Purpose : There have been numerous researches on urine ${\beta}_2$-microglobulin (${\beta}_2$-M) concerned with primary nephrotic syndrome and other glomerular diseases, but not much has been done in relation to pediatric age groups. Thus, our hospital decided to study the relations between the analysis of the test results we have conducted on pediatric patients and renal functions. Methods : Retrospective data analysis was done to 102 patients of ages 0 to 4 with renal diseases with symptoms such as hematuria, edema, and proteinuria who were admitted to Chung-Ang Yongsan Hospital and who participated in 24-hour urine and urine ${\beta}_2$-M excretion test between January of 2003 and January of 2006. Each disease was differentiated as independent variables, and the statistical difference of the results of urine ${\beta}_2$-M excretion of several groups of renal diseases was analyzed with student T-test by using test results as dependent variables. Results : Levels of urine ${\beta}_2$-M excretion of the 102 patients were as follows : 52 had primary nephrotic syndrome [MCNS (n=45, $72{\pm}45{\mu}g/g$ creatinine, ${\mu}g/g-Cr$), MPGN (n=3, $154{\pm}415{\mu}g/g-Cr$), FSGS (n=4, $188{\pm}46{\mu}g/-Cr$], six had APSGN ($93{\pm}404{\mu}g/g-Cr$), seven had IgA nephropathy ($3,414{\pm}106{\mu}g/g-Cr$), 9 had APN ($742{\pm}160{\mu}g/g-Cr$), 16 had cystitis ($179{\pm}168{\mu}g/g-Cr$), and 12 had HSP nephritis ($109{\pm}898{\mu}g/g-Cr$). IgA nephropathy (P<0.05) and APN (P<0.05) were significantly higher than in other renal diseases. Among primary nephrotic syndrome, FSGS with higher results of ${\beta}_2$-microglobulin test had longer treatment period (P<0.01) when compared to the lower groups, but no significant differences in Ccr, BUN, or Cr were observed. Conclusion : IgA nephropathy and APN groups showed significantly higher level of ${\beta}_2$-M excretion value than other groups. Although ${\beta}_2$-microglobulin value is not appropriate as an indicator of general renal function and pathology, it seems to be sufficient in the differential diagnosis of the UTI and in the prediction of the treat-ment period of nephrotic syndrome patients.
Purpose: Thin glomerular basement membrane nephropathy (TBMN) is, along with the IgA nephropathy, the most common cause of asymptomatic hematuria in Korean children. TBMN is usually a benign renal disease not requiring treatment and is associated with a good prognosis, but some cases hematuria is indicative of a state of progressive renal insufficiency. We aimed to retrospectively evaluate clinical manifestations and renal prognosis of patients with TBMN. Methods: Among the 428 renal biopsies performed on children at Yeungnam University Hospital between January 2000 and February 2017, 167 patients were diagnosed as having TBMN. We retrospectively investigated 167 pediatric patients and identified 59 children with follow-up duration >3 years. Results: Among 59 patients, there were 33 boys and 26 girls. Mean age of onset of hematuria was $7.18{\pm}2.64$ years, and mean time from onset of disease until a renal biopsy was performed was $2.48{\pm}2.10$ years. There were no clinical features or laboratory findings among studied children to indicate decreased renal function during follow-up; however, one case progressed to chronic kidney disease (CKD) due to an unknown cause. There were seven patients among these related a positive family history of hematuria or renal insufficiency. Concluson: Although almost all patients had normal renal functions during follow-up, there were one patient who progressed to CKD and seven patients with family history of hematuria or renal insufficiency. Moreover, four among the 428 patients over 17 years underwent repeat renal biopsies, which showed results different from their earlier biopsies.Thus, large-scales studies may be required to determine long-term prognosis of TBMN in children, and further evaluation for Alport syndrome in TBMN cases is essential.
