Highly sensitized kidney transplant candidates face significant immunologic barriers due to high donor-specific antibody (DSA) titers. This study reports the first two highly sensitized living-related kidney transplant recipients successfully desensitized at Ibn Sina Teaching Hospital, Sirte, Libya, using plasmapheresis and rituximab without IVIG. Both patients exhibited DSA >5000 Mean Fluorescence Intensity (MFI) pre-desensitization. After 5–7 plasmapheresis sessions and rituximab, DSA levels fell below 500 MFI, permitting safe transplantation. Both received ATG induction and standard maintenance therapy. Immediate graft function occurred with serum creatinine <1 mg/dL at 72 hours. No delayed graft function, rejection, or infection occurred. These findings demonstrate that simplified desensitization can expand transplant access in developing countries.

Abstract Delayed graft function (DGF) is commonly defined as dialysis needed within one week post-transplant. DGF is a common early post-transplant complication associated with detrimental outcomes. To overcome the shortage of donors, the criteria for selecting deceased donors have been liberalized. Increased associated risks with DGF-associated transplants, including donors with acute kidney injury, older age donors, prolonged cold ischemia time, and out-of-sequence kidneys, have become increasingly prevalent. There is currently no Food and Drug Administration (FDA)-approved DGF-related therapy. Previous strategies implemented to prevent adverse outcomes related to DGF include donor-recipient matching, kidney offers for preemptive transplant with a high risk for DGF, machine perfusion, and more. In this manuscript, we discuss pertinent updates regarding DGF in policy, epidemiology, diagnostics, and therapeutics to supplement the literature and to foster ongoing research.

Background Incidence of delayed graft function (DGF) increases due to the decline in donor kidney quality and the increased use of marginal allografts, while the promising biomarkers for early DGF prediction are lacking. Previous analyses showed that Tenascin-C (TNC) was associated with acute kidney injury; however, its correlation with DGF is unclear. This study aimed to evaluate the ability of TNC to predict DGF. Methods This prospective study included 36 perioperative kidney transplant recipients. Serum and urine samples were collected at regular intervals before and during the 10 days after transplantation to measure TNC and other conventional biomarkers. Pre-implantation graft renal biopsies were analyzed using Remuzzi and TNC staining scores. These data were then combined with clinical risk factors to construct a DGF prediction model. Results In recipients with DGF, sTNC levels peaked on postoperative day 4, and were associated with increased risk of composite events (DGF and rehospitalization). uTNC levels were significantly higher in recipients without DGF, peaking at 8 hours postoperatively. sTNC levels at postoperative day 4 and TNC immunohistochemical scores were identified as independent risk factors for DGF. Incorporating the above two factors into a model comprising recipient age, cholesterol levels, donor cold ischemia time, and surgery duration significantly improved its ability to predict DGF, with the area under the curve increasing from 0.6790 to 0.9321. Conclusion This study highlights the TNC levels in perioperative kidney transplant recipients and their correlation with DGF. sTNC levels and TNC immunohistochemical staining scores may serve as potential biomarker predicting DGF.

Background ABO-incompatible living donor kidney transplantation (ABOi-LDKT) offers a potential solution to organ shortages, but its safety and economic impact in China remain uncertain. This study evaluated short- to mid-term outcomes of ABOi-LDKT in a Chinese population by integrating evidence from a meta-analysis and a single-center cohort. Methods We performed a meta-analysis of 18 studies including 15,611 kidney transplant recipients to compare graft and patient survival between ABOi-LDKT and ABO-compatible LDKT (ABOc-LDKT). In parallel, we conducted a retrospective single-center cohort study of 41 ABOi-LDKT and 132 ABOc-LDKT recipients transplanted between 2021 and 2022. Outcomes included patient and graft survival, renal function, postoperative complications, infections, delayed graft function (DGF), acute rejection, and hospitalization costs. Results The meta-analysis showed lower 1-year graft survival and 3-year patient survival in ABOi-LDKT than in ABOc-LDKT. In contrast, our single-center cohort demonstrated comparable 1- and 3-year patient and graft survival between groups. No significant differences were observed in surgical complications, infections, DGF, or acute rejection. ABOi-LDKT recipients showed better renal function at two weeks post-transplant, with no sustained differences thereafter. Hospitalization costs were higher in the ABOi-LDKT group, reflecting additional desensitization procedures. Conclusion In this Chinese single-center cohort, ABOi-LDKT achieved short- to mid-term clinical outcomes comparable to ABOc-LDKT despite higher upfront costs. When combined with contemporary desensitization protocols, ABOi-LDKT appears to be a safe and feasible strategy to expand access to living donor kidney transplantation in settings with severe organ shortages.

