Continuous Kidney Replacement Therapy and Survival in Children and Young Adults: Findings From the Multinational WE-ROCK Collaborative.

RATIONALE & OBJECTIVE: There are limited studies describing the epidemiology and outcomes in children and young adults receiving continuous kidney replacement therapy (CKRT). We aimed to describe associations between patient characteristics, CKRT prescription, and survival. STUDY DESIGN: Retrospective multicenter cohort study. SETTING & PARTICIPANTS: 980 patients aged from birth to 25 years who received CKRT between 2015 and 2021 at 1 of 32 centers in 7 countries participating in WE-ROCK (Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases). EXPOSURE: CKRT for acute kidney injury or volume overload. OUTCOMES: Death before intensive care unit (ICU) discharge. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Median age was 8.8 years (IQR, 1.6-15.0), and median weight was 26.8 (IQR, 11.6-55.0) kg. CKRT was initiated a median of 2 (IQR, 1-6) days after ICU admission and lasted a median of 6 (IQR, 3-14) days. The most common CKRT modality was continuous venovenous hemodiafiltration. Citrate anticoagulation was used in 62%, and the internal jugular vein was the most common catheter placement location (66%). 629 participants (64.1%) survived at least until ICU discharge. CKRT dose, filter type, and anticoagulation were similar in those who did and did not survive to ICU discharge. There were apparent practice variations by institutional ICU size. LIMITATIONS: Retrospective design; limited representation from centers outside the United States. CONCLUSIONS: In this study of children and young adults receiving CKRT, approximately two thirds survived at least until ICU discharge. Although variations in dialysis mode and dose, catheter size and location, and anticoagulation were observed, survival was not detected to be associated with these parameters. PLAIN-LANGUAGE SUMMARY: In this large contemporary epidemiological study of children and young adults receiving continuous kidney replacement therapy in the intensive care unit, we observed that two thirds of patients survived at least until ICU discharge. However, patients with comorbidities appeared to have worse outcomes. Compared with previously published reports on continuous kidney replacement therapy practice, we observed greater use of continuous venovenous hemodiafiltration with regional citrate anticoagulation.

Blasting off: persistent hypertension in a child with neuroblastoma.

Hypertension in children with neuroblastoma is uncommon and can be difficult to control due to the potential for multiple underlying causes. We present the case of a pediatric patient with high-grade neuroblastoma which was complicated by hypertensive emergency. The patient had imaging suggestive of renal artery compression, as well as significantly elevated normetaphrine levels. Multiple anti-hypertensive agents, including an angiotensin converting enzyme inhibitor, α- and ß-adrenergic receptor blockers, and a tyrosine hydroxylase inhibitor, were initiated prior to tumor excision. While her blood pressure improved during the post-operative period, she continued to require multiple antihypertensive medications due to residual tumor burden. In this report, we highlight the importance of careful, multidisciplinary management to avoid peri-operative complications in patients with catecholamine-producing tumors.

A balancing act: drifting away from the reflexive use of "ab"normal saline.

Maintenance intravenous fluids are the most frequently ordered medications for hospitalized children. Since the American Association of Pediatrics published national guidelines, there has been an increased reflexive use of isotonic solutions, especially 0.9% saline, as a prophylaxis against hyponatremia. In this educational review, we discuss the potential deleterious effects of using 0.9% saline, including the development of hyperchloremia, metabolic acidosis, acute kidney injury, hyperkalemia, and a proinflammatory state. Balanced solutions with anion buffers cause relatively minimal harm when used in most children. While the literature supporting one fluid choice over the other is variable, we highlight the benefits of balanced solutions over saline and the importance of prescribing fluid therapy that is individualized for each patient.

The light at the end of the tunnel: an unusual case of acute kidney injury in a pediatric patient: Answers.

