLA antibodies after kidney transplantation.

Cited by 7 publications

References 60 publications

Pregnancy after Kidney Transplantation—Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health

Pregnancy after Kidney Transplantation—Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health

The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice

Donor-Derived Cell-Free DNA for Kidney Allograft Surveillance after Conversion to Belatacept: Prospective Pilot Study

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