IgA Nephropathy In Children Research Articles

Progress of treatment of IgA nephropathy in children

There is not a unified and specific treatment for IgA nephropathy at present,and the treatments varies with the individuals,because of the great disparity of seriousness,diversity in pathological changes and discrepancy in course of the disease.It is still regarded as the major therapeutic objective in clinical medicine that alleviating the clinical symptoms,protecting the kidney function,and delaying the progress of kidney disease. Key words: IgA nephropathy; Children

Clinicopathologic Changes of IgA Nephropathy in Children During Long-term (average 10.8 yrs) Follow-up

목 적 : 소아 IgA 신병증의 임상 양상 및 병리학적 분류(Haas 분류)와 임상 경과와의 상관 관계를 조사하여 이들이 예후를 반영할 수 있는지 알아보고자 하였다. 방 법 : 병리학적으로 IgA 신병증으로 진단받고 추적 중이던 환자들 중 추적 신생검을 시행한 20명의 환자를 대상으로 후향적으로 자료를 분석하였다. 결 과 : 최초 신생검시 평균 9.5세였고 남자 16명, 여자 4명이었으며, 최종 조직 검사까지 평균 10.8년이 경과하였다. 안지오텐신 전환효소 억제제 등으로 치료를 지속한 후 정상뇨 소견, 정상 혈압, 정상 크레아티닌 청소율(CCr)을 보이는 임상적 관해 상태의 환자는 10명(50%)이었으며, 비관해 상태의 환자 10명(50%)도 초기와 비교하여 호전된 경과를 보였고, CCr이 중등도 이상 저하되거나 말기 신질환 양상을 보이는 환자는 없었다. 최초 Haas 분류는 임상경과와 상관 관계가 없었다. 초기 고혈압은 5명(25%)에서 보였고 이는 임상 경과(P =0.010) 및 최종 Haas 분류(P =0.007)와 유의성이 있었다. 초기 CCr의 중등도 저하는 Haas 분류와 유의성이 있었으나(P =0.048), 임상 경과와는 상관관계가 없었다. 결 론 : 소아 IgA 신병증의 추적 기간 중 임상 경과는 양호하나 최초 Haas 분류로 임상 경과를 예측할 수는 없었으나 적극적인 조기 진단 및 치료로 말기 신질환으로의 진행을 지연시킬 수 있을 것으로 보인다. 초기 고혈압은 임상 경과 및 최종 Haas 분류와 유의한 상관관계를 보여 적합한 예후인자로 보인다. 최초 병리학적 소견은 임상 경과를 반영하지 못하나, 추적 Haas 분류가 예후를 반영할 수 있을지에 대해서는 보다 많은 추적 관찰 및 추적 신생검을 통한 연구가 있어야 할 것으로 보인다. 【Purpose : We know little about the natural course of IgA nephropathy (IgAN) in association with histologic changes especially in children. We investigated clinicopathologic features with long-term follow-up biopsy to clarify the outcomes and prognostic indicators for childhood IgAN. Methods : From our patients' medical records, we retrieved 20 patients with IgAN, to whom renal biopsies had been performed for the initial diagnosis and follow-up to find out any histologic changes. Initial and follow-up biopsies were classified by Haas classification. The changes of these parameters were compared with the evolution of clinical features. Results : Patients were treated with angiotensin-converting enzyme inhibitors in combination with angiotensin receptor blockers (in subclass II or above) and short-term cyclosporine A(in patients showing nephrotic syndrome). Histologic improvement in 7 cases and deterioration in 3 cases were observed. At the time of last biopsy, 10 cases (50%) showed clinical remission and the others showed improved clinical features. These clinical outcomes did not correlate with initial Haas classifications. Hypertension at onset observed in 5 cases (25%) revealed significant correlation with clinical outcome (P =0.01) and last Haas classification (P =0.007). None of the cases showed progression to CRF or ESRD. Conclusion : During a mean follow-up of $10.8{\pm}3.4$ years, childhood IgAN showed good clinicopathologic outcome. Hypertension at onset was only a strong predictor of clinicopathologic outcomes, but initial Haas classification cannot predict outcomes in children. Histologic change of IgAN in long term follow-up period cannot be completely predicted by clinical data and vice versa. Therefore, a renal biopsy should be considered as a part of follow-up plan.】

Interleukin-1 cluster gene polymorphisms in childhood IgA nephropathy

We have carried out a study with the aim of investigating the association between single nucleotide polymorphisms (SNPs) of the IL-1 gene cluster and childhood IgA nephropathy (IgAN). SNPs of the IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist (RN) genes (IL1A, IL1B, and IL1RN, respectively) were analyzed in 182 patients with childhood IgAN and in 500 healthy controls. The IgAN patients were also dichotomized and compared with respect to proteinuria (<4 mg and >or=4 mg/m(2) per hour, respectively), 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. Significant differences in SNP frequencies were observed for the IL1B and IL1RN genes (rs1143627, rs3917356, and rs1143633 in the IL1B gene, and rs928940, rs439154, and rs315951 in the IL1RN gene). Moreover, rs1143627, rs3917356, and rs1143633 of IL1B were found to be significantly associated with the presence of podocyte foot process effacement. Our results suggest that the IL1B and IL1RN genes are associated with increased susceptibility to IgAN in children. They also suggest that the development of proteinuria in IgAN is related to IL1A and that podocyte foot process effacement is associated with IL1B.

