Outcome 10 years after Shiga toxin-producing E. coli (STEC)-associated hemolytic uremic syndrome: importance of long-term follow-up.

BACKGROUND: Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in children. HUS is known as an acute disease followed by complete recovery, but patients may present with kidney abnormalities after long periods of time. This study evaluates the long-term outcome of Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) in pediatric patients, 10 years after the acute phase of disease to identify risk factors for long-term sequelae. METHODS: Over a 6-year period, 619 patients under 18 years of age with HUS (490 STEC-positive, 79%) were registered in Austria and Germany. Long-term follow-up data of 138 STEC-HUS-patients were available after 10 years for analysis. RESULTS: A total of 66% (n = 91, 95% CI 0.57-0.73) of patients fully recovered showing no sequelae after 10 years. An additional 34% (n = 47, 95% CI 0.27-0.43) presented either with decreased glomerular filtration rate (24%), proteinuria (23%), hypertension (17%), or neurological symptoms (3%). Thirty had sequelae 1 year after STEC-HUS, and the rest presented abnormalities unprecedented at the 2-year (n = 2), 3-year (n = 3), 5-year (n = 3), or 10-year (n = 9) follow-up. A total of 17 patients (36.2%) without kidney abnormalities at the 1-year follow-up presented with either proteinuria, hypertension, or decreased eGFR in subsequent follow-up visits. Patients needing extracorporeal treatments during the acute phase were at higher risk of presenting symptoms after 10 years (p < 0.05). CONCLUSIONS: Patients with STEC-HUS should undergo regular follow-up, for a minimum of 10 years following their index presentation, due to the risk of long-term sequelae of their disease. An initial critical illness, marked by need of kidney replacement therapy or plasma treatment may help predict poor long-term outcome.

Continuous renal replacement therapy in neonates and children: what does the pediatrician need to know? An overview from the Critical Care Nephrology Section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC).

Continuous renal replacement therapy (CRRT) is the preferred method for renal support in critically ill and hemodynamically unstable children in the pediatric intensive care unit (PICU) as it allows for gentle removal of fluids and solutes. The most frequent indications for CRRT include acute kidney injury (AKI) and fluid overload (FO) as well as non-renal indications such as removal of toxic metabolites in acute liver failure, inborn errors of metabolism, and intoxications and removal of inflammatory mediators in sepsis. AKI and/or FO are common in critically ill children and their presence is associated with worse outcomes. Therefore, early recognition of AKI and FO is important and timely transfer of patients who might require CRRT to a center with institutional expertise should be considered. Although CRRT has been increasingly used in the critical care setting, due to the lack of standardized recommendations, wide practice variations exist regarding the main aspects of CRRT application in critically ill children.     Conclusion: In this review, from the Critical Care Nephrology section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC), we summarize the key aspects of CRRT delivery and highlight the importance of adequate follow up among AKI survivors which might be of relevance for the general pediatric community. What is Known: • CRRT is the preferred method of renal support in critically ill and hemodynamically unstable children in the PICU as it allows for gentle removal of fluids and solutes. • Although CRRT has become an important and integral part of modern pediatric critical care, wide practice variations exist in all aspects of CRRT. What is New: • Given the lack of literature on guidance for a general pediatrician on when to refer a child for CRRT, we recommend timely transfer to a center with institutional expertise in CRRT, as both worsening AKI and FO have been associated with increased mortality. • Adequate follow-up of PICU patients with AKI and CRRT is highlighted as recent findings demonstrate that these children are at increased risk for adverse long-term outcomes.

Early relapse rate determines further relapse risk: results of a 5-year follow-up study on pediatric CFH-Ab HUS.

BACKGROUND: The complement factor H antibody (CFH-Ab)-associated hemolytic uremic syndrome (HUS) forms a distinct subgroup within the complement-mediated HUS disease spectrum. The autoimmune nature of this HUS subgroup implies the potential benefit of a targeted immunosuppressive therapy. Data on long-term outcome are scarce. METHODS: This observational study evaluates the clinical outcome of 19 pediatric CFH-Ab HUS patients from disease onset until their 5-year follow-up. RESULTS: All but one relapse occurred during the first 2 years, and patients who had no relapse within the first 6 months were relapse-free until the end of the observation period. Kidney function at disease onset determines long-term kidney function: all individuals with normal kidney function at disease onset had normal kidney function after 5 years, and all patients with reduced kidney function at onset had impaired kidney function at the last follow-up. Level of CFH-Ab titer at disease onset was not correlated with a higher risk of recurrences or worse long-term outcome after 5 years. Resolution of CFH-Ab titers after 5 years was common. CONCLUSIONS: CFH-Ab HUS patients have a varied overall long-term course. Early relapses are common, making close surveillance during the first years essential, regardless of the initial CFH-Ab titer.

