Cheryl L. Tran

AKI in Children Hospitalized with Nephrotic Syndrome

BACKGROUND AND OBJECTIVES Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition. RESULTS AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001). CONCLUSIONS AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.

Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group

Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses and potentially serious complications. The typical clinical presentation is microangiopathic hemolytic anemia accompanied by thrombocytopenia with varying degrees of organ ischemia. The differential diagnoses are generally broad, while the workup is frequently complex and can be confusing. This statement represents the joint recommendations from a multidisciplinary team of Mayo Clinic physicians specializing in the management of TMA. It comprises a series of evidence- and consensus-based clinical pathways developed to allow a uniform approach to the spectrum of care including when to suspect TMA, what differential diagnoses to consider, which diagnostic tests to order, and how to provide initial empiric therapy, as well as some guidance on subsequent management.

Inpatient Health Care Utilization by Children and Adolescents With Systemic Lupus Erythematosus and Kidney Involvement

To evaluate inpatient health care utilization for children with systemic lupus erythematosus (SLE) with and without kidney disease.

Membranous nephropathy associated with angiomatoid fibrous histiocytoma in a pediatric patient.

BackgroundThough membranous nephropathy is a much more common cause of nephrotic syndrome in the adult population, it accounts for only a small fraction of cases in pediatrics.Case-Diagnosis/TreatmentWe report a case of a 16-year-old boy with nephrotic syndrome due to membranous nephropathy in the setting of a rare tumor, angiomatoid fibrous histiocytoma. This patient’s nephrotic-range proteinuria completely resolved following resection of this tumor. Angiomatoid fibrous histiocytoma, while known to cause other paraneoplastic syndromes such as anemia, has never been reported to cause membranous nephropathy.ConclusionsThis case highlights a novel and treatable secondary cause of membranous nephropathy. Because secondary causes are more common in children than in adults, a high index of suspicion for other underlying pathology including malignancy should be considered. It also suggests that urinalysis may be a helpful screening tool in cases of angiomatoid fibrous histiocytoma.

Redefining Nephrotic Syndrome in Molecular Terms: Outcome-associated molecular clusters and patient stratification with noninvasive surrogate biomarkers

A tissue transcriptome driven classification of nephrotic syndrome patients identified a high risk group of patients with TNF activation and established a non-invasive marker panel for pathway activity assessment paving the way towards precision medicine trials in NS. Abstract Nephrotic syndrome from primary glomerular diseases can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). Conventional diagnoses using a combination of clinical presentation and descriptive biopsy information do not accurately predict risk for progression in patients with nephrotic syndrome, which complicates disease management. To address this challenge, a transcriptome-driven approach was used to classify patients with minimal change disease and focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network (NEPTUNE). Transcriptome-based classification revealed a group of patients at risk for disease progression. High risk patients had a transcriptome profile consistent with TNF activation. Non-invasive urine biomarkers TIMP1 and CCL2 (MCP1), which are causally downstream of TNF, accurately predicted TNF activation in the NEPTUNE cohort setting the stage for patient stratification approaches and precision medicine in kidney disease.

Suspected thrombotic microangiopathy in a child with Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis

To the Editor: Thrombotic microangiopathy (TMA) is a form of endothelial injury that has been reported as a complication of hemophagocytic lymphohistiocytosis (HLH) in adults.1 We report a case of Epstein–Barr virus (EBV)-induced HLH and suspected TMA in a child. A 9-year-old female was transferred to our intensive care unit with acute liver and renal failure after several days of fever, sore throat, and abdominal pain. She had cervical lymphadenopathy and hepatosplenomegaly. Laboratory studies upon her arrival are shown in Table 1. A peripheral blood smear showed only reactive lymphocytes, but no schistocytes. A diagnosis of EBV-induced HLHwas made as the patient met criteria with five of the eight diagnostic features of the disease.2 Sequencing of HLH associated genes only detected a variant of uncertain significance in the LYST gene. The patient developed pulmonary edema requiring mechanical ventilation, and continuous renal replacement therapy was initiated. Treatment for HLH was initiated using protocol HLH-94 (dexamethasoneandetoposide; cyclosporineomitteddue to renal failure). The patient developed upper gastrointestinal bleeding requiring laparotomy, and in the setting of a worsening clinical picture, rituximab was initiated.3 Abdominal cultures grew Candida albicans, and caspofungin was administered. Computed tomography angiography (CTA) revealed nodularity of the mesenteric arteries and veins. Complement studies showed elevated C3b and C5b-9, consistent with activation of the alternative pathway. Eculizumab was begun. CTA on hospital day (HD) 15 revealed bowel wall thickening, high intraluminal attenuation, and ascites (Supplementary Figure S1). A week later, alemtuzumab was started, followed by anakinra.4 Laparotomy revealed fibrinous exudate coating the intestines, and the liver was biopsied (Supplementary Figure S2). Cultures grew Rhizopus and C. albicans. Liposomal amphotericin was given. On HD 33, life-sustaining measures were withdrawn, and the patient died. An autopsy was declined. We describe a fatal case of EBV-induced HLH complicated by a severe complement-mediated process and fungal infection. TMA has not been previously reported in the setting of pediatric EBV-induced HLH, but is a common complication of hematopoietic stem cell transplantation (HSCT) in children.5 While there are no diagnostic criteria for TMA in the setting of HLH, criteria have been proposed for HSCT recipients.6 These include: (1) lactate dehydrogenase (LDH) above the upper limit of normal for age; (2) de novo thrombocytopenia with <50 platelets per mcl or ≥50% decrease in platelets; (3) de novo anemia with hemoglobin below the lower limit of normal or anemia requiring transfusion support; (4) schistocytes in peripheral blood or histologic evidence of microangiopathy on a tissue specimen; and (5) absence of a coagulopathy to explain the above findings and a negative Coombs TABLE 1 Patients laboratory data

Younger Adults Initiating Hemodialysis: Antidepressant Use for Depression Associated With Higher Health Care Utilization

Objective: To examine associations between antidepressant use and health care utilization in young adults beginning maintenance hemodialysis (HD) therapy. Patients and Methods: Antidepressant use, hospitalizations, and emergency department (ED) visits were examined in young adults (N=130; age, 18‐44 years) initiating HD (from January 1, 2001, through December 31, 2013) at a midwestern US institution. Primary outcomes included hospitalizations and ED visits during the first year. Results: Depression diagnosis was common (47; 36.2%) at HD initiation, yet only 28 patients (21.5%) in the cohort were receiving antidepressant therapy. The antidepressant use group was more likely to have diabetes mellitus (18 [64.3%] vs 33 [32.4%]), coronary artery disease (8 [28.6%] vs 12 [11.8%]), and heart failure (9 [32.1%] vs 15 [14.7%]) (P<.05 for all) than the untreated group. Overall, 68 (52.3%) had 1 or more hospitalizations and 33 (25.4%) had 1 or more ED visits in the first year. The risk of hospitalization during the first year was higher in the antidepressant use group (hazard ratio, 2.35; 95% CI, 1.39‐3.96; P=.001), which persisted after adjustment for diabetes, coronary artery disease, and heart failure (hazard ratio, 1.94; 95% CI, 1.22‐3.10; P=.006). Emergency department visit rates were similar between the groups. Conclusion: Depression and antidepressant use for mood indication are common in young adult incident patients initiating HD and and are associated with higher hospitalization rates during the first year. Further research should determine whether antidepressants are a marker for other comorbidities or whether treated depression affects the increased health care use in these individuals.