Acute renal failure after liver transplantation: incidence, etiology, therapy, and outcome.

Acute renal failure (ARF) was a frequent complication after orthotopic liver transplantation (OLT) when ARF was defined by a calculated glomerular filtration rate decrease of >50% or by a doubled serum creatinine above 2.5 mg/dL within the first week after OLT. We analyzed 1352 liver transplant recipients in retrospective fashion with regard to the incidence, etiology, therapy, and outcome of ARF; 162 patients developed ARF within the first week after OLT (12%), among whom 157 patients (97%) were recompensated by postoperative day 28. Altogether 52 patients (32%) received an average of 6 hemodialysis treatments, excluding the 5 patients (3%) who developed end-stage renal failure. Risk factors for this complication included hepatorenal syndrome type II, a glomerular filtration rate of <50 mL/min, and a diagnosis of hepatitis C.

Withdrawal of steroids: a randomized prospective study of prednisone and tacrolimus versus mycophenolate mofetil and tacrolimus in liver transplant recipients with autoimmune hepatitis.

The aim of this study was to evaluate the success of steroid (PRED) withdrawal due to replacement by mycophenolate mofetil (MMF) in orthotopic liver transplant (OLT) recipients with autoimmune hepatitis (AIH). Thirty patients with AIH > 12 months after OLT randomized to receive either PRED and tacrolimus (TAC) or MMF and TAC were followed for 24 months. Withdrawal of steroids showed no difference regarding graft and patient survival. Also we demonstrated significantly lower glucose levels with lower HbA1c and a reduced need for insulin as well as a significantly lower serum cholesterol in the MMF group. Patients without steroids showed a lower incidence of osteopenia. Maintenance therapy in OLT patients with AIH may be performed safely using MMF instead of prednisone.

The influence of late acute rejection episodes on long-term graft outcome after liver transplantation.

Acute cellular rejection represents the most important single risk factor for the occurrence of chronic rejection after organ transplantation. We correlated late acute rejections with the occurrence of chronic graft failure after liver transplantation. We followed 1426 liver transplants for late acute rejection episodes defined as occurring >3 months after OLT. The overall incidence of chronic rejection in our patient population was 3.7%. In summary, we observed a predictive increase of transaminase levels prior to routine biopsies among patients with histologic evidence of late acute rejections. In contrast to other organ systems, late acute rejection episodes were not associated with the occurrence of chronic graft deterioration in liver grafts.

Massive haemolysis after intramuscular diclofenac in a patient who apparently tolerated oral medication.

BACKGROUND AND OBJECTIVES: Administration of diclofenac may lead to immune haemolytic anaemia (IHA) owing to the presence of drug-dependent antibodies and/or autoantibodies. A relationship with oral or intramuscular drug administration is unknown. Here, we describe a patient who apparently tolerated oral diclofenac but developed severe IHA following intramuscular injection of the drug. PATIENTS AND METHODS: A 66-year-old-female was admitted to hospital because of jaundice and nausea, which were initially presumed to be manifestations of a postcholecystectomy syndrome. The patient soon developed haemolysis and renal failure. Although the symptoms and signs were suggestive of autoimmune haemolytic anaemia (AIHA), the patient had diclofenac-induced IHA. RESULTS: Serological testing, including detection of drug-dependent antibodies, was performed using standard techniques. The patient's serum was found to contain a highly reactive diclofenac-dependent red cell antibody of the immune complex type (titre 256 000). She recovered after 7 weeks of treatment with prednisolone, blood transfusions, haemodialysis and plasma exchange. CONCLUSIONS: Diclofenac-induced IHA should always be considered when a patient on diclofenac develops haemolysis.

Small volume hypertonic hydroxyethyl starch reduces acute microvascular dysfunction after closed soft-tissue trauma.