Lee, Jeong Ju;Kim, Yong-Jin;Shin, Jae Il;Yim, Hyunee;Park, Se Jin
Childhood Kidney Diseases
/
v.17
no.2
/
pp.92-100
/
2013
Purpose: To investigate the clinicopathologic effects of cyclosporine A (CsA) in children with diseases characterized by mesangial immunoglobulin A deposits such as immunoglobulin A nephropathy (IgAN) and Henoch-Sch$\ddot{o}$nlein purpura nephritis (HSPN). Methods: We retrospectively reviewed the clinicopathologic outcomes of 54 children (IgAN, 36; HSPN, 18) treated with CsA. The starting dose of CsA was 5 mg/kg per day, and it was administered in 2 divided doses. The degree of proteinuria and pathologic changes in renal biopsies were evaluated before and after CsA treatment. Results: The mean protein to creatinine ratio decreased from $3.7{\pm}1.5$ to $0.6{\pm}0.4$(P <0.001), and 32 (59.2%) children achieved complete remission of proteinuria after 1-year CsA treatment. Among the 54 children, 24 maintained normal renal function and 25 exhibited microscopic hematuria or proteinuria at the end of CsA treatment. In the HSPN group, 3 children whose initial biopsies indicated class IIIb disease showed class II disease on follow-up, and the follow-up biopsies of 2 children who had class II disease indicated the same class II disease. In the IgAN group, cortical tubular atrophy occurred in 1 child, and no child with IgAN had cortical interstitial fibrosis or tubular atrophy after 1-year CsA treatment. No significant complications were found in the children treated with CsA. Conclusion: Our findings indicate that CsA treatment is effective and beneficial in reducing massive proteinuria and preventing progression to end-stage renal failure in children with glomerular diseases characterized by IgA deposits, such as IgAN and HSPN, within 1 year of treatment.
Kim, Sae Yoon;Lee, Sang Su;Lee, Jae Min;Kang, Seok Jeong;Kim, Yong Jin;Park, Yong Hoon
Childhood Kidney Diseases
/
v.17
no.2
/
pp.49-56
/
2013
Purpose: IgA nephropathy (IgAN) is one of the major causes of end-stage renal disease. Mass school urine screening (SUS) has been performed to enable early detection of chronic renal diseases, including IgAN. We wanted to evaluate the patients with IgAN, including those diagnosed through SUS. Methods: Between 1998 and 2010, 64 children were diagnosed with IgAN based on renal biopsy results obtained at the Pediatric Nephrology Department, ${\bigcirc\bigcirc}$ University Hospital. We divided these patients into the SUS group (37 cases), diagnosed through SUS, and the symptomatic (Sx) group (27 cases), diagnosed clinically. The medical records of both groups were analyzed retrospectively. Results: The mean age of the SUS and Sx groups was $10.8{\pm}2.7$ and $9.5{\pm}3.4$ years (P >0.05), respectively. Both groups had a higher proportion of male patients. The time from the notification of an abnormal urinary finding to a hospital visit or renal biopsy was shorter in the Sx group than in the SUS group. Regarding clinical manifestations, there were fewer cases with gross hematuria (P <0.001) and edema (P =0.008) in the SUS group, but there were no differences in terms of the therapeutic regimen and treatment duration. Regarding laboratory parameters, the Sx group had a higher white blood cell count (P =0.007) and lower hemoglobin (P =0.007) and albumin (P =0.000) levels. There were no differences in the renal biopsy findings in both groups, based on the history of gross hematuria or the severity of proteinuria. However, in all 64 patients with IgAN, the light microscopy findings (Hass classification) were related to a history of gross hematuria or the severity of proteinuria. Conclusion: There were no significant clinical and histological differences between the groups, as both had early stage IgAN. Although SUS facilitates the early detection of IgAN, long-term, large-scale prospective controlled studies are needed to assess the benefits of early diagnosis and treatment in chronic renal disease progression.