Monoclonal gammopathies are a rare diagnosis in pediatric patients. A 19-year-old female patient with past medical history of hypogammaglobulinemia and natural killer cell deficiency and stage III follicular lymphoma, in remission, presented with a right-sided pneumonia, noted to have acute kidney injury and proteinuria. Complement C3 and C4 levels were normal. Anti-double-stranded DNA antibodies, antinuclear antibodies, anti-extractable nuclear antigen antibodies, and antineutrophil cytoplasmic antibodies were negative. A renal biopsy showed numerous fractured tubular casts that were periodic acid-Schiff and silver-stain negative and fuchsinophilic on trichrome stain, with associated giant cells, tubulitis, acute tubular injury, and tubular rupture. The tubular casts had 3+ staining for lambda light chains and 0-1+ staining for kappa light chains. These findings were consistent with light chain cast nephropathy (LCCN). Serum free light chains, serum immunofixation, urine protein electrophoresis, and urine immunofixation studies supported the renal biopsy diagnosis of LCCN. A bone marrow biopsy showed normal trilineage hematopoiesis and also revealed an atypical B cell population detected by flow cytometry. Pathology specimens from lesions in the distal small bowel were characteristic of diffuse large B cell lymphoma (DLBCL). Chemoreduction therapy followed by chemotherapy was initiated for the DLBCL. Three months after initiation of chemotherapy, the patient's creatinine has improved by > 50%. The likely cause of her LCCN was the new diagnosis of a DLBCL. Other risk factors include her history of hypogammaglobulinemia, natural killer (NK) cell deficiency, community-acquired pneumonia, and prior follicular lymphoma. Our patient may be the youngest reported case of LCCN. Treatment of LCCN is based on treating the underlying clonal plasma cell or B cell proliferation, typically with chemotherapy.

Emerging biomarkers of chronic kidney disease in children.

Chronic kidney disease (CKD) has become a significant public health concern, as it is associated with substantial morbidity. Prior research has evaluated multiple novel CKD biomarkers to supplement serum creatinine and proteinuria. The ultimate goal of this research is to find biomarkers that can be used to accurately predict CKD progression and to better time outpatient follow-up, and referral for transplant. Also, an optimal panel of biomarkers can augment the predictive value of proteinuria and serum creatinine by enriching patient enrollment in clinical trials. In this review, we discuss salient findings on 12 candidate plasma and urine biomarkers and their reported association with CKD. We explore the common pathways of CKD progression and the pathophysiologic processes of tubulointerstitial injury, inflammation, repair, and fibrosis that are potentially classified by specific biomarkers. We describe both pediatric and adult findings and highlight the paucity of pediatric research in CKD progression. It will be important for cohorts with longitudinal follow-up to evaluate these CKD biomarkers for potential use in pediatric clinical trials and routine CKD management.

Membrane pressures predict clotting of pediatric continuous renal replacement therapy circuits.

BACKGROUND: Clotting of continuous renal replacement therapy (CRRT) circuits leads to inadequate clearance, decreased ultrafiltration, and increased resource use. We identified factors associated with premature clotting of circuits during CRRT in children. METHODS: In a retrospective cohort of 26 children (median age 11.8 years) receiving 79 CRRT circuits (51 heparin, 22 citrate, 6 using no anticoagulation), we captured hourly pressure, flow, and fluid removal rates along with all activated clotting time (ACT) and circuit ionized calcium measurements. Cox and logistic regression models were used to examine factors associated with premature circuit clotting before the scheduled 3-day circuit change. RESULTS: Of the 79 circuits, 51 (64.6%) underwent unplanned filter change due to filter clotting (median duration 18.25 h, interquartile range [IQR] 9.25, 33.5 h), and 28 (35.4%) underwent scheduled change (median duration 66 h, IQR 61.00, 69.00 h). Patient age, catheter size and location, blood flow rate, and the percentage of pre-filter replacement fluid were not associated with premature clotting. Heparin circuits were less likely than citrate circuits to clot prematurely. Each 1-mmHg increase in the transmembrane or filter pressure was independently associated with a 1.5% (95% confidence interval [CI] 1.0-2.0%) and 1.5% (95% CI 1.0-2.0%) higher risk of clotting, respectively. Higher ACTs were associated with lower transmembrane (p = 0.03) and filter (p < 0.001) pressures. CONCLUSIONS: The majority of circuits in our cohort were subject to unplanned filter changes. Elevated transmembrane and filter pressures were associated with clotting. Our results suggest that maintaining higher ACT may decrease the risk of circuit clotting. Larger studies are needed to examine other factors that may prolong the lifespan of the CRRT circuit in this high-risk population.