A major pathway of closed soft-tissue injury is failure of microvascular perfusion combined with a persistently enhanced inflammatory response. We therefore tested the hypothesis that hypertonic hydroxyethyl starch (HS/HES) effectively restores microcirculation and reduces leukocyte adherence after closed soft-tissue injury. We induced closed soft-tissue injury in the hindlimbs of 14 male isoflurane-anaesthetised rats. Seven traumatised animals received 7.5% sodium chloride-6% HS/HES and seven isovolaemic 0.9% saline (NS). Six non-injured animals did not receive any additional fluid and acted as a control group. The microcirculation of the extensor digitorum longus muscle (EDL) was quantitatively analysed two hours after trauma using intravital microscopy and laser Doppler flowmetry, i.e. erythrocyte flux. Oedema was assessed by the wet-to-dry-weight ratio of the EDL. In NS-treated animals closed soft-tissue injury resulted in massive reduction of functional capillary density (FCD) and a marked increase in microvascular permeability and leukocyte-endothelial cell interaction as compared with the control group. By contrast, HS/HES was effective in restoring the FCD to 94% of values found in the control group. In addition, leukocyte rolling decreased almost to control levels and leukocyte adherence was found to be reduced by approximately 50%. Erythrocyte flux in NS-treated animals decreased to 90 +/- 8% (mean SEM), whereas values in the HS/HES group significantly increased to 137 +/- 3% compared with the baseline flux. Oedema in the HS/HES group (1.06 +/- 0.02) was significantly decreased compared with the NS-group (1.12 +/- 0.01). HS/HES effectively restores nutritive perfusion, decreases leukocyte adherence, improves endothelial integrity and attenuates oedema, thereby restricting tissue damage evolving secondary to closed soft-tissue injury. It appears to be an effective intervention, supporting nutritional blood flow by reducing trauma-induced microvascular dysfunction.

In vivo analysis of microcirculation following closed soft-tissue injury.

Major loss of tissue is an almost invariable consequence of severe closed soft-tissue injury. Clinically, the extent of soft-tissue trauma determines the outcome of complex injuries and significantly influences bone healing. With use of a new animal model, this study quantitatively analyzed microcirculation, i.e., nutritive perfusion and leukocyte-endothelial cell interaction, in skeletal muscle after standardized closed soft-tissue injury. By means of a computer-assisted controlled-impact technique, a severe standardized closed soft-tissue injury was induced in the left hindlimb of 28 rats. The rats were assigned to four experimental groups (n = 7 per group) that differed by time of analysis (1.5, 24, 72, and 120 hours after injury); rats that were not injured served as controls (n = 7). Intramuscular pressure was measured, and microcirculation in the rat extensor digitorum longus muscle was analyzed by in vivo fluorescence microscopy, which allowed assessment of microvascular diameters, functional capillary density, number of rolling and adherent leukocytes in venules, and microvascular permeability. Edema weight gain was quantified by the ratio of wet to dry weight of the extensor digitorum longus muscle. Microvascular perfusion of the skeletal muscle was characterized by a significant reduction in functional capillary density, which was paralleled by an increase in capillary diameter throughout the 120 hours of observation when compared with the controls. Trauma-induced inflammatory response was reflected by a markedly increased rolling and adherence of leukocytes, primarily restricted to the endothelium of postcapillary venules; this was accompanied by increased microvascular permeability, indicative of a substantial loss of endothelial integrity. The microcirculation surrounding the core of the damaged tissue area resembled that of ischemia-reperfusion injury in skeletal muscle, i.e., heterogeneous capillary perfusion, pronounced microvascular leakage, and adherence of leukocytes. Enhanced vascular leakage and leukocyte adherence (24-72 hours after injury) coincided with the maximum intramuscular pressure (which was not indicative of compartment syndrome) and edema formation. These results demonstrate that initial changes, leading to ultimate tissue death, after closed soft-tissue injury are caused on the microcirculatory level. This standardized model provides further insight into microvascular pathophysiology and cellular interactions following closed soft-tissue injury. Thus, it is an adequate tool for testing novel therapeutic interventions.