Recurrent Focal Segmental Glomerulosclerosis in Renal Allograft Recipients: Role of Human Leukocyte Antigen Mismatching and Other Clinical Variables

Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation impacts long-term graft survival and limits access to transplantation. We hypothesized that HLA donor/recipient matching could be used as a surrogate marker of recurrence. In a retrospective study of 42 pediatric and 77 adult subjects with primary FSGS, transplanted from 1990 to 2007 at a single center, we analyzed the degree of donor/recipient HLA compatibility and other clinical variables associated with FSGS recurrence. There were total of 131 allografts for primary FSGS (11 subjects were transplanted twice, and 1 had a third allograft) with 20 cases of FSGS recurrence (17 children) in the primary allograft, and two children who had FSGS recurrence in the second allograft. Fifty-two subjects (40%) were African American, and 66 (50%) Caucasians. Recurrent FSGS and controls were not different for age at transplant, gender, donor source, acute/chronic rejection episodes, and HLA matches. Recurrent FSGS was not associated with HLA mismatches; power equals 83%. Immunosuppressive regimen had no effect on recurrence of FSGS, P = .75. Recurrent FSGS is not associated with HLA mismatching, acute cellular or vascular rejection, and occurs primarily in the pediatric population

Hypertension, Chronic Kidney Disease, and Renal Pathology in a Child with Hermansky-Pudlak Syndrome

We report a child with Hermansky-Pudlak Syndrome (HPS) and chronic kidney disease (stage II) with histological diagnosis of focal segmental glomerulosclerosis (FSGS). A 15-year-old male of Puerto Rico ancestry with history of HPS, hypertension (HTN), asthma, obesity, and chronic kidney disease (CKD) stage II presented with new-onset proteinuria without edema. His blood pressure had been controlled, serum creatinine had been 0.9–1.4 mg/dL, and first morning urine protein/creatinine ratio (UPC) ranged from 0.2 to 0.38. Due to persistent nonorthostatic proteinuria with CKD, renal biopsy was performed and FSGS (not otherwise specified) with chronic diffuse tubulopathy (tubular cytoplasmic droplets) and acute tubular injury was reported. Ceroid-like material is known to infiltrate tissues (i.e., lungs, colon, and kidney) in HPS, but the reason for the renal insufficiency is unknown. Nonspecific kidney disease and in one adult case IgA nephropathy with ANCA-positive glomerulonephritis have previously been reported in patients with Hermansky-Pudlak syndrome. To our knowledge, we report the first pediatric renal pathology case of HPS associated with CKD. This paper discusses presentation and management of renal disease in HPS

Renal and Cardiovascular Morbidities Associated with APOL1 Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis

Background and objectives: African American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression and cardiovascular morbidity in children. Design, setting, participants, & measurements: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.Results: A total of 140 AA children in the CKiD study were genotyped. HR APOL1 genotypes were present in 24% of AA children (33/140) and were associated with FSGS, p 3 mg/L (33% vs. 15%, p=0.12) and obesity (48% vs. 19%, p=0.01). There were no differences in glomerular filtration rate, hemoglobin, iPTH, or calcium-phosphate product. Conclusions: AA children with HR APOL1 genotype and FSGS have increase prevalence of obesity and LVH despite a later age of FSGS onset, while adjusting for socioeconomic status. Treatment of obesity may be an important component of CKD and LVH management in this population

Pediatric Immunization Practices in Nephrotic Syndrome: An Assessment of Provider and Parental Knowledge

Background: Children with nephrotic syndrome (NS) are at high risk for vaccine-preventable infections due to the immunological effects from the disease and concurrent treatment with immunosuppressive medications. Immunizations in these patients may be deferred due to their immunosuppressive treatment which may increase the risk for vaccine-preventable infections. Immunization practices in children with NS continue to vary among pediatric nephrologists. This raises the question of whether children with NS are receiving the recommended vaccinations at appropriate times. Therefore, it is critical to understand the practices and patient education provided by physicians to patients on the topic of vaccinations. Methods: After informed consent, parents/guardians of 153 pediatric patients (\u3c18 years old) diagnosed with NS from 2005 to 2018 and 50 pediatric nephrologists from 11 participating centers completed anonymous surveys to evaluate immunization practices among pediatric nephrologists, assess the vaccine education provided to families of children with NS, assess the parental knowledge of immunization recommendations, and assess predictors of polysaccharide pneumococcal vaccine adherence. The Advisory Committee on Immunization Practices (ACIP) Immunization 2019 Guideline for those with altered immunocompetence was used to determine accuracy of vaccine knowledge and practices. Results: Forty-four percent of providers self-reported adherence to the ACIP guidelines for inactive vaccines and 22% to the guidelines for live vaccines. Thirty-two percent of parents/guardians reported knowledge that aligned with the ACIP guidelines for inactive vaccines and 1% for live vaccines. Subjects residing in the Midwest and provider recommendations for vaccines were positive predictors of vaccine adherence (p \u3c 0.001 and p 0.02, respectively). Conclusions: Vaccine recommendation by medical providers is paramount in vaccine adherence among pediatric patients with NS. This study identifies potential educational opportunities for medical subspecialty providers and family caregivers about immunization recommendations for immunosuppressed patients

Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study

Background: Single-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database. Methods: All neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair at <7 days of life, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition -i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2 to 7. Findings: Incidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to <29 weeks =47·9%; ≥29 to <36 weeks =18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p< 0.001; adjusted OR=4·6 (95% CI=2·5-8·3); p=<0·0001], and longer hospital stay [adjusted parameter estimate 8·8 days (95% CI=6·1-11·5); p<0·0001]. Interpretation: Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients

Genetics of focal segmental glomerulosclerosis

The recent advances in understanding the pathophysiology of focal segmental glomerulosclerosis (FSGS) and molecular function of glomerular filtration barrier come directly from genetic linkage and positional cloning studies. The exact role and function of the newly discovered genes and proteins are being investigated by in vitro and in vivo mechanistic studies. Those genes and proteins interactions seem to change susceptibility to kidney disease progression. Better understanding of their exact role in the development of FSGS may influence future therapies and outcomes in this complex disease

Editorial: Nephrotic Syndrome in Pediatric Patients

Nephrotic syndrome (NS) - characterized by heavy glomerular protein loss (proteinuria), edema, hypoalbuminemia, and hyperlipidemia - has diverse causes and frequently leads to chronic kidney disease. This E-book encompasses articles on a variety of topics in NS, including a historical perspective on understanding and treatment of NS, followed by state-of-the-art reviews of the molecular pathomechanisms, clinical outcomes, as well as current and emerging treatment strategies for NS. We hope that this comprehensive review will help to reduce the gaps between the research and the day-to-day care of patients with NS and inspire new research efforts towards updating and expanding the treatment armamentarium for the future

Diabetes Insipidus Complicating Management in a Child with COVID-19 and Multiorgan System Failure: A Novel Use for Furosemide

Judicious balance of fluids is needed for optimal management of acute respiratory distress syndrome (ARDS). Achieving optimal fluid balance is difficult in patients with disorders of fluid homeostasis such as diabetes insipidus (DI). There is little data on the use of Furosemide to aid in balancing fluid and electrolytes in patients with DI. Here, we present a critically ill 11-year-old female with developmental delay, septo-optic dysplasia, central DI, and respiratory failure secondary to COVID-19 ARDS. She required careful titration of a Vasopressin infusion in addition to IV Furosemide for successful management of fluid and electrolyte derangements. On admission, she demonstrated high-volume urine output with mild hypernatremia (serum sodium 156 mmol/L). Despite her maximum Vasopressin infusion rate of 8 mU/kg/hr, by day two of admission, she voided a total of 4 L resulting in severe hypernatremia (serum sodium 171 mmol/L). With continually high Vasopressin infusion rates, her overall fluid balance became increasingly net positive, although her hypernatremia persisted. Her ARDS continued to worsen. After 48 hours of the addition of intermittent Furosemide, successful diuresis along with resolution of hypernatremia was achieved. The combination of IV Furosemide with Vasopressin infusion resulted in tailored diuresis and more controlled titration of serum sodium levels than adjustment in Vasopressin and fluids alone. These results are in contradistinction to the published literature, which focuses on the use of thiazide diuretics in managing DI. This experience highlights the potential for loop diuretics to aid in establishing a desired fluid and electrolyte status in managing patients with both DI and ARDS

Left Ventricular Hypertrophy in Pediatric Hypertension: A Mini Review

Adults with arterial hypertension (HTN) have stroke, myocardial infarction, end-stage renal disease (ESRD), or die at higher rates than those without. In children, HTN leads to target organ damage, which includes kidney, brain, eye, blood vessels, and heart, which precedes “hard outcomes” observed in adults. Left ventricular hypertrophy (LVH) or an anatomic and pathologic increase in left ventricular mass (LVM) in response to the HTN is a pediatric surrogate marker for HTN-induced morbidity and mortality in adults. This mini review discusses current definitions, clinically relevant methods of LVM measurements and normalization methods, its epidemiology, management, and issue of reversibility in children with HTN. Pediatric definition of LVH and abnormal LVM is not uniformed. With multiple definitions, prevalence of pediatric HTN-induced LVH is difficult to ascertain. In addition while in adults cardiac magnetic resonance imaging is considered “the gold standard” for LVM and LVH determination, pediatric data are limited to “special populations”: ESRD, transplant, and obese children. We summarize available data on pediatric LVH treatment and reversibility and offer future directions in addressing LVH in children with HTN