Variability in measures of mineral metabolism in children on hemodialysis: impact on clinical decision-making.

BACKGROUND: Variability in measures of mineral metabolism has not been studied in pediatric end stage kidney disease. We sought to determine the intra-individual variability in measures of mineral metabolism in children on hemodialysis (HD) and its impact on clinical decision-making. METHODS: We conducted a prospective single-center study of children (3.6-17.3 years old) on chronic HD. Serial twice weekly measures of serum calcium, phosphate and intact parathyroid hormone (PTH), as well as weekly measures of fibroblast growth factor 23 (FGF23) and vitamin D metabolites, were obtained over a 12-week period in 10 children. Samples (n = 226) were assayed in a single batch at the end of the study. RESULTS: The median intra-individual coefficient of variation (CV) calculated by 4-week blocks was 5.1-6.5% for calcium, 9.5-14.9% for phosphate and 32.7-33.4% for PTH. The median overall CV for FGF23 was 44.4%. Using the first value of each block as a reference, subsequent values would dictate a discrepant management decision 33-56%, 19-28%, and 30-33% of the time for calcium, phosphate, and PTH, respectively. Adjusting for sex and age, most of the variability in phosphate and PTH was attributable to within-participant variability. For calcium, 49% of the variability was attributable to day of blood collection (Monday vs. Friday). The median (range) of an individual participant's values within clinical target ranges was 55% (26-86%) for calcium, 58% (0-96%) for phosphate, and 21% (0-64%) for PTH. CONCLUSIONS: There is considerable intra-individual variability in measures of mineral metabolism that serve as surrogate markers for bone health in children on HD. Within a 4-week period, at least 20-30% of measures would dictate a discrepant decision from the referent measure of that month. These findings have important implications for clinical decision-making and underscore the need to base therapeutic decisions on trends rather than single measurements.

What is this chocolate milk in my circuit? A cause of acute clotting of a continuous renal replacement circuit: Questions.

INTRODUCTION: One of the greatest problems associated with continuous renal replacement therapy (CRRT) is the early clotting of filters. A literature search revealed three case reports of lipemic blood causing recurrent clotting and reduced CRRT circuit survival time in adult patients, but no reports of cases in children. DIAGNOSIS/TREATMENT: A 23-month-old male infant with Martinez-Frias syndrome and multivisceral transplant was admitted to the hospital with severe sepsis and hemolytic anemia. He developed acute kidney injury, fluid overload and electrolyte imbalances requiring CRRT and was also administered total parenteral nutrition (TPN) and fat emulsion. The first circuit lasted 60 h before routine change was required. The second circuit showed acute clotting after only 18 h, and brownish-milky fluid was found in the circuit tubing layered between the clotted blood. The patient's serum triglyceride levels were elevated at 988 mg/dL. The lipid infusion was stopped and CRRT restarted. Serum triglyceride levels improved to 363 mg/dL. The new circuit lasted 63 h before routine change was required. CONCLUSION: Clotting of CRRT circuits due to elevated triglyceride levels is rare and has not been reported in the pediatric population. Physicians should be mindful of this risk in patients receiving TPN who have unexpected clotting of CRRT circuits.

A 15-Month-Old with Faltering Growth.

AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 15-month-old with faltering growth and short stature. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.

