An Initial Analysis of the Baseline Levels of Dd-cfDNA After Pancreas Transplantation: A Prospective Study From High-volume Centers in the United States.

Pancreas transplantation offers patients with diabetes an opportunity for glucose homeostasis. Current blood tests to surveil for rejection have poor sensitivity and specificity for identifying rejection, and pancreas biopsies are challenging and associated with morbidity and graft loss. Donor-derived cell-free DNA (dd-cfDNA) is shed from transplanted organs and detectable in peripheral blood. Thus, a potential dd-cfDNA blood test assessing rejection would be clinically advantageous. Methods: One hundred eighty-one dd-cfDNA samples (n) were collected from 77 patients (N) up to 132 mo posttransplant. Results: The median dd-cfDNA level among all subjects was 0.28% (0.13%, 0.71%). In simultaneous pancreas-kidney (SPK) transplant recipients, the median dd-cfDNA level was 0.29% (0.13%, 0.71%), and it was 0.23% (0.08%, 0.71%) in pancreas transplant alone (PTA) recipients. When isolating for when without infection or rejection, the median dd-cfDNA level was 0.28% (0.13%, 0.64%) for SPK and 0.20% (0.00%, 0.32%) for PTA. Both transplant types approached 1.0% ≤1 mo posttransplant followed by a decrease in median dd-cfDNA. During episodes of rejection or infection, median dd-cfDNA levels were greater among all transplant types. Conclusions: The mean dd-cfDNA level for all pancreas transplant recipients is <1.0%, consistent with the published kidney transplant rejection threshold (>1.0%), regardless of SPK or PTA. Early posttransplant dd-cfDNA levels are transiently higher than later measurements. Dd-cfDNA elevation also correlates with rejection and infection and thus is a promising biomarker for surveilling pancreas transplant dysfunction.

Natural Antibodies Are Associated With Rejection and Long-term Renal Allograft Loss in a Multicenter International Cohort.

BACKGROUND: Potentially harmful nonhuman leukocyte antigen antibodies have been identified in renal transplantation, including natural immunoglobulin G antibodies (Nabs) reactive to varied antigenic structures, including apoptotic cells. METHODS: In this retrospective, multicenter study, we assessed Nabs by reactivity to apoptotic cells in sera collected from 980 kidney transplant recipients across 4 centers to determine their association with graft outcomes. RESULTS: Elevated pretransplant Nabs were associated with graft loss (hazard ratio [HR] 2.71; 95% confidence interval [CI], 1.15-6.39; P = 0.0232), the composite endpoint of graft loss or severe graft dysfunction (HR 2.40; 95% CI, 1.13-5.10; P = 0.0232), and T cell-mediated rejection (odds ratio [OR] 1.77; 95% CI, 1.07-3.02; P = 0.0310). High pretransplant Nabs together with donor-specific antibodies (DSAs) were associated with increased risk of composite outcomes (HR 6.31; 95% CI, 1.81-22.0; P = 0.0039). In patients with high pretransplant Nabs, the subsequent development of posttransplant Nabs was associated with both T cell-mediated rejection (OR 3.64; 95% CI, 1.61-8.36; P = 0.0021) and mixed rejection (OR 3.10; 95% CI, 1.02-9.75; P = 0.0473). Finally, elevated pre- and posttransplant Nabs combined with DSAs were associated with increased risk of composite outcomes (HR 3.97; 95% CI, 1.51-10.43; P = 0.0052) and T cell-mediated rejection (OR 7.28; 95% CI, 2.16-25.96; P = 0.0016). CONCLUSIONS: The presence of pre- and posttransplant Nabs, together with DSAs, was associated with increased risk of poor graft outcomes and rejection after renal transplantation.

Donor-derived Cell-free DNA in Infections in Kidney Transplant Recipients: Case Series.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive plasma biomarker to evaluate for transplant allograft rejection. The relationship between infectious complications in kidney allografts and dd-cfDNA has received cursory attention in prior publications. METHODS: Retrospective review of all renal transplant recipients who underwent dd-cfDNA testing between November 2017 and August 2019. RESULTS: We report on 7 cases in whom infections affecting the transplanted kidney were associated with elevation in dd-cfDNA without concomitant rejection or elevation in serum creatinine. Five patients had BK viremia, and 2 patients had urinary tract infection associated with elevated dd-cfDNA levels. CONCLUSIONS: These observations suggest that elevations in dd-cfDNA are not specific to kidney allograft rejection and can be associated with infections affecting the transplanted kidney. This biomarker may be valuable in evaluating infectious complications of kidney allografts.

Successful pancreas transplantation alone is associated with excellent self-identified health score and glucose control: A retrospective study from a high-volume center in the United States.

BACKGROUND: The benefits of pancreas transplantation are often difficult to measure. Here, we sought to determine the difference in quality of life for diabetic patients with and without a functional pancreas transplant alone (PTA). METHODS: Pancreas transplant alone cases from 1993 to 2015 were considered. An IRB-approved survey inclusive of 15 questions spanning four domains was employed. Chi-square, Fisher's exact, and the T test were used where appropriate. RESULTS: A total of 137 PTAs were performed during the study period. Of those reached (n = 32), 94% responded to the survey. Self-reported health scores were better (2.1 vs 3.0) for those with functioning pancreata (n = 18) vs those with a non-functional pancreas (n = 14), respectively (P = .036). Those with a functional pancreas had a HgbA1c of 5.3, vs 7.7 for a non-functional pancreas (P = .016). Significant hypoglycemia was reported in two of 18 with a functional transplant vs nine of 14 patients with a failed transplant (P = .003). Daily frustration with blood sugar affecting quality of life was significantly higher for patients with non-functional pancreas grafts (P < .001). CONCLUSIONS: Pancreas transplantation alone is associated with better glucose control than insulin. In addition, recipients of functional PTAs have improved quality of life and better overall health scores than those with failed grafts.