Background/Aims: Recent evidence shows a critical role of the CD4+ T cell with the Th1/Th2 paradigm as a possible effector mechanism in ischemia and reperfusion injury. We hypothesize that a polarized Th1 activation response may negatively influence the renal IRI through its relationship with chemokine production (MCP-1) and with a protective tissue response (HO-1). Methods: We subjected mice to renal ischemia for 45 min using IL-4 and IL-12 knockout C57BL/6. We then measured serum urea levels, performed histomorphometric analysis for tubular necrosis and regeneration, and evaluated the mRNA expression of HO-1, t-bet, Gata-3 and MCP-1 by real-time PCR at 24, 48 and 120 h after surgery. Results/Conclusions: The IL-4 knockout mice had a statistically significant rise in serum urea levels post IRI compared with control animals. The IL-12-deficient mice were not affected. The IL-4-deficient mice had a statistically significant increase in tubular injury and impairment in cell regeneration. The IRI in IL-4-deficient mice was accompanied by higher levels of HO-1, t-bet and later up-regulation of MCP-1. These findings suggest that the deleterious effects of the Th1 cell involve increased production of chemokines such as MCP-1.

Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure in native and transplanted kidneys. In the transplantation field, immunosuppressive drugs may play an additional role in acute graft dysfunction. Rapamycin may impair renal regeneration post IRI. Heme oxygenase 1 (HO-1) is a protective gene with anti-inflammatory and anti-apoptotic actions. We investigated whether HO-1 played a role in rapamycin-induced renal dysfunction in an established model of IRI. Rapamycin (3 mg/kg) was administered to mice before being subjected to 45 min of ischemia. Animals subjected to IRI presented with impaired renal function that peaked at 24 h (2.05+/-0.23 mg/dl), decreasing thereafter. Treatment with rapamycin caused even more renal dysfunctions (2.30+/-0.33 mg/dl), sustained up to 120 h after reperfusion (1.54+/-0.4 mg/dl), when compared to the control (0.63+/-0.09 mg/dl, P<0.05). Rapamycin delayed tubular regeneration that was normally higher in the control group at day 5 (68.53+/-2.30 vs 43.63+/-3.11%, P<0.05). HO-1 was markedly upregulated after IRI and its expression was even enhanced by rapamycin (1.32-fold). However, prior induction of HO-1 by cobalt protoporphyrin improved the renal dysfunction imposed by rapamycin, mostly at later time points. These results demonstrated that rapamycin used in ischemic-injured organs could also negatively affect post-transplantation recovery. Modulation of HO-1 expression may represent a feasible approach to limit rapamycin acute toxicity.

Summary Ischemic‐reperfusion injury (IRI) triggers an inflammatory response involving neutrophils/macrophages, lymphocytes and endothelial cells. Galectin‐3 is a multi‐functional lectin with a broad range of action such as promotion of neutrophil adhesion, induction of oxidative stress, mastocyte migration and degranulation, and production of pro‐inflammatory cytokines. The aim of this study was evaluate the role of galectin‐3 in the inflammation triggered by IRI. Galectin‐3 knockout (KO) and wild type (wt) mice were subjected to 45 min of renal pedicle occlusion. Blood and kidney samples were collected at 6, 24, 48 and 120 h. Blood urea was analyzed enzymatically, while MCP‐1, IL‐6 and IL‐1β were studied by real‐time PCR. Reactive oxygen species (ROS) was investigated by flow cytometry. Morphometric analyses were performed at 6, 24, 48 and 120 h after reperfusion. Urea peaked at 24 h, being significantly lower in knockout animals (wt = 264.4 ± 85.21 mg/dl vs. gal‐3 KO = 123.74 ± 29.64 mg/dl, P = 0.001). Galectin‐3 knockout animals presented less acute tubular necrosis and a more prominent tubular regeneration when compared with controls concurrently with lower expression of MCP‐1, IL‐6, IL‐1β, less macrophage infiltration and lower ROS production at early time points. Galectin‐3 seems to play a role in renal IRI involving the secretion of macrophage‐related chemokine, pro‐inflammatory cytokines and ROS production.

Background. The results of kidney transplantation are impacted by the categories of events responsible for patient death and graft failure. The objective of this study was to evaluate the causes of death and graft failure and outcomes after graft failure among kidney transplant recipients. Methodology. A retrospective cohort study was conducted with 944 patients who underwent kidney transplantation. Outcomes were categorized in a managed and hierarchical manner. Results. The crude mortality rate was 10.8% (n=102): in 35.3% cause of death was infection, in 30.4% cardiovascular disease, and in 15.7% neoplasia and in 6.8%, it was not possible to determine the cause of death. The rate of graft loss was 10.6%. The main causes of graft failure were chronic rejection (40%), acute rejection (18.3%), thrombosis (17.3%), and recurrence of primary disease (16.5%). Failures due to an acute rejection occurred earlier than those due to chronic rejection and recurrence (p<0.0001). As late causes of graft loss, death with the functioning kidney occurred earlier than recurrence and chronic rejection (p=0.008). The outcomes after graft failure were retransplantation in 26.1% and death in 21.4%, at a mean of 25.5 and 21.4 months, respectively. Conclusion. It was possible to identify more than 90% of the events responsible for the deaths of transplanted patients, predominantly infectious and cardiovascular diseases. Among the causes of graft failure, chronic and acute rejections and recurrence were the main causes of graft failure which were followed more frequently by retransplantation than by death on dialysis.

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