Stereotactic radiofrequency ablation of a variety of liver masses in children.

BACKGROUND AND AIMS: Surgical resection is currently the cornerstone of liver tumor treatment in children. In adults radiofrequency ablation (RFA) is an established minimally invasive treatment option for small focal liver tumors. Multiprobe stereotactic RFA (SRFA) with intraoperative image fusion to confirm ablation margins allows treatment for large lesions. We describe our experience with SRFA in children with liver masses. METHODS: SRFA was performed in 10 patients with a median age of 14 years (range 0.5-17.0 years) suffering from liver adenoma (n = 3), hepatocellular carcinoma (n = 1), hepatoblastoma (n = 2), myofibroblastic tumor (n = 1), hepatic metastases of extrahepatic tumors (n = 2) and infiltrative hepatic cysts associated with alveolar echinococcosis (n = 1). Overall, 15 lesions with a mean lesion size of 2.6 cm (range 0.7-9.5 cm) were treated in 11 sessions. RESULTS: The technical success rate was 100%, as was the survival rate. No transient adverse effects higher than grade II (Clavien and Dindo) were encountered after interventions. The median hospital stay was 5 d (range 2-33 d). In two patients who subsequently underwent transplant hepatectomy complete ablation was histologically confirmed. Follow-up imaging studies (median 55 months, range 18-129 months) revealed no local or distant recurrence of disease in any patient. CONCLUSIONS: SRFA is an effective minimal-invasive treatment option in pediatric patients with liver tumors of different etiologies.

The Effect of Patient- and Treatment-Related Factors on Circuit Lifespan During Continuous Renal Replacement Therapy in Critically Ill Children.

OBJECTIVES: To examine the effects of patient and treatment variables on circuit lifespan in critically ill children requiring continuous renal replacement therapy. DESIGN: Retrospective observational study based on a prospective registry. SETTING: Tertiary referral 30-bed PICU. PATIENTS: One hundred sixty-one critically ill children undergoing continuous renal replacement therapy during an 8-year period (2007-2014) were included in the study. INTERVENTIONS: Continuous renal replacement therapy. MEASUREMENTS AND MAIN RESULTS: During the study period, 161 patients received a total of 22,190 hours of continuous renal replacement therapy, with a median duration of 74.75 hours (interquartile range, 32-169.5) per patient. Of the 572 filter circuits used, 276 (48.3%) were changed due to circuit clotting and 262 (45.8%) were electively changed. Median circuit life was 24.62 hours (interquartile range, 10.6-55.3) for all filters and significantly longer for those electively removed as compared to those prematurely removed because of clotting (35.50 hr [interquartile range, 16.9-67.6] vs 22.00 hr [interquartile range, 13.8-42.5]; p < 0.001). Multivariate regression analyses revealed that admission diagnosis (p < 0.001), anticoagulation type (p < 0.001), access type (p = 0.016), and circuit size (p = 0.027) were associated with prolonged circuit life, as well as, in patients on heparin anticoagulation, with higher doses of heparin (p < 0.001) and a prolonged activated partial thromboplastin time (p < 0.001). CONCLUSIONS: In this study, circuit lifespan in pediatric continuous renal replacement therapy was low and appeared to depend upon the patient's diagnosis, the type of access and anticoagulation used as well as the size of the circuit used.

Severe Deoxyguanosine Kinase Deficiency in Austria: A 6-Patient Series.

Mutations in the nuclear gene DGUOK, encoding deoxyguanosine kinase, cause an infantile hepatocerebral type of mitochondrial depletion syndrome (MDS). We report 6 MDS patients harboring bi-allelic DGUOK mutations, of which 3 are novel, including a large intragenic Austrian founder deletion. One patient was diagnosed with hepatocellular carcinoma aged 6 months, supporting a link between mitochondrial DNA depletion and tumorigenesis; liver transplantation proved beneficial with regard to both tumor treatment and psychomotor development.

