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Nephrology

Kidney Support for Babies: Building a Comprehensive and Integrated Neonatal Kidney Support Therapy Program
 Kidney Support for Babies: Building a Comprehensive and Integrated Neonatal Kidney Support Therapy Program 1024 575 Lauren Dembeck
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Nurse caring for infant in Neonatal Intensive Care Unit (NICU)

Kidney support therapy (KST), commonly referred to as dialysis, is a life-saving procedure used to manage complications associated with acute kidney injury and kidney failure, such as fluid overload and electrolyte imbalances, or to remove toxins, such as those in patients with inborn errors of metabolism. Most KST or dialysis machines are designed for adults…

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High-Risk Genotype Impacts Kidney Disease Trajectory
 High-Risk Genotype Impacts Kidney Disease Trajectory 1024 575 Mary Bates, PhD
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conceptual art of DNA

Patients with focal segmental glomerulosclerosis that possess two variations in the APOL1 gene experience more rapid progression of kidney disease. In a new study, researchers from Nationwide Children’s and other institutions quantified the relationship between a high-risk genotype and kidney disease progression in patients with focal segmental glomerulosclerosis (FSGS). The researchers leveraged data from the…

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Nephrology Education Ripe With Opportunities to Improve Health Equity
 Nephrology Education Ripe With Opportunities to Improve Health Equity 1024 575 Katie Brind'Amour, PhD, MS, CHES
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The Health Care Justice Committee of the American Society of Nephrology has released recommendations for incorporating anti-racism and social justice concepts into education and mentoring with the goal of improving health equity.   In 2020, leaders in the American Society of Nephrology (ASN) reached out to Ray Bignall II, MD, pediatric nephrologist and assistant chief…

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Substantial Variation in Fluid Balance Among Preterm Neonates
 Substantial Variation in Fluid Balance Among Preterm Neonates 1024 575 Lauren Dembeck
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Nurse caring for infant in Neonatal Intensive Care Unit (NICU)

In neonates, approximately 75 to 90% of the body weight consists of body fluid. The amount varies with gestational age, with higher total body fluid percentages in extremely preterm infants, those born at 22 to 28 weeks of gestation. These extremely preterm infants have immature skin and kidneys and thus immature fluid homeostasis regulatory mechanisms,…

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Development of Acute Kidney Injury as a Potential Biomarker of Necrotizing Enterocolitis in Preterm Infants
 Development of Acute Kidney Injury as a Potential Biomarker of Necrotizing Enterocolitis in Preterm Infants 1024 683 Mary Bates, PhD
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Regular measurement of serum creatinine levels could help identify necrotizing enterocolitis sooner. Researchers at Nationwide Children’s neonatal intensive care unit (NICU) evaluated serum creatinine levels and the development of acute kidney injury as a potential biomarker of necrotizing enterocolitis in preterm infants. The retrospective chart review showed that acute kidney injury is more prevalent in…

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Nephrotoxic Medications in the NICU
 Nephrotoxic Medications in the NICU 1024 575 Mary Bates, PhD
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Nurse caring for infant in Neonatal Intensive Care Unit (NICU)

New study shows treatment with nephrotoxic medications in newborns is associated with the development of acute kidney injury, yet remains common. A multicenter analysis of nearly 50 pediatric hospitals showed that newborns are commonly treated with nephrotoxic medications and, troublingly, the prevalence of acute kidney injury is higher in newborns treated with these drugs. The…

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What’s the Scope of Nephritis in Pediatric Patients With IgA Vasculitis?
 What’s the Scope of Nephritis in Pediatric Patients With IgA Vasculitis? 150 150 Jessica Nye, PhD
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A multicenter study from the Pediatric Nephrology Research Consortium found that many pediatric patients with IgA vasculitis nephritis (IgAVN) are treated with immunosuppressive (IS) agents, and some had evidence of chronic kidney disease as early as 12 months after presentation.   IgA vasculitis (IgAV) is the most common vasculitis in children, usually presenting with typical…

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Novel Compound Shows Promise for Treating Nephrotic Syndrome
 Novel Compound Shows Promise for Treating Nephrotic Syndrome 1024 575 Mary Bates, PhD
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PPARγ selective modulator appear to be more efficacious in reducing proteinuria and comorbidities, and has fewer side effects than a traditional PPARγ agonist in a preclinical model of nephrotic syndrome. Nephrotic syndrome, characterized by high proteinuria, is one of the most common forms of glomerular disease. It is typically associated with edema, hypercholesterolemia, hypoalbuminemia, systemic…

