Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation.

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, is a potential therapeutic target. MIF is markedly different from other cytokines because it is constitutively expressed, stored in the cytoplasm, and present in the circulation of healthy subjects. Thus, the concept of targeting MIF for therapeutic intervention is challenging because of the need to neutralize a ubiquitous protein. In this article, we report that MIF occurs in two redox-dependent conformational isoforms. We show that one of the two isoforms of MIF, that is, oxidized MIF (oxMIF), is specifically recognized by three mAbs directed against MIF. Surprisingly, oxMIF is selectively expressed in the plasma and on the cell surface of immune cells of patients with different inflammatory diseases. In patients with acute infections or chronic inflammation, oxMIF expression correlated with inflammatory flare-ups. In addition, anti-oxMIF mAbs alleviated disease severity in mouse models of acute and chronic enterocolitis and improved, in synergy with glucocorticoids, renal function in a rat model of crescentic glomerulonephritis. We conclude that oxMIF represents the disease-related isoform of MIF; oxMIF is therefore a new diagnostic marker for inflammation and a relevant target for anti-inflammatory therapy.

Recently much interest has been focused on the role of immunoregulatory cytokines such as interleukin 1 (IL 1) and interleukin 2 (IL 2) during the pathogenesis of immunological as well as inflammatory diseases. Therefore peripheral blood mononuclear cells (PBMC) of eight patients undergoing hemodialysis (HD) were tested for IL 1 and IL 2 production. Before starting HD, cytokine production by PBMC in culture was not altered in comparison to normal healthy controls, however, a significant increase of IL 1 and IL 2 production was observed within the first HD hour which lasted throughout the end of HD. Moreover direct effects of cellulose membranes on PBMC cytokine production as well as serum IL 1 levels have been investigated. Serum IL 1 levels were already elevated before onset of HD and increased further during HD. The discrepancy between PBMC IL 1 production and serum IL 1 levels may be due to the diminished excretion in patients with end-stage renal disease. Since addition of dialysis membrane particles enhanced monocytes to produce more IL 1 as well as lymphocytes to release more IL 2, a direct stimulatory membrane effect is postulated. The increased release of immunoregulatory cytokines may account for some of the pathologic findings observed during hemodialysis.

No abstract

Abstract. An increasing gap between supply and demand of donor kidneys for transplantation exists. There is concern regarding the allocation of scarce organs to elderly patients, because the benefit obtained by the transplant may be less in elderly compared with younger recipients. It was the objective of this study to determine differences in patient and organ survival between organ recipients Ͼ65 yr and 50 to 64 yr of age at transplantation. A retrospective cohort of 627 patients Ͼ50 yr who received a kidney transplant between 1993 and 2000 was assembled. Detailed information on patient demographics, comorbidities, and immunological and donor characteristics was ascertained before transplantation. Five-year patient and graft survival were evaluated by Kaplan-Meier survival curves and multivariate Cox proportional-hazard models. Five-year patient mortality was similar between patients aged Ͼ65 and 60 to 64 at transplantation (relative risk [RR] ϭ 1.07; 95% confidence interval [CI], 0.66 to 1.74). Patients aged 50 to 59 yr showed a clear trend toward lower 5-yr mortality (RR ϭ 0.66; 95% CI, 0.43 to 1.03). Compared with patients Ͼ65 yr, 5-yr graft loss was not different in patients aged 60 to 64 (RR ϭ 1.28; 95% CI, 0.82 to 2.02) or those aged 50 to 59 yr at transplantation (RR ϭ 1.02; 95% CI, 0.68 to 1.53). After thorough control for confounding, 5-yr graft survival was not materially different by age group. Discrimination against older candidates for kidney transplantation on age-related grounds alone is not warranted.