Pediatric Nephrology最新文献

Background: In kidney transplant recipients (KTR), BK polyomavirus-associated nephropathy (BKPyVAN) is a major cause of graft loss. To facilitate the clearance of BKPyV-DNAemia, reduction of immunosuppression is currently the treatment of choice but may increase the risk of graft rejection.

Methods: This international CERTAIN study was designed to determine the risk of alloimmune response and graft dysfunction associated with immunosuppression reduction for BKPyV treatment in 195 pediatric KTR.

Results: BKPyV-DNAemia was associated with a more than twofold increased risk of late T cell-mediated rejection (TCMR) (HR 2.22, p = 0.024), of de novo donor-specific HLA antibodies (dnDSA) and/or antibody-mediated rejection (ABMR) (HR 2.64, p = 0.002), and of graft function deterioration (HR 2.73, p = 0.001). Additional independent risk factors for dnDSA/ABMR development were a higher HLA mismatch (HR 2.72, p = 0.006) and re-transplantation (HR 6.40, p = 0.000). Other independent predictors of graft function deterioration were TCMR (HR 3.98, p = 0.003), higher donor age (HR 1.03, p = 0.020), and re-transplantation (HR 3.56, p = 0.013).

Conclusions: These data indicate that reduction of immunosuppression for BKPyV-DNAemia management is associated with increased alloimmune response in pediatric KTR. Therefore, regular dnDSA screening and close monitoring of graft function in case of BKPyV-DNAemia followed by subsequent reduction of immunosuppressive therapy are recommended.

Background: Many studies have demonstrated the association between low birth weight (LBW) and chronic kidney disease, estimated glomerular filtration rate (eGFR) and kidney volume (KV). However, studies on twins and those investigating numerous perinatal factors beyond LBW, and their associations with various kidney parameters are scarce.

Methods: A two-center cross-sectional study on five-year-old LBW children was conducted between 2021 and 2023. 110 children were enrolled (8 LBW, 58 very LBW (VLBW), 44 extremely LBW (ELBW)); 56 were twins. We examined associations between birth weight (BW), various prenatal, perinatal and postnatal factors, and eGFR, KV, tubular abnormalities and kidney ultrasound abnormalities, both in singletons and twins.

Results: In children with ELBW, eGFR correlated with BW (r = 0.55, P = 0.0018), while in those with BW ≥ 1000 g, eGFR remained constant. Other factors associated with decreased eGFR were hypertensive disorder of pregnancy (93.86 vs. 87.26 ml/min/1.73m², P = 0.0285) in singletons, decreased growth velocity (β = 0.83, P = 0.0277) in twins, and lower total KV (tKV) and relative KV (rKV) in both singletons (r = 0.60, P < 0.0001 for tKV and r = 0.45, P = 0.0010 for rKV) and twins (β = 0.34, P < 0.0001 for tKV and β = 0.23, P = 0.0002 for rKV). Based on the multivariable models excluding KV, BW and gestational age were associated with eGFR in singletons, while male gender, BW, growth velocity, and coffee drinking during pregnancy were associated with eGFR in twins. However, in models that included KV, BW, gestational age and growth velocity were no longer significant. Total KV was associated with BW (r = 0.39, P = 0.0050 for singletons; β = 2.85, P < 0.0001 for twins), body mass index (r = 0.34, P = 0.0145 for singletons; β = 8.44, P < 0.0001 for twins), and growth velocity (β = 1.43, P = 0.0078). Twins born small for gestational age had lower tKV (70.88 vs 89.20 ml, P < 0.0001). Relative KV showed similar associations. Relative kidney volumes were significantly lower for both kidneys compared to the reference population (55.02 vs 65.42 ml/m², P < 0.0001 for right kidney and 61.12 vs 66.25 ml/m², P = 0.0015 for left kidney); however, only 8.6% of children had rKV below 10^th percentile.

Conclusion: Many factors affect eGFR and KV, some of them differ between twins and singletons. Based on multivariable models, eGFR seems to be better predicted by KV than by BW and gestational age in LBW children. Relative kidney volumes were significantly lower in our cohort compared to the reference population, but only 8.6% of rKV were below 10^th percentile.

Congenital sucrase isomaltase deficiency (CSID) is a rare autosomal recessive monogenic disorder of small intestinal malabsorption and manifests typically in early childhood with chronic osmotic diarrhoea. Though there have been case reports in adults presenting with hypercalcemia and renal calculi in CSID, this is quite rare in children. We hereby report a 6-year-old boy who presented with recurrent episodes of calcium oxalate calculi without any gastrointestinal symptoms and was confirmed as having sucrase isomaltase deficiency by genetic analysis.

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.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder. Pathogenic variants in PKD1 and PKD2 genes are the main causes of ADPKD. Biallelic inheritance of pathogenic variants leading to very early-onset manifestations have been described in the literature. A female fetus was prenatally diagnosed with oligohydramnios, bilateral kidney enlargement, and hyperechogenicity at 31 weeks gestational age. The mother was known to have ADPKD from the family history. However, unusually early and very rapid progressive disease after birth led to genetic testing which found two PKD1 variants inherited from both parents. The patient was suffering from refractory arterial hypertension, chronic kidney disease, and respiratory distress leading to off-label use of tolvaptan in the neonatal period. Although the data on tolvaptan use in neonatal polycystic kidney disease remains limited, a 6-year treatment in this patient was well tolerated and may have mitigated kidney growth and disease progression.

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.