Congenital anomalies of the kidneys and urinary tract (CAKUTs) are one of the most prevalent primary causes of end-stage renal disease (ESRD) in young children, and approximately one-third of these ...children present with lower urinary tract dysfunction (LUTD). Many children with LUTD require therapy with clean intermittent catheterization (CIC). CIC commonly leads to bacteriuria, and considerations have arisen regarding whether CIC in immunosuppressed children is safe or whether repeated febrile urinary tract infections (UTIs) may lead to the deterioration of kidney graft function.
We retrospectively reviewed all cases of primary kidney transplantation performed in our center between 2001 and 2020 in recipients aged less than twelve years. The number of episodes of febrile UTIs as well as the long-term kidney graft survival of children undergoing CIC were compared to those of children with urological causes of ESRD not undergoing CIC, as well as to those of children with nonurological causes of ESRD.
Following successful kidney transplantation in 41 children, CIC was needed in 8 of these patients. These 8 children undergoing CIC had significantly more episodes of febrile UTIs than did the 18 children with a nonurological cause of ESRD (
= 0.04) but not the 15 children with a urological cause of ESRD who did not need to undergo CIC (
= 0.19). Despite being associated with a higher rate of febrile UTIs, CIC was not identified as a risk factor for long-term kidney graft survival, and long-term graft survival did not significantly differ between the three groups at a median follow-up of 124 months.
Our study demonstrates that, under regular medical care, CIC following pediatric transplantation is safe and is not associated with a higher rate of long-term graft loss.
Recognizing risk factors that may negatively affect long-term graft survival following pediatric kidney transplantation is a key element in the decision-making process during organ allocation. We ...retrospectively reassessed all cases of pediatric kidney transplantation performed in our center in the last 20 years with the aim of determining baseline characteristics that could be identified as prognostic risk factors for long-term graft survival. Between 2001 and 2020, a total of 91 kidney transplantations in children under the age of 18 years were undertaken in our center. Early graft failure was observed in six of the 91 patients (7%). The median follow-up of the remaining 85 children was 100 months, and the overall kidney graft survival rates at 5, 10, 15 and 20 years were 85.2%, 71.4%, 46.0% and 30.6%, respectively. Small children with a body surface area of <1 m2 were significantly associated with better long-term graft survival outcomes, while adolescents aged more than twelve years showed poorer graft survival rates than younger children. Body surface area of the recipient of ≥1 m2, pretransplantation duration of the recipient on dialysis ≥18 months, hemodialysis prior to transplantation and donor/recipient age difference of ≥25 years were significantly associated with poorer long-term graft survival.
To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental ...counseling after prenatal and perinatal diagnosis.
A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life.
Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys.
This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.
Increased activity of the epithelial sodium channel (ENaC) in the respiratory airways contributes to the pathophysiology of cystic fibrosis (CF), a genetic disease caused by mutations in the cystic ...fibrosis transmembrane conductance regulator (CFTR) gene. In some patients suffering from atypical CF a mutation can be identified in only one CFTR allele. We recently identified in this group of CF patients a heterozygous mutation (W493R) in the α‐subunit of ENaC. Here, we investigate the functional effects of this mutation by expressing wild‐type αβγENaC or mutant αW493RβγENaC in Xenopus oocytes. The αW493R mutation stimulated amiloride‐sensitive whole‐cell currents (ΔIami) by ∼4‐fold without altering the single‐channel conductance or surface expression of ENaC. As these data suggest that the open probability (Po) of the mutant channel is increased, we investigated the proteolytic activation of ENaC by chymotrypsin. Single‐channel recordings revealed that chymotrypsin activated near‐silent channels in outside‐out membrane patches from oocytes expressing wild‐type ENaC, but not in membrane patches from oocytes expressing the mutant channel. In addition, the αW493R mutation abolished Na+ self inhibition of ENaC, which might also contribute to its gain‐of‐function effects. We conclude that the αW493R mutation promotes constitutive activation of ENaC by reducing the inhibitory effect of extracellular Na+ and decreasing the pool of near‐silent channels. The resulting gain‐of‐function phenotype of the mutant channel might contribute to the pathophysiology of CF in patients carrying this mutation.
Cystic fibrosis (CF) is a common hereditary disease which is usually caused by mutation of a protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which functions as a chloride channel. In some patients, mutations of the epithelial sodium channel (ENaC) may contribute to the disease. We demonstrate that an ENaC mutation (αW493R) identified in patients with an atypical form of CF stimulates ENaC function by increasing the activity of the channels present at the cell surface. Increased ENaC activity may enhance fluid absorption in the respiratory tract of these patients. This may contribute to the formation of sticky mucus, a hallmark of CF.
