A Case of Orthostatic Proteinuria Progressed to Persistent Proteinuria Associated with Renal Pathology

Orthostatic or postural proteinuria is the most common cause of asymptomatic proteinuria in children. As orthostatic proteinuria (OP) is a benign disease with relatively good prognosis, it has no specific management, and patients only need to be observed. However, if OP shows a persistently high level of proteinuria, in theory, glomerular changes can occur. An 11-year-old girl was referred to the hospital due to asymptomatic proteinuria and was diagnosed as having OP based on the results of clinical and laboratory examinations, urinalysis, and protein/creatinine (TP/Cr) ratio at both supine and erect positions. During follow-up observation, the 24-hour TP/Cr ratio was persistently higher than 1.5 mg/mg for 2 years. We performed renal biopsy, which showed mesangial proliferative glomerular lesions with focal effacement of the podocyte foot processes, but without immune depositions. OP can be accompanied by glomerular lesions if moderate to severe proteinuria persists.

A Case of Orthostatic Proteinuria Progressed to Persistent Proteinuria Associated with Renal Pathology

Orthostatic or postural proteinuria is the most common cause of asymptomatic proteinuria in children. As orthostatic proteinuria (OP) is a benign disease with relatively good prognosis, it has no specific management, and patients only need to be observed. However, if OP shows a persistently high level of proteinuria, in theory, glomerular changes can occur. An 11-year-old girl was referred to the hospital due to asymptomatic proteinuria and was diagnosed as having OP based on the results of clinical and laboratory examinations, urinalysis, and protein/creatinine (TP/Cr) ratio at both supine and erect positions. During follow-up observation, the 24-hour TP/Cr ratio was persistently higher than 1.5 mg/mg for 2 years. We performed renal biopsy, which showed mesangial proliferative glomerular lesions with focal effacement of the podocyte foot processes, but without immune depositions. OP can be accompanied by glomerular lesions if moderate to severe proteinuria persists.

The Cyclosporine-A Treatment does not have Harmful Effect on the Linear Growth of Pediatric Patients with Steroid-dependent and Steroid-resistant Nephrotic Syndrome

PURPOSE: This study was performed to evaluate the effects of cyclosporine-A (CsA) on linear growth in pediatric patients with steroid-dependent (SDNS) or resistant nephrotic syndrome (SRNS). METHODS: Thirty-five pediatric patients with SDNS or SRNS undergoing glucocorticoid (GC) and/or CsA treatment were retrospectively reviewed. Seventeen patients were treated with GC alone and 18 were treated with GC and CsA. The cumulative doses of GC and CsA were quantified (mg/kg/day). Linear growth during the follow-up period was defined as the difference in Z-score between the initial and final height according to the follow-up period (Δ height Z score/year). The associations between linear growth and clinical parameters were analyzed. RESULTS: The linear growth of patients in the two groups was not significantly different (P=0.262). The Δ height Z score/year did not show a significant correlation with the cumulative doses of CsA, but was negatively correlated with the cumulative dose of GC and positively correlated with the Z score for height at the time of diagnosis. CONCLUSION: In children with SDNS or SRNS undergoing GC therapy, added CsA treatment may not have harmful effects on linear growth.

Complete Remission from C1q Nephropathy with Disappearance of C1q Deposition after Steroid Therapy / 대한내과학회지

C1q nephropathy is a rare glomerular disease, defined by characteristic mesangial C1q immune deposition seen in immunofluorescence microscopy with no serological evidence of systemic lupus erythematosus. C1q nephropathy can be diagnosed with a subsequent biopsy, as with IgA nephropathy. There are some cases with an initial diagnosis of hematuria and proteinuria with minimal disease changes, focal segmental glomerulonephritis, and mesangial proliferative glomerulonephritis, but lacking C1q nephropathy, in which C1q deposition on immunofluorescence subsequently develops. We report a case that was diagnosed as diffuse mesangial proliferative glomerulonephritis, but a subsequent biopsy showed C1q nephropathy, with C1q deposition in both immunohistochemistry and electron microscopy (EM). We treated the C1q nephropathy with methylprednisolone and confirmed the disappearance of C1q depositions by both immunohistochemistry and EM in a follow-up biopsy.

