Predicting pediatric cardiac surgery-associated acute kidney injury using machine learning.

BACKGROUND: Prediction of cardiac surgery-associated acute kidney injury (CS-AKI) in pediatric patients is crucial to improve outcomes and guide clinical decision-making. This study aimed to develop a supervised machine learning (ML) model for predicting moderate to severe CS-AKI at postoperative day 2 (POD2). METHODS: This retrospective cohort study analyzed data from 402 pediatric patients who underwent cardiac surgery at a university-affiliated children's hospital, who were separated into an 80%-20% train-test split. The ML model utilized demographic, preoperative, intraoperative, and POD0 clinical and laboratory data to predict moderate to severe AKI categorized by Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 or 3 at POD2. Input feature importance was assessed by SHapley Additive exPlanations (SHAP) values. Model performance was evaluated using accuracy, area under the receiver operating curve (AUROC), precision, recall, area under the precision-recall curve (AUPRC), F1-score, and Brier score. RESULTS: Overall, 13.7% of children in the test set experienced moderate to severe AKI. The ML model achieved promising performance, with accuracy of 0.91 (95% CI: 0.82-1.00), AUROC of 0.88 (95% CI: 0.72-1.00), precision of 0.92 (95% CI: 0.70-1.00), recall of 0.63 (95% CI: 0.32-0.96), AUPRC of 0.81 (95% CI: 0.61-1.00), F1-score of 0.73 (95% CI: 0.46-0.99), and Brier score loss of 0.09 (95% CI: 0.00-0.17). The top ten most important features assessed by SHAP analyses in this model were preoperative serum creatinine, surgery duration, POD0 serum pH, POD0 lactate, cardiopulmonary bypass duration, POD0 vasoactive inotropic score, sex, POD0 hematocrit, preoperative weight, and POD0 serum creatinine. CONCLUSIONS: A supervised ML model utilizing demographic, preoperative, intraoperative, and immediate postoperative clinical and laboratory data showed promising performance in predicting moderate to severe CS-AKI at POD2 in pediatric patients.

Predictors of early peritoneal dialysis initiation in newborns and young infants following cardiac surgery.

OBJECTIVE: This single-centre, retrospective cohort study was conducted to investigate the predictors of early peritoneal dialysis initiation in newborns and young infants undergoing cardiac surgery. METHODS: There were fifty-seven newborns and young infants. All subjects received peritoneal dialysis catheter after completion of the cardiopulmonary bypass. Worsening post-operative (post-op) positive fluid balance and oliguria (<1 ml/kg/hour) despite furosemide were the clinical indications to start early peritoneal dialysis (peritoneal dialysis +). Demographic, clinical, and laboratory data were collected from the pre-operative, intra-operative, and immediately post-operative periods. RESULTS: Baseline demographic data were indifferent except that peritoneal dialysis + group had more newborns. Pre-operative serum creatinine was higher for peritoneal dialysis + group (p = 0.025). Peritoneal dialysis + group had longer cardiopulmonary bypass time (p = 0.044), longer aorta cross-clamp time (p = 0.044), and less urine output during post-op 24 hours (p = 0.008). In the univariate logistic regression model, pre-op serum creatinine was significantly associated with higher odds of being in peritoneal dialysis + (p = 0.021) and post-op systolic blood pressure (p = 0.018) and post-op mean arterial pressure (p=0.001) were significantly associated with reduced odds of being in peritoneal dialysis + (p = 0.018 and p = 0.001, respectively). Post-op mean arterial pressure showed a statistically significant association adjusted odds ratio = 0.89, 95% confidence interval [0.81, 0.96], p = 0.004) with peritoneal dialysis + in multivariate analysis after adjusting for age at surgery. CONCLUSIONS: In our single-centre cohort, pre-op serum creatinine, post-op systolic blood pressure, and mean arterial pressure demonstrated statistically significant association with peritoneal dialysis +. This finding may help to better risk stratify newborns and young infants for early peritoneal dialysis start following cardiac surgery.