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Improving Identification of Neonatal Acute Kidney Injury in the NICU
 Improving Identification of Neonatal Acute Kidney Injury in the NICU 1024 575 Mary Bates, PhD
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Approaches at three different institutions all resulted in improved identification and care of acute kidney injury in newborns. In a new study, researchers describe three different approaches to standardizing the identification and care of acute kidney injury (AKI) in the neonatal intensive care unit (NICU), including the approach taken at Nationwide Children’s. They report that…

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Short- and Long-Term Kidney Issues in Children Treated for Leukemia
 Short- and Long-Term Kidney Issues in Children Treated for Leukemia 720 480 Mary Bates, PhD
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While outcomes for childhood acute lymphoblastic leukemia (ALL) have improved, researchers are finding long-term effects on kidney function that require monitoring. In a new study published recently in Pediatric Nephrology, researchers from Nationwide Children’s report the incidence of hypertension and kidney issues in pediatric patients diagnosed with acute lymphoblastic leukemia over a recent nine-year period.…

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How the Antimicrobial Protein RNase 7 Helps Prevent Urinary Tract Infections
 How the Antimicrobial Protein RNase 7 Helps Prevent Urinary Tract Infections 1024 683 Mary Bates, PhD
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Researchers identify genetic variation associated with severe and recurrent UTIs. A new study adds to the growing body of evidence suggesting the antimicrobial protein RNase 7 plays an important role in preventing urinary tract infections (UTIs). The findings, published in The Journal of Clinical Investigation, suggest genetic variations in the RNase 7 gene may increase…

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Old Drug, New Use
 Old Drug, New Use 1024 575 Katie Brind'Amour, PhD, MS, CHES
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Nationwide Children's style illustration showing a row of houses with a prescription in front of it

Researchers have discovered an adult diabetes drug may provide a new and better way to treat children  with nephrotic syndrome.  Nephrotic syndrome is one of the most common kidney diseases seen in children. In most cases the cause is unknown. Nephrotic syndrome involves damage to the filtering units of the kidneys (glomeruli) leading to massive…

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Identifying Which Children with Nephrotic Syndrome Will Respond to Steroids
 Identifying Which Children with Nephrotic Syndrome Will Respond to Steroids 1024 683 Mary Bates, PhD
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New research identifies potential biomarkers in the plasma of children with steroid resistant nephrotic syndrome. Nephrotic syndrome is among the most common forms of kidney disease in children. Although glucocorticoids (i.e., steroids) are the primary treatment, approximately 10 to 20% of children with nephrotic syndrome present with or develop steroid resistance. This is only discovered…

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Kidney and Urinary Tract Protein Demonstrates Antimicrobial Activity
 Kidney and Urinary Tract Protein Demonstrates Antimicrobial Activity 1024 683 Lauren Dembeck
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A little-studied peptide found in the urinary tract is a potential biomarker for urinary tract infection risk and could be developed into a novel therapeutic against drug-resistant bacteria.  Researchers at Nationwide Children’s Hospital have demonstrated that an understudied protein expressed in the human kidney and bladder kills the bacteria that cause urinary tract infections (UTI).…

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Identifying Early Urinary Biomarkers of Kidney Damage in Type 1 Diabetes
 Identifying Early Urinary Biomarkers of Kidney Damage in Type 1 Diabetes 150 150 Mary Bates, PhD
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Markers of renal tubule injury and oxidative stress indicate diabetic nephropathy before microalbuminuria. Diabetic nephropathy is a common complication of type 1 diabetes. Traditionally, measurement of microalbuminuria is used to screen children with diabetes for diabetic nephropathy. However, evidence suggests that damage to the kidneys may begin soon after diagnosis, much earlier than microalbuminuria can…

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Two Novel Biomarkers for Urinary Tract Infection Diagnosis Identified
 Two Novel Biomarkers for Urinary Tract Infection Diagnosis Identified 1024 575 Mary Bates, PhD
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Study identifies two proteins that are elevated in children with UTIs compared to those with culture-negative pyuria. In a new study from Nationwide Children’s, researchers identified two novel biomarkers that could be developed to further fine tune the diagnosis of urinary tract infection (UTI) in children. UTIs are common, but challenging to diagnose, in children.…

