Citations

Outcomes of kidney-alone transplantation (KAT) in former simultaneous liver-kidney (SLK) transplant candidates after liver waitlist delisting are not well defined. Using Scientific Registry of Transplant Recipients (SRTR) data, we identified adult recipients who underwent KAT between 2005 and 2025 after prior SLK listing (RLD-KAT), which was matched 1:5 to primary KAT recipients without liver disease by age, transplant year, and diabetes status. Patient and graft survival were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazards models. We identified 163 RLD-KAT recipients matched to 815 controls. Unadjusted Kaplan-Meier analyses demonstrated lower patient survival in RLD-KAT (p = 0.020), whereas death-censored and overall graft survival were similar (p > 0.05). In multivariable models, death-censored graft survival (HR 0.89; 95% CI 0.51–1.53), overall graft survival (HR 1.00; 95% CI 0.73–1.36), and patient survival (HR 1.07; 95% CI 0.76–1.5) did not differ significantly. Six RLD-KAT recipients (3.7%) subsequently underwent liver transplantation. Kidney-alone transplantation in prior SLK candidates was associated with acceptable patient and graft outcomes and a low incidence of subsequent liver transplantation.

Background. The use of immune checkpoint inhibitors (ICIs) in kidney transplant recipients (KTR) for cancer treatment is limited by concerns of allograft rejection and uncertain oncologic efficacy. Methods. We conducted a single-center retrospective study of KTR with unresectable or metastatic malignancies treated between 2018 and 2025. The primary study cohort included 33 patients treated with ICI, whose outcomes were compared with 20 matched KTR treated with non-ICI systemic chemotherapy (SC). Results. KTR treated with ICI achieved an objective response rate of 36.4% (12/33) versus 30.0% (6/20) with SC, and a clinical benefit rate of 54.5% (18/33) versus 35.0% (7/20); neither difference was statistically significant (objective response rate P = 0.77; clinical benefit rate P = 0.27). Disease progression occurred in 81.8% of ICI-treated patients and 95.0% of SC-treated patients ( P = 0.23), and death because of cancer progression occurred in 63.6% and 75.0%, respectively ( P = 0.58). Median progression-free survival was 7.3 mo (95% confidence interval [CI], 4.3-10.8 mo) in the ICI group versus 4.1 mo (95% CI, 2.8-6.3 mo) in the SC group (log-rank P = 0.156). Median overall survival was 15.1 mo (95% CI, 7.6-37.3 mo) with ICI versus 8.7 mo (95% CI, 4.9-14.8 mo) with SC (log-rank P = 0.079). Posttreatment allograft rejection occurred in 12.1% of ICI-treated patients and 0.0% of SC-treated patients ( P = 0.29), with irreversible graft loss in 3.0%. Grade ≥2 immune-related adverse events occurred in 12.1% of ICI-treated patients, and no treatment-related deaths were observed. Conclusions. ICI therapy was associated with a trend toward longer overall survival when compared with SC and with a low rate of rejection and allograft loss.

Abstract Frailty influences treatment outcomes in older patients with multiple myeloma (MM), yet existing frailty tools capture limited geriatric domains and are incompletely studied in the context of contemporary therapies. We prospectively evaluated patient-reported comprehensive geriatric assessment (CGA) domains and their associations with treatment toxicity and patient-reported outcomes (PRO) in older adults with MM. Patients aged ≥60 years with newly diagnosed or relapsed/refractory MM initiating a new therapy completed electronic CGA and PRO questionnaires at baseline and 4 months. Outcomes included clinician- and patient-reported treatment toxicity, treatment adaptations, health care use, and health-related quality of life (HRQOL). A cumulative deficit frailty index (FI) was derived from CGA and HRQOL domains. Among 90 patients (mean age, 72 years), geriatric impairments were common, particularly physical function domains. High-grade nonhematologic toxicities were significantly associated with older age, comorbidities, patient-reported functional limitations, and anxiety. Toxicity rates on the PRO version of the Common Terminology Criteria for Adverse Events (CTCAE) were higher than on CTCAE, highlighting a discordance between physician- and patient-reported treatment toxicity. Frailty was present in 22% and associated with worse baseline HRQOL and increased high-grade nonhematologic toxicity but not treatment adaptations or health care use. Average CGA and HRQOL scores remained stable over 4 months, although individual trajectories varied. Patient-reported geriatric impairments are prevalent in older adults with MM and strongly associated with nonhematologic toxicities even in the contemporary treatment era. Physician-reported CTCAE may not fully reflect patients' symptom burden. Heterogeneity in individual geriatric trajectories during treatment emphasize the need for longitudinal assessment. This study was registered at www.clinicaltrials.gov as NCT05918185.

