RESUMO
RATIONALE & OBJECTIVE: Donor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 862 deceased donors for 1,137 kidney recipients at 13 centers. EXPOSURES: We measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI. OUTCOMES: The primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year. ANALYTICAL APPROACH: Multivariable Fine-Gray models with death as a competing risk. RESULTS: Mean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA. LIMITATIONS: BPAR was ascertained through for-cause biopsies, not surveillance biopsies. CONCLUSIONS: In a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.
Assuntos
Injúria Renal Aguda , Transplante de Rim , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Lipocalina-2 , Interleucina-18 , Estudos Prospectivos , Injúria Renal Aguda/patologia , Doadores de Tecidos , Biomarcadores , Rejeição de Enxerto/epidemiologia , Sobrevivência de EnxertoRESUMO
OBJECTIVE: To evaluate the effect of a high-fat meal on endothelial function in adolescents with type 1 diabetes mellitus (T1D). STUDY DESIGN: Twenty-three children with T1D, aged 12 to 18 years, and age- and sex-matched healthy control subjects were assessed for baseline macronutrient intake, and endothelial function was measured both fasting and after a standardized fast-food, high-fat breakfast. RESULTS: Endothelial function, assessed noninvasively by peripheral arterial tonometry, was impaired in the T1D group in the fasting state as compared with control subjects (T1D 1.78 +/- 0.4, control subjects 2.06 +/- 0.4, P = .02), and worsened postprandially in both groups (T1D 1.45 +/- 0.3, control subjects 1.71 +/- 0.3, P = .01). Both groups demonstrated significantly elevated triglyceride levels 3.5 hours after ingestion of the high-fat meal (T1D 114.8 +/- 42.8 and control subjects 126.7 +/- 54.9 mg/dL). Nutrient intake in both groups showed higher than recommended intakes of total fat, saturated fat, and cholesterol. CONCLUSIONS: Patients with T1D exhibited worse endothelial function both before and after a high-fat breakfast than their peers. This suggests that patients with T1D are at greater risk of vascular impairment after a high-fat meal, the cumulative effect of which may contribute to the higher atherosclerotic burden observed in T1D.