Outcome of renal transplantation subsequent to liver, heart, or lung transplantation

Renal dysfunction is a growing problem after liver, heart, or lung transplantation with the subsequent need for dialysis or renal transplantation. The aim of this study was to analyze the outcome after a subsequent kidney transplantation (secondary kidney transplantation) in liver, heart, or lung transplantation recipients. All secondary kidney transplantation patients from 1985 to 2006 were identified for the cause of kidney failure, time after initial transplantation, and current kidney function. One thousand two hundred three patient charts were reviewed including 22 (1.8%) secondary kidney transplantations: eight after lung, eight after heart, and six after liver transplantation. Renal failure was the result of perioperative renal failure (n = 3), toxic effects of cyclosporine (n = 16), a combination of cyclosporine nephrotoxicity and vascular ischemia (n = 3), or chronic renal failure due to polycystic kidney disease (n = 1). The median time after the initial organ transplantation was 114 months (range 30 to 241 months). The most recent median creatinine value was 103 micromol/L (82 to 704 micromol/L). Renal transplant rejection was noted in five patients: four in the lung transplant group, and one after heart transplantation. Three patients were deceased, one from secondary renal failure. One renal allograft was removed after renal artery thrombosis. In conclusion, there is sometimes a need for subsequent kidney transplantation after liver, heart, or lung transplantation. The outcome of renal transplantation subsequent to liver, heart, or lung transplantation is good with satisfactory renal function in this study population.     

Thoracic Transplantation

Experimental orthotopic transplantation of the heart was accomplished in 1959. Long-term survival was achieved in 1965 with a chemical immunosuppression protocol substantially different from that used for renal and hepatic transplants. Performance characteristics of the transplanted denervated heart were found to differ only slightly from normal. It appeared by the time of the Clinical Congress of the American College of Surgeons in October 1967 that clinical heart transplantation might be justified if the concept of brain death could be legally recognized. The Stanford program in clinical heart transplantation was inaugurated on January 6, 1968 and has been in continuous operation. To date, more than 1000 patients have undergone transplantation of the heart with the 5-year survival at 75%. The first long-term success in lung transplantation occurred at Stanford in 1981, with transplantation of the heart and both lungs. In 1990 the concept of living pulmonary lobar donors was introduced and is slowly finding its clinical role. The steroid-sparing capability of cyclosporine made possible both successful lung and pediatric heart transplantation. Only the donor shortage remains as a substantial barrier to widespread thoracic transplantation. Xenotransplantation is under intense scrutiny, with some encouraging experimental results. Development of the artificial heart continues to offer some relief for patients with end-stage heart disease.     

Heart and Lung Transplantation in the United States, 1996–2005

This article examines the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients data on heart and lung transplantation in the United States from 1996 to 2005. The number of heart transplants performed and the size of the heart waiting list continued to drop, reaching 2126 and 1334, respectively, in 2005. Over the decade, post-transplant graft and patient survival improved, as did the chances for survival while on the heart waiting list. The number of deceased donor lung transplants increased by 78% since 1996, reaching 1407 in 2005 (up 22% from 2004). There were 3170 registrants awaiting lung transplantation at the end of 2005, down 18% from 2004. Death rates for both candidates and recipients have been dropping, as has the time spent waiting for a lung transplant. Other lung topics covered are living donation, recent surgical advances and changes in immunosuppression regimens. Heart-lung transplantation has declined to a small (33 procedures in 2005) but important need in the United States.     