Mortality of Critically Ill Children Requiring Continuous Renal Replacement Therapy: Effect of Fluid Overload, Underlying Disease, and Timing of Initiation.

OBJECTIVE: To identify risk factors associated with mortality in critically ill children requiring continuous renal replacement therapy. DESIGN: Retrospective observational study based on a prospective registry. SETTING: Tertiary and quaternary referral 30-bed PICU. PATIENTS: Critically ill children undergoing continuous renal replacement therapy were included in the study. INTERVENTIONS: Continuous renal replacement therapy. MEASUREMENTS AND MAIN RESULTS: Overall mortality was 36% (n = 58) among the 161 patients treated with continuous renal replacement therapy during the study period and was significantly higher in patients on extracorporeal membrane oxygenation (47.5%, 28 of 59) than in patients not requiring extracorporeal membrane oxygenation (28.4%, 29 of 102; p = 0.022). According to the admission diagnosis, we found the highest mortality in patients with onco-hematologic disease (77.8%) and the lowest in patients with renal disease (5.6%). Based on multivariate logistic regression analysis, the presence of higher severity of illness score at admission (adjusted odds ratio, 1.49; 95% CI, 1.18-1.89; p < 0.001), onco-hematologic disease (odds ratio, 17.10; 95% CI, 4.10-72.17; p < 0.001), fluid overload 10%-20% (odds ratio, 3.83; 95% CI, 1.33-11.07; p = 0.013), greater than 20% (odds ratio, 15.03; 95% CI, 4.03-56.05; p < 0.001), and timing of initiation of continuous renal replacement therapy (odds ratio, 1.01; 95% CI, 1.00-1.01; p = 0.040) were independently associated with mortality. In our population, the odds of dying increases by 1% for every hour of delay in continuous renal replacement therapy initiation from ICU admission. CONCLUSIONS: Mortality in children requiring continuous renal replacement therapy remains high and seems to be related to the underlying disease, the severity of illness, and the degree of fluid overload. In critically ill children at high risk for developing acute kidney injury and fluid overload, earlier initiation of continuous renal replacement therapy might result in decreased mortality.

Comparing modalities of conducting the six-minute walk test in healthy children and adolescents.

BACKGROUND: The 6-minute walk test (6MWT) in children can be performed in the conventional way, or by using a measuring wheel. This study aimed to compare these test modalities and to determine influencing factors. METHODS: The study included 317 healthy children (172 boys) between 6 and 15 years from elementary schools and high schools, who were randomly assigned to perform a 6MWT either with or without a measuring wheel according to the guidelines of the American Thoracic Society. The 6-minute walk distance (6MWD) was compared between the two measuring modalities as well as different school types. RESULTS: The use of a measuring wheel during the 6MWT led to a significantly greater 6MWD compared to conventional walking. Students of sports schools walked substantially farther than those attending general high schools, irrespective of test modality. In multivariate regression analysis height, post-test heart rate, male sex and the measuring wheel itself were all independently associated with greater 6MWD. CONCLUSIONS: The use of a measuring wheel during a 6MWT reflects physical performance in children and adolescents more accurately as it includes the stretch of way around the cones during lap turns. Test modalities and sports background should be taken into account, especially when performing longitudinal monitoring and multicenter studies.

Therapeutic Plasma Exchange in Critically Ill Children Requiring Intensive Care.

OBJECTIVE: To characterize the clinical indications, procedural safety, and outcome of critically ill children requiring therapeutic plasma exchange. DESIGN: Retrospective observational study based on a prospective registry. SETTING: Tertiary and quaternary referral 30-bed PICU. PATIENTS: Forty-eight critically ill children who received therapeutic plasma exchange during an 8-year period (2007-2014) were included in the study. INTERVENTIONS: Therapeutic plasma exchange. MEASUREMENTS AND MAIN RESULTS: A total of 48 patients underwent 244 therapeutic plasma exchange sessions. Of those, therapeutic plasma exchange was performed as sole procedure in 193 (79%), in combination with continuous renal replacement therapy in 40 (16.4%) and additional extracorporeal membrane oxygenation in 11 (4.6%) sessions. The most common admission diagnoses were hematologic disorders (30%), solid organ transplantation (20%), neurologic disorders (20%), and rheumatologic disorders (15%). Complications associated with the procedure occurred in 50 (21.2%) therapeutic plasma exchange sessions. Overall, patient survival from ICU was 82%. Although patients requiring therapeutic plasma exchange alone (n = 31; 64%) had a survival rate of 97%, those with additional continuous renal replacement therapy (n = 13; 27%) and extracorporeal membrane oxygenation (n = 4; 8%) had survival rates of 69% and 50%, respectively. Factors associated with increased mortality were lower Pediatric Index of Mortality 2 score, need for mechanical ventilation, higher number of failed organs, and longer ICU stay. CONCLUSION: Our results indicate that, in specialized centers, therapeutic plasma exchange can be performed relatively safely in critically ill children, alone or in combination with continuous renal replacement therapy and extracorporeal membrane oxygenation. Outcome in children requiring therapeutic plasma exchange alone is excellent. However, survival decreases with the number of failed organs and the need for continuous renal replacement therapy and extracorporeal membrane oxygenation.

