Stefaan Claus

Epidemiology of infection in critically ill patients with acute renal failure

Objectives: Critically ill patients with infection are at increased risk for developing acute renal failure (ARF), and ARF is associated with an increased risk for infection. Both conditions are associated with prolonged length of stay (LOS) and worse outcome; however, little data exist on the epidemiology of infection in this specific cohort. Therefore, we investigated the occurrence of infection in a cohort of critically ill patients with ARF treated with renal replacement therapy (RRT). In addition, we assessed whether this infection worsened outcome. Design: Retrospective cohort study. Setting: General intensive care unit (ICU) in an academic tertiary care center comprising a 22-bed surgical ICU, eight-bed cardiac surgery ICU, 14-bed medical ICU, and six-bed burn center. Patients: Six hundred forty-seven consecutive critically ill patients with ARF treated with RRT, admitted between 2000 and 2004. Interventions: None. Measurements and Main Results: total of 519 (80.2%), 193 (29.8%), 66 (10.2%), and ten (1.5%) patients developed one, two, three, and four episodes of infection, respectively. Of 788 episodes of infection observed, 364 (46.2%) occurred before, 318 (40.3%) during, and 106 (13.4%) after discontinuation of RRT. Pneumonia (54.3%) was most frequent, followed by intra-abdominal (11.9%) and urinary tract infections (9.7%). Infections were caused by Gram-negative organisms in 33.7%, Gram-positive organisms in 21.6%, and yeasts in 9.8%. Patients with infection had higher mortality (p = 0.04) and longer ICU and hospital LOS. They needed more vasoactive therapy and spent more time on mechanical ventilation and RRT (all p < 0.001) than patients without infection. After adjustment for potential confounders, Acute Physiology and Chronic Health Evaluation II score, age, mechanical ventilation, and vasoactive therapy were associated with worse outcome, but infection was not. Conclusions: Infection occurred in four fifths of critically ill patients with ARF treated with RRT and was in an unadjusted analysis associated with longer LOS and higher mortality. After correction for other covariates, infection was no longer associated with in-hospital mortality.

Impact of local circumstances on outcome of renal casualties in major disasters

BACKGROUND In the aftermath of earthquakes, the cumulative incidence of crush-induced acute kidney injury (AKI) is difficult to predict. Insight into factors determining this risk is indispensable to allow adequate logistical planning, which is a prerogative for success in disaster management. METHODS Data of 88 crush-related AKI patients in the aftermath of the Kashmir earthquake were collected and outcome measures were analysed. Then the findings were compared with the data of 596 crush-related AKI patients of the Marmara earthquake. RESULTS The earthquake in Kashmir occurred in a rural area with lack of medical facilities and difficult transportation conditions while the earthquake in Marmara occurred in an urban area with more efficient transport possibilities. In Kashmir we reported fewer patients with treated AKI (1.2 AKI per 1000 deaths, 1.3 AKI per 1000 victims) than in Marmara (34.1 AKI per 1000 deaths; P < 0.001, 13.6 AKI per 1000 victims; P < 0.001). Time lag between earthquake and admission to hospitals was longer in Kashmir (5.8 +/- 5.8 days) than in Marmara (3.5 +/- 3.7 days; P < 0.001). The frequencies of fasciotomies (P < 0.001), amputations (P < 0.001) and dialysis (P = 0.005) were lower in Kashmir, than in Marmara AKI patients. CONCLUSIONS The cumulative incidence of treated AKI related to number of deaths or victims might differ substantially among earthquakes. Many factors may affect the frequency of AKI: hampered rescue and transport possibilities; destroyed medical facilities on the spot; availability or not of sophisticated therapeutic possibilities and structure of the buildings might all have impacted on different cumulative incidence between Kashmir and Marmara.