Breakthrough cytomegalovirus (CMV) infection during antiviral prophylaxis may result in significant morbidity. The purpose of this study was to identify the incidence of breakthrough CMV infection and subsequent risk factors in kidney and pancreas transplant recipients on antiviral prophylaxis. This single-center retrospective cohort study examined 408 adult kidney and/or pancreas transplant episodes from 2018 to 2021 that received CMV antiviral prophylaxis after transplant. Multivariable Cox regression analysis was utilized to explore the association between breakthrough infection and previously identified risk factors, such as delayed graft function (DGF) and rejection. Breakthrough CMV infection occurred in 125/408 (30.8%) of patients. The median time to detection was 30 days after transplant (IQR: 18-50). Those with breakthrough infection had higher incidence of DGF, longer cold ischemic time, and were more commonly deceased donor transplant recipients. Multivariable Cox regression analysis showed DGF was a significant risk factor for breakthrough infection with an HR of 1.68 (95% CI [1.15, 2.45], p<0.01). Ensuring appropriate dosing of prophylaxis in the setting of DGF may result in decreased risk of breakthrough CMV infection and further complications.

Renal graft imaging: An update and overview.

ABSTRACTIntroductionThere are no effective therapeutic agents for preventing or treating delayed graft function (DGF) among deceased donor kidney transplant recipients (DDKTRs). Donor and recipient factors are important to predicting DGF and associated outcomes, which we hypothesize differed over time.MethodsDDKTRs were stratified by transplant year into four eras—E1 (2000–2005), E2 (2006–2011), E3 (2012–2017), and E4 (2018–2021). We analyzed risk factors for DGF, along with one‐year uncensored graft failure (UCGF), death‐censored graft failure (DCGF), death with a functioning graft (DWFG), and acute rejection (AR) by era.ResultsA total of 3085 DDKTRs were included (E1: 804, E2: 882, E3: 909, E4: 490). The proportion of patients with DGF differed significantly by era. Duration of DGF and median dialysis count were lower in recent eras.In E1‐E4, donation after circulatory death, higher donor terminal serum creatinine, and pretransplant duration of dialysis were risk factors for DGF, while preemptive transplant was associated with lower odds of DGF. Other factors were not consistently associated with DGF across eras.The risk of one‐year AR was significantly lower in E3 (aHR: 0.46; 95% CI: 0.30–0.69, p < 0.001) and E4 (aHR: 0.16; 95% CI: 0.07–0.36, p < 0.001) compared to E1. There were trends towards decreased risk for UCGF and DWFG in E2, E3, and E4.ConclusionSome risk factors for DGF remained consistent, while others differed. Likely due to improved management, the risk for AR in the DGF setting improved in recent eras. There were trends of improved uncensored graft and patient survival in recent eras.

Inhibition of USAG-1 improved delayed graft function in renal transplantation.