Delayed graft function (DGF) is a frequent complication after deceased donor kidney transplantation, yet its long-term impact remains understudied. Heterogeneous populations, short follow-up, and inadequate control of donor-related factors have limited prior studies. Using the Scientific Registry of Transplant Recipients (2005–2024), we evaluated the association between DGF and long-term graft outcomes, including a mate-kidney (same donor, discordant DGF status) analysis to isolate its independent effect. We identified 103,678 dialysis-dependent deceased donor kidney recipients maintained on tacrolimus and mycophenolate. Mixed-effects Cox models, adjusted for donor, recipient, immunologic, and procurement factors. DGF occurred in 30.1% of recipients and was associated with increased death-censored graft failure (HR 1.40; 95% CI 1.33–1.47) and overall graft failure (HR 1.27; 95% CI 1.23–1.31). DGF recipients had higher rejection rates at 6 (6.0% vs. 4.7%) and 12 months (8.9% vs. 7.3%), longer hospital stay, and higher 1-year rehospitalization. In the mate-kidney analysis (6,818 donors), DGF remained strongly associated with death-censored graft failure (HR 1.58; 95% CI 1.39–1.80) and overall graft failure (HR 1.35; 95% CI 1.25–1.46), confirming the independent effect of DGF. DGF is a strong predictor of adverse long-term outcomes irrespective of rejection and warrants targeted prevention strategies and intensified follow-up.

Abstract Background: Kidney transplant recipients (KTRs) have a markedly elevated risk of aggressive malignancies, yet the use of immune checkpoint inhibitors (ICIs) in this population remains limited by concerns for allograft rejection and the absence of prospective evidence. We evaluated real-world antitumor activity, graft safety, and immunosuppression-related outcomes of ICI therapy in KTRs with advanced cancers. Methods: We retrospectively analyzed 57 KTRs with locally advanced unresectable or metastatic malignancies treated between 2018-2025 at a single tertiary center. Thirty-three received ICIs and 24 received non-ICI systemic therapy. Outcomes included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival from diagnosis (OSd), overall survival from treatment initiation (OSt), acute allograft rejection, and immune-related adverse events (irAEs). Tumor response was assessed by RECIST v1.1. Results: ICI-treated patients achieved higher ORR (40.0% vs 26.1%) and CBR (60.0% vs 33.3%) compared with non-ICI therapy. Median OSd was 35.8 vs 23.3 months, and median PFS was 4.3 vs 3.5 months (both not statistically significant). Median OSt was significantly longer with ICIs (15.1 vs 7.9 months; p=0.012). Acute rejection occurred in 12.1% of ICI-treated patients (3% irreversible) versus 4.2% with systemic therapy; rejection events were heterogeneous in timing (3 weeks-14 months) and largely responsive to pulse-dose corticosteroids. IrAEs occurred in 27.3% of ICI patients, with grade ≥2 events in 12.1%, and no treatment-related deaths. In the cutaneous squamous cell carcinoma (cSCC) subgroup (n=33), ICI therapy produced an ORR of 47.4% and CBR of 63.2%, with trends toward improved survival relative to controls. Conclusions: ICIs produced clinically meaningful antitumor activity in KTRs, particularly in cSCC, with a manageable rate of allograft rejection under carefully tailored immunosuppression. Despite higher historical concerns, irreversible graft loss was uncommon. These findings support the feasibility of ICI therapy in selected transplant recipients and highlight the importance of immunosuppression strategy in balancing antitumor efficacy and graft safety. Prospective, biomarker-integrated studies are needed to define optimal immunosuppression during PD-1 blockade in this high-risk population. Citation Format: Ali Rezazadeh Roudkoli, Elena Barbir, Shahin Kavousi, Mohamed A. Aboelatta, Claudia-Denise Haivas, Byron H. Smith, Aleksandra Kukla, Arkadiusz Z. Dudek. Immune checkpoint inhibitor therapy in kidney transplant recipients: Real-world outcomes of antitumor activity and graft rejection risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6544.

ABSTRACT Predicting delayed graft function (DGF) relies on donor, recipient, and perioperative factors. Despite the growing recognition that DGF duration strongly influences patient outcomes, no models currently address or predict its impact—highlighting an important gap in current research and clinical practice. This study aimed to develop an ensemble‐based machine learning model using perioperative data to predict DGF occurrence and duration. The gradient‐boosted decision trees model was trained and validated on 2725 patients, with k‐fold cross‐validation in an external cohort of 284 patients. Model performance was evaluated based on accuracy, ROC‐AUC, and other metrics using R and Python libraries. The binary DGF prediction model achieved a ROC‐AUC of 0.77, while the DGF duration classification model had an accuracy of 79.2%. DGF duration AUC values by time interval were 0.76 for 0–1 weeks, 0.81 for >1–2 weeks, 0.80 for >2–3 weeks, and 0.87 for >3 weeks; the overall macro‐averaged AUC was 0.81. The mean Brier score for multi‐class predictions was 0.14. External validation showed a 78% accuracy for DGF duration prediction. Acute kidney injury (AKI) and donor donation after circulatory death (DCD) status were key DGF predictors. The use of gradient‐boosted decision trees (GBDT) improves the prediction of both the likelihood and duration of DGF, addressing a current gap in kidney transplant patient care. By facilitating personalized transplant care, this model supports more effective perioperative planning and timely interventions, which may contribute to better patient outcomes.