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Does Twinkle Artifact on Ultrasound Indicate a Kidney Stone in Pediatric Patients?
 Does Twinkle Artifact on Ultrasound Indicate a Kidney Stone in Pediatric Patients? 150 150 Mary Bates, PhD
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The presence of twinkle artifact on ultrasound is a useful, though imperfect, tool for diagnosing kidney stones in children. For pediatric patients, ultrasound is the recommended imaging modality used to diagnose kidney stones. Several findings are used to identify stones on ultrasound, including the presence of an echogenic focus, posterior acoustic shadowing, or twinkle artifact.…

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Diuretic Therapy in Preterm Infants With Acute Kidney Injury Is Common: Should It Be?
 Diuretic Therapy in Preterm Infants With Acute Kidney Injury Is Common: Should It Be? 1024 575 Lauren Dembeck
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small baby with nose canula

Lack of efficacy and safety data on diuretic therapy in the critically ill infants is cause for concern. Researchers at Nationwide Children’s Hospital are beginning to fill in the gaps. Despite the common use of diuretic therapy in preterm infants with acute kidney injury, to date, no large studies have evaluated the patterns of prescription…

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Keeping in Touch: Renin-Producing Cells Require Cell Adhesion Molecule to Survive
 Keeping in Touch: Renin-Producing Cells Require Cell Adhesion Molecule to Survive 1024 575 Lauren Dembeck
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Uncovering the molecular mechanisms underlying the renin-angiotensin-aldosterone system may provide insights into the long-term effects of hypertension and antihypertensive medications.  As the main source of renin in the human body, juxtaglomerular (JG) cells are crucial for blood pressure and fluid-electrolyte homeostasis. However, these cells cannot be cultured in vitro, making it challenging to study the…

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Indicators of Blood Clot Potential Directly Relate to Nephrotic Syndrome Severity
 Indicators of Blood Clot Potential Directly Relate to Nephrotic Syndrome Severity 150 150 Katie Brind'Amour, PhD, MS, CHES
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Researchers in the NEPTUNE network and collaborators at Nationwide Children’s Hospital have confirmed their preclinical studies demonstrating a direct correlation between the severity of disease and prothrombotic biomarkers in patients with nephrotic syndrome. Nephrotic syndrome (NS) dramatically increases the risk of a life-threatening blood clot, but until recently, clinicians have had no reasonable biomarker to…

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Incidence and Impact of Acute Kidney Injury in Patients With Hypoplastic Left Heart Syndrome
 Incidence and Impact of Acute Kidney Injury in Patients With Hypoplastic Left Heart Syndrome 150 150 Abbie Miller
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While incidence of severe kidney injury after surgery for hypoplastic left heart syndrome is low, it may be linked to increased 30-day mortality. Acute kidney injury – the abrupt decline of renal function – following pediatric heart surgery leads to worse outcomes, including increased mortality. The overall incidence of acute kidney injury (AKI) after pediatric…

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Pediatric Kidney Care: A Complex Issue for Low-Resource Nations
 Pediatric Kidney Care: A Complex Issue for Low-Resource Nations 1024 575 Eric Butterman
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Children are dying from kidney disease at alarming rates in low-resource nations. And some procedures that could reduce this high mortality would be considered simple and low-cost for many countries, says William Smoyer, MD, vice president and director of the Center for Clinical and Translational Research in the Abigail Wexner Research Institute (AWRI) at Nationwide Children’s Hospital. Dr.…

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Novel Roles of the Urothelium in the Development of Congenital Anomalies of the Kidney and Urinary Tract
 Novel Roles of the Urothelium in the Development of Congenital Anomalies of the Kidney and Urinary Tract 150 150 Lauren Dembeck
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In addition to genetic defects, interactions of the developing urothelium with its underlying mesenchyme and superficial plaque may contribute to congenital anomalies of the kidney and urinary tract. Congenital anomalies of the kidney and urinary tract (CAKUTs) are the leading cause of chronic and end-stage kidney disease in children. Collaborative translational research at Nationwide Children’s…

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What Kids and Kidneys Can Teach Pediatricians About Racism in America
 What Kids and Kidneys Can Teach Pediatricians About Racism in America 1024 575 Ray Bignall
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O.N. Ray Bignall II, MD, FAAP, director of Kidney Health Advocacy and Community Engagement, explores how “race modifiers,” structural racism and health disparities are perpetuated in kidney care for kids, highlighting important areas primed for change.