Acute kidney injury in pediatric hematopoietic cell transplantation: critical appraisal and consensus.

Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI). However, diagnosing HCT patients with AKI early on remains quite difficult. Therefore, this evidence-based guideline, compiled by the Pediatric Continuous Renal Replacement Therapy (PCRRT) working group, presents the various factors that contribute to AKI and recommendations regarding optimization of therapy with minimal complications in HCT patients.

Conversion to permanent vascular access is associated with improved markers of hemodialysis efficacy in children: Pediatric nephrology research consortium study.

BACKGROUND AND OBJECTIVES: Arteriovenous fistulae (AVF) and grafts (AVG) are preferred permanent vascular access (PVA) for chronic hemodialysis (HD) patients. Our objective was to examine the change in markers of HD efficacy after successful establishment of a PVA among children who started HD with a tunneled cuffed catheter (TCC). MATERIALS AND METHODS: Retrospective chart reviews were completed on patients from 20 pediatric dialysis centers. All patients used TCC prior to AVF/AVG, and each patient acted as his/her own control. Data on markers of HD efficacy (single-pool Kt/V, urea reduction ratio (URR), serum albumin and hematocrit (Hct)) were collected at the creation of AVF/AVG and for 2 years thereafter. Statistical methods included hypothesis testing and statistical modeling after adjusting for relevant demographic variables. RESULTS: First PVA was created in 98 individual children: 87 (89%) were AVF and 11 (11%) were AVG. The mean TCC vintage prior to AVF/AVG was 10.4 ± 17.3 months. At 1-year follow-up, Kt/V improved by 0.15 ± 0.06 (p = 0.02) and URR improved by 4.54 ± 1.17% (p < 0.0001). Furthermore, PVA was associated with improved serum albumin by 0.31 ± 0.07 g/dL (p < 0.0001) and Hct by 2.80 ± 0.65% (p < 0.0001) at 1 year. These HD efficacy markers remained statistically significant at 2nd-year follow-up. These observations were further supported by the adjusted models. Conversion to AVF was associated with statistically significant improvement in all four markers of HD efficacy at 1-year follow-up. This trend was not demonstrated for subjects who were converted to AVG. CONCLUSION: Switching to PVA was associated with improved markers of HD efficacy, single-pool Kt/V, URR, serum albumin, and Hct. This improvement was mostly demonstrated at 1 year and maintained for the 2nd year. The potential differential impact of the type of PVA on the trajectory of markers of HD efficacy should be further investigated.

Predictors of time to first cannulation for arteriovenous fistula in pediatric hemodialysis patients: Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Permanent vascular access (PVA) is preferred for long-term hemodialysis. Arteriovenous fistulae (AVF) have the best patency and the lowest complication rates compared to arteriovenous grafts (AVG) and tunneled cuffed catheters (TCC). However, AVF need time to mature. This study aimed to investigate predictors of time to first cannulation for AVF in pediatric hemodialysis patients. METHODS: Data on first AVF and AVG of patients at 20 pediatric dialysis centers were collected retrospectively, including demographics, clinical information, dialysis markers, and surgical data. Statistical modeling was used to investigate predictors of outcome. RESULTS: First PVA was created in 117 children: 103 (88%) AVF and 14 (12%) AVG. Mean age at AVF creation was 15.0 ± 3.3 years. AVF successfully matured in 89 children (86.4%), and mean time to first cannulation was 3.6 ± 2.5 months. In a multivariable regression model, study center, age, duration of non-permanent vascular access (NPVA), and Kt/V at AVF creation predicted time to first cannulation, with study center as the strongest predictor (p < 0.01). Time to first cannulation decreased with increasing age (p = 0.03) and with increasing Kt/V (p = 0.01), and increased with duration of NPVA (p = 0.03). Secondary failure occurred in 10 AVF (11.8%). Time to first cannulation did not predict secondary failure (p = 0.29), but longer time to first cannulation tended towards longer secondary patency (p = 0.06). CONCLUSIONS: Study center is the strongest predictor of time to first cannulation for AVF and deserves further investigation. Time to first cannulation is significantly shorter in older children, with more efficient dialysis treatments, and increases with longer NPVA duration.