Prolonged extracorporeal membrane oxygenation for pediatric necrotizing pneumonia due to Streptococcus pneumonia and influenza H1N1 co-infection: how long should we wait for native lung recovery?

Most children with severe respiratory failure require extracorporeal membrane oxygenation (ECMO) for 7-10 days. However, some may need prolonged duration ECMO (> 14 days). To date, no consensus exists on how long to wait for native lung recovery. Here we report the case of a 3-year-old boy who developed severe necrotizing pneumonia requiring venovenous (VV) ECMO after 19 days of mechanical ventilation. In the first 4 weeks of his ECMO run, he showed no lung aeration, requiring total extracorporeal support. However, after we started strategies for promoting lung recovery such as daily prone positioning and regular use of toilet bronchoscopy and inhalative DNAse to clear secretions, by week five his tidal volumes gradually increased and he was successfully decannulated after 43 days. Moreover, we decided not to proceed to a surgical removal of the necrotic lung area. At present, he is 1-year post discharge and has fully recovered. This report shows that unexpected native lung recovery is possible even after prolonged loss of lung function and that a previous healthy lung can recover from apparent irreversible lung injury.

Standardized training for AVT pacing in paediatric patients with postoperative junctional ectopic tachycardia.

BACKGROUND: Junctional ectopic tachycardia is a serious complication of surgery for paediatric congenital heart disease. R-wave synchronized atrial (AVT) pacing, an innovative temporary pacing technique, restores atrioventricular synchrony in these patients. The method is highly effective but technically complex. A standardized training model exists for doctors but not for paediatric intensive care nurses. AIMS: This study seeks to evaluate whether a standardized programme involving simulation and vignettes increases knowledge of AVT pacing and accuracy of its documentation, as well as recognition and management of specific complications. STUDY DESIGN: This study was an experimental simulation test with before and after descriptive evaluation. METHODS: A custom-made simulation model was used in combination with standardized training. Before and after training, 10 paediatric nurse specialists were asked to document pacing, to identify complications and to intervene as necessary. Four clinical scenarios were presented: effective AVT pacing, ineffective AVT pacing, pacing with narrow interval between atrial pacing and ventricular sensing and pacemaker-induced tachycardia. Identification and management of complications were evaluated using a 3-point scale. RESULTS: Training improved the quality of documentation and complication management. At outset, documentation by 1 of 10 participants was completely correct, and after training, documentation by 8 of 10 participants was completely correct. Before training, 30% of interpretations of the four presented clinical scenarios were correct (12/40) versus 83% (33/40) after training. The decision to notify a doctor of a complication was correct in 83% (33/40) before versus 95% (38/40) after the training. CONCLUSION: Standardized simulation training improves quality and safety in AVT pacing, with more accurate documentation of the pacing mode and better recognition and management of specific complications during pacing. RELEVANCE TO CLINICAL PRACTICE: AVT pacing should be performed in conjunction with standardized simulation training in paediatric cardiac intensive care units.

Therapeutic plasma exchange in children: One center's experience.