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An Imbalance of Immune Cells Leads to Kidney Scarring After Infection
 An Imbalance of Immune Cells Leads to Kidney Scarring After Infection 1024 732 Mary Bates, PhD
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In a preclinical mouse model, researchers identify the immune cell balancing act that determines whether renal scarring will occur following kidney infection More than half of urinary tract infections in children spread from the bladder to the kidneys, causing acute kidney infections that can lead to renal scarring. Renal scarring can have serious repercussions in…

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Does Low Baseline Renal Volume Lead to Renal Insufficiency in Children With Cloacal Anomalies?
 Does Low Baseline Renal Volume Lead to Renal Insufficiency in Children With Cloacal Anomalies? 1024 683 Lauren Dembeck
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According to the results of a recent study published in Urology, children with cloacal anomalies have baseline renal volumes similar to those of children without cloacal anomalies, indicating that the increased risk of renal insufficiency in children with cloacal anomalies appears to be due to postnatal renal injury. “Before we can determine if surgical interventions or…

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What Are the Clinical Implications of Crescentic Glomerulonephritis?
 What Are the Clinical Implications of Crescentic Glomerulonephritis? 1024 732 Abbie Miller
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The Pediatric Nephrology Research Consortium’s most recent study investigates the risk factors for disease progression in children with glomerulonephritis and crescents on kidney biopsy. In patients with glomerulonephritis (GN), the histopathology of the kidney may include crescents, which result from extra-capillary proliferation of cells within the glomerulus. A recent study from the Pediatric Nephrology Research…

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Can a Kidney Failure Risk Equation Validated in Adults Predict Kidney Failure in Children?
 Can a Kidney Failure Risk Equation Validated in Adults Predict Kidney Failure in Children? 1024 575 Lauren Dembeck
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Novel disease-specific biomarkers are needed to improve prediction models in pediatric disease. Obstructive uropathy is a frequent cause of kidney injury in children, and it is estimated to cause approximately one-sixth of pediatric kidney failure cases in North America. However, risk equations to predict kidney disease progression have not yet been developed for children. To…

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Improving Guidelines for Pediatric Hypertension Diagnosis
 Improving Guidelines for Pediatric Hypertension Diagnosis 1024 683 Natalie Wilson
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It is vital to accurately recognize and diagnose hypertension in children to avoid long term morbidity and allow for appropriate treatment. A recent pilot study highlights additional diagnostic criteria for clinicians to consider. Pediatric hypertension, or high blood pressure (BP), has become increasingly common and now affects over 3% of children and adolescents. Untreated, hypertension…

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Determining Ureteropelvic Junction Obstruction Surgical Success Using Biomarkers
 Determining Ureteropelvic Junction Obstruction Surgical Success Using Biomarkers 1024 575 Katie Brind'Amour, PhD, MS, CHES
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Biomarkers initially found to differ among patients with ureteropelvic junction obstruction and healthy controls may also objectively gauge post-surgical resolution of obstruction. A follow-up study of a trial that initially identified four biomarkers that differ between healthy controls and pediatric patients about to undergo surgery for ureteropelvic junction obstruction (UPJO) has confirmed that two of…

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Improving the Care and Management of Urinary Tract Infections Through Collaboration
 Improving the Care and Management of Urinary Tract Infections Through Collaboration 150 150 JoAnna Pendergrass, DVM
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The Urinary Tract Infection Global Alliance (UTIGA) is a new professional society that is dedicated to combatting the many challenges in UTI management and care through collaboration. With nearly 150 million people affected by urinary tract infections (UTIs) annually across the globe, UTIs are a major health problem. Both the term ‘UTI’ and the infection’s…

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Preventing and Ameliorating Acute and Chronic Kidney Damage After Chemotherapy
 Preventing and Ameliorating Acute and Chronic Kidney Damage After Chemotherapy 720 480 Katie Brind'Amour, PhD, MS, CHES
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Research looking at mitochondrial targets in kidney health holds promise for cisplatin-induced kidney injury. Recent work exploring the mitochrondrial metabolism in the kidneys following exposure to cisplatin, a common chemotherapy, has revealed a key role of superoxide (O2•-, an indicator of oxidative stress in renal cells associated with cell damage and death) in both acute…