Cardiopulmonary transplantation

The Registry of the International Society for Heart and Lung Transplantation reported 4196 heart transplants and 3812 lung transplants worldwide in 2015. The 100,000th heart transplant mark has been passed. Heart transplantation is a proven surgical option for selected patients who have advanced heart failure refractory to surgical or medical management. Lung transplantation is the definitive treatment for end-stage lung disease for patients who have failed medical therapy. More than 90% of adult patients presenting for heart transplantation have dilated cardiomyopathy or ischaemic cardiomyopathy. Anaesthetic principles for heart transplantation include full monitoring including transoesophageal echocardiography, cardiostable anaesthesia and cardiac support, and assessment and treatment of pulmonary vascular hypertension. Median survival after cardiac transplantation is 11.9 years. Lung transplantation includes single-lung, double-lung, bilateral sequential single-lung, heart-lung and lobar transplantation. The most common indication is chronic obstructive pulmonary disease, which represents more than one-third of all transplant recipients. Donor criteria are becoming more liberal. Lung transplants may involve cardiopulmonary bypass. Pre-bypass air trapping can compromise cardiac function. Postoperative ventilation management should be guided by pH, not PaCO₂. Thoracic epidural provides optimal analgesia without respiratory depression. Five year survival after lung transplantation is approximately 65%.     

Cardiopulmonary transplantation

The Registry of the International Society for Heart and Lung Transplantation reported 108,034 adult recipients of deceased donor heart transplants between January 1992 and June 2018. The 37th annual adult lung transplant report submitted data to the ISHLT TTX Registry on 67,493 adult recipients of deceased donor transplants between January 1, 1992 and June 30, 2018. In recent years more than 5000 heart transplants and approximately 4000 lung transplants have been performed annually across 388 centres worldwide. Heart transplantation is a proven surgical option for selected patients with advanced heart failure refractory to surgical or medical management. Lung transplantation is the definitive treatment for end-stage lung disease in patients who have failed medical therapy. More than 90% of adult patients presenting for heart transplantation have dilated cardiomyopathy or ischaemic cardiomyopathy. Anaesthetic principles for heart transplantation comprise full monitoring, including transoesophageal echocardiography, cardiostable anaesthesia and cardiac support with assessment and treatment of pulmonary vascular hypertension. Median survival after cardiac transplantation is 11.9 years. Lung transplantation includes single-lung, double-lung, bilateral sequential single-lung, heart–lung and lobar transplantation. The most common indication, representing more than one-third of all transplant recipients, is chronic obstructive pulmonary disease. Donor criteria have become more liberal and lung transplants may involve cardiopulmonary bypass. Pre-bypass air trapping can compromise cardiac function. Postoperative ventilation management should be guided by pH, not P_aCO₂. Thoracic epidural analgesia provides optimal pain relief without respiratory depression. Five-year survival after lung transplantation is approximately 65%.     

Comparison of peak and trough level monitoring of cyclosporine treatment using two modern cyclosporine preparations

AIMS: Determination of the peak cyclosporine blood level instead of the trough level promises to represent an improvement in cyclosporine therapy monitoring due to better correlation with the AUC. In kidney transplant recipients we investigated whether this conclusion applies also to a new dispersion formulation of cyclosporine (Cicloral). PATIENTS: 42 stable kidney transplant recipients were converted from Sandimmun Neoral (NEO) to Cicloral (CIC) in a 1:1 dose relation. METHODS: On the last day of NEO administration and 14 days after conversion to CIC a full 12 h cyclosporine AUC was performed using blood samples obtained prior to and at serial times after dosing. The correlations between cyclosporine levels at these time points and the AUC were determined for NEO and CIC. For each measurement, a predicted AUC was calculated by regression analysis. The prediction error for each sampling time was calculated separately for NEO and CIC. RESULTS: The cyclosporine trough levels showed the poorest correlation with AUC for both preparations (NEO: r = 0.187 vs CIC: r = 0.554). The best correlation was observed for samples obtained at three hours after intake of either CIC (r = 0.807) or NEO (r = 0.611). The number of 2 hours measurements that lead to an unacceptable estimate from the real AUC was somewhat lower for CIC (8/40 vs 11/41 with NEO). CONCLUSIONS: Two- or three-hour cyclosporine level monitoring with the newer cyclosporine preparation Cicloral has at least the same precision as that of the original Neoral(R). In this study, the newer preparation even showed a tendency towards superior monitoring properties.     

