Unrelated living donor kidney transplantation

Since 1966, we have performed 41 renal transplants from unrelated living donors (ULD), 39 of which were emotionally related. All donor-recipient pairs included in the present series were AB0-compatible. Recipients included 37 with primary and 4 with secondary transplants; 2 of the latter were diabetics. We compared these results to those of 41 recipients of cadaver donor kidneys matched for age, sex, immunosuppressive regimen, rank, and year of transplant, focusing our attention of the subgroups of patients under cyclosporin A (CyA) therapy (n=24). We found that ULD transplantation was as successful as cadaver transplantation with good HLA matching: at 3 years, graft survival rates were 81% in ULD versus 86% in the control group under CyA. Moreover, grafts from ULD functioned more rapidly (no post-transplant dialysis and 70% of the patients with serum creatinine below 2 mg/dl within 3 days post-transplant). Graft tolerance was equivalent in both groups (50% of the patients experienced no rejection). We conclude that despite poor HLA matching, ULD transplantation with CyA as the basic immunosuppressive agent offers good results: benefiting from the quality of living donor kidney grafts, it helps to alleviate the persistent shortage of cadaver donors.     

Measurement of the vasoconstrictive substances endothelin,angiotensin II,and thromboxane B2 in cold storage solution can reveal previous renal ischemic insults

In a rat model, the left kidney was subjected to 60 min of normothermic ischemia followed by 15 min of reperfusion, whereas the right kidney, serving as a paired control, was not rendered ischemic. Both kidneys were then perfused in situ with either Euro-Collins (EC) solution (n=12) or University of Wisconsin (UW) solution (n=6) for 10 min. Each kidney was then harvested and stored at 4°C in its respective solution. After 24 and 48 h of cold storage, the following vasoactive substances were measured in the preservation media: endothelin (ET), angiotensin II (A-II), thromboxane (B₂) (TxB₂), and prostaglandin I₂ (PGI₂). After 24 h in EC solution, left kidneys uniformly produced significantly higher concentrations of each vasoactive substance than right kidneys: ET 1.64±0.3 pg/ml vs 0.82±0.1 pg/ml (P0.009); A-II 20.8±6.2 pg/ml vs 7.75+2.3 pg/ml (P0.007); TxB₂ 100.8±17.7 pg/ml vs 40.1±11.7 pg/ml (P0.04); PGI₂ 638.3±41.1 pg/ml vs 318.3±36.4 pg/ml (P0.001), respectively. At 48 h, a similar pattern of results was obtained as the kidney continued to produce TxB₂ and prostacyclins during the 24–48 h period. In the UW solution, basal levels of ET and A-II were lower than those in EC solution, but similarly increased after initial ischemia. At 24 h, the concentrations produced by the left and right kidneys were as follows: ET 0.66±0.1 pg/ml vs 0.48±0.1 pg/ml (P0.14); A-II 10.36±3.7 pg/ml vs 2.14±0.7 pg/ml (P0.006); TxB₂ 178±53 pg/ml vs 52±23.1 pg/ml (P0.001); and PGI₂ 448.3±49 pg/ml vs 323±44.3 pg/ml (P0.01), respectively. After 48 h, the range of concentrations of each substance was similar to that obtained after 24 h. In further studies, the concentrations of ET and A-II were measured in solution previously used to preserve human kidneys (n=7). The mean concentration of ET and A-II in these samples was 3.82±1.14 pg/ml and 21.3±9.2 pg/ml, respectively, whereas in control media both substances were below the limits of detection. These results demonstrate that vasoconstrictive substances can be measured in the preservation media after a kidney has been stored cold and that higher concentrations are found when the organ has been subjected to prior normothermic ischemia. The measurement of these vasoactive substances before transplantation may reveal that the kidney has been subjected to previous ischemic events. Moreover, these vasoactive substances could be involved in the early recovery of renal function after kidney transplantation.     

Long-term discordant xenogeneic (porcine-to-primate) bone marrow engraftment in a monkey treated with porcine-specific growth factors

BACKGROUND: Mixed allogeneic hematopoietic chimerism has previously been reliably achieved and shown to induce tolerance to fully MHC-mismatched allografts in mice and monkeys. However, the establishment of hematopoietic chimerism has been difficult to achieve in the discordant pig-to-primate xenogeneic model. METHODS: To address this issue, two cynomolgus monkeys were conditioned by whole body irradiation (total dose 300 cGy) 6 and 5 days before the infusion of pig bone marrow (BM). Monkey anti-pig natural antibodies were immunoadsorbed by extracorporeal perfusion of monkey blood through a pig liver, immediately before the intravenous infusion of porcine BM (day 0). Cyclosporine was administered for 4 weeks and 15-deoxyspergualin for 2 weeks. One monkey received recombinant pig cytokines (stem cell factor and interleukin 3) for 2 weeks, whereas the other received only saline as a control. RESULTS: Both monkeys recovered from pancytopenia within 4 weeks of whole body irradiation. Anti-pig IgM and IgG antibodies were successfully depleted by the liver perfusion but returned to pretreatment levels within 12-14 days. Methylcellulose colony assays at days 180 and 300 revealed that about 2% of the myeloid progenitors in the BM of the cytokine-treated recipient were of pig origin, whereas no chimerism was detected in the BM of the untreated control monkey at similar times. The chimeric animal was less responsive by mixed lymphocyte reaction to pig-specific stimulators than the control monkey and significantly hyporesponsive when compared with a monkey that had rejected a porcine kidney transplant. CONCLUSION: To our knowledge, this is the first report of long-term survival of discordant xenogeneic BM in a primate recipient.     

Atrial Fibrillation Clinics in Canada: A Nationwide Project Report

The increased prevalence of atrial fibrillation (AF) has led to specialized AF clinics (AFCs) to facilitate management of AF patients. In this article we report on outpatient AFCs in Canada, which is essential to health policies required to standardize the performance of existing AFCs and help design new AFCs. We surveyed 14 clinics in 5 provinces; 100% provided responses to a detailed questionnaire on clinic processes and care practices. Fourteen care maps were analyzed, and 5 models of care were identified; 4 were specific to AFCs. An online survey with 49 questions included items on: (1) process before visit; (2) process at visit; (3) patient education provided; (4) outreach; and (5) specific clinic information. Clinicians’ advice to patients on self-care items such as: (1) amount of alcohol and (2) caffeine intake; (3) exercise activity; (4) stressful events; (5) “when to go to the emergency department”; and (6) lifestyle changes, were evaluated to assess consistency in practice. There were moderate variances in clinicians’ advice to patients in 5 of 6 self-care items. The 1 item that had 100% consistent practice recommendation was when to go to the emergency department. A guideline-based clinical assessment checklist (CAC) was piloted to obtain feedback on its usability in real-world practice; revisions finalized the “simplified CAC” for AF care encompassing 35 data points with rationale. There was 100% positive feedback on its ability to provide baseline elements in AF care. When validated, a “simplified CAC” can facilitate a standardized clinical assessment tool in clinical practice.     

Effectiveness of diaphragmatic stimulation with single-channel electrodes in rabbits

Every year, a large number of individuals become dependent on mechanical ventilation because of a loss of diaphragm function. The most common causes are cervical spinal trauma and neuromuscular diseases. We have developed an experimental model to evaluate the performance of electrical stimulation of the diaphragm in rabbits using single-channel electrodes implanted directly into the muscle. Various current intensities (10, 16, 20, and 26 mA) produced tidal volumes above the baseline value, showing that this model is effective for the study of diaphragm performance at different levels of electrical stimulation