Predictors of patency for arteriovenous fistulae and grafts in pediatric hemodialysis patients.

BACKGROUND: Hemodialysis (HD) guidelines recommend permanent vascular access (PVA) in children unlikely to receive kidney transplant within 1 year of starting HD. We aimed to determine predictors of primary and secondary patency of PVA in pediatric HD patients. METHODS: Retrospective chart reviews were performed for first PVAs in 20 participating centers. Variables collected included patient demographics, complications, interventions, and final outcome. RESULTS: There were 103 arterio-venous fistulae (AVF) and 14 AV grafts (AVG). AVF demonstrated superior primary (p = 0.0391) and secondary patency (p = 0.0227) compared to AVG. Primary failure occurred in 16 PVA (13.6%) and secondary failure in 14 PVA (12.2%). AVF were more likely to have primary failure (odds ratio (OR) = 2.10) and AVG had more secondary failure (OR = 3.33). No demographic, clinical, or laboratory variable predicted primary failure of PVA. Anatomical location of PVA was predictive of secondary failure, with radial having the lowest risk compared to brachial (OR = 12.425) or femoral PVA (OR = 118.618). Intervention-free survival was predictive of secondary patency for all PVA (p = 0.0252) and directly correlated with overall survival of AVF (p = 0.0197) but not AVG. Study center demonstrated statistically significant effect only on intervention-free AVF survival (p = 0.0082), but not number of complications or interventions, or outcomes. CONCLUSIONS: In this multi-center pediatric HD cohort, AVF demonstrated primary and secondary patency advantages over AVG. Radial PVA was least likely to develop secondary failure. Intervention-free survival was the only predictor of secondary patency for AVF and directly correlated with overall access survival. The study center effect on intervention-free survival of AVF deserves further investigation.

Correction to: Predictors of patency for arteriovenous fistulae and grafts in pediatric hemodialysis patients.

The original version of this article unfortunately contained a mistake. The name of Vimal Chadha was presented incorrectly. The corrected author list is given above.

Acute Kidney Injury in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation: Incidence, Risk Factors, and Outcomes.

Acute kidney injury (AKI) is a common adverse event after hematopoietic cell transplantation (HCT). AKI is associated with early death or chronic kidney disease among transplant survivors. However, large-scale pediatric studies based on standardized criteria are lacking. We performed a retrospective analysis of 1057 pediatric patients who received allogeneic HCT to evaluate the incidence and risk factors of AKI according to AKI Network criteria within the first 100 days of HCT. We also determined the effect of AKI on patient survival. The 100-day cumulative incidences of all stages of AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT) were 68.2% ± 1.4%, 25.0% ± 1.3%, and 7.6% ± .8%, respectively. Overall survival at 1 year was not different between patients without AKI and those with stage 1 or 2 AKI (66.1% versus 73.4% versus 63.9%, respectively) but was significantly different between patients without AKI and patients with stage 3 AKI with or without RRT requirement (66.1% versus 47.3% versus 7.5%, respectively; P < .001). Age, year of transplantation, donor type, sinusoidal obstruction syndrome (SOS), and acute graft-versus-host disease (GVHD) were independent risk factors for stages 1 through 3 AKI. Age, donor, conditioning regimen, number of HCTs, SOS, and acute GVHD were independent risk factors for AKI requiring RRT. Our study revealed that AKI was a prevalent adverse event, and severe stage 3 AKI, which was associated with reduced survival, was common after pediatric allogeneic HCT. All patients receiving allogeneic HCT, especially those with multiple risk factors, require careful renal monitoring according to standardized criteria to minimize nephrotoxic insults.

