Kukla, Aleksandra

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 Introduction: Surveillance biopsies after kidney transplantation provide an opportunity to assess early renal disease processes, including diabetic nephropathy, before clinical manifestation. This study aimed to identify proteomic alterations in renal allografts at 5 years post-transplant (5yrPT) and their associations with histologic features in diabetic/obese (DM/OB) versus non-diabetic/non-obese (nDM/nOB) recipients. Methods: We studied protocol biopsies from 17 DM/OB and 14 nDM/nOB kidney transplant recipients at Mayo Clinic (2000–2012). Laser capture microdissection followed by mass spectrometry was used for proteomic profiling. Histologic assessment included Banff and Tervaert scoring and morphometric analysis. Statistical comparisons were performed using ANOVA with Tukey post-hoc testing. Results: DM/OB recipients demonstrated greater histologic and metabolic injury at 5yrPT. Proteomic analysis identified 101 glomerular and 86 non-glomerular proteins differentially expressed between groups. Significant alterations were observed in proteins associated with mitochondrial dysfunction, including VDAC1 (fold change [FC] 2.6, p = 0.03), NDUFB9 (FC 0.15, p = 0.009), and NDUFA9 (FC 1.72, p = 0.01). Extracellular matrix remodeling proteins COL6A1, COL6A2, and COL6A3 were upregulated (FC 1.6–1.8, p < 0.05). Immune and inflammatory markers C9 (FC 1.6, p < 0.03) and TGFBI (FC 1.7, p < 0.001), as well as oxidative stress–related CLU, were increased. GGACT showed the greatest decrease (FC 0.30, p < 0.001), implicating altered energy metabolism. Conclusion: Distinct proteomic signatures at 5yrPT in DM/OB recipients highlight early mitochondrial, metabolic, immune, and extracellular matrix pathways involved in diabetic kidney disease. These changes precede clinical disease and identify candidate biomarkers and therapeutic targets to improve graft longevity.

Background. Pancreas transplantation (PT), historically limited to patients with type 1 diabetes (T1D), is currently performed successfully in selected patients with type 2 diabetes (T2D). However, contemporary practice patterns and eligibility criteria for PT in T2D remain incompletely characterized. Methods. The International Pancreas and Islet Transplant Association Pancreas Transplant Interest Group developed an electronic survey to assess center-level approaches to patient phenotyping, candidacy, and peri- and posttransplant management for PT in patients with T2D. The survey was distributed to international transplant professionals during an International Pancreas and Islet Transplant Association Pre-Congress meeting on June 15, 2025. Results. Thirty-seven participants completed the survey. Most respondents’ programs offer PT for T2D only when a kidney transplant is also indicated. Fewer respondents’ programs also offer PT alone (10%), evaluate T2D candidates on a case-by-case basis (3%), or do not offer PT to patients with T2D (10%). Total daily insulin requirement and body mass index (BMI) were the most selected factors in determining eligibility. Considerable variability existed in metabolic thresholds: 62% of programs reported no C-peptide cutoff, whereas nearly half required a BMI of <30 kg/m 2 for C-peptide-positive candidates. Respondents frequently recommend weight-optimization strategies, including lifestyle modification, glucagon-like peptide-1 receptor agonists, and bariatric surgery for candidates exceeding acceptable BMI thresholds. Surgical technique, induction, and maintenance immunosuppression and early posttransplant glycemic management were largely uniform between T2D and T1D recipients. Conclusions. International practice reflects broad but heterogeneous adoption of PT for T2D, with most participants restricting its use to candidates requiring kidney transplantation and emphasizing integrated clinical phenotyping approaches.

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.