BACKGROUND: Therapeutic plasma exchange (TPE) has evolved to an accepted therapy for selected indications. However, it is technically challenging in children. Moreover, data on safety and efficacy are mainly derived from adult series. The aim of this study was to review the procedure in the context of clinical indications, effectiveness, and safety. STUDY DESIGN AND METHODS: All TPE procedures performed at a tertiary care hospital during a 12-year period (2005-2016) were retrospectively evaluated. RESULTS: Eighteen patients with a median age of 8.5 (0.2-17) years underwent a total of 280 TPE sessions. Eleven (61%) patients were treated for renal diseases. Three (17%) patients were diagnosed with neurological diseases, two had liver failure, and one patient each had sepsis and stem cell transplant-associated thrombotic microangiopathy. Seven patients (39%) were classified as American Society for Apheresis Category I, four (22%) as Category II, two (13%) each as Category III and IV, and two (13%) were not classified. Two patients with atypical hemolytic-uremic syndrome received TPE as long-term therapy over 2 and 5 years. All procedures were performed using the filtration technique and heparin anticoagulation. Twelve (67%) patients showed full or partial recovery after TPE, six had no response or an uncertain response. Minor adverse events occurred in 30/280 (10.6%) procedures, and one major complication (0.4%) was reported. CONCLUSION: TPE is a safe apheresis method in children, even when performed as a long-term therapy. Efficacy is high under selected conditions. A highly skilled and experienced staff is mandatory to ensure patient safety and efficacy.

Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.

Clonidine as a First-Line Sedative Agent After Neonatal Cardiac Surgery: Retrospective Cohort Study.

OBJECTIVES: To determine the cardiovascular tolerance of clonidine used as a first-line sedative after cardiac surgery in small infants. DESIGN: Retrospective chart review. SETTING: A tertiary and quaternary referral cardiac PICU. PATIENTS: All infants younger than 2 months who received a clonidine infusion for sedation after cardiac surgery from October 2011 to July 2013. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Heart rate, blood pressure, central venous and left atrial pressure, vasoactive inotropic score, volume of fluid bolus, and lactate and central mixed venous saturation were assessed. Preinfusion values were compared with postinfusion values. Of 224 potentially eligible patients, only 23 infants met inclusion criteria, as most patients only received high doses of morphine and some received midazolam instead of clonidine. Clonidine administration was started at a median of 12 hours after surgery (Q1-Q3, 5-23), and infusion rate was 0.5-2 µg/kg/hr for a median duration of 30 hours (Q1-Q3, 12-54). Heart rate decreased (maximal mean decrease: 12% [149 beats/min (SD, 17) to 131 beats/min (SD, 17)]; p < 0.0001). Apart from a transient and limited drop in diastolic blood pressure of 13% (maximal mean decrease: from 42.8 mm Hg [SD, 5.9] to 37.1 mm Hg [SD, 4.0]; p = 0.018), all other cardiovascular variables were stable or improved. A contemporaneous cohort of patients who received midazolam, did so sooner after surgery, stayed longer in the PICU and showed less favorable hemodynamics. CONCLUSIONS: IV clonidine as sedative added to morphine in selected patients seems hemodynamically safe. The observed decrease in heart rate and diastolic blood pressure seems of minimal clinical importance as all other hemodynamic variables remained stable or improved. The safety of clonidine given early after cardiac surgery as alternative to midazolam merits further study.

A Comparative Analysis of Preemptive Versus Targeted Sedation on Cardiovascular Stability After High-Risk Cardiac Surgery in Infants.

OBJECTIVE: To compare the effect of two sedation practices on cardiovascular stability during the early postoperative period in young infants following cardiac surgery: the routine early use of midazolam infusion (preemptive sedation) and the discretionary use of sedatives tailored to the patient's clinical condition (targeted sedation). DESIGN: Retrospective cohort study with matched controls. SETTING: A 15-bedded pediatric cardiac ICU. PATIENTS: Sedation strategies were compared by matching patients before and after the introduction of a targeted sedation guideline, replacing the existing practice of preemptive sedation. Inclusion criteria were age less than 6 months and cardiopulmonary bypass time greater than 150 minutes. Matching criteria were surgical procedure, age, and duration of cardiopulmonary bypass and cross-clamp. The main outcome was cardiovascular instability, defined by the presence of one of the following criteria in the first 12 hours after PICU admission: 1) simultaneous administration of greater than or equal to two inotropic or vasopressor drugs; 2) administration of greater than 60 mL/kg fluid boluses. Secondary outcomes were: 1) markers of cardiac output adequacy (heart rate, blood pressure, vasoactive inotropic score, urine output, volume of fluid boluses, central venous oxygen saturation, lactate); 2) occurrence of adverse events (cardiac arrest, extracorporeal membrane oxygenation, death); 3) sedatives administered and depth of sedation. INTERVENTIONS: Introduction of a guideline of targeted sedation. MEASUREMENTS AND MAIN RESULTS: Thirty-three patients with preemptive sedation were matched to 33 patients with targeted sedation. Targeted sedation resulted in less frequent oversedation, without compromising cardiovascular stability, as indicated by similar occurrence of cardiovascular instability (68.8% with preemptive sedation vs 62.5% with targeted sedation; p = 0.53) and adverse events, and similar markers of cardiac output adequacy. Although all preemptively sedated patients received an infusion of midazolam in the first 12 hours after surgery, only 19.4% of patients in the targeted sedation group received a sedative infusion (p < 0.001). CONCLUSIONS: Our data suggest that after high-risk cardiac surgery in young infants, routine sedation with midazolam may not prevent low cardiac output syndrome. When accompanied by a careful assessment of level of sedation, routine sedation of infants after high-risk cardiac surgery can be avoided without compromising hemodynamic stability or patient safety. The potential benefit of this approach is reduced exposure to sedative.

