M e d i c a l E d u c a t i o n CASE PRESENTATION A 95-year-old woman with a past medical history of hypertension and chronic kidney disease presented with abdominal bloating and poor appetite of one week's duration. Physical examination showed conjunctival pallor and mild generalised abdominal tenderness without signs of peritonism. Blood tests revealed anaemia of 6.8 g/dL from a baseline level of 11.5 g/dL. Liver function tests and amylase were within normal limits. Initial chest and abdominal radiographs were unremarkable. Contrast-enhanced computed tomography (CT) of the abdomen and pelvis (Fig. 1) was subsequently performed. What do the images show? What is the diagnosis? CMEArticle
BACKGROUND: Kidney transplantation is the treatment of choice for most patients with end-stage renal disease and existing data suggest that post transplant graft function is a predictor of kidney graft failure. METHODS: Exome sequencing of DNA from kidney graft recipients and their donors was used to determine recipient and donor mismatches at the amino acid level. The number of mismatches that are more likely to induce an immune response in the recipient was computationally estimated and designated the allogenomics mismatch score. The relationship between the allogenomics score and post transplant kidney allograft function was examined using linear regression. RESULTS: A significant inverse correlation between the allogenomics mismatch score and kidney graft function at 36 months post transplantation was observed in a discovery cohort of kidney recipient-donor pairs (r2>=0.57, P<0.05, the score vs. level of serum creatinine or estimated glomerular filtration rate). This relationship was confirmed in an independent validation cohort of kidney recipient-donor pairs. We observed that the strength of the correlation increased with time post-transplantation. This inverse correlation remained after excluding HLA loci from the calculation of the score. Exome sequencing yielded allogenomics scores with stronger correlations with graft function than simulations of genotyping assays which measure common polymorphisms only. CONCLUSIONS: The allogenomics mismatch score, derived by exome sequencing of recipient-donor pairs, facilitates quantification of histoincompatibility between the organ donor and recipient impacting long-term post transplant graft function. The allogenomics mismatch score, by serving as a prognostic biomarker, may help identify patients at risk for graft failure.
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