Costs and length of stay associated with antimicrobial resistance in acute kidney injury patients with bloodstream infection

Abstract Introduction: Antimicrobial resistance negatively impacts on prognosis. Intensive care unit (ICU) patients, and particularly those with acute kidney injury (AKI), are at high risk for developing nosocomial bloodstream infections (BSI) due to multi-drug-resistant strains. Economic implications in terms of costs and length of stay (LOS) attributable to antimicrobial resistance are underevaluated. This study aimed to assess whether microbial susceptibility patterns affect costs and LOS in a well-defined cohort of ICU patients with AKI undergoing renal replacement therapy (RRT) who developed nosocomial BSI. Methods: Historical study (1995-2004) enrolling all adult RRT-dependent ICU patients with AKI and nosocomial BSI. Costs were considered as invoiced in the Belgian reimbursement system, and LOS was used as a surrogate marker for hospital resource allocation. Results: Of the 1330 patients with AKI undergoing RRT, 92 had microbiologic evidence of nosocomial BSI (57/92, 62% due to a multi-drug-resistant microorganism). Main patient characteristics were equal in both groups. As compared to patients with antimicrobial- susceptible BSI, patients with antimicrobialresistant BSI were more likely to acquire Grampositive infection (72.6% vs 25.5%, P<0.001). No differences were found neither in LOS (ICU before BSI, ICU, hospital before BSI, hospital, hospital after BSI, and time on RRT; all P>0.05) or hospital costs (all P>0.05) when comparing patients with antimicrobial-resistant vs antimicrobial-susceptible BSI. However, although not statistically significant, patients with BSI caused by resistant Gram-negative-, Candida-, or anaerobic bacteria incurred substantial higher costs than those without. Conclusion: In a cohort of ICU patients with AKI and nosocomial BSI undergoing RRT, patients with antimicrobial-resistant vs antimicrobial-susceptible Gram-positive BSI did not have longer hospital stays, or higher hospital costs. Patients with resistant “other” (i.e. Gram-negative, Candida, or anaerobic) BSI were found to have a distinct trend towards increased resources use as compared to patients with susceptible “other” BSI, respectively.

Serum urea concentration is probably not related to outcome in ICU patients with AKI and renal replacement therapy

BACKGROUND Acute kidney injury (AKI) is a common complication in patients admitted to the intensive care unit (ICU). Among other variables, serum urea concentrations are recommended for timing of initiation of renal replacement therapy (RRT). The aim of this study was to evaluate whether serum urea concentration or different serum urea concentration cutoffs as recommended in the literature were associated with in-hospital mortality at time of initiation of RRT for AKI. METHODS This is a retrospective single- centre study during a 3-year period (2004-07), in a 44-bed tertiary care centre ICU of adult AKI patients who were treated with RRT. RESULTS Three hundred and two patients were included: 68.9% male, median age 65 years and an APACHE II score of 21. The overall in-hospital mortality was 57.9%. Non-survivors were older (67 versus 64 years, P = 0.016) and had a higher APACHE II score (22 versus 20, P < 0.001). At time of initiation of RRT, they were more severely ill and had a lower serum urea concentration compared to survivors (130 versus 141 mg/dL, P = 0.038). Serum urea concentration, as well as the different historical serum urea concentration cut-offs had low area under the curves for the receiver operating characteristic curve for prediction of mortality. In multivariate analysis, age, and at time of initiation of RRT, potassium, SOFA score with exclusion of points for AKI and RIFLE class were associated with mortality, but serum urea concentration and the different cut-offs were not. CONCLUSIONS This retrospective study suggests that serum urea concentration and serum urea concentration cut-offs at time of initiation of RRT have no predictive value for in-hospital mortality in ICU patients with AKI.

Health implications of antimicrobial resistance for patients with acute kidney injury and bloodstream infection.

Studies have produced conflicting findings on outcomes for patients with antimicrobial-resistant infection. This study evaluated whether infection with an antimicrobial-resistant organism affects outcome in critically ill patients with acute kidney injury treated with renal replacement therapy and whose clinical course is complicated with a nosocomial bloodstream infection. We found that infection with an antimicrobial-resistant organism did not adversely affect clinical outcome in this specific cohort, which already has a high mortality rate.

Therapeutic plasma exchange in children with acute autoimmune central nervous system disorders.