Comparison of Intraoperative Aminophylline Versus Furosemide in Treatment of Oliguria During Pediatric Cardiac Surgery.

OBJECTIVES: To determine if intraoperative aminophylline was superior to furosemide to prevent or attenuate postoperative cardiac surgery-associated acute kidney injury. DESIGN: Single-center, historical control, retrospective cohort study. SETTING: PICU, university-affiliated children's hospital. PATIENTS: Children with congenital heart disease in PICU who received furosemide or aminophylline to treat intraoperative oliguria. INTERVENTIONS: Intraoperative oliguria was treated either with furosemide (September 2007 to February 2012) or with aminophylline (February 2012 to June 2013). The postoperative 48 hours renal outcomes of the aminophylline group were compared with the furosemide group. The primary outcomes were acute kidney injury and renal replacement therapy use at 48 hours postoperatively. Surgical complexity was accounted for by the use of Risk Adjustment for Congenital Heart Surgery-1 score. MEASUREMENTS AND MAIN RESULTS: The study involves 69 months of observation. There were 200 cases younger than 21 years old reviewed for this study. Eighty-five cases (42.5%) developed acute kidney injury. The aminophylline group patients produced significantly more urine (mL/kg/hr) during the first 8 hours postoperatively than furosemide patients (5.1 vs 3.4 mL/kg/hr; p = 0.01). The urine output at 48 hours postoperatively was similar between the two groups. There was no difference in acute kidney injury incidence at 48 hours between the aminophylline and furosemide groups (38% vs 47%, respectively; p = 0.29). Fewer aminophylline group subjects required renal replacement therapy compared to the furosemide group subjects (n = 1 vs 7, respectively; p = 0.03). In the multi-variant predictive model, intraoperative aminophylline infusion was noted as a negative predictive factor for renal replacement therapy, but not for cardiac surgery-associated acute kidney injury. CONCLUSION: The intraoperative use of aminophylline was more effective than furosemide in reversal of oliguria in the early postoperative period. There were less renal replacement therapy-requiring acute kidney injury in children in the aminophylline group. Future prospective studies of intraoperative aminophylline to prevent cardiac surgery-associated acute kidney injury may be warranted.

A novel CLCN5 mutation in a boy with asymptomatic proteinuria and focal global glomerulosclerosis.

Dent disease is an X-linked proximal tubulopathy that typically presents with hypercalciuria, low-molecular-weight proteinuria and slow progression to endstage renal disease. We report the case of a 5-year-old boy who presented with asymptomatic nephrotic range proteinuria and was later diagnosed with Dent disease. Absence of specific glomerular pathology in the first kidney biopsy led to erroneous treatment for presumably unsampled primary focal segmental glomerulosclerosis. Aggressive angiotensin blockade and immunosuppression resulted in significant side effects with marginal benefit. The continued nonspecific findings after a second kidney biopsy 2 years later led to the suspicion of a congenital tubulopathy. We detected a novel CLCN5 gene mutation, c.1396G > C, that creates a G466R missense change in the ClC-5 protein. Dent disease should be considered in the differential diagnosis of asymptomatic proteinuria for male patients. Profiling proteinuria in these patients by spot urine albumin/creatinine ratio may give the first clue to a tubulopathy. Determining the extent to which the clinical work-up should proceed for females with Dent phenotype or asymptomatic proteinuria remains to be a challenging clinical dilemma.

Persistent Increase in Serum Ferritin Levels despite Converting to Permanent Vascular Access in Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study.

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = 0.049) and baseline serum ferritin level (p = 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.

Use of Aminophylline to Reverse Acute Kidney Injury in Pediatric Critical Care Patients.