Heart transplantation during the first 12 years of life. Loma Linda University Pediatric Heart Transplant Group

Since November 1985, forty-four heart transplants have been accomplished in 43 infants and children younger than 12 years of age. Indications for transplantation included structural heart disease (31 patients), idiopathic or viral cardiomyopathy (10 patients), and combined structural and myopathic disease (2 patients). Postoperative recipient surveillance was achieved noninvasively during the first year of life; endomyocardial biopsy was employed in children. Maintenance immunosuppression included cyclosporine and azathioprine therapy during the first year after transplantation in young infants, graduating to cyclosporine therapy alone beyond the first year. Azathioprine therapy was continued indefinitely in children. There have been 5 perioperative deaths and 1 late death in this series of recipients. Overall survival was 86%. Growth, development, and psychosocial adjustments generally have been excellent. Donor heart growth has been normal. Coronary artery disease has not yet been observed. Our findings indicate that heart transplantation seems to be effective therapy for selected incurable pediatric cardiac diseases.     

Peak cyclosporine levels (Cmax) correlate with freedom from liver graft rejection: results of a prospective, randomized comparison of neoral and sandimmune for liver transplantation (NOF-8)

BACKGROUND: Despite two decades of use, there are limited data on the best way to administer and monitor cyclosporine (CsA) for liver transplantation. The present study was undertaken (1) to determine whether treatment with a new formulation of CsA, Neoral, would improve the results of liver transplantation; and (2) to study the relationships between pharmacokinetic parameters and clinical outcomes after transplantation. METHODS: A double-blind, randomized, comparison of Sandimmune (SIM) with Neoral (NEO) was conducted at five Canadian centers in 188 consecutive adults undergoing primary orthotopic liver transplantation. Patients were induced with intravenous CsA then switched to NEO or SIM. Dose adjustments were made daily, or as needed, to reach a target trough CsA level of 350 ng/ml in both groups. Pharmacokinetic studies were performed on days 5, 10, 15, and 16 weeks after transplantation. RESULTS: The NEO group was slightly younger, with a median age of 50 years (range: 23-70) versus 55 years (range: 24-71) for SIM (P = 0.007); otherwise the two groups were well balanced. The NEO group stopped intravenous CsA earlier (5.8+/-2.6 days vs. 8.7+/-4.7 days, P<0.0001). This group required a lower median daily oral dose (7.5 mg/kg vs. 9.0 mg/kg, P<0.01) to maintain comparable trough CsA levels. Five SIM patients, but no NEO patients, discontinued the study due to the inability to reach target trough levels of CsA within the prescribed time (P<0.05). At 4 months, there were no differences between the two groups with respect to patient survival (93% NEO vs. 91% SIM), graft survival (90% NEO vs. 86% SIM), and rejection-free survival (54.1% NEO, 51.8% SIM). The incidence of serious adverse events was also similar and did not correlate with CsA pharmacokinetic profiles. The NEO group had a higher area under the drug concentration curve for the first 6 hr after the dosing interval (AUC0-6) and peak CsA levels (Cmax). There was a strong correlation between freedom from graft rejection during the first month after transplantation and (a) AUC0-6 and (b) Cmax at days 5 and 10 after transplantation, but only in the NEO group did this reach statistical significance. In contrast, there was a poor correlation between trough CsA and graft rejection. In patients on NEO, the concentration of CsA 2 hr after dosing (C2) closely reflected AUC0-6 (r2 = 0.93), whereas there was a poorer correlation in patients on SIM (r2 = 0.73) CONCLUSIONS: Cmax and/or AUC0-6 may provide better markers than trough levels for monitoring CsA-based immune suppression after orthotopic liver transplantation. Prospective studies are underway to determine whether dosing to C2, which provides a good estimation of Cmax, can be used to take full advantage of NEO's improved absorption profile.     

