Early-onset neonatal seizures: lidocaine toxicity as a rare differential diagnosis to hypoxic ischaemic encephalopathy.

A term newborn girl presented with apnoea and seizures at approximately 20 min of life following an uneventful vaginal delivery. She required admission to the Neonatal Intensive Care Unit following intubation and was commenced on conventional ventilation. Her mother had received a local lidocaine injection for an episiotomy prior to delivery. Initial investigations confirmed electrographic seizures for which she received an anticonvulsant with successful termination of seizure activity. Investigations for hypoxic injury, intracranial trauma, structural brain abnormalities, metabolic disorders and infection were unremarkable. Her blood lidocaine level was subsequently found to be elevated, confirming lidocaine toxicity as the cause of presentation. She demonstrated clinical improvement with no evidence of complications at time of discharge or on early follow-up.

Molecular biomarker candidates of acute kidney injury in zero-hour renal transplant needle biopsies.

The aim of this study was to assess gene expression levels of four biomarker candidates [lipocalin 2 (LCN2), the kidney injury molecule 1 (HAVCR1), netrin 1, and the cysteine-rich, angiogenic inducer, 61] in the tubulointerstitial and the glomerular compartment of zero-hour kidney biopsies in order to predict developing delayed graft function (DGF). Thirty-four needle kidney biopsy samples of deceased donors were manually microdissected. Relative gene expression levels were determined by real-time RT-PCR. For the validation of the biomarker candidates, we calculated a mixed model comparing kidneys with DGF, primary function and control samples from the healthy parts of tumor nephrectomies. Significant biomarker candidates were analyzed together with donor age in multivariable regression models to determine the prognostic value. Expression levels of LCN2 and HAVCR1 in the tubulointerstitium were significantly upregulated in the DGF group (LCN2: fold change = 3.78, P = 0.031 and HAVCR1: fold change = 3.44, P = 0.010). Odds ratios of both genes could not reach significance in the multivariable model together with donor age. The area under the curve of the receiver operating characteristic ranges between 0.75 and 0.83. LCN2 and HAVCR1 gene expression levels in zero-hour biopsies show potential to act as early biomarkers for DGF.

Antithymocyte globulin use for treatment of biopsy confirmed acute rejection is associated with prolonged renal allograft survival.

Antithymocyte globuline (ATG) and OKT3 have been used for treatment of severe biopsy confirmed acute renal allograft rejection (BCAR). We report results on graft and patient survival including 399 subjects diagnosed with BCAR treated with either ATG or OKT3. Multivariable analyses including Banff scores were performed following three different strategies to account for confounding variables. Fifty per cent of subjects in the OKT3 group had a functioning graft 6.3 years after diagnosis of BCAR, but 74% of ATG patients' grafts were still functioning at that time point (log rank P = 0.006). Median actual graft survival was only 4.6 years in the OKT3 subjects, but 9.5 years for ATG-treated patients (log rank P = 0.004). Multivariable analysis revealed that the risk for functional graft loss was significantly elevated in the OKT3 compared to ATG patients (HR = 1.79, 95% CI 1.06-3.02, P = 0.029). The risk for actual graft loss, counting death as event, was also significantly elevated in the OKT3 patients (HR = 1.73, 95% CI 1.09-2.74, P = 0.019). The hazard of death was not different between the groups (HR = 1.55, 95% CI 0.87-2.77, P = 0.137). These data suggest that rejecting renal allografts treated with ATG exhibit longer graft survival than OKT3 treated transplant kidneys. Causal inference, however, cannot be drawn from this associational study.

Mycophenolate mofetil use is associated with prolonged graft survival after kidney transplantation.

BACKGROUND: Mycophenolate mofetil has replaced azathioprine in many transplant centers, but data on hard outcomes such as graft and patient survival are lacking. METHODS: We analyzed graft and patient survival of the 1219 first renal allograft recipients at the Medical University of Vienna who were treated with azathioprine or mycophenolate mofetil over the past decade. Cox's proportional hazards models were used to compute crude and confounder-adjusted hazard ratio estimates of azathioprine versus mycophenolate mofetil. Model building was performed by applying the purposeful selection algorithm, confounding by indication was addressed by propensity scores and marginal structural models. RESULTS: Five years after transplantation, 12% of mycophenolate mofetil users experienced functional graft loss whereas 26% of the azathioprine users had lost their graft (P<0.001). The hazard ratio for functional graft loss was 2.15 (95% confidence interval 1.16-4.02, P=0.016) in azathioprine versus mycophenolate mofetil patients. Actual graft loss at five years had occurred in 25% of the mycophenolate mofetil patients and 49% of the azathioprine users (P<0.001); hazard ratio 2.04 (95% confidence interval 1.22-3.39, P=0.006). Patient survival was not different in any of the analyses. CONCLUSION: The data from our observational study suggest that mycophenolate mofetil use was associated with a lower risk of graft loss than azathioprine-based immunosuppression.

Molecular predictors for anaemia after kidney transplantation.

BACKGROUND: Anaemia of chronic kidney disease is a well-studied comorbidity, but the molecular predictors of post-transplant anaemia remain elusive. METHODS: In this case-control study, 25 subjects with post-transplant anaemia, defined as erythropoiesis-stimulating agent (ESA) requirement within the first post-transplant year, were matched to 25 control recipients with comparable demographics but no anaemia using the Austrian Dialysis and Transplant Registry. Genome-wide gene expression analyses of deceased donor kidney biopsies obtained immediately before engraftment were performed using custom cDNA microarrays. Significant molecular features were included together with clinical variables in a multivariable logistic regression analysis and further analysed with respect to their molecular functions, biological processes and cellular locations using gene ontology terms and protein-protein interactions. RESULTS: Immunity response molecules were over-represented in the up-regulated gene list suggesting the involvement of the inflammation cascade as a predictor of ESA requirement after engraftment. From the initial list of the 34 differentially expressed genes, we identified the best three genes predicting ESA requirement in the first year by a stepwise gene selection algorithm. SPRR2C (OR = 0.24, 95% CI 0.07-0.85, P = 0.027) and GSTT1 (OR = 2.40, 95% CI 1.21-4.77, P = 0.013) remained significant after adjusting for donor age, eGFR, BCAR and CRP. CONCLUSION: In summary, we identified three biomarkers (SPRR2C, B3GALTL and GSTT1) of post-transplant anaemia in donor kidney biopsies that correctly predicted ESA requirement within the first year after transplantation in 93% of the cases.