Successful living-related renal transplantation in a patient with factor H antibody-associated atypical hemolytic uremic syndrome.

CFH-Ab-associated aHUS requires different diagnostic and therapeutic approaches and then the genetically defined aHUS forms. The risk of post-transplant recurrence with graft dysfunction in CFH-Ab aHUS is not well documented. It is suggested that recurrence can be expected if a significant CFH-Ab load persists at the time of transplantation. A pretransplant procedure to reduce CFH-Ab titer seems reasonable, but accurate recommendations are lacking. Whether further prophylactic interventions after transplantation are necessary has to be decided on an individual basis. We report the case of a late diagnosed CFH-Ab HUS with initial ESRD and a successful living-related renal transplantation over a post-transplant period of four and a half years on the basis of a prophylactic pretransplant IVIG admission.

De novo tacrolimus-induced thrombotic microangiopathy in the early stage after renal transplantation successfully treated with conversion to everolimus.

BACKGROUND: Calcineurin inhibitor (CNI)-induced thrombotic microangiopathy (TMA) is a rare complication after renal transplantation. It may be difficult to distinguish from CNI toxicity and acute antibody-mediated rejection (AMR). Its clinical presentation may vary from isolated localised forms up to catastrophic systemic presentations. CASE: We report a case of tacrolimus-induced TMA soon after renal transplantation in an 11-year-old boy who received his second renal transplantation. His first graft was lost because of AMR. On day 12 after his second renal transplantation, his renal function started worsening and a kidney biopsy was performed, which showed histopathological signs of TMA. The diagnosis of tacrolimus-induced TMA was established after excluding AMR and other causes of de novo TMA. Genetic complement investigation disclosed two complement factor H risk polymorphisms as possible modifiers of TMA emergence. Treatment was based on replacing tacrolimus with everolimus, with a subsequent normalisation of renal function. CONCLUSION: A prompt diagnosis of de novo TMA by early allograft biopsy is essential for the allograft outcome and genetic investigations for possible complement abnormalities are reasonable, not only for patients with a systemic aspect of their post-transplant TMA. Replacing tacrolimus with everolimus effectively controlled the TMA and stabilised renal function in our patient.

Severe visual loss caused by unrecognized malignant hypertension in a 15-year-old girl.

A 15-year-old girl presented with acute bilateral loss of central visual acuity due to hypertensive retinopathy level IV. She was found to have unrecognized malignant arterial hypertension associated with end-stage renal failure. At the time of diagnosis she also had severe left ventricular hypertrophy (LVH). Hypertension was successfully treated with combined anti-hypertensive therapy, but renal function did not recover. The patient underwent successful kidney transplant 4 months later and over a period of 20 months hypertensive retinopathy and LVH gradually resolved. This report emphasizes the importance of routine measurement of blood pressure and describes the possible consequences of unrecognized arterial hypertension in children. Early diagnosis and appropriate treatment are necessary to avoid development and progression of target organ damage and promote better long-term cardiovascular prognosis.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults.

Importance: In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. Objective: To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). Design, Setting, and Participants: This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. Exposure: The primary exposure was time to CRRT initiation from intensive care unit admission. Main Outcomes and measures: The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Results: Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]). Conclusions and Relevance: In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.