ABO Incompatible Kidney Transplantation Without B-cell Depletion is Associated With Increased Early Acute Rejection: A Single-Center Australian Experience.

We performed a single-center retrospective cohort study of 66 consecutive ABO incompatible kidney transplants (ABOiKT) performed without B-cell depleting therapy. Outcomes were compared to an earlier era performed with rituximab (n = 18) and a contemporaneous cohort of ABO compatible live donor transplants (ABOcKT). Acute rejection within 3 months of transplant was significantly more common after rituximab-free ABOiKT compared to ABOiKT with rituximab (OR 8.8, p = 0.04) and ABOcKT (OR 2.9, p = 0.005) in adjusted analyses. Six recipients of rituximab-free ABOiKT experienced refractory antibody mediated rejection requiring splenectomy, and a further two incurred early graft loss with no such episodes amongst ABOiKT with rituximab or ABOcKT cohorts. Patient and graft survival were similar between groups over a median follow-up of 3.1 years. This observational evidence lends strong support to the continued inclusion of rituximab in desensitization protocols for ABOiKT.

The Utility of Pre- and Post-Transplant Oral Glucose Tolerance Tests: Identifying Kidney Transplant Recipients With or at Risk of New Onset Diabetes After Transplant.

Background: New onset diabetes after transplant (NODAT) is common in kidney transplant recipients (KTRs). Identifying patients at risk prior to transplant may enable strategies to mitigate NODAT, with a pre-transplant oral glucose tolerance test (OGTT) suggested by the KDIGO 2020 Guidelines for this purpose. Methods: We investigated the utility of pre- and post-transplant OGTTs to stratify risk and diagnose NODAT in a retrospective, single-centre cohort study of all non-diabetic KTRs transplanted between 2003 and 2018. Results: We identified 597 KTRs who performed a pre-transplant OGTT, of which 441 had their post-transplant glycaemic status determined by a clinical diagnosis of NODAT or OGTT. Pre-transplant dysglycaemia was identified in 28% of KTRs and was associated with increasing age (p < 0.001), BMI (p = 0.03), and peritoneal dialysis (p < 0.001). Post-transplant dysglycaemia was common with NODAT and impaired glucose tolerance (IGT) occurring in 143 (32%) and 121 (27%) patients, respectively. Pre-transplant IGT was strongly associated with NODAT development (OR 3.8, p < 0.001). Conclusion: A pre-transplant OGTT identified candidates at increased risk of post-transplant dysglycaemia and NODAT, as diagnosed by an OGTT. Robust prospective trials are needed to determine whether various interventions can reduce post-transplant risk for candidates with an abnormal pre-transplant OGTT.

Evolution of Glycemic Control and Variability After Kidney Transplant.

BACKGROUND: The evolution of glycemic changes after kidney transplantation has not been described. We prospectively examined glycemic control and variability over time from transplantation using continuous glucose monitoring (CGM). METHOD: Continuous glucose monitoring devices were fitted for 3 to 5 days at time of transplant, month 3, and month 6 posttransplant. Indices of glucose control (mean glucose, percent time in hyperglycemic range, and Glycemic Risk Assessment Diabetes Equation score) and variability were calculated. An oral glucose tolerance test was performed at month 3. RESULTS: Twenty-eight patients (mean age, 45 ± 15 years) were enrolled, 64% male, 75% white, receiving tacrolimus, mycophenolate, and prednisolone (93%). Of 24 patients with complete CGM data at month 0, 3 had prior diabetes and 6 (25%) developed new-onset diabetes after transplant (NODAT). Hyperglycemia (>11.1 mM) was evident in 79% during days 0 to 3 posttransplant, particularly between 1 and 9 PM. Compared with recipients without diabetes, recipients with prior diabetes had higher mean glucose (7.8 mM; 95% confidence interval [CI], 7.4-8.2 vs 9.9 mM; 95% CI, 8.9-10.8; P < 0.001), Glycemic Risk Assessment Diabetes Equation (GRADE) score (4.5; 95% CI, 3.7-5.4 vs 7.8; 95% CI, 5.6-10.4; P = 0.003) and percent time with hyperglycemia. Glycemic control was also inferior in those that subsequently developed NODAT (mean glucose, 8.8 mM; 95% CI, 8.2-9.4; P = 0.004, GRADE: 6.2, 95% CI, 5.2-7.7; P = 0.04 vs no diabetes). Glucose variability was increased in patients with prior diabetes (glucose standard deviation, 1.99; 95% CI, 1.72-2.27 vs 2.97; 95% CI, 2.27-3.67; P = 0.006) but not in NODAT. All measures of glucose control and variability significantly improved over time after transplantation (P < 0.001). CONCLUSIONS: Dysglycemia is very common after renal transplantation, exhibiting a distinct diurnal pattern of afternoon and evening hyperglycemia. The magnitude of hyperglycemia and variability are maximal in recipients with preexisting diabetes and significant in those who go on to develop NODAT. Dysglycemia improves with time.

Effects of acute intermittent hypercapnic hypoxia on insulin sensitivity in piglets using euglycemic clamp.

Continuous hypoxia is associated with insulin resistance, altered glucose metabolism, and increased sympathetic nervous activity. This study examined the effect of 2 successive exposures to intermittent hypercapnic hypoxia (IHH) on glucose metabolism and insulin sensitivity in neonatal piglets. Piglets were assigned to 2 groups. One group was exposed to 2 x 90 minutes of hypercapnic hypoxia (8% O(2), 7% CO(2)), intermittently in 6-minute cycles alternating with 6-minute air. The second group was given 2 x 90 minutes of air. Blood pressure, blood gases, glucose, insulin, and lactate were measured during exposures. Insulin sensitivity was assessed using the euglycemic clamp before and after the exposures. Piglets in the IHH group exhibited reduced PO(2) (from 111.4 +/- 14.2 to 43.3 +/- 21.7), increased PCO(2) (from 33.6 +/- 1.9 to 49.4 +/- 5.4), and lactic acidosis. Compared with air, IHH decreased blood glucose (control [CON] 4.44 +/- 0.72 mmol/L vs IHH 2.67 +/- 1.2 mmol/L, P = .007), insulin (CON 12.5 +/- 7.4 microU/mL vs IHH 3.6 +/- 3.1 microU/mL, P = .03), and mean arterial pressure (CON 143.0 +/- 7.9 mm Hg vs IHH 112.5 +/- 9.5 mm Hg, P < .001) over 90 minutes. Maximal insulin-stimulated glucose disposal was not different between the groups on either day, nor was endogenous glucose production. Overall, exposure to hypoxia in an intermittent pattern reduced sympathetic drive as indicated by blood pressure and did not alter insulin sensitivity, resulting in decreases in blood glucose and insulin. We speculate that an intermittent hypoxic stimulus results in failure of initiation of compensatory responses to increased energy requirements that would usually be observed during sustained exposure to hypoxia.