Post-transplant increase in soluble human leukocyte antigen-G associated with non-severe cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the single most important long-term limitation to heart transplantation. This study aimed to assess the value of monitoring soluble human leukocyte antigen-G (sHLA-G) during the first year post-transplantation to predict the severity of CAV, in 21 out of 77 heart recipients assessed by intravascular ultrasound (IVUS). Serum sHLA-G concentration increased after transplant in recipients free of severe CAV, but decreased in recipients suffering from severe CAV, significant differences between these two groups were found 6 to 12 months post-transplantation. The optimal value of the change in post-transplant sHLA-G for identifying severe CAV was ≥0.062%, which maximized sensitivity (80%) and specificity (100%). Importantly, increases in post-transplant sHLA-G were inversely associated with severe CAV, but directly associated with human cytomegalovirus reactivation. In addition, recipients presenting non-severe CAV or an increased sHLA-G post-transplantation, showed higher numbers of CD8(+)CD28(-) T cells and a down-modulation of CD28 on CD4(+) lymphocytes, which typically identifies CD8(+) regulatory T cells and anergic/tolerogenic T helper cells, respectively. In conclusion, quantification of sHLA-G might offer a complementary non-invasive method for identifying recipients at risk of more severe CAV and who might benefit from earlier preventive therapies, although these results need to be confirmed in larger series.

CD28 and KIR2D receptors as sensors of the immune status in heart and liver transplantation.

Viral infections and cellular acute rejection (AR) condition immunosuppressive therapy and compromise the evolution of allografts. Immune monitoring can be useful for ascertaining rejection and for differentiating allo-reaction from activation induced by infections. This work analyzes the usefulness of monitoring the expression of CD28 and KIR2D receptors in peripheral blood T lymphocytes by flow cytometry, to ascertain the immune response in heart and liver transplant recipients. In both types of transplant, the up-regulation of CD28 in CD4(+) lymphocytes in the periods of greatest AR frequency indicates an effective allo-response, whereas the post-transplantation emergence of circulating CD8(+)CD28(-) and CD8(+)CD28(-)KIR2D(+) T cells correlates with better early clinical results. Cytomegalovirus (CMV) infection, but not hepatitis C virus (HCV) or other infections, abrogated both CD28 up-regulation and CD8(+)CD28(-)KIR2D(+) T-cell expansion. Our results show that monitoring the expression of CD28 and KIR2D receptors on T lymphocytes might be considered as sensors of the immune status of heart and liver recipients.

Steroid use in heart transplant patients in Spain in the current era: a multicenter survey.

OBJECTIVE: Steroid withdrawal (SW) from maintenance therapy in heart transplant patients is still a controversial subject. We designed a questionnaire to ascertain the attitudes and procedures of a number of Spanish heart transplant units (16) regarding the use/withdrawal of steroids as part of the immunosuppressive maintenance therapy. MATERIALS AND METHODS: We sent an 11-item questionnaire to the clinical director in charge of each unit. The questionnaire was completed and returned by 14 units. RESULTS: In 21.5% of the centers SW was performed in all patients, while 78.5% of the centers only performed SW in selected patients. In 57% of units SW was performed at 12 months posttransplantation and between 6 and 12 months in the rest. Fewer than 20% of patients were steroid-free in 46% of units while in 23% of units this proportion was >50%. In 11 units, the minimum prednisone dose administered was

Independent predictors of renal dysfunction after heart transplantation in patients with normal pretransplant renal function.

