Editors’ Picks

Macrophages Contribute to Cellular But Not Humoral Mechanisms of Acute Rejection in Rat Renal Allografts. Ma FY, Woodman N, Mulley WR, Kanellis J, Nikolic-Paterson DJ. Transplantation. December 15, 2013. Acute allograft rejection in nonsensitized recipients is a T cell-dependent response characterised by both cellular and antibody-mediated effector responses. Consequently, strategies for preventing acute rejection focus mainly on blocking adaptive immunity by targeting T cell activation and proliferation. While macrophages are common in acutely rejecting organ allografts, their contribution to acute rejection has received relatively little attention. This is at least in part because clinically applicable therapeutic strategies that effectively target macrophages have not until recently been available. Colony stimulating factor-1 (CSF-1), otherwise known as macrophage stimulating factor, is an essential growth factor for monocyte production and macrophage proliferation. In this issue, Ma et al. report the effects of targeting CSF-1 to selectively deplete monocyte/macrophages in a rat model of acute renal allograft rejection. Administration of a c-fms kinase inhibitor effectively reduced infiltration of allografts by macrophages and dendritic cells. Grafts in treated animals were infiltrated by T cells but they showed reduced levels of activation. These changes in the graft cellular infiltrate were associated with less graft dysfunction than seen in grafts in unmodified control animals. However, treatment with c-fms-1 did not prolong graft survival and recipients rejected their grafts rapidly by alloantibody-dependent rather than cell-mediated effector mechanisms. These findings are of interest because the use of a c-fms kinase inhibitor to inhibit macrophage/monocyte activity is potentially clinically applicable. While targeting macrophages may help to control cellular rejection, however, it seems clear that it will do little to impair antibody-mediated graft rejection.FIGURE 1: (Ma et al.). fms-I reduced renal allograft damage on day 5. A, serum creatinine. B, blood urea nitrogen (BUN). C, percentage of injured tubules. D, interstitial inflammation score (0Y4). Real-time reverse transcription-PCR (RT-PCR) analysis of mRNA levels in normal kidney, day 5 isograft control, and vehicle and fms-IYtreated day 5 allografts for (E) KIM-1 and (F) TNF->. PAS staining for (G) normal rat kidney, (H) day 5 vehicle-treated allograft, and (I) day 5 fms-IYtreated allograft. **PG0.01; ***PG0.001 vs. normal. Original magnification, 160 for GYI.Predictors and Consequences of Fatigue in Prevalent Kidney Transplant Recipients. Chan W, Bosch JA, Jones D, Kaur O, Inston N, Moore S, McLean A, McTernan PG, Harper L, Phillips AC, Borrows R. Transplantation. December 15, 2013. Kidney transplantation offers patients with end-stage renal disease an improved quality of life and a greater feeling of well-being. Fatigue is a common and distressing problem for many patients on long-term dialysis and it might have been assumed that symptoms of fatigue might no longer be a significant problem after transplantation. In this issue, Chan et al. report that such an assumption is incorrect and that fatigue remains a serious problem in stable kidney transplant recipients without evidence of intercurrent disease. In a single centre cross-sectional study, Chan et al. found that fatigue was present in 59% of patients and was in the severity range seen in chronically unwell patients with other diseases. Fatigue markedly impacted quality of life and was seen more often in males, non Caucasians and those of older age. Potentially modifiable predictors of fatigue included poor sleep quality, anxiety, depression, high BMI and a raised C reactive protein level signifying chronic inflammation. This study is important because it clearly identifies fatigue as a major problem after renal transplantation and points to potential interventions that may help alleviate it. Longitudinal studies of larger patient cohorts are now required to further quantify the problem and to assess potential life style and other interventions that may reduce the incidence and severity of fatigue.