Nutritional status influences outcomes after pediatric kidney transplantation. While obesity is associated with delayed graft function (DGF) in adults, prior pediatric literature has reported inconsistent associations between body mass index (BMI) and early graft function, leaving uncertainty about whether higher BMI contributes to early dysfunction in children. We studied pediatric kidney-only recipients in the Organ Procurement and Transplantation Network (OPTN) registry. Exclusions were age < 2 years, prior or multi-organ transplants, or missing BMI, dialysis, or hospital length of stay (HLOS) data. BMI was classified using Centers for Disease Control and Prevention growth charts. Outcomes were DGF, slow graft function (SGF), and HLOS. Trend testing evaluated ordered associations across BMI categories. Logistic regression estimated adjusted associations between BMI category and DGF and SGF, and linear regression was used for HLOS. Among 9098 recipients, the incidence of DGF increased progressively across BMI groups, from 3.9% in underweight to 5.9% in obese recipients (trend p = 0.016). In adjusted models, each higher BMI category was associated with greater odds of DGF (OR 1.16, 95% CI 1.07-1.27, p < 0.001) and SGF (OR 1.20, 95% CI 1.06-1.35, p = 0.004). HLOS was modestly longer in higher-BMI groups (median 9 vs. 8 days; p < 0.001). Higher BMI is associated with modest differences in early graft dysfunction in pediatric kidney transplantation. Trend analyses demonstrate a graded association between BMI and DGF and SGF, with small absolute differences across BMI categories.

ABSTRACTBackgroundThe allocation and acceptance of deceased‐donor kidneys in the United States is influenced by theKidney Donor Profile Index (KDPI). We conducted a national analysis of high‐KDPI kidney transplants performed from 2014 to 2021 to identify key predictors of post‐transplant outcomes beyond those incorporated in KDPI.MethodsThis retrospective cohort study used data extracted from the Scientific Registry of Transplant Recipients (SRTR). Adult, first‐time recipients of kidney‐only deceased‐donor transplants with KDPI greater than 85% were included. Regression models were used to identify independent predictors of delayed graft function (DGF), primary graft nonfunction (PGNF), patient survival, overall graft survival, and death‐censored graft survival.ResultsAmong 4,911 recipients, DGF occurred in 33.8% and PGNF in 4.0%. DGF was independently associated with donation after circulatory death, terminal donor creatinine > 1.5 mg/dL, recipient obesity, dialysis duration > 3 years, and cold ischemia time (CIT) ≥ 24 h, whereas machine perfusion was protective. PGNF was associated with donation after circulatory death, terminal donor creatinine > 2.0 mg/dL, high‐risk cytomegalovirus (CMV) serostatus, and donor injury patterns within the high‐KDPI range, including younger donor age. Five‐year patient and graft survival were 72% and 62%, respectively. Graft loss was independently associated with DGF, elevated intrarenal resistive index (RI), recipient diabetes, prolonged dialysis exposure, and high‐risk CMV/EBV serostatus.ConclusionsOutcomes after high‐KDPI kidney transplantation reflect both KDPI‐defined donor risk and additional recipient, immunologic, and perioperative factors. A multidomain, offer‐time assessment may support more individualized acceptance decisions and improve utilization.

ABSTRACTIntroductionDual kidney transplantation (DKT), an uncommonly performed procedure, provides a unique opportunity to transplant nonstandard kidneys that might otherwise not be utilized. We compared perioperative and five‐year posttransplant outcomes between DKT, and single kidney transplants (SKT) performed at our institution.MethodsWe analyzed all adult deceased donor kidney‐alone transplant recipients at our center between 2001 and 2020. Recipients of pediatric en bloc kidney transplants were excluded. Perioperative outcomes of interest included delayed graft function (DGF), posttransplant length of stay (LOS), rehospitalization, and reoperation. Five‐year outcomes included biopsy‐proven acute rejection (AR), death‐censored graft failure (DCGF), uncensored graft failure (UCGF), and death with functioning graft (DWFG).ResultsA total of 100 DKT and 3125 SKT recipients were included. DKT recipients were older (p < 0.001), more often male (68%), and more often underwent early steroid withdrawal (p = 0.04). In comparison to SKT, after adjustment for multiple variables, DKT was not independently associated with DGF (aOR: 1.25; 95% CI 0.76–2.08); prolonged LOS (linear coefficient 0.42; −0.9–1.7); reoperation (aOR: 0.73; 95% CI: 0.21–2.51) or rehospitalization (aOR 0.98; 95% CI: 0.55–1.74). However, within five years, DKT had a lower adjusted incidence rate ratio (aIRR) for AR (aIRR: 0.28; CI 0.12–0.64); DCGF (aIRR: 0.30; 95% CI 0.13–0.68), and UCGF (aIRR: 0.53; 95% CI: 0.33–0.86), without statistically significant differences in DWFG (aIRR: 0.83; 95% CI: 0.46–1.53).ConclusionIn selected recipients, DKT offered superior medium‐term outcomes compared to SKT without compromising perioperative outcomes. DKT can mitigate concerns associated with medically complex donor kidneys, increase organ utilization, and increase access to transplantation.