Objectives : The current treatment regimens for patients with nephrotic syndrome due to membranous nephropathy(MN) are based on steroids or immunosuppressive therapy with the aim of reducing proteinuria and improving outcome. Although these treatments attenuate the deterioration of renal function in MN patients, it has been suggested that all are burdened by significant toxicity. Therefore, more specific and less toxic therapies are needed. This study was to evaluate the effects of Coptidis Rhizoma Extract(CRE) on the MN induced by cBSA in mice. Methods : Mice were divided into 4 groups. One group named for 'Normal' was injected with a saline solution not to be immunized. The rest groups were treated as follows; After mice were immunized with 0.2 mg of cBSA and Freund's complete adjuvant one time every two weeks for 6 weeks, they received intra-peritoneal injection of 10 mg/kg of cBSA daily for 4 weeks. Also, they were divided into 3 groups. The first named for 'Control' was not given CRE. The second for 'CRE-250' was given oral administration of 250 mg/kg of CRE daily for 4 weeks. The third for 'CRE-500' was given 500 mg/kg of CRE. All of mice were sacrificed 4 weeks after the first immunization. We measured a body weight and 24hrs proteinuria as well as serological analysis. The morphologic changes of renal glomeruli were also observed with a light microscope and an electron microscope. Results : The levels of 24 hrs proteinuria, triglyceride, IgG, IL-6 were significantly decreased in both CRE groups. And the level of IgM was significantly decreased in CRE-250 group. In histological findings of kidney tissue, thickening of GBM and deposition of electron-density were consideraly decreased in both CRE groups. Conclusions : The present study suggests that CRE is highly effective when treating mice with MN induced by cBSA. More clinical data and studies are to be done for efficient application.
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 (${\leq}4$ and >$4mg/m^2/h$, ${\leq}40$ and >$40mg/m^2/h$, 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 (>$4mg/m^2/h$) and those without proteinuria (codominant model OR 0.36, 95% CI 0.19-.66, P <0.001; dominant model OR 0.35, 95% CI 0.17-.69 P =0.002; recessive model OR 0.12, 95% CI 0.01-.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.
Objective: The purpose of our study was to show the effects of Hwalhyulmaksung-bang (Huoxiemoxing-fang, HHMSB) treatment on cBSA-induced in MN Mouse Model. Methods: We divided the 20 mice into 4 groups. One group, named NR, was not treated. The second group, named CT, was treated with cBSA (7mg/kg i.p) only. The third group, named HH-250, was treated with cBSA (7mg/kg i.p) and HHMSB extract (250mg/kg, p.o). The fourth group, named HH-500, was treated with cBSA (7mg/kg i.p) and HHMSB extract (500mg/kg, p.o). 4 weeks after cBSA, proteinuria, serum albumin, total cholesterol, serum creatinine, BUN, total cell number of spleen and kidney of all groups were measured. CD3e+/CD19+ and CD4+/CD8 cells ratio of peripheral blood, kidney and spleen of all groups were analyzed. $IL-1{\beta}$ and TNF-$\alpha$, IL-6, IgG, IgM, and IFN-$\gamma$ levels of all groups were gauged. Histological analysis of kidney tissue and immunohistochemical staining (CD4, CD8) of kidney were observed. Results: The level of proteinuria significantly decreased and serum albumin increased in the group treated with cBSA and HHMSB extract compared with the control. Total cholesterol decreased but not significantly. CD3e+/CD19cells ratio of peripheral blood is decreased, but CD4+/CD8cells ratio has no significancy. CD3e+/CD19+ and CD4+/CD8 cells percentage of kidney and spleen has no significancy. Level of $IL-1{\beta}$, IL-6 is significantly decreased, and IFN-$\gamma$ is significantly increased on HHMSB compared with control. Total IgG level significantly decreased on HHMSB compared with the control. Thickness of GBM decreased on histological analysis of kidney. Deposition of CD4 and CD8 decreased on immunohistochemical staining of kidney. Conclusions: We conclude that Hwalhyulmaksung-bang treatment may could be a useful remedy agents for treating Membranous Neuropathy(MN) induced by cationized bovine serum albumin.
