Single gene pathogenic mutations have been implicated in up to 30% of pediatric steroid-resistant nephrotic syndrome (SRNS) cases, mostly in infantile patients. Among them is
LAMA5
, which has been ...recently discovered and encodes the laminin α5 chain. The laminin α5β2γ1 heterotrimer is an essential component of the glomerular basement membrane and is necessary for embryogenesis and immune modulation. Biallelic
LAMA5
variants have been identified in one adult and ten pediatric nephrotic syndromes (NS) patients with variable phenotypes. Biallelic truncating mutations in this gene have recently been proven to cause SRNS. Here, we present another case of infantile SRNS related to novel compound heterozygous variations of
LAMA5
(c.3434G > A, p.Cys1145Tyr and c.6883C > T, p.Gln2295*), the first reported case with one missense and one nonsense allele. A 10-month-old female patient presented with eyelid edema and massive proteinuria without any extrarenal symptoms or family history. The patient was diagnosed with SRNS. Renal biopsy revealed focal segmental glomerulosclerosis with widely effaced epithelial foot processes and a “moth-eaten” appearance. She progressed to end stage kidney disease (ESKD), requiring dialysis at 31 months of age, and underwent a deceased-donor kidney transplant at 6 years of age. Four months after transplantation, she developed Ebstein-Barr Virus (EBV) infection related to post-transplantation lymphoproliferative disorder (PTLD). After chemotherapy, the patient remained healthy with adequate renal function without disease recurrence for the past 7 years. We also identified previous cases of biallelic
LAMA5
variants associated with the nephrotic phenotype and analyzed the available clinical and genetic information. All reported patients had an onset of NS ranging from 3 months to 8 years, with no other syndromic features. Response to therapy and renal outcomes varied greatly; most patients exhibited steroid resistance, five progressed to ESKD, and two received kidney transplantation (KT). There was one report of PTLD. Our patient’s phenotype was markedly more severe than those with biallelic missense variants and somewhat less severe than those with two truncating variants.
LAMA5
defects may also play a role in PTLD, though no conclusions can be made with such limited cases.
LAMA5
should be considered a candidate gene for SRNS and should be actively tested in cases with no other genetic diagnosis.
Background:
X-linked hypophosphatemia (XLH) is the most frequent form of hypophosphatemic rickets and is caused by mutations in the
PHEX
gene. We analyzed genotype-phenotype correlations in XLH ...patients with proven
PHEX
mutations.
Methods:
PHEX
mutations were detected in 55 out of 81 patients who clinically presented with hypophosphatemic rickets. The patients were grouped into nontruncating (
n
= 9) and truncating (
n
= 46) mutation groups; their initial presentation as well as long-term clinical findings were evaluated according to these groups.
Results:
Initial findings, including presenting symptoms, onset age, height standard deviation scores (SDS), and laboratory tests, including serum phosphate level and tubular resorption of phosphate, were not significantly different between the two groups (onset age: nontruncating mutation group, 2.0 years, truncating mutation group, 2.2 years; height SDS: nontruncating mutation group, −1.9, truncating mutation group, −1.7; serum phosphate: nontruncating mutation group, 2.5 mg/dL, truncating mutation group, 2.6 mg/dL). However, at their last follow-up, the serum phosphate level was significantly lower in patients with truncating mutations (nontruncating mutation group: 3.2 mg/dl, truncating mutation group: 2.3 mg/dl;
P
= 0.006). Additionally, 62.5% of patients with truncating mutations developed nephrocalcinosis at their last follow-up, while none of the patients with nontruncating mutations developed nephrocalcinosis (
P
= 0.015). Orthopedic surgery due to bony deformations was performed significantly more often in patients with truncating mutations (52.3 vs. 10.0%,
P
= 0.019).
Conclusion:
Although considerable inconsistency exists regarding the correlation of truncating mutations and their disease phenotype in several other studies, we cautiously suggest that there would be genotype-phenotype correlation in some aspects of disease manifestation after long-term follow-up. This information can be used when consulting patients with confirmed XLH regarding their disease prognosis.
Background
The impact of renal replacement therapy (RRT) on the long‐term survival outcomes of pediatric liver recipients remains controversial.
Methods
A total of 224 patients aged <18 years, who ...underwent liver transplantation (LT), were divided into two groups: patients who underwent renal replacement therapy (RRT) (group R, n = 25, 11.2%) and those who did not (group N, n = 199, 88.8%). The posttransplant patient survival outcomes according to RRT use constituted the primary end‐point. RRT was initiated preoperatively in 12 patients (48.0%) and postoperatively in 13 early: <6 months after LT (n = 5, 20.0%) and late: ≥6 months after LT (n = 8, 32.0%). The indications for RRT included liver disease involving the kidney (44.0%) and hepatorenal syndrome (56.0%).