Abstract Frailty predicts adverse outcomes in multiple myeloma (MM), yet an objective frailty biomarker is lacking. Circulating senescence-associated secretory phenotype (SASP) factors correlate with frailty and adverse outcomes in chronic diseases, but their relevance in MM is unclear. In this study, we investigated the relationship between 36 plasma SASP factors, frailty, and clinical outcomes in: (1) a historical cohort using stored specimens from 59 patients with newly diagnosed MM, and (2) a prospective cohort of 36 patients initiating new MM treatment. Several SASP factors were significantly associated with frailty after adjusting for age, sex, and body mass index; GDF-15, TNF-RI, IL-6, and IL-8 showed positive correlations with both cumulative-deficit based and physical frailty indices. Additionally, significant age-adjusted associations were observed between SASP factors and treatment outcomes, including overall survival (OS), high-grade toxicity, and healthcare utilization. We developed a 5-factor SASP model that demonstrated superior predictive performance for OS compared to chronological age, R-ISS stage, and clinical frailty, and TNF-RI alone (5-year OS AUC: 0.90). These findings highlight the association between senescence biomarkers and frailty and OS, and support further investigation of SASP factors as objective frailty biomarkers in MM.

ABSTRACT Background In pediatric kidney transplant recipients, native nephrectomy is sometimes performed to manage conditions such as polyuria, nephrotic syndrome, and recurrent infections. To minimize surgical morbidity, our center adopted a technique from the adult transplant program involving ligation of native ureters at the time of transplantation as an alternative to native nephrectomy in selected patients. Methods This retrospective study describes our center's experience with pediatric patients who underwent ureteral ligation at transplantation between December 2008 and December 2022. Patient selection was based on clinical judgment rather than predefined criteria. Results Sixteen patients underwent ureteral ligation, with polyuria (12/16) and proteinuria associated with focal segmental glomerulosclerosis (4/16) as the primary indications. Ligation was unilateral in 5 patients and bilateral in 11. The average follow‐up was 5.7 years. No operative complications directly attributable to ureteral ligation were observed, including native kidney pyelonephritis or need for reoperation. Although post‐transplant imaging often revealed hydronephrosis of the native kidneys, it had no clinical consequences. Late postoperative hypertension occurred in 31% of the ligation group compared to 47% of controls without ligation, while new‐onset hypertension was more common in the ligation group (18.8% vs. 5.1%). Pain scores postoperatively were comparable between groups. Conclusions This technical report suggests that native ureteral ligation at pediatric kidney transplantation is feasible in selected patients but represents an empirical, non‐standard‐of‐care approach. Prospective comparative studies are needed to refine patient selection and assess long‐term outcomes.

Key Points In a cohort of children, 79% of families with kidney cysts had a monogenic diagnosis. Resolved cases were more likely to have a family history of kidney cysts and unresolved cases more often had unilateral cysts. Broad genetic testing revealed genetic diversity and informed prognosis and clinical management in childhood kidney cysts. Background Pediatric kidney cysts may indicate an underlying genetic disorder, yet the full spectrum of causes remains incompletely defined. With advances in genetic testing enabling broader evaluation, this study assessed the diagnostic utility of comprehensive genetic testing in a broad pediatric cohort with kidney cysts and characterized the underlying etiological diversity. Methods This observational cohort study included patients younger than 18 years enrolled between January 2020 and June 2024 at a single tertiary center. Genetic testing used targeted multigene or custom curated exome/genome sequencing panels, with segregation analysis when available. Eligible participants had at least two cysts without family history, one cyst with positive family history, or enlarged echogenic kidneys on prenatal ultrasound; those with congenital anomalies of the kidney and urinary tract associated with cysts were excluded. Clinical presentation was categorized as symptomatic, incidental, prenatal, or family screening. Primary outcomes were diagnostic yield and distribution of pathogenic variants. Results Among 109 patients (median age 7.6 years, 53% female), genetic testing identified a definitive diagnosis in 81 of 100 tested patients (81%) from 72 families (79%; 14 disorders). PKD1 variants were most common (45%), while PKD2 accounted for 7%. Other causes included HNF1B or 17q12 deletions (13%), minor autosomal dominant polycystic kidney disease genes (11%; GANAB, NEK8, IFT140 ), monoallelic PKHD1 (3%), and biallelic PKHD1 (8%), while syndromic ciliopathy genes accounted for 5%. A positive family history of cystic kidney disease was more common among patients with a genetic diagnosis (54% versus 11%; P = 0.008). Patients without an identified genetic diagnosis more often had unilateral cysts (26% versus 4%; P = 0.53). Diagnosis by clinical symptoms was the most genetically diverse category. Conclusions Comprehensive genetic testing in pediatric kidney cysts achieved high diagnostic yield in a selected cohort and identified diverse causes beyond major autosomal dominant polycystic kidney disease/autosomal recessive polycystic kidney disease genes, supporting early evaluation to improve diagnostic accuracy, inform prognosis, and guide management, even in the absence of family history.