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Transforming Medical Science Through Research Affinity Groups
 Transforming Medical Science Through Research Affinity Groups 150 150 Katie Brind'Amour, PhD, MS, CHES
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Purposeful synergy drives the most meaningful medical science. Nephrology physician-scientists require tissue samples, urologists desire tests to know which patients truly require surgery, and basic scientists must find ways to meaningfully assess new animal models to yield clinically valuable data. If each of these professionals had a defined network of colleagues from the other disciplines…

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What is the Association Between Kidney Injury and Fluid Balance in Premature Newborns?
 What is the Association Between Kidney Injury and Fluid Balance in Premature Newborns? 1024 575 Mary Bates, PhD
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Nurse caring for infant in Neonatal Intensive Care Unit (NICU)

A positive fluid balance is associated with acute kidney injury and worse outcomes in a new study of premature infants. According to new research, there is an association between fluid balance and outcomes in preterm newborns, with a negative fluid balance during the first week of life emerging as a potential therapeutic target. Premature infants…

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Kidney Biopsy Analysis Reveals High Risk for Disease in Patients With Sickle Cell Disease
 Kidney Biopsy Analysis Reveals High Risk for Disease in Patients With Sickle Cell Disease 1024 732 Mary Bates, PhD
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Patients with SCD are at high risk for significant kidney disease. A retrospective study of biopsy findings from the Pediatric Nephrology Research Consortium shows just how high. Kidney damage is a progressive complication of sickle cell disease (SCD), sometimes eventually leading to kidney failure. As the life expectancy of individuals with SCD has improved, the…

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Answers to Burning Questions About Pediatric Urinary Tract Infections
 Answers to Burning Questions About Pediatric Urinary Tract Infections 1024 683 Abbie Miller
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Nationwide Children’s urologists and nephrologists recently co-hosted a Twitter chat for primary care providers, answering common questions about pediatric urinary tract infections (UTIs). Below is a summary of the questions and answers, adapted for brevity and clarity. Q: What causes UTIs in children? A: UTIs are typically caused by uropathogenic E. coli bacteria that invade the urinary…

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Nephritis Identified as High Research Priority Area For Childhood-Onset Lupus
 Nephritis Identified as High Research Priority Area For Childhood-Onset Lupus 150 150 Lauren Dembeck
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In an effort to establish research priorities in childhood-onset systemic erythematous lupus (cSLE), researchers at Nationwide Children’s Hospital partnered with the Lupus Foundation of America (LFA) and Childhood Arthritis and Rheumatology Research Alliance (CARRA). Their findings are recently published in Pediatric Rheumatology. According to the results of their multidisciplinary prioritization survey of leading rheumatology, dermatology and…

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Why Advocate?
 Why Advocate? 1024 575 Ray Bignall
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Several months ago, I had the privilege of attending a panel discussion on health in the African American community hosted by my local church. It was an opportunity for our largely African American congregation to hear from Black health professionals promoting health-seeking behavior in communities of color. Sitting in the audience, I listened as each…

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In Defense Against Peritonitis, Antimicrobial Peptides May Help on Multiple Fronts
 In Defense Against Peritonitis, Antimicrobial Peptides May Help on Multiple Fronts 150 150 Kevin Mayhood
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Study suggests AMPs have potential as biomarkers for peritonitis, risk stratification and treatment. Antimicrobial peptides (AMPs) in the Ribonuclease A Superfamily exhibit distinct patterns when children and adults undergoing chronic peritoneal dialysis (PD) suffer from peritonitis, researchers have found. The findings, published in Scientific Reports, suggest that AMPs in peritoneal fluid are potentially useful as…

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Largest Study of Glomerular Diseases Sheds Light on Pediatric Subtypes
 Largest Study of Glomerular Diseases Sheds Light on Pediatric Subtypes 150 150 Cyndie Trapasso
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In one of the first papers published from the largest study of glomerular diseases, researchers have found significant differences between patients who have IgA nephropathy and a subtype of the disease, IgA vasculitis, and between children and adults with these diagnoses. The paper is from Cure Glomerulonephropathy (CureGN) — a longitudinal observational study of nearly…