Results
The age at the time of LT (71.6 vs. 19.1 months) was higher, the pediatric end‐stage liver disease score was lower (9.9 vs. 21.2), and the duration of hospitalization posttransplantation (41.0 vs. 27.0 days) was longer, while the rates of hepatic artery thrombosis (8.0% vs. 3.5%) were higher in group R (p < .05). The number of patients (60.0% vs. 93.0%; p < .001) and graft survival rates (68.0% vs. 93.0%; p < .001) were significantly lower in group R. Multivariate analysis revealed that posttransplant RRT and hepatic artery complications were risk factors for patient survival outcomes. Renal function was recovered in 7 patients (28.0%) in group R, and 9 (36.0%) eventually underwent kidney transplantation.
Conclusion
The survival outcomes of children requiring posttransplant RRT were significantly worse than those of children, who did not undergo RRT. Physicians should pay meticulous attention to patients requiring post‐LT RRT.
Donor-recipient size mismatching is commonly occurs in pediatric kidney transplantation (KT). However, its effect on graft survival remains unknown. This study aimed to determine the effect of ...donor-recipient size mismatch on the long-term survival rate of transplant kidneys in pediatric KT.
A total of 241 pediatric patients who received KT were enrolled. The medical records of all patients were retrospectively reviewed, and the correlation between donor-recipient size mismatch and graft function and long-term graft outcome was analyzed according to donor-recipient size mismatch.
Recipients and donors' mean body weight at the time of KT were 34.31 ± 16.85 and 56.53 ± 16.73 kg, respectively. The mean follow-up duration was 96.49 ± 52.98 months. A significant positive correlation was observed between donor-recipient body weight ratio (DRBWR) or donor-recipient body surface area ratio (DRBSR) and graft function until 1 year after KT. However, this correlation could not be confirmed at the last follow-up. The results of long-term survival analysis using Fine and Gray's subdistribution hazard model showed no significant difference of the survival rate of the transplant kidney according to DRBWR or DRBSR.
Donor-recipient size mismatch in pediatric KT is not an important factor in determining the long-term prognosis of transplant kidneys.
Purpose: Nephrotic syndrome (NS) is the most common form of glomerulopathy in children. Most pediatric patients respond to glucocorticosteroid treatment (steroid-sensitive NS, SSNS), while ...approximately 10–15% will remain unresponsive or later become steroid-resistant. There has been a long-standing effort to find biomarkers that may predict steroid responsiveness.Methods: We systematically reviewed current studies which investigated clinically relevant biomarkers for predicting steroid responsiveness in pediatric NS. We performed a PubMed and EMBASE search to identify eligible articles. We collected data on urinary markers, blood/serum markers (including cellular phenotypes and mRNA expression), genotypes and HLA allele frequency.Results: A total of 659 articles were identified following electronic and manual searches. After reviewing the titles, abstracts, and full texts, 72 eligible articles were finally included. Vitamin D-binding protein (VDBP) seemed to be significantly elevated in SRNS than in SSNS, in both serum and urine specimen, although further validation is required.Conclusions: The present paper narratively illustrates current understandings of potential biomarkers that may help predict steroid responsiveness. Further investigation and collaboration involving a larger number of patients are necessary.
Background
We evaluated the long-term clinical outcomes of nephrocalcinosis (NC) according to etiology and grade in preschool-age children with NC.
Methods
We retrospectively analyzed the clinical ...outcomes and disease grade of children with NC classified into three groups according to etiology: prematurity, tubular disorders, and others.
Results
Overall, 67 children were diagnosed with NC median age, 0.76 years; interquartile range (IQR) 0.46–2.14 years. The etiologies of NC included prematurity (28.4%), tubular disorders (25.4%), and others (46.3%). Moreover, 56 (83.6%) children were asymptomatic and diagnosed accidentally through kidney ultrasonography. Newly diagnosed underlying diseases were greater in the tubular disorders group than in the other two groups (
P
= 0.001). Significantly more newly diagnosed NCs were grade 3 than grade 1 (
P
= 0.003). The median estimated glomerular filtration rate (eGFR) changed from 96.1 (IQR 68.8–119.2) ml/min/1.72 m
2
at diagnosis to 90.9 (IQR 76.4–106.4) ml/min/1.72 m
2
at the last follow-up, without a significant difference (
P
= 0.096). Changes in the kidney function did not differ according to etiology. However, patients without improvement in NC grade showed a decrease in eGFR from 98.1 (IQR 71.1–132.9) to 87.4 (IQR 74.0–104.1) ml/min/1.73 m
2
(
P
= 0.023), while patients with improved NC grade did not show any change in the kidney function.
Conclusions
Early recognition, especially in NC grade 3, can help uncover further diagnoses, such as tubular disorders. Long-term kidney function depends on whether the NC grade improves.
Background
Immunoglobulin A nephropathy (IgAN) is one of the most common primary forms of glomerulonephritis, while IgA vasculitis (IgAV) is the most common systemic vasculitis in children.
