Pediatric Nephrology最新文献

Background: Pneumococcal vaccines have been available worldwide since the early 2000s; consequently, few reports exist of poststreptococcal acute glomerulonephritis (PSAGN) or complications of pneumococcal infection. We describe a patient with PSAGN and bacteremia with Streptococcus pneumoniae serotype 22F (not covered by the 13-valent pneumococcal vaccine (PCV 13)).

Case diagnosis/treatment: A 5-year-old boy received the PCV13 vaccine and was admitted to our hospital with a fever and gross hematuria. A throat swab was positive for a streptococcal antigen, and his serum anti-streptolysin O and creatinine levels were increased. Low serum C3 levels suggested PSAGN, with an infiltrating shadow on chest X-ray. His blood culture isolated S. pneumoniae serotype 22F, and he was administered intravenous ceftriaxone for 10 days. His kidney function, pneumonia, and bacteremia improved.

Conclusions: Children with PSAGN should be evaluated for pneumococcal bacteremia due to strains not covered by the vaccine.

Background: Primary hypertension (HTN) in children is on the rise and linked to the childhood obesity epidemic. Recent studies support the role of hyperuricemia in the pathogenesis of HTN. With this study we intend to evaluate the effect of body mass index (BMI) and uric acid levels on daily blood pressure (BP) parameters/phenotypes and target organ damage (TOD).

Methods: A mean ambulatory systolic and/or diastolic BP ≥ 95th percentile or above the adolescent cut points was defined as 'HTN'. Patients were grouped as group 1 normal weight, and group 2 overweight/obese.

Results: Of the 140 children (89 male/51 female) with a mean age of 13.9 ± 2.6 years, 21 were overweight and 86 were obese. Mean 24-h systolic BP (SBP) and daytime SBP were higher in group 2 (p = 0.015, p = 0.011). BMI was positively correlated with 24-h SBP (r = 0.272, p = 0.001) and daytime SBP (r = 0.280, p = 0.001). Uric acid level showed a moderate correlation with daytime SBP (r = 0.311, p < 0.01). Logistical regression analysis showed that daytime SBP is independently associated with obesity (OR 7.44, 95%CI 2.7-20.6, p < 0.001) and male sex (OR 4.60, 95%CI 2.0-10.2, p < 0.001), but not uric acid. Left ventricular hypertrophy was more common in non-dippers (p = 0.044).

Conclusions: Male sex and BMI are independently associated risk factors for systolic BP. The association between non-dipping pattern and TOD suggests the widespread use of ambulatory blood pressure monitoring (ABPM) in childhood HT. In this paper, we could not demonstrate an independent association between uric acid and SBP. The effect of uric acid on SBP seems to be regulated by other metabolic factors in addition to uric acid.

Background: Much of the global chronic kidney disease burden is experienced in low- and middle-income countries. Children living with chronic kidney disease (CKD) face medical and social challenges, and they need support at the individual and family levels. This study aimed to explore children's experiences living with kidney replacement therapy (KRT) who attend the largest pediatric nephrology department in Guatemala.

Methods: This qualitative study used photovoice and asked children to take pictures that represented what is like to live with CKD. Each child and their caregiver underwent an interview where the photos were used to elicit and facilitate discussion. The interviews were recorded, transcribed, and then analyzed using thematic analysis.

Results: Eight children and their mothers participated in the study. Three themes were identified: interactions with the health system, changing and difficult family dynamics, and strains on social interactions. Children face social challenges including self-isolation and alienation. The family dynamics and familial structures often are forced to change, inducing stress. This is all exacerbated by the difficulties that arise in navigating the Guatemalan health system.

Conclusions: Photovoice techniques are a feasible way to understand the experiences of children and their families who face CKD. The disease affects all aspects of life and recognizing this while advising and administering care can help provide a comprehensive level of care. Health systems need to make efforts aimed at improving the quality of care as well as the multidisciplinary support available to children and their families.

Background: Genetic kidney disease is an important cause of persistent microscopic haematuria in children and young people. We aimed to determine the frequency of variants in the Alport syndrome genes (COL4A3, COL4A4 or COL4A5) in individuals under 18 years of age presenting with persistent microscopic haematuria to a single specialist centre in the UK over a 10-year period.

Methods: We conducted a retrospective longitudinal study of individuals referred to a tertiary paediatric nephrology service with persistent microscopic haematuria between April 2012 to 2022.

Results: A total of 224 individuals (female 51.8%) were evaluated with persistent microscopic haematuria of greater than 6 months duration. The age at presentation was 7.5 ± 4.3 years (mean ± SD) with a duration of follow-up of 6.8 ± 4.6 years (mean ± SD). Targeted exome sequencing was performed in 134 individuals and 91 (68%) had a pathogenic or likely pathogenic variant in COL4A3, COL4A4 or COL4A5. Only 49.5% of individuals with identified variants had a family history of microscopic haematuria documented and 37.4% (34/91) had additional proteinuria at presentation. COL4A5 was the most common gene affected and missense variants affecting glycine residues were the most common variant type.

Conclusion: Over two-thirds of children and young people who underwent genetic testing had an identifiable genetic basis for their microscopic haematuria and over half did not have a documented family history. Genetic testing should be part of the evaluation of persistent microscopic haematuria despite a negative family history.