OBJECTIVE: Acute kidney injury (AKI) is a complication encountered in 18% to 51% of pediatric critical care patients admitted for treatment of other primary diagnoses and is an independent risk factor for increased morbidity and mortality. Aminophylline has shown promise as a medication to treat AKI, but published studies have shown conflicting results. Our study seeks to assess the reversal of AKI following the administration of aminophylline in critically ill pediatric patients. METHODS: We performed a single-institution retrospective chart review of pediatric inpatients who were diagnosed with AKI and subsequently treated with non-continuous dose aminophylline between January 2016 and December 2018. Data were collected beginning 2 days prior to the initial dose of aminophylline through completion of the 5-day aminophylline course. RESULTS: Nineteen therapies among 17 patients were included in analysis. Twelve of the therapies resulted in resolution of AKI during the study period. We observed urine output increase of 19% (p = 0.0063) on the day following initiation of aminophylline therapy in the subset of patients whose AKI resolved. Trends toward decreased serum creatinine and lower inotropic support were also noted. CONCLUSIONS: Based on these findings, aminophylline could be considered a potentially effective medication for use as rescue therapy in critically ill children with AKI. Limitations include small study population and retrospective nature. Further research in this area with a larger study population and a randomized control trial would allow for better characterization of the efficacy of aminophylline in reversal of AKI.

Detecting the prevalence of bacterial colonization on tunneled cuffed hemodialysis catheters using quantitative PCR targeting 16S rRNA and scanning electron microscopy.

BACKGROUND AND OBJECTIVES: Tunneled cuffed hemodialysis catheters (TCC) get colonized by microorganisms, increasing risk for catheter related bacteremia (CRB). Our objective was to detect the prevalence of bacterial colonization of TCC by using quantitative PCR (qPCR) targeting 16S rRNA and by determining the intraluminal adherent biological material (ABM) coverage. METHODS: A total of 45 TCC were investigated. The 16S rRNA qPCR technique was used to detect bacterial colonization after scraping the intraluminal ABM. Proximal, middle, and distal TCC were evaluated by scanning electron microscopy (SEM) to determine the percentage (%) of intraluminal ABM coverage. All catheters were cultured following sonication. RESULTS: A total of 45 TCC were removed: 7 due to CRB, 3 for suspected CRB and 35 were removed for non-infectious etiologies. Bacterial colonization was detected in 27 TCC by documenting 16S rRNA qPCR (+) results (60%). Seven of these 16S rRNA qPCR (+) catheters were removed due to CRB. There was no difference in demographic, clinical, or laboratory values between the 16S rRNA (+) versus (-) TCC. The 16S rRNA qPCR (-) outcome was highly associated with CRB-free status with negative predictive value of 100%. Bacterial colonization was documented in 10 TCC using catheter cultures (22%), which was significantly less compared to qPCR method (p = 0.0002). ABM were detected in all catheter pieces, with mean intraluminal surface coverage (ABMC) of 68.4 ± 26.1%. ABM was unlikely to be microbial biofilm in at least 36% of removed TCC as their 16S rRNA qPCR and catheter culture results were both negative. CONCLUSIONS: Detecting bacterial colonization of TCC was significantly higher with 16S rRNA qPCR compared to catheter cultures. The 16S rRNA qPCR (-) cannot be predicted and was strongly associated with absence of CRB. Intraluminal ABM was not associated with microbial presence in about 1/3 of the TCC. These pieces of evidence may help to improve prophylactic strategies against CRB.

PREFABL: predictors of failure of antibiotic locks for the treatment of catheter-related bacteraemia.