Background There is a growing evidence for autoimmunity in acute central nervous system (CNS) disorders and treatment with therapeutic plasma exchange (TPE) may be considered. The aim was to share our experience on the clinical application of TPE in these disorders and to present a reproducible protocol which can be used even in small children. Methods We present a series of 8 children aged 2-12 years with transverse myelitis, Bickerstaffs brainstem encephalitis, neuromyelitis optica, and acute paraneoplastic or unspecified encephalitis in whom TPE was used as a second-line or rescue treatment. Results A total of 104 TPE sessions were performed where 80–110 ml/kg of plasma was exchanged using 4% albumin solution and fresh frozen plasma. Six episodes of TPE-related adverse events were documented. Fibrinogen concentrations decreased after the first TPE, whereas platelets decreased gradually. One patient died in the course of the acute illness. Three children achieved a complete resolution of symptoms, 2 children have mild sequelae; whereas 2 children remain paraplegic after a follow-up of 3 to 17 months. Conclusions We report 8 children with presumably autoimmune-mediated, acute CNS disorders treated with TPE as a rescue therapy. Although the effect of TPE can only be inferred, 5 children had a good clinical outcome. TPE is feasible even in small children with acute autoimmune CNS disorders.

Intensive therapeutic plasma exchange in children with acute autoimmune neurological disorders

