Factors associated with 1-year changes in serum fibroblast growth factor 23 levels in pediatric patients with chronic kidney disease.

BACKGROUND: Fibroblast growth factor 23 (FGF23) levels increase as kidney function decreases and are associated with increased mortality in patients with chronic kidney disease (CKD). Inflammation has also been shown to increase FGF23 production in adults; however, this has not been validated in pediatric patients with CKD. Furthermore, previous studies on children involved a single measurement of FGF23 without a follow-up, and a few studies have examined changes in FGF23 levels. METHODS: We measured the levels of serum intact FGF23, tumor necrosis factor-α (TNF-α), and interleukin-6 as parameters of inflammation and other variables related to bone metabolism at baseline and after 1 year in 62 pediatric patients with CKD (stages 2-5D, 1-16 years old). Factors related to changes in FGF23 levels were investigated. RESULTS: The median age of patients at the evaluation was 10.5 years (interquartile range 6.0-14.0), and the estimated glomerular filtration rate (eGFR) was 59.0 mL/min/1.73 m2 (45.1-69.3). Primary diseases included congenital anomalies of the kidney and urinary tract, ischemic kidney, and glomerulonephritis. The baseline value of FGF23 was 66.5 pg/mL (48.3-96.4), and percent change in FGF23 levels after 1 year was 8.5% (- 29.9-74.7). The percent change in FGF23 levels showed a negative correlation with that in eGFR (P = 0.010), and a positive correlation with that in TNF-α levels (P = 0.035). A multivariate linear regression analysis identified TNF-α as an independent factor increasing FGF23 levels. CONCLUSIONS: An increase in TNF-α levels is associated with elevation of FGF23 levels in pediatric patients with CKD.

Reduction in urinary angiotensinogen levels and improvement of proteinuria by renin-angiotensin system blockade in pediatric chronic kidney disease patients with very low birth weight.

BACKGROUND: Children with low birth weight (LBW) have an increased risk of developing chronic kidney disease (CKD), and no effective strategies have been established to prevent the progression of CKD in these patients. Urinary angiotensinogen (UAGT) may represent a useful marker of intrarenal renin-angiotensin system (RAS) activation, which has been suggested to play a critical role in the development of hypertension and CKD. Herein, we conducted a prospective study to determine whether RAS blockade is beneficial for suppressing the progression of CKD in children with LBW, using UAGT as a surrogate marker of renal impairment. METHODS: Nine children with CKD (stages: 1-2) who had very low birth weight (VLBW; < 1500 g) were started on RAS blockade with candesartan. We measured blood pressure and laboratory parameters, including urinary concentrations of angiotensinogen, protein, albumin, creatinine (Cr), and estimated glomerular filtration rate (eGFR), before and after candesartan treatment. RESULTS: Birth weight was 712 g (range, 536-800 g). Age at evaluation was 11.6 years (range, 10.3-15.6 years). After candesartan treatment for 47.6 ± 25.0 months, the UAGT to urinary Cr ratio decreased from 61.9 ± 44.7 to 16.8 ± 14.4 µg/g (p = 0.015). The urinary protein to Cr and albumin to Cr ratios also decreased (p = 0.008 and p = 0.012, respectively), whereas there was no significant change in eGFR. CONCLUSIONS: RAS blockade reduced UAGT levels and improved proteinuria/albuminuria in children with CKD who had VLBW. Suppression of intrarenal RAS activity may slow the progression of CKD in children with LBW.

Risk factors associated with a decreased estimated glomerular filtration rate based on cystatin C levels in school-age children with extremely low birthweight.