Background Uncontrolled hypertension is common in chronic kidney disease (CKD) patients. Electro-hydraulic acoustic therapy (eHAT) is a non-invasive treatment that may lower blood pressure (BP), but its safety and efficacy in CKD remain unclear. This study aimed to evaluate eHAT's feasibility and safety in this population. Methods In this single-arm, prospective, single-center proof-of-concept study, CKD patients received six eHAT treatments over three weeks. BP was assessed in-office (attended and unattended) at baseline and at 4-, 12-, 24-, and 48-weeks post-treatment. Ambulatory BP monitoring (ABPM) was performed at baseline, 12, and 48 weeks. The primary endpoint was change in systolic office BP (OBP) from baseline to 12 weeks. Secondary endpoints included additional BP measurements, kidney function, and safety. Results Fifteen patients completed all follow-ups. At 12 weeks, mean systolic OBP decreased by 9.73 mmHg (SD 14.77; p = 0.0032) and remained significantly lower at 24 weeks (−7.67 mmHg; p = 0.0335) and 48 weeks (−19.40 mmHg; p &lt; 0.0001). Diastolic OBP reductions were significant at 12 ( p = 0.0413) and 48 weeks ( p = 0.0022). By 12 weeks, 26% of participants reduced the number or dose of antihypertensive medications. Kidney function remained stable throughout. No safety signals were detected. Conclusion Our study highlights the feasibility and tolerability of eHAT in patients with CKD and HTN. Nonetheless, due to the small sample size and lack of a control group, these findings should be considered preliminary.

Obesity is increasingly prevalent among living kidney donor candidates, presenting complex clinical, ethical, and logistical challenges. Although obesity is linked to increased post-donation hypertension, diabetes, proteinuria, and chronic kidney disease, the overall absolute risks are modest and may differ depending on metabolic health and patterns of fat distribution. Current reliance on body mass index alone fails to capture the full spectrum of obesity-related risks, leading to inconsistent donor selection practices and potential inequities. This review examines the pathophysiological mechanisms of obesity-related kidney injury and available evidence on comorbidities and postdonation outcomes related to obesity. We discuss tools for better risk stratification, such as imaging-based adiposity assessment and personalized weight management strategies, and note that some risks may remain after weight loss. Barriers such as rigid body mass index cutoffs, limited access to treatment, and lack of long-term follow-up exacerbate disparities in access to donation. We argue for a shift toward individualized, risk-based evaluation supported by multidisciplinary care. We underscore the importance of donor counseling and advocate for a comprehensive, rather than paternalistic approach to living kidney donor selection. Advancing safe and equitable living donation in the context of rising obesity rates will necessitate revised guidelines, improved access to treatment, and an ongoing commitment to donor well-being.

Background. Living kidney donation (KD) evaluation particularly focuses on glomerular filtration rate (GFR). Assessing GFR in living kidney donors can be done by estimation (eGFR) or measurement (mGFR). This study aims to evaluate the impact of eGFR equations, focusing on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation for donor eligibility screening and the reclassification of donors excluded by eGFR criteria to mGFR assessments. Methods. Retrospective, single-center observational study of 2512 kidney donors evaluated between 2011 and 2023, at the Mayo Clinic. We performed analyses and comparisons of 4 eGFR formulae and 2 mGFR methods in terms of performance, eligibility criteria according to Kidney Disease: Improving Global Outcomes guidelines/age-adjusted criteria, eligibility reclassification, and subgroup analyses. Results. The CKD-EPI 2021 resulted in a higher percentage of patients being eligible for KD (81.4%) and achieved the highest P10 (32%–34%) and P30 (87%–88%) across all mGFR methods. When patients were deemed eligible for donation by any eGFR formula, 95% retained this status on reassessment with mGFR. Conversely, when an eGFR formula classified a patient as ineligible, this was revised to be eligible in about 90% of cases on reassessment with mGFR, with a higher reclassification rate observed when the IoCl was used instead of CrCl. Conclusions. The CKD-EPI 2021 performs best for screening potential KD. If a KD is deemed ineligible by CKD-EPI 2021, there is a high likelihood that they will be reclassified as eligible when assessed with mGFR. This study strongly supports using mGFR in donor evaluations, especially when the eGFR does not meet the criteria to ensure equity of access to being a living donor.