While up to 50% of children requiring kidney replacement therapy have congenital anomalies of the kidney and urinary tract (CAKUT), they represent only a fraction of the total patient population with CAKUT. The extreme variability in clinical outcome underlines the fundamental need to devise personalized clinical management strategies for individuals with CAKUT. Better understanding of the pathophysiology of abnormal kidney and urinary tract development provides a framework for precise diagnoses and prognostication of patients, the identification of biomarkers and disease modifiers, and, thus, the development of personalized strategies for treatment. In this review, we provide a state-of-the-art overview of the currently known genetic causes, including rare variants in kidney and urinary tract development genes, genomic disorders, and common variants that have been attributed to CAKUT. Furthermore, we discuss the impact of environmental factors and their interactions with developmental genes in kidney and urinary tract malformations. Finally, we present multi-angle translational modalities to validate candidate genes and environmental factors and shed light on future strategies to better understand the molecular underpinnings of CAKUT.

Background: Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder caused by bi-allelic genetic variants in the 4 hydroxy-2 oxoglutarate aldolase (HOGA-1) gene. We report the natural history of PH3 in a 16-patient cohort, 15 from a unique genetically isolated population.

Methods: This retrospective single-center study followed PH3 patients between 2003 and 2023 with demographic, clinical, radiographic, genetic, and biochemical parameters. Genetic population screening was performed in four villages to determine carrier frequency and identify couples at risk in a genetically isolated population.

Results: Sixteen patients with biallelic (or homozygous) pathogenic variants (PV) in HOGA-1 (c.944_946 del, c.119C > A, c.208C > T) were included in the study, 15 Druze and one Jewish, aged 0-63 years at diagnosis (4 adults and 12 pediatric patients). All symptomatic patients had clinical or imaging signs of nephrolithiasis. One developed chronic kidney disease (CKD) stage 5; biopsy showed focal mesangial sclerosis and chronic tubulo-interstitial changes with few oxalate deposits. Two other patients had CKD stage 2 (eGFR 87 and 74 mL/min/1.73 m²) upon their last visit. The remaining cohort showed preserved kidney function until the latest follow-up. Of 1167 healthy individuals screened, 90 carriers were found, a rate of 1:13 in the genetically unique cohort screened.

Conclusions: A high prevalence of PH3 patients was found among a unique cohort, but probably still underdiagnosed due to relatively mild disease course. The carrier rate is high. There is no specific therapy for PH3, but early diagnosis can prevent redundant diagnostic efforts and provide early treatment for kidney stone disease. Even in our homogeneous cohort, kidney stone disease severity and CKD degree were variable, supporting a suspected contribution of yet unknown genetic or environmental factors.

Ciliopathies encompass a broad spectrum of diseases stemming from dysfunction of the primary (non-motile) cilia, present on almost all cells in the human body. These disorders include autosomal dominant and recessive polycystic kidney diseases, nephronophthisis, and multisystem ciliopathies such as Joubert, Meckel, Bardet-Biedl, Alström, oral-facial-digital syndromes, and skeletal ciliopathies. The majority of these ciliopathies are associated with fibrocystic kidney disease resulting in progressive kidney dysfunction. In addition, many ciliopathies are associated with extra-renal manifestations including congenital hepatic fibrosis, retinal dystrophy, obesity, and brain and skeletal anomalies. The diagnoses may be challenging due to their overlapping clinical features and molecular heterogeneity. To date, over 190 genes encoding proteins that localize to the primary cilia have been identified as disease-causing. This review will discuss the clinical features of the most frequently encountered disorders of primary cilia.

Nucleoporins (Nups) are a class of proteins that assemble to form nuclear pore complexes, which are related to nucleocytoplasmic transport, gene expression, and the cell cycle. Pathogenic variants in six genes encoding Nups, NUP85, NUP93, NUP107, NUP133, NUP160, and NUP205, cause monogenic steroid-resistant nephrotic syndrome (SRNS), referred to as nucleoporin-associated SRNS. In this paper, we review the epidemiology, structure and function of Nups, pathogenesis, phenotypes and genotypes, and management of nucleoporin-associated SRNS as well as implications for genetic counseling. Affected individuals exhibit autosomal recessive isolated and syndromic SRNS, whose extrarenal manifestations include neurological disorders, growth and development disorders, cardiovascular disorders, and congenital malformations. The median ages at onset of NUP85-, NUP93-, NUP107-, NUP133-, NUP160-, and NUP205-associated SRNS are 7, 3, 4.1, 9, 7, and 2 years, respectively. Kidney biopsies reveal focal segmental glomerulosclerosis in 89% of patients. Most affected individuals are resistant to immunosuppressants. For the six subtypes of nucleoporin-associated SRNS, patients show progression to kidney failure at median ages of 8.5, 3.7, 6.9, 13, 15, and 7 years, respectively. Only two patients with NUP93-associated SRNS with nephrotic syndrome relapse post-transplant have been reported, and the recurrence rate is 12.5%. Next-generation sequencing using a targeted gene panel is recommended in cases of suspected nucleoporin-associated SRNS for genetic diagnosis. Renin-angiotensin-aldosterone system inhibitors are recommended for patients with nucleoporin-associated SRNS. Once genetic diagnosis is confirmed, immunosuppressant discontinuation should be considered, and kidney transplant is preferred when patients progress to kidney failure. Genetic counselling should be provided for asymptomatic siblings and future siblings of an affected individual. Further studies on the pathogenesis of nucleoporin-associated SRNS are needed to seek new therapeutic interventions.