A multi-institutional report of intermediate-term kidney outcomes in uterus transplant recipients

Uterus transplant (UTx) is a treatment for uterine factor infertility (UFI). Globally, the number of UTx recipients increasing (1Brannstrom M, Tulius SG, Brucker S et al. Registry International Society Transplantation: First Report. Transplantation 2022; online ahead print.Google Scholar, 2Johannesson L. Testa G. Putman J.M. al.Twelve Live Births After in Dallas UtErus Transplant Study.Obstet Gynecol. 2021 1; 137: 241-249Crossref PubMed Scopus (33) Google 3Vali S. Jones B.P. Saso Yazbek J. Quiroga I. Smith J.R. A 50-Year Journey.Clin Obstet 65: 92-100Crossref (1) Scholar). Many have Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH); MRKH may include unilateral kidney agenesis addition to congenitally absent uterus and vaginal aplasia (4Chen N. Pan H. Luo al.Clinical characteristics 1,055 Chinese patients with syndrome: nationwide multicentric study.Fertil Steril. 2021; 116: 558-565Abstract Full Text PDF (15) Thus, dysfunction potential complication UTx. We previously demonstrated that experience decrease estimated GFR (eGFR) early posttransplant (5Sawinski D. Johannesson Kristek al.A multi-institutional study renal outcomes renal-related pregnancy recipients.Am J Transplant. 2022 Jul 13; (online print)https://doi.org/10.1111/ajt.17149Abstract (0) Scholar), persists into postpartum period. also incidence acute injury (AKI) pre-eclampsia (28%) are increased However, unique paradigm - after childbearing complete, graft hysterectomy performed immunosuppression discontinued. The cumulative effect pregnancy, AKI episodes, pre-eclampsia, temporary calcineurin inhibitor (CNI) exposure on longer-term function remains undefined.We undertook this cohort representing most United States population selected participants from Europe elucidate intermediate-term among recipients. Twenty-two women who received 9/2016-2/2020 across four institutions were included (Table Supplementary Methods/References; Supplemental Table 1). All had at least one successful pregnancy; five delivered two children. At last follow-up, 20 discontinued immunosuppression; retained their uteri an additional pregnancy. Most as etiology UFI (95.5%) only radiological evidence solitary kidney. Mean pretransplant serum creatinine overall was 0.76mg/dL (±0.08mg/dL) mean eGFR 106.5ml/min/1.73m2 (±11.4ml/min/1.73m2). Median follow up since 3.01 years (IQR 2.23-3.43 years) median 2 1.2-3.1 years). (92.1ml/min/1.73m2± 18.4 ml/min/1.73m2) significantly lower than (pre 106.4 ml/min/1.73m2 ±11.8ml/min/1.73m2, p= 0.001) (Supplemental Figure 1).Table 1Demographics cohort.UTx recipientsN=22Mean age (±SD)31 (±4.9)RaceBlackMiddle EasternWhite1 (4.5%)1 (4.5%)20 (90.9%)Etiology Uterine infertilityMRKHHysterectomy21 (95.5%)1 (4.5%)Solitary kidney1 (4.5%)Transplant typeLivingDeceased14 (63.6%)8 (36.4%)Mean creatinine, mg/dL (±SD)0.76 (±0.08)Mean eGFR, (±SD)106.5 (±11.4)On up2 (9.1%)AKI any time during pregnancy10 (45.5%)Pre-eclampsia5 (22.7%)SD: standard deviation; MRKH: syndrome; eGFR: glomerular filtration rate; AKI: Open table new tab SD: 1a-c depicts slope. Using linear mixed models, we while 25.7 (95%CI 18.7-32.7 values. rebounds discontinuation by average 11.6 6.1 – 17.1 ml/min/1.73m2); however, off still 14.1 8.5-19.8 pretransplant. Rebound smallest (rebound 8.0 ml/min/1.73m2, 95%CI: 1.9-14.1 9.9 95%CI 3.7-16.0 1 3 months stopping) but later timepoints (15.0 8.8-21.2 6 months). slope 12 -10.2 (Figure 1a). examined factors hypothesized moderate change. Participants experiencing (6.3 greater decline, -4.8 17.3 (7.3 95% CI: -5.4-20.0 declines baseline differences not statistically significant. duration small (0.1 difference per 100 days immunosuppression, -1.1-1.4 ml/min/1.73m2). For every 10ml/min/m2 decline pre-UTx embryo transfer, observed 5.2ml/min/m2 (95% CI 3.4-7.0 ml/min/m2) demonstrate 3-years up, risk ongoing dysfunction, manifested persistent reduction 10.2ml/min/1.73m2, despite withdrawal. trend towards experienced or This study, more longer extends our previous observations Scholar) numerically significant both versus estimates has important implications long-term health An annual -3ml/min/1.73m2/year confers 31% increase all-cause mortality (6Turin T.C. Coresh Tonelli M. al.Change rate over mortality.Kidney Int. 2013; 83: 684-691Abstract (98) Scholar,7Rifkin D.E. Shlipak M.G. Katz R. Fried L.F. Siscovick Chonchol al.Rapid older adults.Arch Intern Med. 2008; 168: 2212-2218Crossref (289) exceeds typical loss rates -0.3-1ml/min/1.73m2/1.73m2/year expected individuals without comorbidities proteinuria (8Kidney Disease: Improving Global Outcomes CKD Work GroupKDIGO 2012 clinical practice guideline evaluation management chronic disease.Kidney Suppl. 2003; 3: 1-150Google Immunosuppression did completely restore function, being healthy, rigorously pre-screened systemic illnesses having normal (in contrast other solid organ often including pre-existing disease). young life expectancies; therefore, particularly concerning. Chronic disease (CKD), where stage I defined ≤90ml/min/1.73m2, negative health, mortality, cardiovascular disease, AKI, end-stage life-saving procedure risks must be weighed against benefits. Longer needed determine if stabilizes several continues. In general population, episodes been associated future (9, S8). cohort. observation useful when counseling considering second first could risk. Our findings highlight need mitigation strategies. Effective options prevent limited. maintained low-dose aspirin, intervention (S9). infrequent common those transplants (S10); fluctuations inaccuracies whole blood CNI measurements contribute (S11). While minimal, efforts reduce exposure, such reducing interval between transfer withdrawing immediately hysterectomy, warranted. Dedicated studies ideal trough levels optimize dosing would beneficial. CNIs well-described nephrotoxicity. Alternatives, belatacept, exist extensively studied (S12) there theoretical concerns regarding fetal toxicity (S13). highlights prospective targeted interventions, CNI-free immunosuppressive regimens, mitigate some deleterious effects function. notable strengths. represents large, multi-center international group serial measurements. used models examine trends eGFR. Linear naturally handle missing data enhanced multiple different timepoints. able account impact pre-eclampsia. There limitations work: lack consistent assessments, variation candidate center-level protocols. Compared trajectory, size small; should bias null. established moving care; persist beyond period which immunosuppression. Reduction outcomes. It will clarify contribution aspects Further required delineate these provided optimal informed consent candidates. authors no relevant financial conflicts interest disclose. 9Kristensen J.H. Basit Wohlfahrt Damholt M.B. Boyd H.A. Pre-eclampsia disease: study.BMJ. 2019; 365: I1516Crossref Scholar. Download .pdf (.17 MB) Help pdf files