Alport syndrome (AS) is a progressive hereditary nephritis that is often accompanied by sensorineural hearing loss and ocular abnormalities. It is inherited in three modes of X-linked AS (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ARAS and ADAS are caused by those in COL4A3 or COL4A4. There is currently no curative treatment for AS; however, angiotensin-converting enzyme inhibitors (ACEi) can improve the outcome of AS. In the past decade, multiple studies have shown that early intervention with ACEi upon isolated microscopic hematuria or microalbuminuria could delay disease progression, and early diagnosis is crucial for early treatment. Therefore, a new classification of AS based on molecular diagnoses has been proposed, including the paradigm shift of re-classifying female "carriers" to "patients" and "thin basement membrane nephropathy" to "ADAS." In addition, with the detection of COL4A mutations in some patients with biopsy-confirmed IgA nephropathy, focal segmental glomerulosclerosis, and chronic kidney disease of unknown origin, it is suggested that the phenotype of AS should be expanded. In this review, we highlight the landmark studies and guidelines published over the past decade and introduce strategies for early diagnosis and treatment to improve the outcomes of AS.
Purpose : The urinary mass screening program for the detection of proteinuria in school aged population has been performed in Seoul since 1981. Systematic evaluation in corporation with the Seoul School Health Center for students with proteinuria identified in the mass screening has been performed from 1987. The results of urinary mass screening up to 1994 was reported. I report here the results of urinary mass screening from 1995 to 1997 and compare them with previous results and attempt to reveal the significance of urinary mass screening. Objects and Methods : In the 3-year period between 1995 and 1997, annually about 460,000 students comprising 3 different age groups; 5th grade of elementary school, 2nd grade of middle school and 2nd grade of high school were chosen, corresponding to the approximate ages of 11, 14, and 17 years, respectively. These subjects accounted for 26% of total school aged children in Seoul. The screening program was carried out in 3 steps. The 1st test was performed with dipstick at school and the 2nd at the Seoul School Health Center. Those students who showed proteinuria in the 1st and 2nd tests were referred to the hospital. Laboratory examinations including renal biopsies were performed to those students with pathologic proteinuria to clarify the incipient renal diseases. Results : 1) The prevalence of asymptomatic proteinuria was 0.28% in the 1st test. It peaked at the group of 14 years old as 0.34%, compared with 0.26% at the group of 11 years old and 0.24% at the group of 17 years old. It reached to 0.26% in male and 0.30% in female. 2) 25 percent of those having proteinuria at the first test were positive at the second test. 3) The proportion of patients with proteinuria by 3rd test were as follows; 25% of transient proteinuria, 55% of orthostatic proteinuria, 6% of constant proteinuria, 12% of proteinuria with hematuria, and 2% of transient proteinuria with isolated hematuria. Pathologic proteinuria were totaled as 20%. The prevalence of renal diseases among the age group of 7-18 years old was estimated to be 1.4 per 10,000. 4) Renal biopsy performed on 38 children with proteinuria at the third test revealed IgA nephropathy in 17(44%), focal segmental glomerusclerosis in 5(13%), minimal change disease in 4(11%), membranoproliferative glomeronephritis in 3(8%), $Henoch-Sch\"{o}nlein$ purpura nephritis in 3(8%), and others in 6(16%). Therefore, the prevalence of IgA nephropathy among the age group of 7-18 years old was estimated to be 0.64 per 10,000. 5) The prevalence of chronic renal failure was estimated to be 5.7 per 1 million of 7 to 18 years age group. Conclusions : 1) The prevalence of proteinuria in the first screening test was 0.28% and finally only 5% of them showed the pathologic proteinuria at the third test. 2) The prevalence of IgA nephropathy and chronic renal failure were 0.63 per 10,000 and 5.7 per 1 million, respectively among school-aged children in Seoul.
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