Long-term Results of Endoscopic Deflux(R) Injection for Vesicoureteral Reflux in Children

PURPOSE: We evaluated the long-term results of endoscopic Deflux(R) injection for treating vesicoureteral reflux (VUR) in children. METHODS: Between September 2004 and September 2014, 243 children (137 boys and 106 girls) with a mean age of 53 months underwent Deflux(R) injection. Our clinical protocol included radionuclide voiding cystography (RNC) at postoperative 3 months, 1 year and 3 years to assess the VUR resolution. RESULTS: The cure rates at 3 months, 1 year, and 3 years by patients were 70.8%, 64.3%, and 65.6% for the total patients and 79.2%, 75.2%, and 76.4%, for the ureters, respectively. The recurrence rate of postoperative febrile urinary tract infection (UTI) was 20% in patients without VUR at postoperative 1 year. Twenty patients undergoing ureteroneocystostomy (UNC) significantly had younger age (P=0.003), higher VUR grade (P<0.001), and lower success rates of Deflux(R) injection (P<0.05). On univariate analysis, older age (P=0.014) and lower grade of VUR (P=0.031) were the significant predictors of a successful outcome. But there was none on multivariate analysis. Younger age, especially age of 0-12 month-old, was the only significant predictor of postoperative febrile UTI recurrence on both univariate and multivariate analysis. CONCLUSION: Deflux(R) injection is efficacious with a low complication rate for the anti-reflux procedure in children. There is low recurrence rate of UTI though VUR persists, and high probability of no VUR at 3 years if no VUR at 1 year. It is recommendable not to perform follow-up RNC at 3 years routinely if no VUR at 1 year.

Long-term Results of Endoscopic Deflux(R) Injection for Vesicoureteral Reflux in Children

PURPOSE: We evaluated the long-term results of endoscopic Deflux(R) injection for treating vesicoureteral reflux (VUR) in children. METHODS: Between September 2004 and September 2014, 243 children (137 boys and 106 girls) with a mean age of 53 months underwent Deflux(R) injection. Our clinical protocol included radionuclide voiding cystography (RNC) at postoperative 3 months, 1 year and 3 years to assess the VUR resolution. RESULTS: The cure rates at 3 months, 1 year, and 3 years by patients were 70.8%, 64.3%, and 65.6% for the total patients and 79.2%, 75.2%, and 76.4%, for the ureters, respectively. The recurrence rate of postoperative febrile urinary tract infection (UTI) was 20% in patients without VUR at postoperative 1 year. Twenty patients undergoing ureteroneocystostomy (UNC) significantly had younger age (P=0.003), higher VUR grade (P<0.001), and lower success rates of Deflux(R) injection (P<0.05). On univariate analysis, older age (P=0.014) and lower grade of VUR (P=0.031) were the significant predictors of a successful outcome. But there was none on multivariate analysis. Younger age, especially age of 0-12 month-old, was the only significant predictor of postoperative febrile UTI recurrence on both univariate and multivariate analysis. CONCLUSION: Deflux(R) injection is efficacious with a low complication rate for the anti-reflux procedure in children. There is low recurrence rate of UTI though VUR persists, and high probability of no VUR at 3 years if no VUR at 1 year. It is recommendable not to perform follow-up RNC at 3 years routinely if no VUR at 1 year.

