IgA nephropathy: Long-term prognosis for pediatric patients

Wyatt, Robert; Kritchevsky, Stephen B.; Woodford, Susan Y.; Miller, P M; Roy, Shane; Holland, Nancy H.; Jackson, Elizabeth; Bishof, Nancy A.

doi:10.1016/s0022-3476(95)70027-7

Cited by 123 publications

(86 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In adults, the proportion of crescents is also a major prognosis factor, but the discriminating point may be lower than 50% (58 -61). In the context of Berger disease, it has been shown that renal histologic lesions are of good prognostic value in children (62,63) and in adults (24,64,65). Indeed, diffuse proliferative glomerulonephritis, the extent of global glomerular sclerosis, interstitial sclerosis, and crescents were identified as markers of poor prognosis (24,65).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Expression of the CD71 Mesangial IgA1 Receptor in Berger Disease and Henoch-Schönlein Nephritis

Haddad¹,

Moura²,

Arcos-Fajardo³

et al. 2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

ABSTRACT. IgA nephropathy (IgA-N) that comprises Berger disease and Henoch-Schönlein Purpura (HSP) nephritis is defined by mesangial IgA deposits. Recently, this group has characterized a new receptor for IgA, the transferrin receptor (CD71), expressed on mesangial cells. To assess whether CD71 was involved in the pathogenesis of IgA-N, its expression was analyzed together with IgA deposits on 16 kidney biopsies from 16 patients with Berger disease (n = 4) or HSP (n = 12). These biopsies were compared with 17 kidney biopsies of a group of 15 patients (control group) with other glomerulonephritis, including systemic lupus erythematosus, poststreptococcal acute glomerulonephritis, membranoproliferative glomerulonephritis, steroid-sensitive minimal change nephrotic syndrome, steroid-resistant idiopathic nephrotic syndrome with focal and segmental glomerulosclerosis, and persistent and isolated proteinuria with minimal change on kidney biopsy. In this control group, IgA deposits could be observed in eight kidney biopsies of seven patients. These biopsies were also compared with normal kidney specimens (normal group). In normal kidney, it was found that CD71 was linearly expressed on tubular epithelium but was either not expressed or very dimly in glomeruli. In contrast, CD71 was strongly expressed in 105 of the 107 glomeruli of the kidney biopsies from the IgA-N group. For the control group, it was found that expression of CD71 in glomeruli was correlated to the presence of IgA deposits. Indeed, among the 87 glomeruli of nine kidney biopsies (eight patients) without IgA fixation, 78 exhibited no CD71 expression and nine exhibited a very dim one. On the other hand, all 49 glomeruli of the eight kidney biopsies (seven patients) in which IgA deposits were detected exhibited CD71 expression (P < 10−4). Performance of dual-labeling studies with confocal microscopy on kidney biopsies of IgA-N patients demonstrated that most of the IgA deposits co-localized with CD71. It was also demonstrated that the intensity of the expression of CD71 was not linked to the intensity of clinical or biologic findings but to the intensity of cellular proliferation in both IgA-N and control groups. These results show that mesangial CD71 expression is not specific to IgA-N. However, the association between IgA deposits and CD71 expression and their co-localization in the mesangium provide strong evidence that CD71 is a major IgA receptor on mesangial cells. Email: elie.haddad@rdb.ap-hop-paris.fr

show abstract

Section: Discussionmentioning

confidence: 99%

Enhanced Expression of the CD71 Mesangial IgA1 Receptor in Berger Disease and Henoch-Schönlein Nephritis

Haddad¹,

Moura²,

Arcos-Fajardo³

et al. 2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Proteinuria is considered a hallmark of glomerular diseases. Clinical studies that analyzed the outcome of glomerular diseases such as IgA nephropathy, FSGS, and membranoproliferative glomerulonephritis have shown nephrotic-range proteinuria (Ͼ2.5 g/d) to represent a poor prognostic factor (1)(2)(3). Therefore, a reduction in the degree of proteinuria has been a goal of treatment and used as a parameter to monitor the response to therapy.…”

mentioning

confidence: 99%

Mitochondria Are the Major Targets in Albumin-Induced Apoptosis in Proximal Tubule Cells