Altered P-selectin and CD44 expression in the renal tissues and peripheral blood of children with IgA nephropathy

To understand the role of P-selectin (CD62P) and CD44 in mediating immune inflammation in the nephrotic process of children with IgA nephropathy (IgAN), cooperative expression of CD62P and CD44 in peripheral blood and renal tissues of IgAN children was investigated and its association with changes of histopathologic, serologic, and urinary properties was tested. Forty-six IgAN children were divided into three groups according to pathologic grades and clinical features. Fifteen blood samples from normal children and four normal renal biopsy specimens were used as controls. Plasma level of CD62P was detected by double antibody sandwich immunoradiometric assay; ELISA was used to determine serum level of CD44. Expression of CD62P and CD44 in renal tissues was determined by immunohistochemistry. Cooperative expression of CD62P and CD44 was detected in renal tissues and peripheral blood of IgAN children. Altered expression of CD62P and CD44 in peripheral blood significantly correlated not only with hematuria, proteinuria, serum cholesterol, and albumin, and with urine NAG and beta(2)-MG, but also with degree of tubulointerstitial injury in IgAN children. The evidence supported CD62P and CD44 as initial and promoting factors mediating immune inflammation in the nephrotic process in IgAN children. The cooperative expression profiles of CD62P and CD44 in renal tissues and peripheral blood combined with serologic and urinary predictors may be important in diagnosis of progression in children with IgAN.

Accumulation of Macrophages Expressing Myeloid-Related Protein 8 Associated with the Progression of Sclerotic Changes in Children with IgA Nephropathy

Myeloid-related protein (MRP) 8 is a calcium-binding protein of the S100 family. The renal accumulation of macrophages expressing MRP8 is associated with the inflammatory activity of glomerulonephritis. We evaluated the renal accumulation of macrophages expressing MRP8 in children with IgA nephropathy (IgAN). We collected data on 25 IgAN children who had been treated with prednisolone and divided these patients into two groups: Favorable group, consisting of 11 patients with normal urine and 6 with minor urinary abnormalities at 4.3 +/- 1.3 years after initial treatment; and Unfavorable group, consisting of 8 patients with persistent nephropathy. The pathological renal findings were compared between both groups. The second biopsy was performed at two years after first biopsy at 5.5 +/- 4.9 months from onset. In Favorable group, the glomerular accumulation of macrophages expressing MRP8, and mesangial cells expressing alpha-smooth muscle actin (alpha-SMA) were lower in the second biopsy specimens than those of the first biopsy specimens. In Unfavorable group, the glomerular accumulation of macrophages expressing MRP8 detected in the second biopsy specimens was similar to that of the first biopsy, while the number of mesangial cells expressing alpha-SMA and the index of renal sclerosis were higher in the second biopsy than in the first biopsy. The indexes of renal sclerosis were higher in children with more macrophages expressing MRP8 than in children with less macrophages expressing MRP8. Our results suggest that renal macrophages expressing MRP8 may be involved in the progression of sclerotic changes in children with IgAN.

IgA Nephropathy in children and adults: comparison of histologic features and clinical outcomes

While some studies have reported that IgA nephropathy has a relatively benign clinical course in children, others have shown that renal outcomes of paediatric patients with IgA nephropathy followed into adulthood are similar to those of patients diagnosed as adults. Some of this variability may be related to differences in histologic severity of cohorts of patients diagnosed as children versus adults. We retrospectively examined correlations between renal biopsy findings, clinical features at presentation and renal survival in 99 children and adolescents (<or=17 years old) with IgA nephropathy and compared these findings to those of 125 adults with IgA nephropathy. Compared with adults, paediatric patients were more likely to have minimal histologic lesions (24% versus 14%) and less likely to have advanced chronic lesions (3% versus 17%). Similar fractions of paediatric and adult patients showed focal and diffuse glomerulonephritis (GN), respectively. Among these latter two groups, renal survival was significantly better in patients diagnosed as children than as adults by univariate and multivariate analyses. By multivariate analysis, other significant, independent predictors of renal survival were estimated percent interstitial fibrosis and histologic grade (diffuse versus focal GN). In patients with proliferative IgA nephropathy, the clinical course is more likely to be benign when the disease is diagnosed in childhood versus adulthood. This difference can be accounted for only in part by more advanced disease at the time of biopsy in adults.

