The Evaluation Of Platelet Parameters For Predicting Delayed Renal Graft Function

Background Organ transplantation is currently the most effective treatment for end stage diseases, among them, the kidney transplantation is the earliest and the most mature organ transplantation. Allograft renal transplantation is the best treatment for chronic renal insufficiency uremia stage. With renal transplantation technology progress and management of perioperative application of continuous improvement and new type immunosuppressants, kidney transplantation success rate continuously improved, postoperative complications has gradually become a key factor in the survival of grafts. At all of them, delayed graft function (DGF) is a common complication after transplantation. Someone has reported that, in different regions, different transplantation center cadaveric kidney the incidence rate of DGF was 2%-50%, early diagnosis and timely treatment of DGF can significantly improve the long-term renal transplant success rate and survival rate of renal transplantation.At present there is no clear definition of DGF.Most transplant centers define DGF as required at least once dialysis a week after transplant surgery or serum creatinine did not decline to 400umol/l within a week after renal transplantation as a diagnostic index. DGF may cause acute rejection, graft loss, and influence of the patients’ long-term survival of kidney transplantation.DGF as a result of interaction of multiple factors, the main pathological mechanism of ischemic reperfusion damage theory and basic research in recent years found cytotoxicity, acquired immune factors, inflammation factors mechanisms may also be involved in DGF occurrence and development.Ischemic makes renal tubular endothelial cells from oxygen metabolism to anaerobic metabolism, a direct result of the decrease of ATP production, residual ATP rapid decomposition to hypoxanthine, cell surface Ca2+ and Na+-K+ pump dysfunction, intracellular calcium overload, intracellular calcium dependent enzymes such as cysteine protease and endothelial cell nitric oxide synthase cytokine activation, stimulate the damage response mechanism, formation of a large amount of oxygen free radicals, some adhesion molecules and chemotaxis factor (such as ELR-CXC, IL-8, etc) expression increased, start cytotoxic and inflammatory reaction, resulting in serious damage to the cell membrane cytoskeleton and cell apoptosis or death, resulting in graft direct or indirect tissue damage. With the cryopreservated and ischemia injury of transplanted kidney being resumption of blood supply, the graft rewarming, change anaerobic metabolism to aerobic metabolism, a series of factors that lead to further damage on the basis of ischemic injury. First of all, substantial generation of reactive oxygen species in response to ischemia (mainly oxygen free radical) transform to the superoxide anion and hydrogen peroxide in the oxidation reaction, resulting in a large number of cytotoxic hydroxyl free radical, start cytotoxic reaction, damage to the normal cell membrane lipid structure. Simultaneously,with the change of hemodynamics, instant reperfusion blood pressure leads to endothelial cell damage directly.In addition, adhesion molecules and chemokine factor on cell surface expression further increased, aggregation of neutrophils and monocytes, release of the reactive oxygen species, initiates inflammatory reaction, start renal parenchymal cells apoptosis or death and residual cell debris blocking the tubular lumen, resulting in the increased pressure within the kidney, renal swelling, further reducing glomerular filtration rate, thus changing the hemodynamics of renal transplantation, reduced blood flow to the kidney, such a vicious cycle lead to more injury of the graft. DGF main pathology performance for the damage and necrosis of parenchymal cells of renal transplantation, especially acute tubular necrosis ATN. Exclusion to AR and other complications, DGF lasted a few days to a few months time, until the necrosis of renal tubular epithelial cell regeneration and DGF gradually recovery.In the pathogenesis of DGF, inflammatory reaction plays an important role.In the inflammatory response, except neutrophils, monocytes, eosinophils and other traditional inflammatory cells, in recent years, the study found that platelet is a newly discovered of non-specific immune cells can cause inflammation. There are a large number of platelet membrane phospholipase A2 (PLA2), in the inflammatory response to cytokine stimulation to platelet membrane phospholipids skeleton release arachidonic acid. Arachidonic acid product through a variety of metabolic pathways:lipoxygenases LXs, leukotrienes (LTS), prostaglandins (PGs) and thromboxane (TXs)etc, including leukotrienes and thromboxane are important chemotactic factors to promote inflammation, and lipoxygenase prime and prostaglandin inhibition inflammatory reaction. These bioactive substances have important roles on vascular endothelial function while active the platelet and leukocyte function. In addition, PLA2 can make the platelet activating factor changes chemical structure into 1-alkyl-2-Glycerophosphorylcholine(hemolysis PAF), then using acetyl coenzyme A (acetyl CoA) provided into PAF. PAF induced