Robotic-Assisted Simultaneous Bilateral Native Nephrectomy and Living Donor Kidney Transplantation.

Complement system overactivation contributes to transplanted kidney injury in both ischemia-reperfusion and antibody-mediated rejection, ultimately affecting post-transplant renal function. C1 esterase inhibitor (C1-INH) may reduce complement-mediated injury, yet its effects on renal function and safety outcomes remain uncertain in randomized trials. Four RCTs were included, all focusing on the use of C1-INH in kidney transplant recipients, comparing it with control groups receiving saline. The studies were evaluated for methodological quality using the Jadad scoring system and the Cochrane Risk of Bias tool. Meta-analysis was performed using RevMan software, assessing outcomes such as renal function (eGFR), AMR incidence, and SAE occurrences. This study included four randomized controlled trials encompassing 148 kidney transplant recipients. The findings suggest that treatment with C1-INH may be associated with an improvement in renal function, as reflected by eGFR. No statistically significant difference was observed in the incidence of delayed graft function or antibody-mediated rejection between the treatment and control groups. The overall incidence of serious adverse events was comparable between groups, with no significant differences detected in infection-related, renal, cardiovascular, or gastrointestinal events. The use of C1-INH may be associated with improved graft renal function following kidney transplantation. However, no significant benefit was observed with respect to delayed graft function or antibody-mediated rejection. The available evidence suggests an acceptable safety profile for C1-INH in this setting. Nevertheless, given the clinical heterogeneity of the included studies and the limited cumulative sample size, these findings should be interpreted as preliminary. Larger, well-designed randomized controlled trials are required to further clarify the therapeutic role of C1-INH in kidney transplantation.

Recovery from post-renal transplant lymphopenia predicts graft function and survival.

Following implementation of the U.S. Kidney Allocation System (KAS) in 2014, deceased donor kidneys with a kidney donor profile index (KDPI) < 35% are prioritized for allocation to pediatric candidates. Early post-KAS data suggested this prioritization may have led to more frequent delayed graft function compared to pre-KAS, when pediatric allocation priority was based on donor age < 35 years. We sought to understand the impact of this allocation change on longer-term pediatric kidney transplant outcomes. We used SRTR data to identify all deceased donor kidney transplants with pediatric recipients during two eras: "Pre-KAS" (12/1/2009-11/30/2014) and "KAS" (12/1/2015-11/30/2020). We used Cox proportional hazards models to calculate the association between study era and all-cause graft failure (graft failure or death) after adjusting for recipient characteristics. Among 4502 included transplants, 2175 (48%) were in the pre-KAS era and 2327 (52%) in the KAS era. KAS-era donors were older (median age 23 years, 13% age ≥ 35 years vs. median age 21, 1% age ≥ 35 years), less likely to have diabetes and hypertension, and had lower serum creatinine. Transplantation during the KAS era was associated with a lower hazard of graft failure after adjusting for recipient characteristics (adjusted HR 0.690.790.91, p = 0.001). Results were similar in sensitivity analyses limited to recipients < 10 years old and recipients alive with a functioning graft 90 days post-transplant. KDPI-based prioritization of kidneys for pediatric allocation was associated with a lower risk of graft failure compared to donor age-based prioritization. Further refining donor risk scores may enable additional improvements in graft survival.

Tubule-derived growth differentiation factor 15 limits renal transplant injury by reprogramming macrophage responses.