Objective
...Herein we aimed to uncover single nucleotide polymorphism (SNP) markers associated with these two related diseases by applying association tests and Sanger sequencing.
Methods
Within the discovery stage, genomic DNA in blood samples from 101 enrolled patients were genotyped by the Korean Biobank Array. Association tests were performed with 397 Korean reference genomes. In the validation stage, 26 independent samples were genotyped by Sanger sequencing.
Results
Four SNPs were identified (P < 5 × 10
–8
) in the discovery stage. To determine whether the genotypes determined by SNP array were accurate, additional genotyping via Sanger sequencing was performed. As a result, only one SNP, rs9428555, was properly genotyped. In the validation stage, the minor allele (A > G) was found in as many as 15 out of 26 samples (minor allele frequency = 0.288), even though this minor allele is rare in East Asians (< 3%).
Conclusions
We found rs9428555 as a novel susceptible locus associated with the development of both IgAN and IgAV in Koreans. Though we cannot conclude rs9428555 is the unique susceptible locus of IgAN and IgAV, it is likely a good marker as the minor allele of this SNP occurred much more often in the patient group here versus within East Asians as a whole.
Alport syndrome (AS) is one of the most frequent hereditary nephritis leading to end-stage renal disease (ESRD). Although X-linked (XLAS) inheritance is the most common form, cases with autosomal ...recessive inheritance with mutations in
or
are being increasingly recognized. A systematic review was conducted on autosomal recessive Alport syndrome (ARAS). Electronic databases were searched using related terms (until Oct 10th, 2018). From 1601 articles searched, there were 26 eligible studies with 148 patients. Female and male patients were equally affected. About 62% of patients had ESRD, 64% had sensorineural hearing loss (SNHL) and 17% had ocular manifestation. The median at onset was 2.5 years for hematuria (HU), 21 years for ESRD, and 13 years for SNHL. Patients without missense mutations had more severe outcomes at earlier ages, while those who had one or two missense mutations had delayed onset and lower prevalence of extrarenal manifestations. Of 49 patients with kidney biopsy available for electron microscopy (EM) pathology, 42 (86%) had typical glomerular basement membrane (GBM) changes, while 5 (10%) patients showed GBM thinning only. SNHL developed earlier than previously reported. There was a genotype phenotype correlation according to the number of missense mutations. Patients with missense mutations had delayed onset of hematuria, ESRD, and SNHL and lower prevalence of extrarenal manifestations.
Acute kidney injury (AKI) is abrupt deterioration of renal function, and its diagnosis relies upon creatinine measurements and urine output. AKI is associated with higher morbidity and mortality, and ...is a risk factor of development of chronic kidney disease. There is no proven medication for AKI. Therefore prevention and early detection are important. Physicians need to be aware of the risk factors for AKI, and monitor renal function in high risk patients. AKI management includes optimization of volume status and renal perfusion, avoidance of nephrotoxic agents, and sufficient nutritional support. Continuous renal replacement therapy becomes widely available for critically ill children, and of which basic knowledge is introduced in this review. It is recommended that the patients who had experienced AKI are followed for renal function, blood pressure, and proteinuria for a long time.
This study evaluated the diagnostic performance of contrast-enhanced voiding urosonography (ce-VUS) using a second-generation ultrasound contrast agent for the diagnosis of vesicoureteral reflux ...(VUR) and intrarenal reflux (IRR), and compared it with that of standard fluoroscopic voiding cystourethrography (VCUG).
Thirty-two consecutive children from April to September 2019 were included in this study. ce-VUS and VCUG were performed simultaneously by two operators with intravesical infusion of a mixture of ultrasound contrast medium, iodinated contrast medium and water. Two pediatric radiologists independently reviewed the ce-VUS and VCUG images and reported the presence and degree of VUR (grades I-V), and the presence and type of IRR.
Twenty-seven of 63 urinary systems showed VUR. Interobserver agreement for VUR grading was very good for both examinations (κ=0.87; 95% confidence interval CI, 0.82 to 0.92 for ce-VUS and κ=0.92; 95% CI, 0.87 to 0.96 for VCUG). The detection rate of VUR showed no significant difference between the two examinations (P=0.370). Four cases of VUR were missed on ce-VUS, while one case of VUR was missed on VCUG. All four false-negative cases on ce-VUS were grade 1 VUR. The two examinations showed very good agreement regarding VUR grading (κ =0.89; 95% CI, 0.81 to 0.96). IRR was more frequently detected with ce-VUS than with VCUG (10 cases with ce-VUS vs. 3 cases with VCUG, P=0.016).
ce-VUS showed very good agreement with VCUG for detecting grade 2 VUR and above, while grade 1 VUR was sometimes missed with ce-VUS. IRR was more frequently detected with ce-VUS than with VCUG.
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