Cardiopulmonary transplantation

More than 7000 cardiopulmonary transplants were carried out worldwide in 2009 across the 388 centres reporting to the International Registry. The 100,000th heart transplant mark has been passed. Heart transplantation is a proven surgical option for selected patients who have advanced heart failure refractory to surgical or medical management. Lung transplantation is the definitive treatment for end-stage lung disease for patients who have failed medical therapy. More than 90% of adult patients presenting for heart transplantation have dilated cardiomyopathy or ischaemic cardiomyopathy. Anaesthetic principles for heart transplantation include full monitoring including transoesophageal echocardiography, cardiostable anaesthesia and cardiac support, and assessment and treatment of pulmonary vascular hypertension. Median survival after cardiac transplantation is 11 years. Lung transplantation includes single-lung, double-lung, bilateral sequential single-lung, heart-lung and lobar transplantation. The most common indication is chronic obstructive pulmonary disease, which represents more than one-third of all transplant recipients. Donor criteria are becoming more liberal. Most lung transplants involve cardiopulmonary bypass. Pre-bypass air trapping can compromise cardiac function. Postoperative ventilation management should be guided by pH, not PaCO₂. Thoracic epidural provides optimal analgesia without respiratory depression. Five-year survival after lung transplantation is approximately 65%.     

Neoral in de novo liver transplantation: Adequate immunosuppression without intravenous cyclosporine

Absorption of cyclosporine from the traditional oral formulation Sandimmune (Novartis Pharma, Basel, Switzerland) is particularly unpredictable in the early stages after liver transplantation. The absorption of cyclosporine is influenced by liver function, postoperative paralytic ileus, and graft dysfunction. Oral absorption of cyclosporine from Sandimmune is also bile dependent; cholestasis and external biliary drainage are associated with low cyclosporine absorption. Postoperative administration of intravenous Sandimmune is therefore often necessary to obtain adequate immunosuppression, despite the increased risk of renal and neurological toxicity. A microemulsion formulation of cyclosporine, Neoral (Novartis), has been developed to overcome the problems of poor and variable absorption of cyclosporine from Sandimmune. Uptake of cyclosporine from Neoral is rapid and less dependent on bile secretion so that higher peak concentrations are reached and absorption is less variable than with Sandimmune. A review of several open studies in which Neoral was administered to liver transplant patients immediately after transplantation is presented. The results suggest that the use of Neoral as a primary immunosuppressive therapy provides adequate cyclosporine trough levels, minimizing or obviating the need for intravenous cyclosporine administration. In addition, Neoral appears to reduce the risk of acute rejection episodes compared with immunosuppressive regimens involving intravenous cyclosporine. (Liver Transpl Surg 1997 Nov;3(6):571-7)     

The long-term outcome of kidney transplantation in patients under cyclosporine--a developing country experience

The introduction of cyclosporine revolutionized the practice of solid organ transplantation. Although early studies showed better short-term results, the long-term benefits of cyclosporine appear to be more contentious. Our study investigated the outcome of sustained cyclosporine usage on patient and renal allograft survival in a developing country setting. All patients receiving primary renal transplants at our institution over a 23-yr period were included and data analysed for patient and graft survival rates using the Kaplan-Meier actuarial method. The patients receiving cyclosporine were compared with historical controls receiving conventional treatment. Early graft survival was superior in patients under cyclosporine but this benefit disappeared after the first year. There was no significant improvement in early patient survival in patients under cyclosporine but late survival was better in patients under conventional treatment. In our setting cyclosporine only improves early graft survival and does not have long-term benefit either on patient or graft survival.     

Use of extracorporeal membrane oxygenation in pediatric thoracic organ transplantation.