Background/Objectives: Donor kidney function measured by glomerular filtration rate (GFR) is widely used as a selection criterion in kidney transplantation (KT). This study addresses the knowledge gap regarding the relationship between donor GFR at organ procurement and graft function in deceased donor KT. Methods: We retrospectively analyzed 918 deceased donor KTs and compared donor GFRs at procurement and recipient GFRs after KT at hospital discharge and in the one-year follow-up. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was used to estimate and compare GFRs. Donor baseline GRF was defined as the last available estimated GRF prior to organ procurement. The Kaplan-Meier analysis was used to estimate recipient and graft survival. Results: The median donor GFR was 92.8 mL/min/1.73 m2, while the median recipient GFR at hospital discharge was 37.5 mL/min/1.73 m2 (-60% to donor baseline, p < 0.001), increasing to 51.4 mL/min/1.73 m2 (+37%, p < 0.001) at one-year follow-up. One-year graft and patient survival rates were 95.3% and 98.1%, respectively. Except for grafts from donors with a GFR < 15 mL/min/1.73 m2 due to acute renal failure that resulted in a significantly higher delayed graft function (DGF) rate and inferior graft survival (71.4%), no correlation was observed between baseline GFRs and DGF occurrence nor graft survival. Conclusions: Excellent results can be achieved in KT with subnormal donor GFR. The decision to refuse a kidney offer for KT should not solely be based on donor GFR. Kidneys from donors with very low GFR (<15 mL/min/1.73 m2) may be transplanted, but our observation is based on a very small sample (n = 7) and should therefore be interpreted with caution, particularly given the associated higher risk of DGF and lower graft survival.

BackgroundKidney transplantation (KT) from elderly donors (aged ≥65 years) with acute kidney injury (AKI) remains controversial and these organs might be underutilized. To date, clear evidence supporting the safety of KT from donors with AKI exists solely for younger donor populations. We hypothesized that, when appropriately selected, graft survival and function in recipients of kidneys from AKI and non-AKI donors aged ≥65 years are comparable.MethodsWe conducted a retrospective cohort study analyzing KT outcomes from donors aged ≥65 years with and without AKI that were performed between 2006 and 2021 at three German transplant centers. AKI was defined according to KDIGO criteria. Death-censored graft survival, overall graft survival, patient survival up to 7 years, eGFR up to 5 years as well as incidence of delayed graft function and biopsy proven acute rejection were compared. Kaplan-Meier analyses and multivariable Cox regression were performed.ResultsOf 685 KT recipients, 183 received kidneys from AKI donors, and 502 from non-AKI donors. Most KTs were from donors with KDIGO stage 1 AKI (n = 151; 81.6%). Delayed graft function occurred similarly often in AKI and non-AKI recipients (32.8% vs. 32.8%, p = 1.0). Death-censored graft survival was comparable between AKI and non-AKI groups (7 years: 59.0% vs. 61.3%; p = 0.87). Median eGFR at 12 months was 33.8 mL/min/1.73 m2 (IQR 27.3, 44.2) in the AKI group and 35.5 mL/min/1.73 m2 (IQR 26.3, 44.8) in the non-AKI group (p = 0.79). These results remained unchanged after adjustment for known risk factors of graft survival in the multivariable Cox regression.ConclusionIn this study, KT from ≥65-year-old donors with mostly mild AKI resulted in similar short and long-term graft survival and function compared to KT from ≥65-year-old donors without AKI. These findings support the utilization of AKI kidneys from elderly donors to expand the donor pool without compromising outcomes.

Is Age Just a Number? Access to and Outcomes in Kidney Transplant Recipients ≥65 Years.

BackgroundPreviously we reported on the therapeutic monoclonal anti-human C2 antibody empasiprubart that inhibits activation of the classical and lectin pathways of complement. Preclinical studies with this antibody are hampered by its low affinity for C2 of animal species other than primates.Methods and resultsWe developed a high affinity, Ca2+-dependent anti-rat C2 antibody using the sequences and structural data of empasiprubart. Pharmacokinetics and pharmacodynamics of the resulting antibody in Sprague Dawley rats were assessed and used for an intervention study in a rat model of delayed graft function following kidney transplantation. The anti-rat C2 antibody improved kidney function and health in the rats within the first 2 weeks post-transplantation.ConclusionOur study shows the successful development of an analogue of empasiprubart that can be used in preclinical in vivo disease models and highlights the potential of C2-blocking as a therapeutic strategy for preventing delayed graft function following kidney transplantation.