AIM: A single centre retrospective cohort study was designed to investigate the estimated glomerular filtration rate (eGFR) in school-age children born with extremely low birthweight (ELBW) and to determine risk factors predictive of decreased eGFR. METHODS: We compared eGFR based on cystatin C (CysC-eGFR) between school-age children born with ELBW (ELBW group, n = 48; median gestational age: 26.9 weeks; median birthweight: 792 g) and children born at term (control group, n = 48). The ELBW group was then further divided into a decreased CysC-eGFR subgroup (eGFR <90 mL/min per 1.73 m2 , n = 20) and a normal CysC-eGFR subgroup (n = 28), and perinatal background factors were compared. RESULTS: The ELBW group showed a significantly lower CysC-eGFR compared with the control group (P < 0.001). Comparison between the decreased and normal CysC-eGFR subgroups in the ELBW group showed that children with lower birthweight, shorter gestational age, lower 5-min Apgar score, longer length of mechanical ventilation, lower weight gain in the first 11 weeks, chronic lung disease, and postnatal corticosteroid administration had significantly decreased CysC-eGFR. Multivariate logistic regression showed that a lower 5-min Apgar score was the only independent risk factor for decreased CysC-eGFR. CONCLUSIONS: CysC-eGFR might already be decreased at school age in children born with ELBW. Renal assessment in regular follow-up examinations is recommended.

A case of a preschool child with a successful kidney transplant following the long-term administration of antibiotics to treat peritoneal dialysis-related ESI/peritonitis by Mycobacterium abscessus.

A preschool child with refractory peritoneal dialysis-related exit-site infection (ESI)/peritonitis caused by Mycobacterium abscessus (M. abscessus) received multidrug antibacterial therapy for 6 months and then successfully underwent living-donor kidney transplantation. The patient was a 2.7-year-old boy and the primary disease was bilateral hypo/dysplastic kidneys. Peritoneal dialysis (PD) was initiated at the age of 4 months. Purulent drainage from the PD catheter exit site was observed, and pus and PD effluent cultures were negative. Since living kidney transplantation was scheduled for 2 months later, the PD catheter was replaced. Due to dialysate leakage from the exit site, the new PD catheter was removed and hemodialysis was initiated. M. abscessus subsequently grew from the PD effluent and abscesses that formed at the exit site continued to present bacteria even after catheter removal; therefore, additional debridement was performed. He received combination treatment with antibiotics, amikacin, clarithromycin, imipenem/cilastatin sodium, and tigecycline, for 6 months. After a 4-month observation period without antibiotics, the patient underwent living-donor kidney transplantation. The post-transplantation course was uneventful without the recurrence of infection for 2 years. Although PD-related ESI/peritonitis caused by M. abscessus was intractable, PD catheter removal, multiple debridement, and 6-month antibiotic combination therapy led to improvements. Follow-up observations for 4 months after the cessation of antibacterial treatment confirmed no recurrence of M. abscessus infection, which allowed kidney transplantation. The establishment of an appropriate treatment strategy and observation period for M. abscessus infection ahead of kidney transplantation requires further case accumulation.

Six-month survival of a monochorionic monoamniotic twin with sirenomelia.

BACKGROUND: Sirenomelia is a congenital malformation of the lower body characterized by a single midline lower limb and severe urogenital and gastrointestinal malformations. Sirenomelia is rare (estimated incidence of approximately 1/100,000) and usually lethal in the perinatal period. CASE: A 2,042 g Japanese male infant, one of monochorionic monoamniotic twins, was born at 34 weeks of gestation by elective caesarean section. Sirenomelia was prenatally diagnosed. Single midline lower limb, bilateral dysplastic kidneys, an omphalomesenteric fistula, colon atresia, imperforate anus, indiscernible genital structures, and myelomeningocele were detected at birth. The amniotic fluid volume was normal throughout the pregnancy course, which led to appropriate lung maturation of the twin with sirenomelia. Although renal replacement therapy was initiated soon after birth, stable peritoneal dialysis was difficult because of the limited intraperitoneal space, and the infant frequently developed peritonitis. He died of sudden cardiorespiratory arrest at 6 months of age. Postmortem examination showed bilateral dysplastic kidneys, agenesis of the ureters and urinary bladder, abnormal branching and agenesis of the distal colon, bilateral inguinal hernias, and small testes. CONCLUSION: Infants with sirenomelia, even those with end-stage kidney disease at birth, may survive if they have a stable cardiorespiratory status at birth and renal replacement therapy is appropriately initiated.