Long-term Follow-up of Metaphyseal Sclerotic Lines in Children Treated with Pamidronate

PURPOSE: Bisphosphonates are widely used for the management steroid-induced osteoporosis (SIO) in children. With the increasing use of bisphosphonates, there have been reports of abnormal radiological findings in the growing skeleton. Therefore, their use in pediatric patients remains controversial. The present study was conducted to evaluate the long-term follow-up radiographic features, particularly metaphyseal sclerotic lines, in children who receive pamidronate therapy for nephropathy. METHODS: Twenty-four children with nephropathy treated with oral calcium and pamidronate (mean duration, 9 months; dose, 100 mg daily), were evaluated retrospectively. All patients had SIO secondary to chronic glucocorticoid therapy for treating nephropathy. Long bone radiographic imaging was performed before treatment with pamidronate, and at follow-up, several years later. Physeal growth rates were estimated by measuring the distance that the sclerotic lines moved on the radiographs during the corresponding time intervals. RESULTS: The mean follow-up period was 138 months. Long bone radiographs showed well-defined sclerotic lines at the metaphyseal ends, progressively moving from the physeal plate to the diaphysis, in all patients. The mean rate of movement of the sclerotic line was 6.21 mm per year. In 12 patients, the lines disappeared. The mean rate of growth in height was 7.33 cm per year. CONCLUSIONS: Results of long-term follow-up suggest that the metaphyseal sclerotic lines associated with pamidronate treatment tend to disappear without affecting overall skeletal growth. Bisphosphonate treatment for SIO in children with nephropathy seems to be safe, although further studies in larger number of patients are needed.

Association of HLA-G gene promoter haplotype with childhood IgA nephropathy in the Korean population / 소아과

PURPOSE: IgA nephropathy (IgAN) is the most commonly occurring form of chronic glomerulonephritis in pediatric cases. Human leukocyte antigen (HLA) genes have been implicated in various inflammatory and autoimmune diseases. The present study was conducted to investigate the association between 2 single nucleotide polymorphisms (SNPs) of the HLA-G gene and childhood IgAN. METHODS: The authors analyzed and compared HLA-G gene SNPs (rs1736936 and rs2735022) in 174 patients with childhood IgAN and in 438 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to proteinuria (4 mg/m2/hour), the presence or absence of podocyte foot process effacement, and the presence of pathologically early and advanced disease markers such as interstitial fibrosis, tubular atrophy, or global sclerosis. RESULTS: No significant SNP frequency differences were observed for the HLA-G gene between IgAN patients and the control group. Moreover, no significantly associated SNP was observed with the presence of proteinuria, podocyte foot process effacement, or pathologically advanced markers. However, the haplotype, composed of rs1736936 and rs2735022, showed a significant association with the susceptibility to develop childhood IgAN (haplotype T/C: dominant model, P=0.049; haplotype C/T: recessive model, P=0.030). CONCLUSION: Our results indicate that rs1736936 and rs2735022 as the HLA-G gene promoter haplotype might be associated with the susceptibility to develop childhood IgAN in the Korean population.

Recent Advances of Oral Rehydration Therapy (ORT)

Diarrheal disease is one of the leading causes of worldwide morbidity and mortality, especially in children. It causes loss of body fluid, which may lead to severe dehydration, electrolyte imbalance, shock and even to death. The mortality rate from acute diarrhea has decreased over the last few decades. This decline, especially in developing countries is largely due to the implantation of the standard World Health Organization-oral rehydration solution (WHO-ORS). However, the use of standard ORS has been limited by its inability to reduce fecal volume or diarrhea duration. Subsequently, this has led to various attempts to modify its compositions. And these modifications include the use of reduced osmolarity ORS, polymer-based ORS and zinc supplementation. Some of these variations have been successful and others are still under investigation. Therefore, further trials are needed to progress toward the ideal ORS. In this article, we briefly reviewed the pathophysiologic basis of the ORS, followed by the standard WHO-ORS and several modifications to improve the ORS.