polymorphonuclear leukocyte, monocyte aggregation and adhesion, increase white blood cells of the trend of and release a variety of inflammatory cytokines and enhanced macrophage phagocytosis, while releasing active oxygen free radicals and a variety of proteolytic enzymes, resulting in the injury of vascular endothelial cells. platelet surface also attached to Fc and IgE receptor, Fc receptor and soluble immune together induced platelet aggregation and secretion of various inflammatory factors. Platelet induced inflammatory response in cerebral infarction, angina, ischemic encephalopathy, atherosclerosis and ischemic heart disease and some due to in the immune system function disorder in autoimmune diseases and certain kidney diseases play an important role.Our research team is dedicated to the study of non specific immunity in the role of complications after renal transplantation in recent years. We found that closely related to the occurrence of platelet parameters and changes of DGF after renal transplantation, the incidence of DGF with the corresponding change of platelet parameters. The DGF group MPV,PDW and P-LCR are higher than non DGF group continuously, including postoperative 7th,10th and 15th day of two groups of MPV, PDW, P-LCR have significant difference. This shows that transplantation of inflammatory reaction of plants can be reflected by the platelet parameters. This finding suggests that platelets participate in inflammation leads to more consumption because the number of PLT in the DGF group, resulting in the phenomenon of platelet activation and bone marrow hematopoietic activity.Five platelet parameters and renal transplantation acute rejection occurrence and development are equally relevant. The AR group and control group showed no significant difference in PLT, PCT, MPV, or P-LCR before the surgery, but the PDW was significantly higher in the AR group.These parameters were similar within 5 postoperative days between the two groups, but in postoperative days 6-15, the AR group showed significantly increased MPV, PDW and P-LCR compared with the control group. In postoperative days 6-9, MPV, PDW and P-LCR became stable in AR group but tended to decrease in the control group, showing obviously different patterns of variation between the two groups. Monitoring the variations of MPV, PDW and P-LCR may help in the diagnosis of acute graft rejection early after renal transplantation.Our study found that renal transplant recipients after early renal transplantation in the changes of platelet parameters is very obvious, platelet activation is closely related with in the process of DGF occurred, but it is not yet clear role of platelet parameters in the process of DGF. This paper on the basis of the previous research increased sample size and further deepen to explore the platelet parameters of renal allograft function delayed recovery of the predictive value of clinical outcomes, summed up is useful in the early diagnosis of renal allograft function delay recovery method, and further in-depth study of platelet parameters and renal transplantation other diseases to provide reference data and technology.Objective To investigate the clinical predictive value of the five parameters of platelet to delayed graft function (DGF).Methods We retrospectively analyzed clinical datas of preoperation and postoperation within 2 months of 330 cases of renal transplant recipients.They divided into two groups which is the DGF cases (DGF group)and did not occur DGF cases (Non DGF group),and analysis on the relationship between delayed graft function after renal transplantation and the variation of blood platelet parameters including platelet count(PLT), large platelet ratio (P-LCR), platelet volume distribution width (PDW), mean platelet volume(MPV) and platelet hematocrit(PCT).Results The comparison of platelet parameters between DGF group recipients and non DGF group recipients suggested that there is no statistically significant difference before surgery. However, on postoperative 7 days (the day diagnosis DGF), compared with two groups of platelet parameters have a statistically significant difference (P> 0.05). PLT and PCT in DGF group are significantly lower than those in non DGF group (P< 0.05, P< 0.02), while MPV, PDW and P-LCR are significantly higher than those in non DGF group (P=0.01, P< 0.01, P=0.036). Moreover, AUC of P-LCR, PDW and MPV are 0.611±0.047,0.603±0.048 and 0.762±0.037,significantly higher than the opportunity reference area (P< 0.05), the cut-off values are 34.80%.12.95fl和11.55fl. Among them, the sensitivity, specificity and Youden index of MPV are in higher level. PDW and P-LCR is more sensitive, but a low specificity, both are the reference value for the prediction of DGF, but MPV predict DGF is better. PLT and AUC of PCT were 0.37 and 0.38, and the predictive value of DGF is not obvious.Conclusions When DGF diagnosised,platelet parameters with DGF group and the control group have statistically significant differences. After renal transplantation, monitoring the changes of MPV, PDW, P-LCR are helpful to diagnosis and treatment of DGF in early stage. The clinical value of MPV prediction of DGF reached medium(0,7-0.9) and when MPV> 11.55fl,we need to be vigilant of the patient’s risk of DGF.