Association of Pre-Existing Type 2 Diabetes on Kidney Transplant Outcomes and Factors Correlating With Survival: A Single-Center Analysis.

INTRODUCTION: Kidney transplantation (KT) is the treatment of choice for end-stage renal disease. Diabetes mellitus is the most common indication for KT, with most recipients having type 2 diabetes mellitus (T2DM). Previous studies have shown inferior patient survival in T2DM KT recipients. This single-center study aimed to understand the individual factors associated with negative long-term outcomes. METHODS: This is a single-center retrospective analysis of adult KT recipients, with and without T2DM from 2012 to 2017 with a follow-up through December 2022. Primary Outcomes were graft loss and patient survival. Univariate, Multivariate Cox regression, and Kaplan-Meier analyses were used to assess KT outcomes. RESULTS: We analyzed 1185 patients, 288 (24.3%) with T2DM. T2DM patients tended to be older, 56.6 ± 9.8 versus 47.1 ± 13.7 y. (P < 0.01), male (66.3% versus 58.2% P < 0.001) had a higher body mass index, 31.3 ± 5.4 versus 27.4 ± 5.7 P < 0.01) and less likely to get a living donor transplant (46.5% versus 58.4%, P < 0.01). T2DM patients after KT had a 50% higher risk for graft loss (hazard ratio 1.509, 95% CI 1.15-1.95, P < 0.001) and a 106% higher risk of death (hazard ratio 2.06 (95% CI 1.48-2.87, P < 0.0001). Among the T2DM patients, the most common cause of death was infection (39.9%). The average HbA1c at 1 y after transplant was 7.8%. CONCLUSIONS: The present study shows that T2DM is strongly associated with an increased risk of graft loss and death after KT, particularly in older recipients of deceased donor transplants with longer cold ischemia time that experience delayed graft function. This underscores the importance of avoiding delayed graft function in older, type 2 diabetic kidney transplant recipients and prioritizing living donors.

Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice.

Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Benign tumors might exhibit de novo expression of immunogens, targetable by immunotherapy. As tumors may rely on ganglioside D3 (GD3) expression for mTORC1 activation and growth, we compared GD3 expression in tissues from patients with TSC and controls. GD3 was overexpressed in affected tissues from patients with TSC and also in aging Tsc2+/- mice. As GD3 overexpression was not accompanied by marked natural immune responses to the target molecule, we performed preclinical studies with GD3 chimeric antigen receptor (CAR) T cells. Polyfunctional CAR T cells were cytotoxic toward GD3-overexpressing targets. In mice challenged with Tsc2-/- tumor cells, CAR T cells substantially and durably reduced the tumor burden, correlating with increased T cell infiltration. We also treated aged Tsc2+/- heterozygous (>60 weeks) mice that carry spontaneous Tsc2-/- tumors with GD3 CAR or untransduced T cells and evaluated them at endpoint. Following CAR T cell treatment, the majority of mice were tumor free while all control animals carried tumors. The outcomes demonstrate a strong treatment effect and suggest that targeting GD3 can be successful in TSC.