OBJECTIVE: Mechanical cardiorespiratory support is occasionally required before or after pediatric thoracic organ transplantation. Extracorporeal membrane oxygenation is the most commonly used mechanical support technique in children. The goal of this study was to examine the indications for initiation and outcomes after peritransplant use of extracorporeal membrane oxygenation. METHODS: A retrospective study was conducted of 65 patients who received peritransplant extracorporeal membrane oxygenation between November 1994 and June 2000. The pretransplant group included 45 patients (average age, 38 months) supported with extracorporeal membrane oxygenation and listed for transplantation (31 heart, 8 lung, and 6 heart-lung), and the post-transplant group included 20 patients (average age, 83 months) who required extracorporeal membrane oxygenation after thoracic organ transplantation (12 heart, 6 lung, and 2 heart-lung transplants). Hospital course and outcomes were evaluated. RESULTS: With regard to pretransplant extracorporeal membrane oxygenation, patients listed for heart transplants were more likely to survive to transplantation than were those listed for lung or heart-lung transplants (12/31 [39%] vs 1/14 [7%], P =.03). There was no difference in long-term survival between heart transplant patients after extracorporeal membrane oxygenation and those without extracorporeal membrane oxygenation (12-month actuarial survival, 83% vs 73%; P =.68). Patients who survived for prolonged periods on extracorporeal membrane oxygenation (>250 hours) typically received heart transplants (7/8 [88%]). With regard to post-transplant extracorporeal membrane oxygenation, patients receiving lung or heart-lung transplants had better short-term outcomes than those receiving heart transplants (63% survived to discharge vs 33%). All 3 patients with early graft dysfunction receiving lung transplants survived to discharge. CONCLUSIONS: Long-term outcomes among those undergoing heart transplantation after support with an extracorporeal membrane oxygenator are comparable with those of patients not receiving extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation can be a useful post-transplant support device, particularly in patients undergoing lung transplants.     

Pharmacokinetics of oral cyclosporine (Neoral) in heart transplant recipients during the immediate period after surgery

Neoral cyclosporine has better absorption characteristics than the original Sandimmun formulation. This has allowed Neoral to be administered orally in circumstances where Sandimmun had been ineffective, including the postoperative phase of liver transplantation. Sampling strategies, such as the measurement of drug concentration 2 h after oral administration, have been used in a variety of settings to estimate systemic exposure to Neoral (measured as the area under the blood concentration curve (AUC) of the drug) in blood. We conducted a pilot study to determine whether Neoral could be administered orally immediately after heart transplantation and to determine which pharmacokinetic parameters reflect systemic drug exposure in this setting. Eight male patients (mean age 50 years) undergoing a first heart transplant were studied. Neoral was administered orally before surgery and at 12-h intervals via a nasogastric tube after surgery. Twelve-hour pharmacokinetic profiles were obtained on postoperative days 1, 3 and 5. Cyclosporine concentrations were measured with the Dade Behring Emit assay, which is specific for the parent drug. Drug concentrations were dose-normalised and drug exposure was measured by the AUC. Drug exposure following administration (AUC(0-12)) was low on day 1 but increased by 99% between postoperative day 1 and day 5 ( P<0.05), indicating more complete absorption of cyclosporine; exposure in the first 4 h post-dose (AUC(0-4)) increased by 126% ( P<0.01), reflecting more rapid cyclosporine absorption, and the maximum blood concentration observed increased by 137% ( P<0.05) during the same period. The correlation between the cyclosporine trough concentration and AUC(0-12) was low on all days. Due to the changing pattern of cyclosporine absorption, concentration measurements at a single time point could not accurately predict 12-h exposure to the drug on all study days. However, the drug concentration at 2 h post-dose had a high correlation with drug exposure during the first 4 h (correlation of C(2) to AUC(0-4): r(2)>0.93 on all days). Absorption of Neoral was low immediately after heart transplantation but improved substantially during the first 5 days after surgery. No single timed measurement of drug concentration reflected cyclosporine exposure; however, the 2-h concentration did provide an accurate measure of the early phase of drug absorption (AUC(0-4)). Oral administration of Neoral may result in inadequate immunosuppression immediately after heart transplantation unless it is supplemented either by intravenous cyclosporine or by the use of an induction agent.     