Pediatric IgA Nephropathy: Clinical and Therapeutic Perspectives

IgA nephropathy (IgAN) is the most common glomerular disease in children and adolescents, accounting for 20% of the glomerular diseases diagnosed by renal biopsy and 30% to 40% of biopsies performed because of hematuria and/or proteinuria in children. It is likely that several cases are missed because IgAN is mostly asymptomatic and is not detectable in the majority of children who do not undergo screening programs. The natural history of IgAN in children represents, with few exceptions, the early phase of the entire course. The disease had been considered more benign than in adults, however, this was found not to be true in long-term follow-up evaluations, and the 20-year survival rates were similar in the 2 age groups. The interest on IgAN in children has increased after the consideration that most subjects with IgAN entering dialysis are young adults and, because the decline of renal function in these patients is slow (25% need dialysis in 20 years), the realization that their disease had begun in childhood. Hence, detecting IgAN at the beginning of its natural history may offer the possibility of early treatment of the nephritis and/or its complications, with benefits for patients at the pediatric age, but even more benefits later in life.

THE PATHOGENESIS AND TREATMENT OF IgA NEPHROPATHY

IgA nephropathy (IgAN) is one of the most common causes of glomerulonephritis in the world. The proliferative and crescentic forms of IgA are found in up to 30% of cases and are associated with nephritic-range proteinuria, accelerated hypertension, and accelerated decline toward ESRD. Thus, it is important to investigate the mechanism of the onset of IgAN and to identify the most appropriate treatment. We herein review the pathogenesis and treatment of IgA nephropathy. As to the pathogenesis, we found that CB4 provoked exacerbation of renal pathologic findings in HIGA mice via endothelial injury, IFN-gamma production, and dysfunction of the mesangial pathway and could possibly become one of the factors involved in the mechanism of the onset or evolution of human IgAN. As to the treatment of IgAN, we evaluated the efficacy of tonsillectomy plus prednisolone, warfarin, and dipyridamole including methylprednisolone pulse therapy (tonsillectomy plus pulse therapy) and prednisolone, warfarin, and dipyridamole including mizoribine (PWDM) for the treatment of diffuse IgAN in children. These therapies were effective in ameliorating the proteinuria and histological severity of patients with IgAN. Furthermore the detail investigations into the pathogenesis of IgAN and double-blind randomized control studies on children with IgAN will be necessary.

Long-term course after tonsillectomy in treatment of IgA nephropathy in children

Long-term course after tonsillectomy in treatment of IgA nephropathy in children

Abnormal glycosylation of serum IgG in patients with IgA nephropathy

We postulated that IgA nephropathy (IgAN) involved alterations of serum IgG. The present study was undertaken to elucidate changes in serum IgG oligosaccharide structure analysis and to assess the diagnostic usefulness of this analysis in IgAN. The subjects were 28 children who were definitively diagnosed as having IgAN on the basis of renal biopsy and who had not received treatment for this disease; 27 healthy children; 15 untreated adults definitely diagnosed as having IgAN; 5 patients with other nephropathies; and 61 healthy adults. Oligosaccharide analyses of IgG were performed by reverse-phase high-performance liquid chromatography (HPLC) developed by Takahashi and colleagues. In both the children and the adults, the peak area ratio of isomers with two different galactosyl-N-acetylglucosamine (Gal-GlcNAc) binding sites was significantly lower in the presence of IgAN than in the healthy subjects (P<0.05 in children and P<0.001 in adults). The ratio of Gal-free oligosaccharides to Gal-positive oligosaccharides did not differ according to the presence or absence of IgAN in children or in adults. The analysis of the oligosaccharide structure of serum IgG seems to be useful in diagnosing IgAN.

Histological differences in new-onset IgA nephropathy between children and adults

It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.

Treatment of IgA nephropathy in children

SUMMARY: IgA nephropathy is the most common primary glomerulonephritis in the world, and about 20–50% of patients develop progressive renal failure. The pathogenesis is still unknown and treatment has not yet been established. Knowledge concerning childhood IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to end‐stage renal disease is also becoming apparent in children. This communication focuses on the treatment of IgA nephropathy in children.

Treatment of IgA nephropathy in children

SUMMARY: IgA nephropathy is the most common primary glomerulonephritis in the world, and about 20–50% of patients develop progressive renal failure. the pathogenesis is still unknown and treatment has not yet been established. Knowledge concerning childhood IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to end‐stage renal disease is also becoming apparent in children. This communication focuses on the treatment of IgA nephropathy in children.

IgA nephropathy in children.

IgA nephropathy in children.

Pathophysiology and treatment of IgA nephropathy in children.

