Recipient-derived neoangiogenesis of arterioles and lymphatics in quilty lesions of cardiac allografts.

BACKGROUND: The contribution of extracardiac cells to tissue turnover in heart allografts has recently been demonstrated. Complex subendocardial infiltrates, known as Quilty lesions, are frequently observed in cardiac allografts. The origin of the different cellular components of Quilty lesions is not known. METHODS: Different constituents of these lymphonodular infiltrates were analyzed with regard to donor or recipient derivation. Laser-assisted microdissection with subsequent short tandem repeat polymerase chain reaction (PCR)-based "genetic fingerprinting" was employed. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for confirmation in cases of gender-mismatched transplantation. Expression of angiogenic factors (FGF-2, PDGF-alpha, PDGF-alpha-receptor, and VEGF-alpha) was analyzed by quantitative real-time reverse-transcription PCR and immunohistochemistry. RESULTS: The inflammatory, nonvascular component of Quilty lesions was completely recipient-derived. Blood vessels were of mixed origin. Different compartments of blood vessels displayed different rates of recipient derivation (endothelium up to 50%, smooth muscle cells up to 15%). Lymphatic vessels were mainly recipient-derived. Of the angiogenic molecules, VEGF-alpha expression was significantly increased in the adjacent myocardium, compared to controls and the Quilty lesions themselves. CONCLUSIONS: The inflammatory compartment of Quilty lesions is of recipient origin and shows chimeric neoangiogenesis of blood and lymphatic vessels. VEGF-alpha produced in the adjacent myocardium appears to stimulate the chimeric neoangiogenesis.

The renal arterial resistance index and renal allograft survival.

BACKGROUND: Most renal transplants fail because of chronic allograft nephropathy or because the recipient dies, but no reliable factor predicting long-term outcome has been identified. We tested whether a renal arterial resistance index of less than 80 was predictive of long-term allograft survival. METHODS: The renal segmental arterial resistance index (the percentage reduction of the end-diastolic flow as compared with the systolic flow) was measured by Doppler ultrasonography in 601 patients at least three months after transplantation between August 1997 and November 1998. All patients were followed for three or more years. The combined end point was a decrease of 50 percent or more in the creatinine clearance rate, allograft failure (indicated by the need for dialysis), or death. RESULTS: A total of 122 patients (20 percent) had a resistance index of 80 or higher. Eighty-four of these patients (69 percent) had a decrease of 50 percent or more in creatinine clearance, as compared with 56 of the 479 patients with a resistance index of less than 80 (12 percent); 57 patients with a higher resistance index (47 percent) required dialysis, as compared with 43 patients with a lower resistance index (9 percent); and 36 patients with a higher resistance index (30 percent) died, as compared with 33 patients with a lower resistance index (7 percent) (P<0.001 for all comparisons). A total of 107 patients with a higher resistance index (88 percent) reached the combined end point, as compared with 83 of those with a lower resistance index (17 percent, P<0.001). The multivariate relative risk of graft loss among patients with a higher resistance index was 9.1 (95 percent confidence interval, 6.6 to 12.7). Proteinuria (protein excretion, 1 g per day or more), symptomatic cytomegalovirus infection, and a creatinine clearance rate of less than 30 ml per minute per 1.73 m2 of body-surface area after transplantation also increased the risk. CONCLUSIONS: A renal arterial resistance index of 80 or higher measured at least three months after transplantation is associated with poor subsequent allograft performance and death.