Association between polymorphisms in Interleukin-17 receptor A gene and childhood IgA nephropathy / 소아과

PURPOSE: Interleukin-17 (IL-17) is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN). Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs) in IL-17 receptor A (IL-17RA) gene and childhood IgAN. METHODS: We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (4 mg/m2/h, 40 mg/m2/h, respectively) and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. RESULTS: No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (>4 mg/m2/h) and those without proteinuria (codominant model OR 0.36, 95% CI 0.19-0.66, P<0.001; dominant model OR 0.35, 95% CI 0.17-0.69 P=0.002; recessive model OR 0.12, 95% CI 0.01-1.06 P=0.025). CONCLUSION: Our results indicate that the SNP in IL-17RA (rs2895332) may be related to the development of proteinuria in IgAN patients.

Association Study between CCL-2 and CCL-5 Polymorphisms and Clinicopathological Characteristics of Childhood IgA Nephropathy

PURPOSE: Previous studies have suggested that Chemokine (C-C motif) ligand-2 (CCL-2; also known as MCP-1) and CCL-5 (also known as RANTES) are possibly associated with the pathogenesis of various inflammatory and non-inflammatory renal diseases. The present study was conducted to investigate association of polymorphisms of CCL-2 and CCL-5 genes with childhood IgA nephropathy (IgAN). METHODS: The authors analyzed six single nucleotide polymorphisms (SNPs) of CCL-2 and CCL-5 in 196 pediatric IgAN patients and in 285 healthy controls. We compared variations in SNPs between two several sets of IgAN subgroups, allocated by presence of proteinuria (>4 mg/m2/hour), podocyte foot process effacement, and pathologically advanced disease markers, such as interstitial fibrosis, tubular atrophy, or global sclerosis. RESULTS: Genotypic data of IgAN patients and controls showed no significant SNP frequency difference in both of of CCL-2 and CCL-5. Even though two linkage disequilibrium blocks were formed, there was no significance in the haplotype analysis. In the patient subgroup analysis, no SNP of CCL-2 and CCL-5 was found to be associated with the presence of proteinuria, podocyte foot process effacement, and pathologically advanced disease markers. CONCLUSION: Our data indicate that no association exists between CCL-2 and CCL-5 SNPs and childhood IgAN susceptibility, and presence of proteinuria, podocyte foot process effacement, and pathologic progression of IgAN.

Research Related to Chronic Kidney Disease in BMI >25 Overweight Children

PURPOSE: Chronic kidney disease (CKD) and obesity are the worldwide public health problem. Obesity is an already well-established risk factor for CKD. The objective of this study is to evaluate the relationship between high BMI and increased risk for nephropathy by clinical data. METHODS: Study group were 26 patients who had BMI> or =25 kg/m2 and control group were 49 patients with BMI<25 kg/m2. Both groups received renal biopsy in Kyung Hee Medical Center between 2003. Jan.-2007. Dec. BMI was calculated from measured weight and height when they were admitted to the hospital. We collected laboratory data such as CBC and blood chemistry. RESULTS: Our hypothesis was that overweight and obesity are associated with incidence and progression of CKD. From kidney biopsy, we found IgAN 17, MesPGN 5, HSPN 2, Intestitial nephritis 1, IgMN 1 (total 26) in the study group whereas IgAN 22, MesPGN 17, HSPN 3, MGN 3, benign hematuria 2, MPGN 1, Intestitial nephritis 1, (total 49) were found in the control group. There was no significant difference between the two groups. Overweight patients demonstrated significantly higher platelet, TG, ALT, and uric acid level compared to control group. CONCLUSION: We identified a significant relationship between overweight and development of CKD. These results suggest that overweight children have an increased risk for CKD than those who are not obese. So, we should pay attention to children with overweight who have CKD and earlier weight management is crucial to prevent aggravation of CKD.

