ABO incompatible renal transplantation without antibody removal using conventional immunosuppression alone.

ABO incompatible living donor renal transplantation (ABOi) can achieve outcomes comparable to ABO compatible transplantation (ABOc). However, with the exception of blood group A2 kidneys transplanted into recipients with low titer anti-A antibody, regimens generally include antibody removal, intensified immunosuppression and splenectomy or rituximab. We now report a series of 20 successful renal transplants across a range of blood group incompatibilities using conventional immunosuppression alone in recipients with low baseline anti-blood group antibody (ABGAb) titers. Incompatibilities were A1 to O (3), A1 to B (2), A2 to O (2), AB to A (2), AB to B (1), B to A1 (9), B to O (1); titers 1:1 to 1:16 by Ortho. At 36 months, patient and graft survival are 100%. Antibody-mediated rejection (AbMR) occurred in one patient with thrombophilia and low level donor-specific anti-HLA antibody. Four patients experienced cellular rejection (two subclinical), which responded to oral prednisolone. This series demonstrates that selected patients with low titer ABGAb can undergo ABOi with standard immunosuppression alone, suggesting baseline titer as a reliable predictor of AbMR. This reduces morbidity and cost of ABOi for patients with low titer ABGAb and increases the possibility of ABOi from deceased donors.

New-onset diabetes after kidney transplantation-changes and challenges.

Despite substantial improvement in short-term results after kidney transplantation, increases in long-term graft survival have been modest. A significant impediment has been the morbidity and mortality attributable to cardiovascular disease (CVD). New-onset diabetes after transplantation (NODAT) is an independent predictor of cardiovascular events. This review examines recent literature surrounding diagnosis, outcomes and management of NODAT. Amongst otherwise heterogeneous studies, a common finding is the relative insensitivity of fasting blood glucose (FBG) as a screening test. Incorporating self-testing of afternoon capillary BG and glycohemoglobin (HbA(1c) ) detects many cases that would otherwise remain undetected without the oral glucose tolerance test (OGTT). Assessing the impact of NODAT on patient and graft survival is complicated by changes to diagnostic criteria, evolution of immunosuppressive regimens and increasing attention to cardiovascular risk management. Although recent studies reinforce a link between NODAT and death with a functioning graft (DWFG), there seems to be little effect on death-censored graft loss. The significance of glycemic control and diabetes resolution for patient outcomes remain notably absent from NODAT literature and treatment is also a neglected area. This review examines new and old therapeutic options, emphasizing the need to assess ß-cell pathology in customizing therapy. Finally, areas warranting further research are considered.

Successful ABO-incompatible kidney transplantation with antibody removal and standard immunosuppression.

ABO-incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited by the requirement for additional immunosuppression. Here, we describe the outcomes of 37 patients undergoing ABOi kidney transplantation utilizing perioperative antibody depletion and receiving an identical tacrolimus-based immunosuppressive regimen to contemporaneous ABO-compatible (ABOc) recipients, with the exception that mycophenolate was commenced earlier (7-14 days pretransplant). Antibody depletion was scheduled according to baseline anti-ABO antibody titer (tube IAT method: median 1:128, range 1:8 to 1:4096). Patient and graft survival for the 37 ABOi recipients was 100% after a median 26 months (interquartile range [IQR] 18-32). Eight rejection episodes (two antibody-mediated and six cellular) in ABOi recipients were successfully treated with biopsy-proven resolution. Latest median eGFR is 50 mL/min × 1.73 m² (IQR 40-64) for ABOi patients and 54 mL/min × 1.73 m² (IQR 44-66) in the ABOc patients (p = 0.25). We conclude that ABOi transplantation can be performed successfully with perioperative antibody removal and conventional immunosuppression. This suggests that access to ABOi transplantation can include a broader range of end-stage kidney disease patients.

SOCS-3 is tyrosine phosphorylated in response to interleukin-2 and suppresses STAT5 phosphorylation and lymphocyte proliferation.

Members of the recently discovered SOCS/CIS/SSI family have been proposed as regulators of cytokine signaling, and while targets and mechanisms have been suggested for some family members, the precise role of these proteins remains to be defined. To date no SOCS proteins have been specifically implicated in interleukin-2 (IL-2) signaling in T cells. Here we report SOCS-3 expression in response to IL-2 in both T-cell lines and human peripheral blood lymphocytes. SOCS-3 protein was detectable as early as 30 min following IL-2 stimulation, while CIS was seen only at low levels after 2 h. Unlike CIS, SOCS-3 was rapidly tyrosine phosphorylated in response to IL-2. Tyrosine phosphorylation of SOCS-3 was observed upon coexpression with Jak1 and Jak2 but only weakly with Jak3. In these experiments, SOCS-3 associated with Jak1 and inhibited Jak1 phosphorylation, and this inhibition was markedly enhanced by the presence of IL-2 receptor beta chain (IL-2Rbeta). Moreover, following IL-2 stimulation of T cells, SOCS-3 was able to interact with the IL-2 receptor complex, and in particular tyrosine phosphorylated Jak1 and IL-2Rbeta. Additionally, in lymphocytes expressing SOCS-3 but not CIS, IL-2-induced tyrosine phosphorylation of STAT5b was markedly reduced, while there was only a weak effect on IL-3-mediated STAT5b tyrosine phosphorylation. Finally, proliferation induced by both IL-2- and IL-3 was significantly inhibited in the presence of SOCS-3. The findings suggest that when SOCS-3 is rapidly induced by IL-2 in T cells, it acts to inhibit IL-2 responses in a classical negative feedback loop.

Pulmonary toxicity following MOPP chemotherapy.

Pulmonary toxicity is a well recognised side effect of anticancer agents particularly bleomycin, cyclophosphamide, methotrexate, and busulphan. In contrast this problem has been infrequently reported following MOPP (nitrogen mustard, vincristine, prednisolone, procarbazine) chemotherapy for Hodgkin's disease and has been attributed principally to the procarbazine. We report a further instance of MOPP associated pulmonary toxicity. This case and a review of previously published cases indicate that MOPP chemotherapy may be associated with the development of permanent lung damage as well as an acute reversible hypersensitivity lung disease.