Circulating angiotensin-converting enzyme 2 activity in kidney transplantation: a longitudinal pilot study.

BACKGROUND/AIMS: Angiotensin-converting enzyme 2 (ACE2) is the only known active homologue of ACE, and degrades angiotensin (Ang) II and Ang I to Ang(1-7) and Ang(1-9), respectively. The role of ACE2 in kidney transplant (KT) is unknown. Our objective was to investigate circulating ACE2 activity in KT patients, and the relationship between serum ACE2 activity and age, gender, graft function and cardiovascular risk markers in KT patients. METHODS: 113 KT patients with stable graft function were included in this cross-sectional study. Circulating ACE2 activity was assessed using a fluorescent assay. RESULTS: Circulating ACE2 activity was detectable in KT patients and was increased in KT with ischemic heart disease as compared to KT without ischemic heart disease (105.9 ± 8.7 vs. 97.1 ± 7.05 relative fluorescence units (RFU)/µl/h, p < 0.05). ACE2 activity was increased in male KT as compared to females (105.2 ± 9.1 vs. 84.7 ± 6.9 RFU/µl/h, p = 0.05). ACE2 activity correlated positively with serum creatinine (r = 0.27), serum urea (r = 0.29), age (r = 0.24), aspartate transaminase (r = 0.39), alanine transaminase (r = 0.48), γ-glutamyl transferase (γ-GT) (r = 0.52), age (r = 0.24), and glycosylated hemoglobin (r = 0.19) (p < 0.05). By multiple regression analysis, age, serum creatinine, and serum γ-GT were independent predictors of serum ACE2 activity (r = 0.66, p < 0.001). CONCLUSIONS: Circulating ACE2 activity is measurable in KT patients and directly correlates with age, renal allograft and liver function parameters. These findings suggest that measurement of serum ACE2 may be used as a non-invasive marker to understand the role of the renin-angiotensin system in KT patients.

Efficacy of influenza A H1N1/2009 vaccine in hemodialysis and kidney transplant patients.

BACKGROUND AND OBJECTIVES: Data are needed to assess safety and efficacy of the 2009 pandemic influenza A H1N1 vaccine in renal patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We prospectively evaluated seroconversion, predictors of response, and vaccine safety in renal patients. Hemagglutination inhibition tests to detect serum antibodies against a new influenza A-H1N1 virus were performed in 79 transplant patients, 48 hemodialysis patients, and 15 healthy workers before and 1 month after vaccination. Healthy controls and 88 of 127 renal patients were vaccinated. Seroconversion was defined as at least 2 dilutions increase in titer. RESULTS: We excluded 19 individuals seroprotected (≥1/40) against the novel H1N1 in the initial sample. Efficacy rate in the 96 vaccinated individuals was 43.7% (42 of 96 seroconverted versus four of 27 nonvaccinated patients, P = 0.007). For vaccinated subgroups, efficacy was 41.8% in transplant patients (P = 0.039 versus nonvaccinated), 33.3% in hemodialysis patients (P = 0.450), and 81.8% in controls. Healthy controls showed better response to vaccine than transplant (P = 0.021) and dialysis (P = 0.012) patients. For the transplant subgroup, longer time after transplantation (P = 0.028) was associated with seroconversion, but no influence was found for age, gender, renal function, or immunosuppression. In the hemodialysis subgroup, younger age was associated with response (55.7 ± 20.8 versus 71.6 ± 10.1 years, P = 0.042), but other specific variables, including Kt/V or time on dialysis, were not. No serious adverse events were reported, and kidney function was stable. CONCLUSION: The novel influenza A 2009 H1N1 vaccine was safe in renal patients, although administration of a single dose of adjuvanted vaccine induced a poor response in these patients.

Stroke in renal transplant recipients: epidemiology, predictive risk factors and outcome.

BACKGROUND: Cerebrovascular and cardiovascular diseases are the most important causes of increased morbidity and mortality in patients with end-stage renal disease. Stroke has been widely reported in chronic dialysis patients, but there is scarce information about stroke in renal transplant recipients (RTR), although cerebrovascular events are the most common and potentially life-threatening neurological complications in them. Our aim is to analyze the prevalence, risk factors, etiopathogenia, clinical aspects and outcome of stroke in RTR. METHODS: We analyzed 403 patients who received one or more renal grafts between 1979 and 2000: group A = patients who had stroke (n = 19); group B = those who did not (n = 384). Medical records and pertinent data were compiled. The risk of stroke was studied using univariate and multivariate Cox regression models. RESULTS: prevalence of stroke in RTR was 7.97% at 10 yr. Time elapsed between renal transplantation (RT) and stroke: 49.3 months. Possible risk factors based on the univariate analyses were: diabetic nephropathy (DN) (p < 0.001) and autosomal-dominant-polycystic-kidney-disease (p = 0.049) as original nephropathies, peripheral vascular disease (PVD) (p < 0.001), diabetes mellitus prior to RT (p = 0.005), age older than 40 yr (p = 0.037) and hypertension (p = 0.049). Other analysed risk factors such as gender, renal function, cytomegalovirus infection, hyperlipidemia, hyperuricemia, erythrocytosis or hypertensive donor failed to show any significant predictive value for stroke in these patients. When multivariate analyses were carried out, we found that DN (OR = 4.8; p = 0.010), PVD (OR = 8.2; p < 0.001) and age > 40 yr (OR = 3.3; p = 0.019) were predictive risk factors for stroke. For group A, hypertension was present in all patients, 68.4% had hyperlipidemia and 42.1% reported previous stroke. Cerebral hemorrhage occurred in seven of 19 (36.84%) of the stroke patients, but no subarachnoid hemorrhage occurred in them. Seven of 12 ischemic strokes were atherotrombotic. Considering all strokes, basal ganglia was the predominant localization. The outcome was poor, as nearly half of the patients died in the 3 months following stroke. CONCLUSIONS: Prevalence of stroke in our RTR population was 7.97%. Cerebral hemorrhage appears to be more prevalent in RTR than in general population. More than that, the cerebral hemorrhage rate we found is higher than that reported elsewhere in RTR. The main predictors of stroke were DN, PVD and age. No patient with interstitial nephropathy suffered stroke. Mortality is high in RTR with stroke.