Abstracts 48th ESPN Meeting, Brussels, September 2015s 48th ESPN Meeting, Brussels, September 2015 O 01 CAN EARLY RECOGNITION OFAKI IN CHILDREN BE ACHIEVED BY USING AN ALGORITHM (PRELIMINARY RESULTS): ON BEHALF OF BRITISH ASSOCIATION FOR PAEDIATRIC NEPHROLOGY Jelena Stojanovic, Nabil Melhem, Sheetal Bhojani, Manish D Sinha, David Milford Evelina London Childrens Hospital, London, UK; Royal Hospital for Sick Children, Glasgow, Scotland; Birmingham Childrens Hospital, Birmingham, UK Introduction: The aim of the study was to validate recently proposed algorithm ‘Standardising early identification of Acute Kidney Injury’ introduced byNHSEngland in a paediatric setting and to investigate recognition and management of AKI. This multi-centre national project was supported by UK Renal Registry and British Association for Paediatric Nephrology. Material and methods: In part one of the audit, all creatinine measurements performed at each of six centres over a six month period were evaluated electronically using the algorithm. In part two, 180 children from six centres were randomly selected and their case notes reviewed. Here, we report preliminary results on data analysed from two tertiary children’s and one district general hospital in the UK. Information was obtained from paper and electronic patient’s notes. AKI stage 1 is a rise of >1.5x baseline creatinine level; AKI stage 2 is a rise of>2x baseline and AKI stage 3 is a rise of>3x baseline. Results: 33,663 creatinine measurements were analysed during the study period using the AKI algorithm.We identified 1,940 AKI 1 episodes (604 children), 479 AKI 2 (158 children) and 756 AKI 3 (112 children). Overall 666 unique children had one or more AKI episodes.We reviewed case notes of 66 children (39 boys) age range 28 days to 17 years. On clinical review of case notes, AKI was recognised in 18 patients (27.3%) only. Of all patients, 17% had prexisting renal condition. 94% children had a follow up arranged with creatinine normalising in 75% of those tested. A third of patients had urine tested and two thirds had medication dosage adjusted to estimated GFR. Conclusions: The proposed algorithm provides an electronic means of identifying children with AKI and highlighting its severity. Our preliminary data suggest that AKI remains clinically under recognised in clinical settings. Timely recognition and optimal management of AKI is important to improve longer term renal outcomes. O 02 EPIGENETIC REGULATION BY HDAC PROTEINS PLAYSACRITICALROLE INTHEPROGRESSIONOFRENAL FIBROSIS Scott Manson, Qiusha Guo, Katelynn Moore, Paul Austin Washington University, Washington, The United States of America Introduction: Chronic kidney disease is associated with changes in the expression of approximately 10% of the genome. The histone deacetylases (HDACs) are a family of 10 related proteins which are among the most widely expressed and crucial regulators of gene transcription. In this study, we examine the biologic and therapeutic importance of HDAC proteins during disease progression. Material and methods: Chronic renal injury was modeled in vivo in mice by unilateral ureteral obstruction (UUO). The role of HDAC proteins was assessed by using a variety of molecular techniques and treatment with the broad spectrumHDAC inhibitor Trichostatin A (TSA). Results:UUO leads to a dramatic increase in the protein levels of 9 of the 10 HDAC isoforms. Notably, there is a 6.1-fold increase in HDAC8 expression that localizes specifically to pericyte-derived myofibroblasts, the cell population which accounts for the majority of matrix production during renal fibrosis. To better understand the importance of these findings, we treated mice with the HDAC inhibitor TSA. This resulted in a 3.4-fold increase in the anti-fibrotic gene BMP7, a 41.6% decrease in the matrix protein COLIA1, and a 61.6% decrease in the myofibroblast differentiation marker α-SMA following UUO. These changes in gene expression culminate in a 77.9% decrease in the interstitial proliferative response, a 43.0% decrease in myofibroblast number, 31.1% decrease in renal fibrosis, 42.8% decrease in apoptosis, and a 43.4% decrease in the loss of renal architecture. [All results are p<0.05] Conclusions: Chronic renal injury is associated with a dramatic increase in HDAC protein levels that stimulates pro-fibrotic gene expression and suppresses anti-fibrotic gene expression. Importantly, treatment with HDAC inhibitors reverses these changes in gene expression and inhibits the development of renal fibrosis. This suggests that HDAC inhibitors may serve as effective therapies to inhibit disease progression. O 03 ECULIZUMAB TREATMENT IN SEVERE PEDIATRIC STEC-HUS, A MULTICENTRIC RETROSPECTIVE STUDY Percheron Lucas, Gramada Raluca, Decramer Stephane, Harambat Jerome, Eckart Philippe, Bourdat-michel Guylhene, Leroy Valerie, Sellier-leclerc Anne-laure, Adra Anne-laure, Allain-launay Emma, Berard Etienne, Bouchireb Karim, Fila Marc, Pietrement Christine, Merieau Elodie, Lapeyraque Anne-laure, Chehade Hassid, Fremeaux-bacchi Veronique, Dimeglio Chloe, Garnier Arnaud Service De Nephrologie Medecine Interne, Hopital Des Enfants, Chu Purpan, Toulouse, France; Service De Neuroradiologie Diagnostique Et Thérapeutique, Chu Purpan, Toulouse, France; Service De Nephrologie Pediatrique, Hopital Pellegrin-enfants, Chu Bordeaux, Bordeaux, France; Service De Pediatrie Medicale, Hopital Cote De Nacre, Chu Caen, Caen, France; Service De Pediatrie, Hopital Couple-enfants, Chu Grenoble, Grenoble, France; Service De Nephrologie Pediatrique, Hopital Jeanne De Flandre, Chu Lille, Lille, France; Service De Nephrologie Pediatrique, Hopital Femme Mere Enfant, Hospices Civils De Lyon, Lyon, France; Service De Nephrologie Pediatrique, Hopital Arnaud De Villeneuve, Chu Montpellier, Montpellier, France; Service De Nephrologie Pediatrique, Hopital Mere-enfants, Chu Nantes, Nantes, France; Service De Nephrologie Pediatrique, Hopital Archet 2, Chu Nice, Nice, France; Service De Nephrologie Pediatrique, Hopital Necker Enfants Malades, Assistance Publique-hopitaux De Paris, Paris, France; Service De Nephrologie Pediatrique, Hopital Robert Debre-paris, Assistance Publique-hopitaux De Paris, Paris, France; Service De Pediatrie, Hopital Americain, Chu Reims, Reims, France; Service De Nephrologie, Hopital Clocheville, Chu Tours, Tours, France; Service De Nephrologie Pediatrique, Chu De Sainte-justine, Montreal, Canada; Service De Nephrologie Pediatrique, Chu De Lausanne, Lausanne, Switzerland; Laboratoire D’immunologie, Hopital Europeen Georges Pompidou, Assistance Publique-hopitaux De Paris, DOI 10.1007/s00467-015-3158-7 Pediatr Nephrol (2015) 30:1543–1730• OnabotulinumtoxinA is a safe and effective treatment for therapy resistant OAB in non-neuropathic children. • It can be a useful treatment option for therapy resistant incontinence and/or enuresis. • With one single treatment, over 50% cure rate may be achieved in a therapy resistant patient population. • The aim of this study is to analyze results and side effects after OnabotulinumtoxinA detrusor injection treatment in children in order to define its place in the treatment of non-neuropathic OAB • Effect on both incontinence and enuresis is reported. • Therapy resistant enuresis is to our knowledge not previously reported as indication for the use of OnabotulinumtoxinA RESULTS OF ONABOTULINUMTOXIN-A IN CHILDREN WITH THERAPY RESISTANT OVERACTIVE BLADDER: 10-YEAR EXPERIENCE