Erkan¹,

Devarajan²,

Schwartz³

2007

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Nephrotic-range proteinuria is considered a poor prognostic factor. A correlation between tubulointerstitial injury and the degree of proteinuria is well established. In an attempt to explain the tubular atrophy that is observed in advanced glomerulonephritides, this study investigated apoptotic mechanisms in cultured human proximal tubule cells (HKC-8) that were exposed to endotoxin-free albumin (5, 10, and 20 mg/ml). Apoptosis was detected by Hoechst 33342; annexin staining; and assays for caspases 3, 8, and 9. The apoptotic effect of albumin was maximal at 10 mg/ml albumin, and necrosis prevailed in cells that were incubated with 20 mg/ml. Increase in caspase-9 and -3 activity was observed starting at 6 and maximally at 16 to 24 h. The proapoptotic Bcl-2 protein Bax was upregulated at 6 h, associated with translocation of cytochrome-c from mitochondria to cytosol and alteration in the mitochondrial membrane potential. Production of reactive oxygen species (ROS) was significant at 6 h but declined at 16 and 24 h. Treatment with ROS scavenger dimethylthiourea or antioxidant N-acetylcysteine did not alleviate caspase-3 production. Pan protein kinase C inhibitor bisindolylmaleimide-1 protected the cells from apoptosis. It is concluded that albumin induces apoptosis in human proximal tubule cells by stimulating mitochondrial apoptotic pathway independent of ROS production.

show abstract

“…We thus evaluated the association between 4G/5G and other poor prognostic factor (16), such as ≥1,000 mg/day proteinuria and hypertension. The remission rate of IgAN was approximately 34% and the possible progression rate was approximately 19%, which partially consisted with the long-term outcomes of IgAN (25). The frequency of the 4G/4G genotype in the progressor group was 5-fold higher than that in the remissor group.…”

Section: Control Total Gn Igan Mespgn -------------------------------mentioning

confidence: 96%

Impact of the -675 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene on childhood IgA nephropathy

Han

Kim

Lee

2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of the fibrinolytic pathway and extracellular matrix (ECM) turnover. The -675 4G/5G polymorphism in the PAI-1 promoter is associated with altered PAI-1 transcription, suggesting that this polymorphism may be a candidate risk factor for diseases characterized by ECM accumulation, such as immunoglobulin A nephropathy (IgAN) and mesangial proliferative glomerulonephritis (MesPGN). We genotyped childhood patients with biopsy-confirmed IgAN (n=111) and MesPGN (n=47), and healthy control subjects (n=230) for the -675 4G/5G PAI-1 polymorphism by polymerase chain reaction-restriction fragment length polymorphism methods. The distribution of the 4G/4G (27.9%), 4G/5G (45.1%) and 5G/5G (27.0%) genotypes in IgAN patients was significantly different from the healthy controls (32.2, 54.3 and 13.5%, respectively) (p=0.0092). There was no significant difference in the genotype distributions of the 4G/5G polymorphism between MesPGN patients and the healthy controls. Regarding the impact of the polymorphism on IgAN, the 4G/4G genotype was markedly increased in patients with proteinuria (≥1,000 mg/day) and/or hypertension when compared to patients without proteinuria and hypertension (OR=5.23, 95% CI 1.34-20.38, P=0.0183). These findings indicate that the PAI-1 gene polymorphism may affect the susceptibility of childhood IgAN.

show abstract

IgA nephropathy: Long-term prognosis for pediatric patients

Cited by 123 publications

References 19 publications

Enhanced Expression of the CD71 Mesangial IgA1 Receptor in Berger Disease and Henoch-Schönlein Nephritis

Enhanced Expression of the CD71 Mesangial IgA1 Receptor in Berger Disease and Henoch-Schönlein Nephritis

Mitochondria Are the Major Targets in Albumin-Induced Apoptosis in Proximal Tubule Cells

Impact of the -675 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene on childhood IgA nephropathy

Contact Info

Product

Resources

About