Review of childhood genetic nephrolithiasis and nephrocalcinosis.

Nephrolithiasis (NL) is a common condition worldwide. The incidence of NL and nephrocalcinosis (NC) has been increasing, along with their associated morbidity and economic burden. The etiology of NL and NC is multifactorial and includes both environmental components and genetic components, with multiple studies showing high heritability.

Investigating the use of finerenone in children with chronic kidney disease and proteinuria: design of the FIONA and open-label extension studies.

Introduction: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria.

Prospective Study of the Multisite Spread of a Medication Safety Intervention: Factors Common to Hospitals With Improved Outcomes.

Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital.

Evaluating the impact of accessible low-cost pediatric genetic testing on underserved communities in the United States.

Background: Genetic testing is at the forefront of medical diagnosis, management, and preventative care particularly within the field of nephrology, but such testing can be prohibitively expensive for patients from disadvantaged backgrounds. This study is aimed at exploring how use of a low-cost, comprehensive commercial panel could increase availability of genetic testing to patients served by an inner-city American hospital and overcome many of the obstacles faced by these patients, including lack of availability of pediatric geneticist and genetic counselors, leading to delay in care and management, cost of genetic testing, and inaccessibility of genetic testing to underserved populations.

Methods: Single-center retrospective analysis patients who underwent genetic testing with NATERA Renasight Kidney Gene Panels run between November 2020 and October 2021.

Genetic testing in children with nephrolithiasis and nephrocalcinosis.

Background: Diagnosing genetic kidney disease has become more accessible with low-cost, rapid genetic testing. The study objectives were to determine genetic testing diagnostic yield and examine predictors of genetic diagnosis in children with nephrolithiasis/nephrocalcinosis (NL/NC).

Methods: This retrospective multicenter cross-sectional study was conducted on children ≤ 21 years old with NL/NC from pediatric nephrology/urology centers that underwent the Invitae Nephrolithiasis Panel 1/1/2019-9/30/2021.

Vitamin D supplementation in children and young adults with persistent proteinuria secondary to glomerular disease.

Background: Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects.

A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial.

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes.

Early and late acute kidney injury: temporal profile in the critically ill pediatric patient.

Background: Increasing AKI diagnosis precision to refine the understanding of associated epidemiology and outcomes is a focus of recent critical care nephrology research. Timing of onset of acute kidney injury (AKI) during pediatric critical illness and impact on outcomes has not been fully explored.

Methods: This was a secondary analysis of the Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) database.

Continued reduction in peritonitis rates in pediatric dialysis centers: results of the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative.

Background: In its first 3 years, the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative demonstrated a statistically significant increase in the likelihood of compliance with a standardized follow-up care bundle and a significant reduction in peritonitis. We sought to determine if compliance with care bundles and low peritonitis rates could be sustained in centers continuously participating for 84 months.

Methods: Centers that participated from collaborative launch through the 84-month study period and provided pre-launch peritonitis rates were included.

Novel genetic testing model: A collaboration between genetic counselors and nephrology.

Many barriers to genetic testing currently exist which delay or prevent diagnosis. These barriers include wait times, staffing, education, and cost. Specialists are able to identify patients with disease that may need genetic testing, but lack the genetics support to facilitate that testing in the most cost, time, and medically effective manner.

Ambulatory blood pressure monitoring: A nurse practitioner run program.

Background: Ambulatory blood pressure monitoring (ABPM) is a standard screening tool for the diagnosis of hypertension in children, adolescents, and adults. However, there is confusion and misunderstanding about which guidelines can provide the most accurate diagnostic values.

Local Problem: At a large, free-standing pediatric hospital, ABPM testing was historically being conducted by both nephrology and cardiology departments.

Digenic Heterozygous Mutations in SLC34A3 and SLC34A1 Cause Dominant Hypophosphatemic Rickets with Hypercalciuria.

Context: Hypophosphatemia and metabolic bone disease are associated with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) due to biallelic mutations of SLC34A3 encoding the NPT2C sodium-phosphate cotransporter and nephrolithiasis/osteoporosis, hypophosphatemic 1 (NPHLOP1) due to monoallelic mutations in SLC34A1 encoding the NPT2A sodium-phosphate cotransporter.

