Hemodynamics and Metabolic Parameters in Normothermic Kidney Preservation Are Linked With Donor Factors, Perfusate Cells, and Cytokines

Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of the kidney has been studied extensively during the last two decades and implemented in clinical trials. Biomarker research led to success in identifying molecules with diagnostic, predictive and therapeutic properties in chronic kidney disease. However, perfusate biomarkers and potential predictive mechanisms in NMP have not been identified yet. Twelve discarded human kidneys (n = 7 DBD, n = 5 DCD) underwent NMP for up to 24 h. Eight were perfused applying urine recirculation (URC), four with replacement of urine (UR) using Ringer's lactate. The aim of our study was to investigate biomarkers (NGAL, KIM-1, and L-FABP), cells and cytokines in the perfusate in context with donor characteristics, perfusate hemodynamics and metabolic parameters. Cold ischemia time did not correlate with any of the markers. Perfusates of DBD kidneys had a significantly lower number of leukocytes after 6 h of NMP compared to DCD. Arterial flow, pH, NGAL and L-FABP correlated with donor creatinine and eGFR. Arterial flow was higher in kidneys with lower perfusate lactate. Perfusate TNF-α was higher in kidneys with lower arterial flow. The cytokines IL-1β and GM-CSF decreased during 6 h of NMP. Kidneys with more urine output had lower perfusate KIM-1 levels. Median and 6-h values of lactate, arterial flow, pH, NGAL, KIM-1, and L-FABP correlated with each other indicating a 6-h period being applicable for kidney viability assessment. The study results demonstrate a comparable cytokine and cell profile in perfusates with URC and UR. In conclusion, clinically available perfusate and hemodynamic parameters correlate well with donor characteristics and measured biomarkers in a discarded human NMP model.

Effects of the donor factors and freezing protocols on the bovine embryonic lipid profile

Embryo lipid profile is affected by in vitro culture conditions, that lead to an increase in lipids. Efforts have been made to optimize embryo lipid composition as it is associated with their quality. The objective of this study was to evaluate whether the diet supplementation of donor cows (n-3 or n-6 PUFA), or the slow freezing protocols (ethylene glycol sucrose EG-S vs. glycerol trehalose GLY-TRE), or the physiological stage of the donor (nulliparous heifers vs. primiparous lactating cows) may impact the bovine embryo lipid profile. Lipid extracts of 97 embryos were individually analysed by liquid chromatography-high resolution mass spectrometry, highlighting 246 lipids including 85% being overabundant in cow embryos compared to heifer embryos. Among 105 differential lipids, 72 were overabundant after EG-S protocol, including a single glycerophosphate PA(32:1) representing 27.3% of the significantly modulated lipids, suggesting that it is degraded when GLY-TRE is used. No lipids were different according to the n-3 or n-6 supplementation of the donor cows. In conclusion, the embryonic lipid profile was mainly affected by the physiological stage of the donors and the slow freezing protocols. The overabundance of lipids in lactating cow embryos and the resulting lower quality of these embryos is consistent with the lower pregnancy rate observed in cows compared to heifers. Unlike GLY-TRE protocol, EG-S freezing allowed to preserve glycerophospholipids potentially improving the slow freezing of in vitro-produced embryos. Further studies are required to modulate embryo quality and freezability by modulating the lipidome and integrating all stages of embryonic production.

Effect of donor and host factors on corneal graft transparency

Objective: To study the correlation between donor factors and recipients' factors on graft clarity.Materials and methods: The study comprised 30 cases of Keratoplasty surgery with a follow up of6 months. All donor corneas were evaluated by Konan specular microscope for endothelial cellcount; details of the donor like age, cause of death were noted. The patients were divided into twogroups, Group 1 had graft failure, and Group 2 had clear corneas. Observation and Result: Therewere 12 patients in group 1 and 18 patients in group 2 with six months of follow up. The meanendothelial cell count in group 1 was 1942.3/mm2, and group 2 was 2334.8/mm2. There is asignificant difference in the mean endothelial cell count between the two groups. On analysing theindication for Keratoplasty in two groups, the outcome was best for the corneal opacity group duringworst for the graft failure group. Conclusion: Donor endothelial cell count significantly influencedgraft outcome; rest donor factors (age, death enucleation interval, enucleation surgery interval)don't affect graft survival. Indication for Keratoplasty is a significant predictor of graft survival.

Short- and Long-Term Impact of Smoking Donors in Lung Transplantation: Clinical and Pathological Analysis

Background: The use of smoking donors (SD) is one strategy to increase the organ pool for lung transplantation (LT), but the benefit-to-risk ratio has not been demonstrated. This study aimed to evaluate the impact of SD history on recipient outcomes and graft alterations. Methods: LTs in 293 patients were retrospectively reviewed and divided into non-SD (n = 225, group I), SD < 20 pack-years (n = 45, group II), and SD ≥ 20 pack-years (n = 23, group III) groups. Moreover, several lung donor biopsies before implantation (equally divided between groups) were evaluated, focusing on smoking-related lesions. Correlations were analyzed between all pathological data and smoking exposure, along with other clinical parameters. Results: Among the three groups, donor and recipient characteristics were comparable, except for higher Oto scores and age in group III. Group III showed a longer intensive care unit (ICU) and hospital stay compared with the other two groups. This finding was confirmed when SD history was considered as a continuous variable. However, survival and other mid- and long-term major outcomes were not affected by smoking history. Finally, morphological lesions did not differ between the three groups. Conclusions: In our study, SDs were associated with a longer post-operative course, without affecting graft aspects or mid- and long-term outcomes. A definition of pack-years cut-off for organ refusal should be balanced with the other extended criteria donor factors.

Effect of Donor Variables on Platelet Yield Among Donor Undergoing Plateletpheresis at Transfusion Medicine Department, Dhaka Medical College Hospital (Experience of 350 Procedures)

Background: The platelet transfusions help in prevention of bleeding related complications and thus prevents morbidity and mortality in thrombocytopenic patients. Platelet transfusion plays an important role in the treatment of haematological, oncological, surgical, and transplant patients. Platelets are transfused by two methods i) by fractionation of whole blood and ii) by platelet apheresis. Over the last decade there has been a trend towards the use of SDPs rather than pooled random donor platelets in thrombocytopenic patients. Optimization of platelet yield is an emerging issue to identify factors which may help in selecting donors to obtain higher platelet yields in shorter time and consequently better clinical outcome. Objective: The quality of single donor platelets (SDP) in terms of yield influences the platelet recovery in the recipient. The aim was to identify the SDP donor factors that influence platelet yield. Methods: The study was undertaken at transfusion medicine department, DMCH from 1st January 2017 to 31st December 2017. The study included 350 plateletpheresis procedures. All procedures were performed according to manufacturer’s manual and standard operating procedure. Results: During the period of study, 350 platelet pheresis donors were studied. All of the donors were male. Platelet yield showed high statistical significance with pre donation platelet count and its indices. (p=0.000). Statistical significant negative correlation was seen between pre donation Hb concentration and the platelet yield. (p =0.005). No statistical significance was seen height (p=0.933), weight (p=0.760) of donor on platelet yield. Conclusion: Platelet recovery in the patient is influenced by the transfused dose of platelets, which in turn is dependent on the quality of the platelet product in terms of yield. Various donor factors such as pre donation platelet count and haemoglobin concentration may affect platelet yield. J Dhaka Medical College, Vol. 28, No.2, October, 2019, Page 179-183