BACKGROUND: Antibiotic lock (ABL) solutions can effectively treat catheter-related bacteraemia (CRB) without the need for catheter exchange. This approach does not increase secondary infectious complications. We evaluated the risk factors that contribute to failure when CRB is treated with ABLs and systemic antibiotics in paediatric haemodialysis patients. METHODS: A retrospective chart review of 72 children on haemodialysis between January 2004 and June 2006 was performed. We evaluated risk factors for ABL treatment using patients' characteristics, CRB/catheter characteristics and patients' biochemical profiles. The first CRB of each catheter was included in the statistical analysis. Our end points were outcome at 2 weeks of treatment and at 6 weeks following treatment. Compound symmetry covariance structure was employed for statistical analysis. RESULTS: We treated 149 CRB in 50 patients. The incidence was 3.4 CRB/1000 catheter days. Thirty CRB failed to be cleared with the use of ABL and systemic antibiotics at 2 weeks of treatment (30/149, 20 vs 80%, P < 0.001). Twenty-four of these catheters required exchange. Thirty-nine of the treated catheters got re-infected within the next 6 weeks (39/125, 31 vs 69%, P < 0.001). CRB aetiology was the only statistically significant independent variable for 2-week outcome (P = 0.033). Coagulase-negative Staphylococcus CRB had higher odds of being cleared at 2 weeks compared with other CRB aetiologies. For the 6-week outcome, the statistically significant independent variables in the final model included age (P = 0.048) and serum phosphorous level (P < 0.001). Younger age and higher serum phosphorous levels were independent risk factors for failure at 6 weeks with re-infection. Area under the receiver operating characteristic (ROC) curve for the model of the 2-week outcome was 0.736 with the percentage of correct predictions at 81.2%. Area under the ROC curve for the model of the 6-week outcome was 0.689 with the percentage of correct predictions at 75.5%. CONCLUSIONS: CRB can effectively be treated with ABLs and systemic antibiotics. CRB aetiology is the only independent variable of early treatment failure. Younger age and higher serum phosphorous levels are independent risk factors for re-infection at 6 weeks.

Chlorhexidine-based antiseptic solutions effectively reduce catheter-related bacteremia.

The aim of this retrospective study was to investigate if the application of chlorhexidine-based solutions (ChloraPrep) to the exit site and the hub of long-term hemodialysis catheters could prevent catheter-related bacteremia (CRB) and prolong catheter survival when compared with povidone-iodine solutions. There were 20,784 catheter days observed. Povidone-iodine solutions (Betadine) were used in the first half of the study and ChloraPrep was used in the second half for all the patients. Both groups received chlorhexidine-impregnated dressings at the exit sites. The use of ChloraPrep significantly decreased the incidence of CRB (1.0 vs 2.2/1,000 catheter days, respectively, P = 0.0415), and hospitalization due to CRB (1.8 days vs 4.1 days/1,000 catheter days, respectively, P = 0.0416). The incidence of exit site infection was similar for the two groups. Both the period of overall catheter survival (207.6 days vs 161.1 days, P = 0.0535) and that of infection-free catheter survival (122.0 days vs 106.9 days, P = 0.1100) tended to be longer for the catheters cleansed with ChloraPrep, with no statistical significance. In conclusion, chlorhexidine-based solutions are more effective for the prevention of CRB than povidone-iodine solutions. This positive impact cannot be explained by decreased number of exit site infections. This study supports the notion that the catheter hub is the entry site for CRB.

Prophylaxis of catheter-related bacteremia using tissue plasminogen activator-tobramycin locks.

This retrospective study was designed to investigate the effectiveness of tissue plasminogen activator-tobramycin antibiotic lock solutions (TPA/tobra ABLs) for prophylaxis of catheter-related bacteremia (CRB) in high-risk children on long-term hemodialysis. During the first 6 months (Era 1), the high-risk group was defined. These patients received TPA/tobra ABL prophylaxis after every hemodialysis treatment for the next 6 months (Era 2). The prophylaxis regimen was applied once a week for the third 6-months period (Era 3). Primary endpoints were CRB and infection-free catheter survival. There were 16,412 catheter days, and 95 cases of CRB in 43 children. The incidence of CRB was 5.8/1,000 catheter days. Significant decrease in the incidence of CRB was observed when prophylactic TPA/tobra ABL was used in the high-risk group (P = 0.0201). There was a tendency for less CRB when prophylactic ABL was applied after every hemodialysis session compared with once a week (P = 0.0947). The catheters in the high-risk group had shorter survival times than those in the average-risk group in Era 1 (P < 0.0001). However, both the overall and infection-free survival of the catheters in the high-risk group significantly improved while the patients were receiving TPA/tobra ABL prophylaxis, becoming similar to the outcomes of the catheters in the average-risk group and exhibiting statistically non-significant differences (P = 0.5571 and P = 0.9711, respectively). In conclusion, the TPA/tobra ABLs may effectively reduce the rate of CRB, and this may prolong both the overall and infection-free survival times of the catheters in the high-risk group.