Summary
Objective
Alterations in the growth hormone–insulin‐like growth factor (IGF) axis have been considered as a causal factor for intrauterine growth restriction (IUGR) and for the increased risk ...of metabolic disease in later life. We compared members of the IGF axis in umbilical cord blood between IUGR neonates, small for gestational age without foetal restriction (SGA) and appropriate for gestational age (AGA) neonates.
Design
Prospective controlled multicenter study.
Patients
Sixteen ultrasound‐proven IUGR, 8 SGA and 40 AGA neonates.
Measurements
Concentrations of total IGF‐I and total IGF‐II by immunoassays, bioactive IGF by cell‐based bioassay and IGFBP‐I in mixed venous and arterial umbilical cord blood samples at birth. Auxological parameters at birth.
Results
IGF‐I concentrations in IUGR 17·7 μg/l (CI 13·8;21·6) were clearly below those in AGA 48·3 μg/l (CI 43·7;52·9) and SGA neonates 36·0 μg/l (CI 26·6;45·4). IGF‐II levels were significantly reduced in IUGR 201·4 μg/l (CI 190·2;212·6) compared to AGA neonates 231·2 μg/l (CI 220·6;241·9). A trend for lower IGF‐II concentrations was observed in IUGR when compared to SGA neonates 232·0 μg/l (CI 207·2;256·8). These differences could not be explained by confounding. For IGFBP‐1, a trend towards higher values in IUGR was observed.
Conclusions
Low IGF‐I cord blood concentrations in hypotrophic neonates after IUGR might not only result from low birthweight per se, but also reflect prenatal placental environment. Alterations of the IGF axis could be in the causal pathway of IUGR and thus constitute a potential surrogate marker for IUGR in the assessment of foetal programming.
Summary
Objective Animal studies suggest pathological foetal programming of hypothalamic circuits regulating food intake in the setting of leptin deficiency and intrauterine growth restriction ...(IUGR). We aimed to compare placental leptin synthesis and leptin‐binding capability in venous cord blood between IUGR newborns and neonates born appropriate for gestational age (AGA).
Design Prospective controlled multicentre study.
Patients Twenty‐one ultrasound‐proven IUGR and 33 AGA neonates.
Measurements The concentration of leptin and soluble leptin receptor (sOB‐R) in venous cord blood at birth was determined. Moreover, placental gene and protein expression of leptin and placental mRNA expression of functional and total leptin receptor isoforms were measured.
Results Whereas log‐leptin concentration in venous cord blood did not differ between IUGR and AGA newborns, the concentration of log‐sOB‐R was elevated in IUGR neonates (pconfounder adjusted = 0·009). Placental leptin protein synthesis as well as leptin mRNA was significantly higher in IUGR than in AGA infants (log‐transformed, relative gene expression, pconfounder adjusted = 0·004). Analysis of gene expression of functional and total leptin receptor isoforms did not show any difference between both groups.
Conclusions Leptin‐binding capability in venous cord blood is increased in IUGR newborns. Thus, via foetal programming, reduced biologically active leptin levels might contribute to a perturbed regulation of appetite.
Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic ...syndrome early in life between IUGR and appropriate for gestational age (AGA) infants.
Data for 9 infants with IUGR defined by a birth weight<10
percentile and ultrasound-proven placental insufficiency and 11 AGA children were available.
Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT).
All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ.
In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.
ABSTRACT
Objective:
Development of the mucosal immune system is essential for controlling antigenic response. External factors are known to influence the immune system, such as breast‐feeding or the ...mode of delivery. The aim of the present study was to investigate maturation of the enteric immune system.
Patients and Methods:
In stool samples of 59 preterm and term‐born infants we measured the concentration of human β‐defensin 2 (HBD 2), an endogenous antimicrobial peptide, and tumor necrosis factor‐α (TNF‐α), a cytokine playing a central role in mucosal inflammation, by enzyme‐linked immunosorbent assay.
Results:
Mode of delivery as well as nutrition (breast‐feeding or formula) had no influence on the fecal concentration of HBD‐2 or TNF‐α, but there was a significant increase in the concentration of HBD‐2 in correlation with gestational age. TNF‐α showed no change in concentration.
Conclusions:
Low fecal HBD‐2 may be a risk factor in preterm infants to develop neonatal enteric disease, such as necrotizing enterocolitis.
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