Bartonella henselae infection-mediated shunt nephritis.

Serum anti-neutrophil cytoplasmic antibody (ANCA) positivity with membranoproliferative pattern on renal biopsy can be due to ANCA-associated vasculitis as well as chronic indolent infections. We present the case of an adolescent boy with congenital heart disease and history of cardiac surgery who presented with severe acute kidney injury requiring hemodialysis. Renal biopsy showed membranoproliferative glomerulonephritis with full-house immunofluorescence pattern. Low serum complements, PR3 ANCA positivity and elevated Bartonella immunoglobulin titers suggested a diagnosis of infective endocarditis-associated glomerulonephritis. Cardiac shunt revision and antibiotic therapy lead to improvement in kidney function. Chronic infections lead to formation of immune complexes that may cause deposit within the renal parenchyma and induce production of ANCA. The distinction of ANCA-associated vasculitis and chronic infections causing acute kidney injury is important in determining therapeutic management. While rare in the pediatric population, we highlight the importance in considering indolent infections in patients with acute glomerulonephritis and ANCA positivity, especially with risk factors.

Physician knowledge, attitudes, and practices regarding physical activity restrictions in pediatric hemodialysis patients.

INTRODUCTION: Epidemiologic studies of physical activity among pediatric hemodialysis (HD) patients are lacking. A sedentary lifestyle in End-Stage Kidney Disease is associated with a higher cardiovascular mortality risk. In those patients receiving HD, time spent on dialysis and restrictions on physical activity due to access also contribute. No consensus exists regarding physical activity restrictions based on vascular access type. The aim of this study was to describe the patterns of physical activity restrictions imposed by pediatric nephrologists on pediatric HD patients and to understand the basis for these restrictions. METHODS: We conducted a cross-sectional study involving US pediatric nephrologists using an anonymized survey through Pediatric Nephrology Research Consortium. The survey consisted of 19 items, 6 questions detailed physician characteristics with the subsequent 13 addressing physical activity restrictions. FINDINGS: A total of 35 responses (35% response rate) were received. The average years in practice after fellowship was 11.5 years. Significant restrictions were placed on physical activity and water exposure. None of the participants reported accesses damage or loss that was attributed to physical activity and sport participation. Physicians practice is based on their personal experience, standard practice at their HD center, and clinical practices they were taught. DISCUSSION: There is no consensus among pediatric nephrologists about allowable physical activity in children receiving HD. Due to the lack of objective data, individual physician beliefs have been utilized to restrict activities in the absence of any deleterious effects to accesses. This survey clearly demonstrates the need for more prospective and detailed studies to develop guidelines regarding physical activity and dialysis access in order to optimize quality of care in these children.

Pediatric Mineral and Bone Disorder of Chronic Kidney Disease and Cardiovascular Disease.

Chronic kidney disease is common and causes significant morbidity including shortened lifespans and decrease in quality of life for patients. The major cause of mortality in chronic kidney disease is cardiovascular disease. Cardiovascular disease within the chronic kidney disease population is closely tied with disordered calcium and phosphorus metabolism and driven in part by renal bone disease. The complex nature of renal, bone, and cardiovascular diseases was renamed as mineral and bone disorder of chronic kidney disease to encompass how bone disease drives vascular calcification and contributes to the development of long-term cardiovascular disease, and recent data suggest that managing bone disease well can augment and improve cardiovascular disease status. Pediatric nephrologists have additional obstacles in optimal mineral and bone disorder of chronic kidney disease management such as linear growth and skeletal maturation. In this article, we will discuss cardiovascular and bone diseases in chronic kidney disease and end-stage kidney disease patients with a focus on pediatric issues and concerns.

Rare cause of xanthinuria: a pediatric case of molybdenum cofactor deficiency B.