Decision Factors on Mycophenolic Acid Dose after Renal Transplantation / 대한이식학회지

BACKGROUND: Triple immunosuppressant therapy including anti-metabolites is the representative immunosuppressive therapy after renal transplantation. This study is to evaluate the factors that influence Mycophenolate sodium (MPS, Myfortic, Novartis, Basel, Switzerland) dosage patterns in renal transplantation patients who take MPS as an inosine monophosphate dehydrogenase (IMPDH) among antimetabolites. METHODS: From May 2007 to April 2008, 16 clinical departments of 14 transplantation centers in Korea retrospectively performed a survey on 650 renal transplantation recipients taking MPS. This survey collected personal information, clinical factors related to transplantation and immunosuppressive therapy. RESULTS: The mean age of the patients was 43.0+/-12.0 (7~75) and the study included 364 males (56.0%) and 286 females (44.0%). The average follow up period after renal transplantation was 49.5+/-53.4 (1~307) months. There were 366 (56.3%) living related cases, 145 (22.3%) living non-related cases and 139 (21.4%) deceased donor cases. Cyclosporine was the most common calcineurin inhibitor (CNI) used in combination therapy with MPS (476 cases, 73.2%) followed by tacrolimus (169 cases, 26.0%). The mean daily dose of MPS was 909.7+/-336.3 (180~1,620)mg and the mean daily dose per kg was 15.3+/-5.9 (2.65~32.73)mg/kg. The daily dose showed significant positive correlation with patient body weight but the daily dose per kg showed negative correlation. The daily dose of MPS was significantly higher in the combination therapy with cyclosporine than that with tacrolimus. The daily dose and the dose per kg decreased with increment of recipient age and post-transplant period. CONCLUSIONS: Our study concluded that MPS dosages correlated with the combined type of CNI, post-transplant period and age.

The Comparison between FSGS and MCNS Using Proteomic Method in Childhood Nephrotic Syndrome; Preliminary Study

PURPOSE: FSGS do not respond well to any kind of therapy and gradually progress to end-stage renal disease. This study was conducted to investigate the difference of protein expression between MCNS and FSGS as a preliminary study for understanding the pathophysiology of FSGS. METHODS: Renal biopsy samples of MCNS and FSGS were obtained, which was diagnosed by one pathologist. They were solubilized with a conventional extraction buffer for protein extraction. The solution was applied on immobilized linear gradient strip gel (pH 4-7) using IPGphor system. Silver staining was carried out according to standard method. Protein identification was done by searching NCBI database using MASCOT Peptide Mass Fingerprint software. RESULTS: The differences in protein expressions between MCNS and FSGS were shown by increased or decreased protein spots. Most prominently expressed spot among several spots in FSGS was isolated and analyzed, one of which was glutathione S-transferase (GST) P1-1, whereas it was not found in MCNS. So GSTP1-1 was considered as the one of the key biomarkers in pathogenesis of FSGS. CONCLUSION: This result would be helpful in diagnosing FSGS and researching FSGS. Further studies for glutathione S-transferase P1-1 might be necessary to elucidate the mechanisms regarding FSGS.

A Case of Urachal Cyst Infection Occurring During Corticosteroids Therapy in a Patient with IgA Nephropathy

The urachus is a normal embryonic remnant of the primitive dome. It generally exists as a fibrous cord extending from the dome of the bladder to the umbilicus. Disorders of the urachus are developed as a result of its incomplete regression. The urachal cyst is the most common urachal anomaly, and is usually asymptomatic in infancy and childhood. However, when the cysts are large or accompanied with secondary infection, they may be detected in its early stage. A sonography or CT scan may be helpful to confirm the diagnosis of urachal cyst. The managements of infected urachal cyst are varied from simple drainage to radical excision. Here, we report an unusual case of urachal cyst infection that occurred during corticosteroids therapy in a girl with IgA nephropathy.