Controlling exit site infections: does it decrease the incidence of catheter-related bacteremia in children on chronic hemodialysis?

The aim of this retrospective study was to investigate whether the application of a chlorhexidine-impregnated dressing (Biopatch) at the exit site of tunneled-cuffed hemodialysis catheters has any effect on the incidence and etiology of catheter-related bacteremia (CRB). This study was carried out over a 5-year period in a single center, where, in the first 2(1/2) years, the exit sites were cleansed with betadine at every hemodialysis session and then covered with a transparent dressing (pre-Biopatch Era). During the next 2(1/2) years, Biopatch was applied to the exit site once a week after cleansing with betadine, and then covered with a transparent dressing (Biopatch Era). The application of Biopatch significantly decreased the incidence of exit site infections (ESI) (P<0.05). However, there was no difference in the incidence of CRBs or their microbiological distribution. The improved ESI rate had no effect on the overall catheter survival time. The antimicrobial sensitivities of the Gram-positive microorganisms were statistically different for the 2 different types of infections (P<0.05). In conclusion, even though Biopatch is effective in decreasing the incidence of ESI, it has no effect on the incidence of CRB, the etiology of CRB, or the overall catheter survival time. The distinct difference between the antimicrobial sensitivities of the ESI and CRB suggests that they are not a spectrum of the same pathogenesis. These preliminary data support the intraluminal pathogenesis of CRB, rather than the exit site as a possible entry point for the extraluminal route.

Comparison of tissue plasminogen activator-antibiotic locks with heparin-antibiotic locks in children with catheter-related bacteraemia.

BACKGROUND: An accepted pathogenesis of catheter-related bacteraemia (CRB) is the seeding of microorganisms from the intraluminal biofilm of central venous catheters. Antibiotic locks (ABL) are solutions containing high concentrations of antimicrobials with or without anticoagulants that aim to destroy the biofilm. METHODS: In this study, two different ABL solutions, tissue plasminogen activator (TPA)-based and heparin-based ABL, used in conjunction with systemic antibiotics, were prospectively compared in the treatment of CRB. RESULTS: A total of 42 children on chronic haemodialysis with 11,016 catheter-days were observed for signs and symptoms of CRB over a period of 10 months. Twenty-four CRBs were diagnosed in 18 children (2.2 CRB/1000 catheter-days) and were treated with the protocol. Symptoms of CRB resolved in 83% within 48 h of treatment. None of the infected catheters required early emergent exchange or removal for poorly controlled CRB. Six children had recurrence of CRB within 6 weeks, of which four required catheter exchange. There was no specific microorganism or type of CRB that predisposed to higher recurrence rates. The mean infection-free survival of the catheters following TPA-ABL treatment was shorter than that following heparin-ABL treatment, but was not statistically significant by the log-rank test (126.8 +/- 81.6 days versus 154.5 +/- 70.4 days). CONCLUSION: Both TPA-ABL and heparin-ABL used in conjunction with systemic antibiotics can effectively clear CRB without significant late recurrence at 6 weeks. Early use of ABL for management of CRB can potentially decrease the need for catheter removal, thus salvaging vascular access sites.

CLCN2 chloride channel mutations in familial hyperaldosteronism type II.

Primary aldosteronism, a common cause of severe hypertension 1 , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) 2 and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proband. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. Channel opening depolarizes glomerulosa cells and induces expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis. Mutant channels show gain of function, with higher open probabilities at the glomerulosa resting potential. These findings for the first time demonstrate a role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. They establish the cause of a substantial fraction of early-onset primary aldosteronism.