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Uroplakin Plaque Key to Protecting Kidney During Urinary Tract Obstruction
 Uroplakin Plaque Key to Protecting Kidney During Urinary Tract Obstruction 150 150 Kevin Mayhood
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Plaque appears to help remodel urothelium, allowing kidney to hold excess urine without damage, Urinary tract obstruction (UTO) is the leading cause of chronic kidney disease and end-stage renal disease in children. But the extent of damage caused by obstruction differs from child to child. Researchers at Nationwide Children’s Hospital studying why suggest that uroplakin…

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Could Antimicrobial Peptides Be Biomarkers for Obstructive Uropathy?
 Could Antimicrobial Peptides Be Biomarkers for Obstructive Uropathy? 1024 683 Katie Brind'Amour, PhD, MS, CHES
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New research reveals the expression of antimicrobial peptides — long associated only with infections — in children with obstructive uropathy, creating the potential for a wide range of clinical applications. Previously only studied in the context of urinary tract and other infections, antimicrobial peptides (AMPs) — naturally occurring antibiotic molecules that our bodies may use…

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Is Whole Exome Sequencing the Future of Kidney Stone Management?
 Is Whole Exome Sequencing the Future of Kidney Stone Management? 150 150 Katie Brind'Amour, PhD, MS, CHES
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The first use of whole exome sequencing for monogenic causes of kidney stone disease reveals the diagnostic tool is ripe for clinical application. In the first-ever study of whole exome sequencing for early-onset kidney stone disease, an international team of researchers led by clinician-scientists at Boston Children’s Hospital expanded on their prior finding that many…

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Why Patients With Diabetes Have More UTIs
 Why Patients With Diabetes Have More UTIs 150 150 Mary Bates, PhD
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Insulin regulates an antimicrobial peptide that is suppressed in patients with diabetes. A recent study led by clinicians and researchers at Nationwide Children’s Hospital reports a potential explanation for why urinary tract infections (UTIs) are so common in patients with diabetes – insulin regulates an antimicrobial peptide (AMP) that is suppressed in those patients. Patients…

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Childhood Kidney Stones: Their Surprising Connection to Future Disease
 Childhood Kidney Stones: Their Surprising Connection to Future Disease 150 150 Jeb Phillips
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Once thought to be an adult condition, urinary stone disease is increasingly found in children – and may be related to the development of cardiovascular disease, chronic kidney disease and low bone density. By one well-regarded estimate, the risk of developing urinary stone disease in childhood doubled between 1997 and 2012. That’s worrying enough on…

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Predicting Risk for Chronic Renal Disease in Children
 Predicting Risk for Chronic Renal Disease in Children 150 150 Kevin Mayhood
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Studies using a new contrast agent have the potential to determine if infants born premature develop a full complement of nephrons. A new magnetic resonance imaging contrast agent enables researchers to see the number and volume of blood-filtering nephrons in rodent kidneys and donated human adult kidneys, potentially offering a way to diagnose chronic renal disease far earlier than current…

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Childhood Kidney Stones Associated With Atherosclerosis
 Childhood Kidney Stones Associated With Atherosclerosis 150 150 Katie Brind'Amour, PhD, MS, CHES
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Research could lead to early interventions to improve cardiovascular health. Kidney stones in children are increasingly common, and until recently were believed to be an isolated medical problem. But a study conducted by clinician-scientists at Nationwide Children’s Hospital has identified for the first time a significant association between kidney stones and atherosclerosis in children. Previous…

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A Shift in the Antibiotic Prophylaxis Debate?
 A Shift in the Antibiotic Prophylaxis Debate? 150 150 Katie Brind'Amour, PhD, MS, CHES
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The RIVUR trial laid to rest certain questions surrounding antimicrobial prophylaxis in children with vesicoureteral reflux. But it also launched a new debate. The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trialwas supposed to provide clear direction for pediatric urologists. To date, it is the largest double-blind, placebo-controlled, randomized, multicenter study examining urinary tract infection…

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Body, Heal Thyself: Harnessing Our Innate Immunity
 Body, Heal Thyself: Harnessing Our Innate Immunity 150 150 Katie Brind'Amour, PhD, MS, CHES
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What the urinary tract’s front-line defenses can teach us about our innate ability to self-heal …. and thwart antibiotic resistance. Antibiotic resistance is on the rise, health care-acquired infections are becoming harder to treat and even simple infectious illnesses account for billions of dollars per year in spending in the United States alone. As with…

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