IgA nephropathy is the most-common primary glomerulonephritis worldwide, and about 20%-50% of patients develop progressive renal failure. The pathogenesis is still unknown and treatment has not yet been established. Knowledge concerning childhood IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to end-stage renal disease is also becoming apparent in children. This review focuses on the pathophysiology and treatment of IgA nephropathy in children.

Primary IgA nephropathy in children: association of clinical and pathological findings with prognosis.

Primary IgA nephropathy is a disease characterized by recurrent macroscopic or microscopic hematuria and diffuse mesangial IgA deposition. Although IgA nephropathy had previously been suggested to have a benign prognosis, long term follow-up of the patients revealed that it might lead to chronic renal failure. In this study, the association of the initial clinical and laboratory findings with the renal histological changes was evaluated in 14 cases with primary IgA nephropathy who were at follow-up with a mean duration of 43.07 +/- 16.88 months. Finally the correlation between the clinicopathological findings and prognosis was investigated. In 92.8% of the patients, macroscopic hematuria was the presenting complaint. Proteinuria was detected in 42.9% of the cases mild proteinuria in 14.3% and moderate in 28.6%. Renal biopsy specimens, evaluated according to Churg-Sobin's classification, showed grade 1 changes in 35.7% cases, grade 2 in 35.7%, grade 3 in 14.3% and grade 4 in 14.3%. Both the patients with grade 4 histology had moderate proteinuria, and developed chronic renal failure requiring hemodialysis. Prognosis was found to be associated with the degree of proteinuria and the severity of the histopathological findings.

Urinary podocyte in IgA nephropathy in children

Urinary podocyte in IgA nephropathy in children

Histological changes in steroid‐responsive IgA nephropathy in children

NephrologyVolume 4, Issue s1 p. A35-A35 Histological changes in steroid-responsive IgA nephropathy in children Y AKIOKA, Y AKIOKA Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this authorM HATTORI, M HATTORI Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this authorY YAMAGUCHI, Y YAMAGUCHI Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this authorS WATANABE, S WATANABE Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this authorK ITO, K ITO Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this author Y AKIOKA, Y AKIOKA Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this authorM HATTORI, M HATTORI Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this authorY YAMAGUCHI, Y YAMAGUCHI Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this authorS WATANABE, S WATANABE Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this authorK ITO, K ITO Kidney Center, Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, JapanSearch for more papers by this author First published: 28 March 2007 https://doi.org/10.1111/j.1440-1797.1998.tb00446.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume4, Issues1June 1998Pages A35-A35 RelatedInformation

Macrophages in childhood IgA nephropathy

The role of glomerular macrophages in IgA nephropathy in children was investigated using a new monoclonal antibody (KP1) as a probe. The average number of glomerular macrophages per patient (ANM/P) was closely correlated with the degree of hematuria (P < 0.01) as well as with the degree of leukocyturia (P < 0.01) in the absence of any correlation with proteinuria, serum IgA levels or the interval between the detection of urine abnormalities and renal biopsy. ANM/P was significantly higher in patients diagnosed pathologically as having focal and diffuse proliferative glomerulonephritis than in patients with minor glomerular abnormalities or advanced sclerosis (P < 0.05). Among various types of glomerular morphology in individual patients, macrophages predominantly infiltrated glomeruli with cell-proliferative lesions despite an absence of any increase in glomeruli with minor abnormalities or with sclerosis. Macrophages were mainly localized within the capillary lumen in association with endocapillary proliferative lesions (tuft necrosis), they accumulated in areas of mesangial proliferation, and they were attached to Bowman's capsule in segmental lesions. Macrophages were less evident in sclerosis. Furthermore, ultrastructural analysis revealed macrophages in the paramesangial areas in close proximity to lytic changes in the glomerular basement membrane and effacement of epithelial foot processes. In addition, some cases in repeat biopsy shows prolonged or increased values of ANM/P after several years of interval in association with progression of proliferative lesions. These results suggest that macrophages infiltrate glomeruli during acute glomerular inflammation, and that they are involved in mesangial proliferation or the development of extracapillary lesions in the absence of apparent clinical symptoms. Furthermore, recurrence or prolonged infiltration may promote progression of IgA nephropathy.

IgA nephropathy in children and adults.

Knowledge concerning IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to the endstage renal disease is becoming apparent in children and adults. IgA nephropathy is a slowly progressive glomerular disease. Once renal function impairment develops, eventual progression to uremia is inevitable, and so a prophylactic approach to the progression of IgA nephropathy, based on an arbitrary period of therapy early in the course of disease, warrants serious consideration and investigation. A program of urinalysis screening in schools and an appropriate renal biopsy policy make an early diagnosis of IgA nephropathy possible. The development of successful therapy during childhood will offer a great potential for reducing the high morbidity and mortality associated with this disease in adults.