Renal transplantation following previous heart, liver, and lung transplantation: an 8-year single-center experience

BACKGROUND: Long-term follow-up of heart, liver, and lung transplantation has led to an increased recognition of secondary end-stage renal failure (ESRF) in transplant recipients. This study examines our center's experience with renal transplantation following previous solid organ transplantation. METHODS: From January 1, 1992, to September 30, 1999, our center performed 18 renal transplants in previous solid organ recipients. During the same period, 815 total renal transplants were performed. One- and 3-year graft and patient survival, recipient demographics, donor type, and reason for transplantation were compared between these groups. RESULTS: Of the 18 recipients, 7 had prior heart transplants, 4 had prior liver transplants, and 7 had prior lung transplants. Cyclosporine toxicity contributed to renal failure in 17 (94.4%) of the patients-either as a sole factor (11 patients) or in combination with hypertension, renal artery stenosis, or tacrolimus toxicity (6 patients). Kaplan-Meier 1- and 3-year patient survival was 82.9% and 73.7%, compared with 95.5% and 90.7% in all renal transplant recipients. No surviving patient has suffered renal allograft loss. Mean current creatinine level is 1.4 mg/dL. CONCLUSIONS: Renal transplantation is an excellent therapy for ESRF following prior solid organ transplantation. One and 3-year patient and graft survival demonstrate the utility of renal transplantation in this patient population.     

Middle East Society for Organ Transplantation (MESOT) Transplant Registry

During the seventies, sporadic renal transplants were performed in few MESOT-region countries, mainly Turkey, Iran, Egypt, and Lebanon. Since the introduction of cyclosporine in the early eighties, transplantation has become the preferred therapeutic modality for end-stage renal failure. In 1986, the Islamic theologians (Al Aloma) issued what became known as the Amman declaration, in which they accepted brain death and retrieval and transplantation of organs from living and cadaveric donors. Based on this and similar declarations, all Middle Eastern countries except Egypt passed laws that allow cadaveric transplantation and regulate live donations. Iran, Turkey, Saudi Arabia, Kuwait, Tunisia, Jordan, and Lebanon all have current active cadaveric programs and perform liver, heart, pancreas, and lung transplants. More than 5088 renal transplants/year are performed in the region with Iran leading with 1600. The cumulative number of renal transplant patients is now nearly 60,000. With a 2003 population of 600,682,175, the rate/million for renal transplantation in the MESOT region is a mere 9/million. Rates of renal transplantation range from 31/million in some countries to 0 in others. The major obstacle in establishing an accurate number of transplants is "tourist transplantation," in which the same transplanted patients are registered in different countries. Although cadaveric programs have been active for more than 10 years, live-related and nonrelated transplants account for nearly 85% of the total transplants. The data presented were collected from MESOT representatives in the region and from publications. For proper compilation of the registry, a format is being proposed that will be presented at the Congress for review and adaptation. Even with the limited resources in the region, immunosuppressive drugs for induction and maintenance therapy are available and are used. Costs for transplantation and immunosuppressive therapy are either totally or heavily supported by governmental agencies.     

Abdominal Transplant Surgery and Transplant Coordination University Hospitals Leuven 1997–2007: an Overview

The transplant surgery and transplant coordination department was created in 1997 to meet up with the demand of the growing abdominal transplant surgery and organ procurement activity at the University Hospitals in Leuven. Since then, the procurement activity has increased and is currently distributed within the University Hospital Gasthuisberg and a network of ~25 collaborative hospitals. The profile of the donors has changed with older donors and more co-morbidity factors (obesity, hypertension, etc.). This donor activity represents ~30% of the national donor pool. Over the last 10 years, more than 1100 kidneys, more than 500 livers, ~50 pancreas, and 5 intestines have been transplanted in both adults and children. One year survival equal to-or exceeding 90% has been achieved for all abdominal organs and this compares favorably with international registries. More than 40 multi-visceral transplants {liver in combination with abdominal (kidney, pancreas, intestine) or thoracic (heart, double lung, heart-lung) organs} have been performed with results equivalent to isolated liver transplants and very little immunological graft loss (probably due to the immunoprotective effect of the liver). A live donation program was started for the kidney (40 cases) and for the liver (10 cases) in adults and children and no surgical graft loss has been seen so far. Introduction of new machine perfusion systems (and development of donor protocols) has made it possible to restart a non-heart-beating donor program for kidney transplantation. Experimental demonstration that livers tolerate short periods of warm ischemia has also allowed to start liver transplantation from non-heart-beating donors. In the future, machine perfusion of livers, viability testing, and biological modulation are likely to widen the use of marginal livers for transplantation and improve the results. An immunomodulatory protocol proven in the lab to induce the development of regulatory T cells has been applied clinically to 5 consecutive intestinal transplants. All 5 - at the time of writing - have been rejection-free and have achieved nutritional independence. Continuous research and development is warranted to increase the organ donor pool (currently the solely limiting factor of transplantation) and to optimize long-term graft and patient outcome.     

