Plasma exchange and intravenous immunoglobulin in the treatment of antibody-mediated rejection after kidney transplantation: a single-center historic cohort study.

BACKGROUND: Antibody-mediated rejection (AMR) of a kidney graft has been increasingly recognized as an important cause of graft failure. Our historic cohort study sought to analyze its treatment and outcomes at our center. METHODS: All patients with AMR between 2005 and 2011 were treated with plasma exchange (PE), intravenous low-dose cytomegalovirus (CMV) hyperimmune globulin, and adjustment of basal immunosuppression. We analyzed data regarding baseline characteristics, rejection treatment with focus on PE, complications, and 1-year outcomes. RESULTS: Twenty-three AMRs occurred in 23 patients (10 male, 13 female) of mean age 41 ± 16 years, all recipients of deceased-donor kidneys with a median of 3 HLA mismatches. The subjects had a median peak panel-reactive antibodies (PRA) of 7% (interquartile range [IQR] 1%-10%). Basal serum creatinine was 174 ± 84 µmol/L estimated glomerular filtration rate (eGFR) (eGFR 42 ± 22 mL/min/1.73 m(2)), while 3 patients were dialysis- dependent. Median period between transplantation and rejection was 38 months (IQR 1.5-88.5). Concomitant T-cell-mediated rejection was treated in 78% of cases. Median number of PE procedures per patient was 10 (range, 5-17). Treatment was estimated to be successful in 83%. Donor-specific antibodies documented in 12 patients (52%) disappeared or showed reduced titers in 7/10 patients with repeated measurements. An infection was present during treatment in 7 (30%) patients. Among 237 PE, there was 1 (0.4%) mild allergic reaction to fresh frozen plasma and significant metabolic alkalosis occurred after 7 (3%) procedures. One year after rejection the mean serum creatinine level was 144 ± 52 µmol/L and Kaplan-Meier estimated graft and patient survival rates were 62% and 95%, respectively. CONCLUSIONS: Intensive treatment with PE, intravenous immunoglobulin, and adjustment of basal immunosuppression were safe and effective to reverse AMR with improved graft function in the majority of patients. However, AMR was associated with markedly decreased 1-year graft survival and the optimal treatment remains uncertain.

Optimizing timing of ventricular defibrillation.

OBJECTIVE: Our intent was to evolve a prognosticator that would predict the likelihood that an electrical shock would restore a perfusing rhythm. Such a prognosticator was to be based on conventional electrocardiographic signals but without constraints caused by artifacts resulting from precordial compression. The adverse effects of "hands off" intervals for rhythm analyses would therefore be minimized. Such a prognosticator was further intended to reduce the number of electrical shocks and the total energy delivered and thereby minimize postresuscitation myocardial dysfunction. DESIGN: Observational study. SUBJECTS: Medical research laboratory of a university-affiliated research and educational institute. SUBJECTS: Domestic pigs. INTERVENTIONS: Ventricular fibrillation was induced in an established porcine model of cardiac arrest. Recordings of scalar lead 2 over the frequency range of 4-48 Hz were utilized. The area under the curve representing the amplitude and frequency was defined as the amplitude spectrum area (AMSA). MEASUREMENTS AND MAIN RESULTS: A derivation group of 55 animals yielded a threshold value of AMSA that uniformly predicted successful resuscitation. A separate group of 10 animals, a validation group, confirmed that an AMSA value of 21 mV.Hz predicted restoration of perfusing rhythm after 7 of 8 electrical shocks and failure of electrical conversion in 21 of 23 electrical shocks, yielding sensitivity and specificity of about 90%. The negative predictive value of AMSA was 95% and statistically equivalent to that of coronary perfusion pressure, mean amplitude, and median frequency. The positive predictive value that would prompt continuation of cardiopulmonary resuscitation without interruption for an unsuccessful defibrillation attempt was greatly improved with AMSA (78%) as compared with coronary perfusion pressure (42%), mean amplitude (32%), and median frequency (29%). CONCLUSION: AMSA has the potential for guiding more optimal timing of defibrillation without adverse interruption of cardiopulmonary resuscitation or the delivery of unsuccessful high energy electrical shocks that contribute to postresuscitation myocardial injury.

Are insulin metabolism and night-time blood pressure related to left ventricular hypertrophy?

Essential hypertensives in whom blood pressure does not fall during sleep (non-dippers) are thought to be at greater risk of cardiovascular morbidity. Insulin resistance is also suggested to be a risk factor for cardiovascular morbidity. The purpose of the present study was to evaluate the relationship of insulin metabolism to left ventricular hypertrophy in dippers and non-dippers. Thirty male, non-diabetic out-patients with newly diagnosed arterial hypertension were included in the study: 21 dippers (mean age 45+/-13 years; body mass index 28.2+/-4.0 kg/m2) and nine non-dippers (mean age 48+/-10 years, body mass index 28.6+/-3.9 kg/m2). Patients were subdivided into dippers and non-dippers on the basis of 24-h ambulatory blood pressure monitoring. Insulin and glucose responses to an oral glucose load have been evaluated. C-peptide levels were determined. Left ventricular mass was assessed by echocardiography. Non-dippers had significantly higher mean night-time systolic (non-dippers: 148+/-9; dippers: 123+/-16 mmHg; P<0.001), diastolic blood pressure (non-dippers: 90+/-8; dippers: 77+/-8 mmHg; P<0.001) and non-significantly higher left ventricular mass (279+/-92 g) and left ventricular mass index (135+/-46 g/m2). No significant difference was found between C-peptide, insulin, glucose levels and incremental areas between the two groups. Night-time blood pressure, insulin, C-peptide and glucose did not correlate with left ventricular mass in non-dippers. Dippers showed a positive correlation between fasting C-peptide and left ventricular mass (r=0.48, P=0.02) and between glucose and left ventricular mass (r=0.42, P=0.05). Our data indicate that night-time blood pressure and insulin are not related to left ventricular hypertrophy in patients with essential hypertension.