BACKGROUND: Renal dysfunction (RD) is a common complication after heart transplantation (HT), but predictors of post-HT RD have not been clearly identified. METHODS: We studied 262 HT patients (mean age 54 years, 221 men) with normal baseline renal function. Potential risk factors examined were age, sex, pre-HT ischemic cardiomyopathy, pre- and post-HT diabetes mellitus, pre- and post-HT arterial hypertension, initial immunosuppressive protocol (before 1998 [high cyclosporine, azathioprine, and prednisone] vs after 1998 [low cyclosporine, mycophenolate mofetil, and prednisone]), occurrence of rejection episodes > or =ISHLT Grade 3A, and creatinine level 1 month after HT. RD was considered mild if creatinine level was 1.5 to 2.5 mg/dl, moderate if creatinine level was >2.5 mg/dl, and severe if dialysis or kidney transplant was required. RESULTS: The cumulative incidence of RD (creatinine >1.5 mg/dl) was 35% at 12 months, 42% at 24 months, and 47% at 60 months (mean follow-up 59 +/- 31 months). Only 1% of patients had severe RD 60 months after HT. Independent predictors of RD 24 months after HT were older age (odds ratio [OR] 1.1 [95% confidence interval (95% CI) 1.0-1.1]; p = 0.001), male sex (OR 3.3 [95% CI 1.3-8.1]; p = 0.008), pre-1998 immunosuppressive protocol (OR 2.8 [95% CI 1.4-5.4]; p = 0.003), and creatinine level 1 month after HT (OR 3.2 [95% CI 1.0-5.4]; p < 0.0001). CONCLUSIONS: The cumulative incidence of RD in HT patients treated with calcineurin inhibitors increased with time after HT. Age, male sex, an immunosuppressive protocol with relatively high cyclosporine levels and creatinine level 1 month after HT were independent predictors of the presence of RD 24 months after HT.

Hypotension, acidosis and vasodilation syndrome after heart transplant: incidence, risk factors, and prognosis.

BACKGROUND: HAV syndrome, the combination of hypotension, acidosis and vasodilation (HAV), is a serious postoperative complication after heart transplantation (HT). Its etiology and prognosis are poorly understood. AIM: To determine the incidence and prognosis of post-HT HAV syndrome and examine possible risk factors. METHODS: Retrospective examination of the records of 85 consecutive patients who underwent HT between December 1999 and June 2002 sought the HAV criteria: systolic BP <85 mm Hg plus HCO3 <19 mEq/l whole excluding cardiogenic, hypovolemic and septic shock. Donor variables included sex, age, weight, height, cause of death, time in ICU, and ischemic time; while recipient variables, sex, age, weight, height, etiology of cardiopathy, previous cardiopulmonary bypass surgery, preoperative amiodarone, beta-blockers, catecholamines, mechanical ventilation or intra aortic balloon pump (IABP), RVP, time on waiting list, pump time, reoperations, polytransfusion, preoperative creatinine, GOT, GPT and GGT, induction with OKT3 or anti-CD25, bypass-to-HAV time, duration of catecholamine treatment, and 1 month survival after HT. RESULTS: The 11 HAV cases (13%) appeared between 1 and 72 h after HT (75% in the first hour). Catecholamines were used for 1 to 6 days; control was achieved within 48 h in 58% of cases. Two HAV patients (18%) died within the first month versus six non-HAV patients (8.1%) (P=.275). Only polytransfusion showed more than a borderline value to predict HAV syndrome. CONCLUSIONS: HAV syndrome has an incidence of 13% and a mortality of 18% within 1 month post-HT. The only likely risk factor is polytransfusion.

Renal dysfunction after orthotopic heart transplantation: incidence, natural history, and risk factors.

BACKGROUND: Renal dysfunction is a common complication after orthotopic heart transplantation (HT). The importance of factors other than exposure to immunosuppressive drugs is unclear. The purpose of this study was to determine the incidence and natural history of renal dysfunction following heart transplantation, and to evaluate a number of variables as risk factors for this condition. METHODS: We examined the creatinine levels at 1, 6, 12, 24, and 60 months in 262 consecutive heart transplant patients who survived at least 1 year. The potential risk factors included pre- and posttransplantation diabetes mellitus, arterial hypertension, and drugs used to control arterial hypertension. RESULTS: 17.2% of patients showed mild renal dysfunction (creatinine 1.5-2.5 mg/dL) and 1.9% moderate dysfunction (creatinine >2.5 mg/dL) at 1 month; 29.8% showed mild and 1.1% moderate dysfunction at 6 months; 33.2% showed mild and 1.9% moderate dysfunction at 1 year; 40% showed mild, 0.9% moderate and 0.4% severe dysfunction (requiring dialysis or renal transplantation) at 2 years; and 43.6% showed mild, 1.7% moderate and 0.9% severe dysfunction at 5 years. None of the conditions analyzed as possible risk factors showed a significant association with renal dysfunction except the use of diuretics. CONCLUSION: The incidence of renal dysfunction after orthotopic heart transplantation was 33.6% within the first year after transplant and 44% within the first five years, although more than 95% of cases were mild. The incidence increased with time after transplantation. Renal dysfunction seems likely to be multifactorial in origin, but no individual risk factors were identified.