Why should we implement living donation in renal transplantation?

BACKGROUND: Renal transplantation started with living donor transplants. However, after the introduction of cyclosporine, the improved results of kidney transplants from cadaveric donors have raised controversy regarding the use of living donors. There are various reasons as to why some transplant centers tend to refuse living donation: first of all, the possibility that unilateral nephrectomy can be harmful to a healthy individual. SUBJECTS AND METHODS: By reviewing the medical literature on the various aspects of living donation, postoperative mortality in connection with living donation has been calculated to be 1:3,000. RESULTS: Long-term follow-up investigations of donors demonstrated that the risk of progressive renal failure, hypertension, and proteinuria was not increased by nephrectomy per se, but other causes were responsible for that in occasional patients. From these studies, one can conclude that unilateral nephrectomy is not harmful to a healthy individual. In addition, there are other valid reasons to expand living donation: 1) the need for cadaveric donor kidneys for transplantation far exceeding the supply; 2) the better kidney quality from living donors due to the shorter ischemia time, the lack ofagonal phase and cytokines release that follows brain death; 3) the continuing improved results of kidney transplants from living donors in comparison with those from cadaveric donors in the cyclosporine era also. This appears to be true also for kidney transplants from unrelated living donors in spite of complete incompatibility with recipients. 4) Pre-emptive transplantation, based on living donors, not only avoids the risks, cost, and inconvenience of dialysis, but is also associated with better graft survival than transplantation after a period of dialysis, particularly within the live donor cohort. CONCLUSIONS: In conclusion, living donor transplants should be part of any transplant center's activity. To encourage living donation, every center should have a formal recipient family education program in conjunction with national organ donation campaigns.     

Heart and lung transplantation for pulmonary hypertension

Seventeen patients received combined heart and lung transplants at Stanford University between March 1981 and December 1983. All recipients were suffering from end-stage pulmonary hypertension. Five patients died within the first few postoperative weeks, but the remainder were well between 2 and 35 months after operation. Immunosuppression consisted of cyclosporine with an initial course of rabbit antithymocyte globulin, and azathioprine was given for the first 2 postoperative weeks. Maintenance immunosuppression was achieved with cyclosporine and prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with intravenous methylprednisolone. The functional status of the survivors has been good, and upon discharge from the hospital, all returned to normal activity. Our preliminary experience indicates that cardiopulmonary transplantation represents a realistic therapeutic approach for patients with end-stage pulmonary disease.     

Role of MICA antibodies in solid organ transplantation

As a potential transplant antigen, major histocompatibility complex class I chain‐related gene A (MICA) antigen, has attracted increased attention because of its possible role in solid organ transplantation. There are two MICA forms, and MICA antibodies and soluble MICA (sMICA) have been found in the serum of transplant recipients. We searched MEDLINE, EMBASE, and the Cochrane Library for original reports of clinical studies involving the effect of MICA on outcomes of renal, heart, lung, and liver transplantation. In addition to the human leukocyte antigen antigens, which elicit a strong immune response, the polymorphic MICA antigens induce production of MICA antibodies and sMICA. A number of clinical studies have shown that MICA antibodies correlate with an increased incidence of rejection and a decreased allograft survival rate following renal or heart transplantation. Although it is clearly associated with chronic rejection of lung allografts, no such correlation was found for liver transplantation. Moreover, sMICA showed a negative association with acute rejection (AR) and may be a good predictor of heart transplant outcomes. These data suggest MICA expression patterns and regulatory function may be tissue specific and that different transplants have different organ‐specific outcomes.