Molybdenum cofactor is essential for the activity of multiple enzymes including xanthine dehydrogenase. Molybdenum cofactor deficiencies are rare inborn errors of metabolism. Clinically, they present with intractable seizures, axial hypotonia, and hyperekplexia. They further develop cerebral atrophy, microcephaly, global developmental delay and ectopia lentis. We report a 5-year-old female with clinically, biochemically and genetically confirmed molybdenum cofactor deficiency type B due to compound heterozygous pathogenic variants in the molybdenum cofactor synthesis 2 gene found on whole exome sequencing. The xanthine stones were a key clue towards diagnosis. No mutation was detected in XDH gene. Implementation of a low-purine diet, urine alkalization and hydration lead to a near complete decrease in stone burden. The patient received pyridoxine supplementation with improvement in energy levels and attentiveness. Despite reports of high mortality at a young age, our patient was 9 years old at the time of this writing. Molybdenum cofactor deficiencies should be considered in neonates with early-onset seizures, hypotonia, and feeding difficulties. Screening with serum uric acid levels and empiric treatment may be considered while awaiting genetic results.

Pain Management in Pediatric Chronic Kidney Disease.

Pain is a common problem in children with chronic kidney disease (CKD); however, limited data exist regarding its management. Although most pain is managed pharmacologically, in some instances non-pharmacologic management can aid in safely ameliorating discomfort. Because of the accumulation of toxic metabolites, many common pain medications have adverse effects on kidney function or altered pharmacokinetics in the setting of CKD. Decreased clearance impacts safe dosing of analgesics. The pain management of patients on renal replacement therapy requires an understanding of drug clearance due to the different modalities of dialysis. This educational review highlights pain medications that are safe, albeit often with adjusted dosing, as well as drugs best avoided in the management of pediatric kidney disease. Acetaminophen should be used as a first-line therapy for pain management in children with CKD. Opioids may be added to control moderate to severe pain. Although data are currently lacking, buprenorphine holds promise as a potentially useful drug for the treatment of pain in pediatric patients with CKD. The addition of adjuvant pain medications and non-pharmacologic therapies maybe also be helpful. Despite these options, pain often remains difficult to treat in children with CKD.

Using the newer Kidney Disease: Improving Global Outcomes criteria, beta-2-microglobulin levels associate with severity of acute kidney injury.

Beta-2-microglobulin (B2M) is a marker of proximal tubular injury and glomerular filtration. Analyses using older/non-standardized definitions have shown low efficacy of B2M to predict acute kidney injury (AKI). We assessed if elevated levels of B2M would associate with either the diagnosis of AKI [under current Kidney Disease: Improving Global Outcomes (KDIGO) criteria] or recovery from AKI. We performed a retrospective study, including children who had urine B2M (uB2M) and/or serum B2M (sB2M) measured by immunoturbidimetry in our clinical laboratory between January 2011 and December 2015. We defined AKI based on KDIGO criteria [increase of serum creatinine (sCr) 0.3 mg/dL over 48 h or >50% baseline over 7 days] or urine output <0.5 mL/kg/h for 24 h. Recovery from AKI was defined as a return to baseline sCr within 6 months. We calculated receiver operating characteristics (ROC) area under the curve (AUC). Of 529 patients, 245 developed AKI. Serum and uB2M associated with AKI development (AUCs 0.84 and 0.73, respectively). Patients had a graded higher median sB2M and uB2M with each higher AKI stage. sB2M differentiated Stage I from Stage III AKI (P < 0.001) and Stage II from Stage III AKI (P = 0.004). However, neither uB2M nor sB2M levels associated with recovery from AKI. Only older age {hazard ratio [HR] 0.97, [95% confidence interval (CI) 0.94-0.99]} and need for dialysis [HR 0.39 (95% CI 0.23-0.61)] predicted incomplete recovery after AKI. Using KDIGO criteria, sB2M and uB2M associate with the severity of AKI. Given its relative ease and lower cost, we suggest more widespread use of B2M for AKI detection.