Objective: To identify a genetic cause of apparent dominant transmission of HHRH.

Design And Setting: Retrospective and prospective analysis of clinical and molecular characteristics of patients studied in 2 academic medical centers.

A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children.

Nephrotoxic medication (NTMx) exposure is a common cause of acute kidney injury (AKI) in hospitalized children. The Nephrotoxic Injury Negated by Just-in time Action (NINJA) program decreased NTMx associated AKI (NTMx-AKI) by 62% at one center. To further test the program, we incorporated NINJA across nine centers with the goal of reducing NTMx exposure and, consequently, AKI rates across these centers.

Dextran-Sulfate Plasma Adsorption Lipoprotein Apheresis in Drug Resistant Primary Focal Segmental Glomerulosclerosis Patients: Results From a Prospective, Multicenter, Single-Arm Intervention Study.

Focal segmental glomerulosclerosis (FSGS) causes end stage renal disease (ESRD) in significant proportion of patients worldwide. Primary FSGS carries poor prognosis and management of FSGS patients, refractory to standard treatments or resistant to steroids, remains a major challenge. Lipoprotein apheresis is a therapeutic approach for drug resistant primary FSGS and post-renal transplant primary FSGS recurrence.

Using Electronic Health Record Data to Rapidly Identify Children with Glomerular Disease for Clinical Research.

Background: The rarity of pediatric glomerular disease makes it difficult to identify sufficient numbers of participants for clinical trials. This leaves limited data to guide improvements in care for these patients.

Methods: The authors developed and tested an electronic health record (EHR) algorithm to identify children with glomerular disease.

LDL-apheresis-induced remission of focal segmental glomerulosclerosis recurrence in pediatric renal transplant recipients.

Background: Focal segmental glomerulosclerosis (FSGS) in pediatric patients is typically difficult to treat and will progress to end-stage renal disease (ESRD) in about 10% of cases. Following kidney transplantation, FSGS can recur in up to 56% of renal allografts-with a near 100% recurrence in subsequent transplants.

Methods: Four different pediatric centers across the USA and the UK employed a protocol using LDL-apheresis (LDL-A) and pulse solumedrol to treat recurrent FSGS after transplantation in seven patients.

Global Variation of Nutritional Status in Children Undergoing Chronic Peritoneal Dialysis: A Longitudinal Study of the International Pediatric Peritoneal Dialysis Network.

While children approaching end-stage kidney disease (ESKD) are considered at risk of uremic anorexia and underweight they are also exposed to the global obesity epidemic. We sought to investigate the variation of nutritional status in children undergoing chronic peritoneal dialysis (CPD) around the globe. The distribution and course of body mass index (BMI) standard deviation score over time was examined prospectively in 1001 children and adolescents from 35 countries starting CPD who were followed in the International Pediatric PD Network (IPPN) Registry.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial.

Background And Objectives: There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial.

Design, Setting, Participants, & Measurements: Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment.

Poor adherence to early childhood blood pressure measurement guidelines in a large pediatric healthcare system.

Background: Children who were born prematurely, those with a very low birthweight, or who have survived the neonatal intensive care unit (NICU) are at risk for the development of hypertension and chronic kidney disease (CKD), and thus require blood pressure screening less than 3 years of age, per American Academy of Pediatrics (AAP) 2004 and 2017 guidelines.

Methods: We reviewed the practice patterns of a large pediatric health care system and assessed adherence to the AAP clinical practice guidelines on blood pressure measurements in children less than 3 years of age for hypertension and CKD with the following risk factors: prematurity, very low birthweight, and a neonatal intensive care setting encounter. This retrospective chart review included a total of 9965 patients with a median gestational age of 34 weeks.

Pharmacokinetics of ferric pyrophosphate citrate administered via dialysate and intravenously to pediatric patients on chronic hemodialysis.

Background: Iron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients.

Dyslipidaemia in nephrotic syndrome: mechanisms and treatment.

This corrects the article DOI: 10.1038/nrneph.2017.

Dyslipidaemia in nephrotic syndrome: mechanisms and treatment.

Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B-containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9.