The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy

The enabled homolog gene (ENAH, hMena) is abundantly expressed in mesangial tissue, and might play an important role in inflammatory processes of IgA nephropathy (IgAN). The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the ENAH and childhood IgAN. We analyzed 12 SNPs of ENAH in 176 patients with childhood IgAN and 397 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to several clinical and pathological parameters. Genotyping data showed significant differences between IgAN patients and controls in the frequency of rs2039620, rs12034829, and rs3795443. On comparison of patients with proteinuria to those without proteinuria ( 4 mg/m2/h), rs12043633 was significantly different between the two groups. With regard to maximum proteinuria ( 4 mg/m2/h), rs3795443, rs4653643, rs6751, rs10799319, rs7555139, rs576861, and rs487591 showed significant allele frequency differences. For patients with and without gross hematuria, rs4653643, rs6751, rs10799319, rs7555139, rs576861, and rs487591 showed significant allele frequency differences. The rs3795443 was found to be associated with progression of pathological findings. Our results suggest that ENAH polymorphisms are associated with increased susceptibility, development of proteinuria and gross hematuria, and pathological progression of childhood IgAN.

Current status of pediatric kidney transplantation / 소아과

Renal transplantation is the treatment of choice for children with end-stage renal disease. The outcome of pediatric kidney transplantation has improved dramatically in recent years, with lower acute rejection rates, superior graft survival, and low mortality. These improvements have allowed increased attention to other aspects of care for long-term survivors. Taking this into consideration, this review article will focus on the key issues related to pediatric kidney transplantation such as growth, neurocognitive function, nonadherence, and posttransplantation infectious complications, including lymphoproliferative disease, to broaden the understanding of pediatricians who provide pre-and postoperative care to children with end-stage renal disease.

Two Korean Infants with Genetically Confirmed Congenital Nephrotic Syndrome of Finnish Type

Congenital nephrotic syndrome is defined as nephrotic syndrome which manifests in utero or during the first 3 months of life. The prototype of congenital nephrotic syndrome is congenital nephrotic syndrome of Finnish type (CNF, OMIM #602716), which is caused by loss-of-function mutations of the nephrin gene (NPHS1). There have been few clinical case reports of CNF in Korea, but none of which was confirmed by genetic study. Here, we report two children with congenital nephrotic syndrome. Genetic analysis of the NPHS1 gene revealed compound heterozygous frame-shifting mutations (c.2156_2163 delTGCACTGC causing p.L719DfsX4 and c.3250_3251insG causing p.V1084GfsX12) in one patient and a missense mutation (c.1381G>A causing p.R460Q) and a nonsense mutation (c.2442C>G causing p.Y814X) in the other patient. The nonsense mutation was novel. The clinical courses of the patients were typical of CNF. This is the first report of genetically confirmed CNF in Korea to date. The early genetic diagnosis of CNF is important for proper clinical management of the patients and precise genetic counseling of the families.

A Case of Vancomycin-Resistant Enterococci P eritonitis in a Pediatric P atient on CAPD Successfully Treated with Linezolid

Peritonitis is one of the major complications of CAPD(continuous ambulatory peritoneal dialysis). Recently, multidrug-resistant organisms, such as vancomycin-resistant enterococcus (VRE) have been rarely reported by the pathogen as of CAPD-associated peritonitis. But, there is limited information on choices of effective therapy for VRE peritonitis in patients undergoing CAPD. We present a pediatric case of successful treatment of CAPD-associated peritonitis due to VRE with linezolid, and review of the literature.

A Case of Diabetic Nephropathy in a Child with Type 1 Diabetes

Diabetes mellitus(DM) is a metabolic syndrome caused by deficiency of insulin secretion and a consequence of insulin resistance. Poor glycemic control is a common finding in children with Type 1 DM(T1DM). Approximately 60% of the young patients with T1DM develop abnormalities in the eyes and 15-20% in the kidney. Diabetic nephropathy (DN) is a serious metabolic complication of T1DM that leads to renal failure. Some clinical studies report that the duration of prepubertal diabetes may contribute less to the development of microvascular complications than pubertal and postpubertal duration. There have been few cases of DN in prepubertal patients with T1DM in Korea. Thus we report a case of a 12-year-old female with T1DM who had poor glycemic control and was diagnosed as DN in a prepubertal period. It was proven by renal biopsy after microscopic hematuria and proteinuria were detected through the mass school urinary screening program.