Survival predictors in paraquat intoxification and role of immunosuppression.

Paraquat poisoning resulted in multiorgan failure and is associated with high mortality. We audited 83 historical cases of paraquat poisoning in past 2 years treated with conventional decontamination and supportive treatment, followed by enrolling 85 patients over a 2 year period into additional immunosuppression with intravenous (i.v.) methylprednisolone and i.v. cyclophosphamide. Our results showed that age, poor renal function and leucocytosis are the main predictors of fatal outcome. Immunosuppression regime rendered higher survival (6 out of 17 patients (35.3%)) versus historical control (1 out of 18 patients (5.6%)) (p = 0.041) in the cohort with admission eGFR < 50 ml/min/1.73 m2 and WBC count > 11,000/µL. In contrast, there was no difference in survival with immunosuppression regime (38 out of 64 patients (59.4%)) compared to historical control (30 out of 52 patients (57.7%)) (p = 0.885) in those with eGFR > 50 ml/min/1.73 m2 or WBC < 11,000/µL at presentation. Multivariable logistic regression showed survival probability = exp(logit)/(1 + exp(logit)), in which logit = 13.962 - (0.233 × ln(age (year))) - (1.344 × ln(creatinine (µmol/L))) - (1.602 × ln(rise in creatinine (µmol/day))) - (0.614 × ln(WBC (,000/µL))) + (2.021 × immunosuppression) and immunosuppression = 1 if given and 0 if not. Immunosuppression therapy yielded odds ratio of 0.132 (95% confidential interval: 0.029-0.603, p = 0.009). In conclusion, immunosuppression therapy with intravenous methylprednisolone and cyclophosphamide may counteract immune mediated inflammation after paraquat poisoning and improve survival of patients with admission eGFR < 50 ml/min/1.73 m2 and WBC count > 11,000/µL.

Association of a change in immunosuppressive regimen with hemodynamic and inflammatory markers of cardiovascular disease after kidney transplantation.

BACKGROUND: Although rejection rates and short-term graft survival have significantly improved in kidney transplantation with the introduction of calcineurin inhibitor (CNI), cardiovascular disease (CVD) and metabolic complications are being increasingly recognized as important causes of morbidity and mortality. We hypothesize that non-CNI proliferation signal inhibitor (PSI)-based immunosuppressive regimen is associated with improved arterial stiffness after kidney transplantation compared with CNI-based immunosuppressive regimens. METHODS: This is a prospective, single-center study of renal transplant (RT) recipients comparing the metabolic, cardiovascular (pulse wave velocity and aortic augmentation index (AI) adjusted for heart rate (AI × 75)), inflammatory cytokines (interleukins (ILs) 6, 12, and 18) and graft-related outcomes at 3 and 15 months posttransplantation between RT recipients maintained on CNI- (CNI-CNI) or PSI-based (CNI-PSI) regimens including sirolimus and everolimus. RESULTS: Fifty and 17 RT recipients maintained on CNI-CNI and CNI-PSI, respectively, were included in this study. Median time to PSI conversion from CNI was 5 months. Compared with CNI-CNI recipients, CNI-PSI recipients had significantly lower fasting blood glucose in nondiabetics (coefficient = -16.2; 95% confidence interval (CI) = -14.4 to -18.0; P < 0.01), lower IL-18 levels (coefficient = -229.16; 95% CI = -343.94 to -114.38; P < 0.01), and lower AI × 75 (coefficient = -5.14; 95% CI = -9.99 to -0.28; P = 0.04) at 15 months posttransplant in the multivariable models. CONCLUSIONS: Our study suggests from the elimination of CNI for PSI may lower AIx75 and IL-18, both surrogate markers of CVD, but adequately powered, randomized, controlled studies are required to establish the causal relationship between immunosuppressive agents and CVD risk.

Outcome of coronary artery bypass grafting in end stage renal disease patients.

INTRODUCTION: End stage renal disease (ESRD) patients have a much higher rate of cardiac disease and cardiac mortality as compared with the general population. Revascularisation such as coronary artery bypass grafting (CABG) may also carry a higher rate of complications and morbidity. We compared our ESRD patients who underwent CABG with the general population and ESRD population. METHODS: This is an observational study of ESRD patients who underwent CABG in our centre from 2003-2009 with case-control matching comparison with non-ESRD patients for ICU and hospital stay; and ESRD patients without CABG for survival. Patients with concomitant valvular operation were excluded. The primary outcomes were peri-operative complications and survival. RESULTS: Eleven patients with mean age of 57.5 +/- 8.5 were included. All except 1 were diabetics. One patient had excessive haemorrhage requiring immediate re-thoracotomy, and this was complicated with thrombosed AVF. Four patients experienced intradialytic hypotension postoperatively but all resolved within 1 week. Both ESRD and non-ESRD patients had equal number of ICU stay (3.1 versus 3.2 days, p = 0.906) and hospital stay (7.6 versus 6.9 days, p = 0.538). With average of 3.3 years follow-up (range from 1 to 7 years), 4 deaths were observed but only one from cardiac cause. Both ESRD cohorts with or without CABG have compatible left ventricular mass: 295 +/- 86 vs 343 +/- 113 g (p=0.226) and left ventricular mass: 174 +/- 54 vs. 206 +/- 63 g/m2 (p = 0.157). The outcome of CABG ESRD patients was comparable to matched ESRD patients without CABG with 90.9 % versus 91.9% 1 year survival, 95.5% versus 77.7% 2 year survival, 71.4% versus 70.3% 3 year and 40.0% versus 40.3% at 5 year survival (p = 0.627, 0.386, 0.659 and 0.683 respectively). CONCLUSION: CABG in ESRD patients carries an acceptable perioperative complication rate. They have acceptable ICU and hospitalization duration in comparison to non-ESRD patients. Their long term survival was at least as good as matched ESRD patients without CABG.