Skip Navigation


NDT Advance Access originally published online on February 10, 2008
Nephrology Dialysis Transplantation 2008 23(8):2537-2545; doi:10.1093/ndt/gfn014
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
23/8/2537    most recent
gfn014v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Haas, M.
Right arrow Articles by Bartosh, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Haas, M.
Right arrow Articles by Bartosh, S. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


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

Mark Haas1, M. Hafizur Rahman2,3, Richard A. Cohn4, Sahar Fathallah-Shaykh4, Adeel Ansari1 and Sharon M. Bartosh5

1 Department of Pathology 2 Department of Medicine, Johns Hopkins Medical Institutions 3 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 4 Division of Kidney Diseases, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL 5 Department of Paediatrics, University of Wisconsin Medical School, Madison, WI, USA

Correspondence and offprint requests to: Mark Haas, Department of Pathology, Johns Hopkins University School of Medicine, 600 N. Wolfe Str., Pathology 712, Baltimore, MD 21287, USA. Tel: +1-410-614-5631; Fax: +1-410-614-7110; E-mail: mhaas{at}jhmi.edu



   Abstract
Top
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. 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.

Methods. We retrospectively examined correlations between renal biopsy findings, clinical features at presentation and renal survival in 99 children and adolescents (≤17 years old) with IgA nephropathy and compared these findings to those of 125 adults with IgA nephropathy.

Results. 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).

Conclusions. 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.

Keywords: Berger's disease; glomerulonephritis; IgA nephropathy; renal biopsy; renal failure



   Introduction
Top
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 References
 
IgA nephropathy is the most common form of primary glomerular disease worldwide [1]. Although all cases of IgA nephropathy are characterized morphologically by dominant or co-dominant glomerular deposits of IgA [2], both clinical and histologic features of IgA nephropathy are highly variable [3–8]. As thoroughly reviewed by D’Amico [9], a number of different clinical parameters have been found to be associated with an increased risk of developing end-stage renal disease (ESRD) in nearly all studies of adults with IgA nephropathy, including elevated serum creatinine, proteinuria of ≥1 g/day, and systemic hypertension. Furthermore, in most studies, histologic parameters, most often including the severity of interstitial fibrosis and tubular atrophy, the extent of global and/or segmental glomerular sclerosis and a severe histologic grade (IV or V) using one of the two most widely used histologic grading systems proposed for IgA nephropathy [3,4] have been found to be associated with an increased risk of ESRD, although these correlations tend to be weaker than with the clinical parameters in multivariate analyses [9,10].

A much smaller number of studies have examined renal survival rates in children diagnosed with IgA nephropathy, although generally clinical and histologic risk factors for disease progression identified in these studies are similar to those noted above for adults [9,11–16]. Still, whether there are intrinsic differences in IgA nephropathy presenting in childhood compared with that presenting in adults remains unclear. A Japanese study comparing outcomes in children and adults with IgA nephropathy found 10- and 20-year renal survival rates of 95% and 80%, respectively, in children versus 82% and 50%, respectively, in adults [12]. A study of 103 paediatric IgA nephropathy patients from Kentucky and Tennessee showed an actuarial renal survival rate of 87% at 10 years and 70% at 20 years [13]; adults with IgA nephropathy in the same region had earlier been shown to have a 10-year renal survival rate of 78% [17]. In a study of 34 Swedish children with IgA nephropathy followed for 8–14 years, only 3 (9%) had reduced glomerular filtration rate (GFR) and 18 (53%) had no clinical signs of disease (including urinary abnormalities) at last follow-up [16]. Among children and adolescents, those diagnosed with IgA nephropathy before age 16 were found to have a more benign course than those diagnosed at ages 16–17 [15].

While these findings suggest the possibility that IgA nephropathy is more often manifested as a mild disease in children than in adults, alternative explanations for these results may be that children are simply diagnosed earlier in the course of their disease, and/or that clinical thresholds for performing a renal biopsy in a child versus an adult are often different. Consistent with the latter explanations, several studies comparing histologic findings in biopsies of children and adults with IgA nephropathy reported higher frequencies of a number of different lesions in adults, including segmental glomerulosclerosis, crescent formation, tubular atrophy, interstitial fibrosis and a higher overall grade of glomerular pathology [12,14,18,19]. As such, resolving the question whether IgA nephropathy tends to be a more benign disease in children than in adults would appear to require comparing cohorts of patients with histologically similar lesions.

In this study, we retrospectively analyzed and examined correlations between renal biopsy findings, clinical features at presentation and renal survival in 99 children and adolescents (≤17 years old) diagnosed with IgA nephropathy, and compared findings in these patients with those of 125 adults with IgA nephropathy. In comparing paediatric and adult patients with focal or diffuse proliferative IgA nephropathy, our findings suggest that the clinical course is more likely to be benign when the disease is diagnosed in childhood and that this can be only partially accounted for by histopathologic differences between paediatric and adult IgA nephropathy.



   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 References
 
Patients
Patients in this study included (1) all patients having a native renal biopsy interpreted at the University of Chicago Hospitals between 1980 and 1994, including paediatric (defined as <18 years old) and adult (≥18 years old) patients, with a diagnosis of IgA nephropathy (20 paediatric and 89 adult patients); (2) all patients undergoing a native renal biopsy at Johns Hopkins Hospital between 1984 and 2003, including paediatric and adult patients, with a diagnosis of IgA nephropathy (24 paediatric and 36 adult patients); (3) all patients undergoing a native renal biopsy at the University of Wisconsin Children's Hospital between 1993 and 2001 with a diagnosis of IgA nephropathy (24 paediatric patients) and (4) all patients having a native renal biopsy interpreted at Children's Memorial Hospital (Chicago) between 1985 and 1996 with a diagnosis of IgA nephropathy (31 paediatric patients), who were followed for at least 18 months after the biopsy or who developed ESRD within 18 months of the biopsy. All biopsies also met the following criteria: (1) there were ≥6 glomeruli (not including globally sclerotic glomeruli) present for light microscopic evaluation; (2) there was no evidence of Henoch-Schonlein purpura, systemic lupus erythematosus, human immunodeficiency virus (HIV) infection, or chronic liver disease; (3) there was no evidence of a superimposed systemic disease involving the kidney (e.g. diabetic nephropathy) and (4) immunofluorescence studies showed at least 1+ (0–4+ scale), diffuse mesangial deposition of IgA, with IgA being the dominant or co-dominant immunoglobulin present. One hundred nine of the patients (from the University of Chicago) were included in a previous study [3].

All study procedures were approved by the institutional review boards of each participating center.

Evaluation of biopsies
One histologic slide from each biopsy, stained with periodic acid-Schiff (PAS), was used for histologic grading, which was done blinded to all clinical data. For the 109 University of Chicago biopsies that were included in a previous study [3], histologic scoring done by a single renal pathologist (M.H.) at the time of that study was used for the present study. The remaining biopsies were graded independently by two observers (M.H. and A.A.), with any differences in grading resolved by viewing the slide together under a two-headed microscope. All biopsies were assigned a histologic subclass (I–V) according to the following, previously described schema [3]: (I) normal histology or mild increase in mesangial matrix, without segmental lesions; (II) focal and segmental glomerular sclerosis, without glomerular hypercellularity or crescents; (III) focal (involving ≤50% of glomeruli present, exclusive of globally sclerotic glomeruli) mesangial and/or endocapillary proliferative glomerulonephritis; (IV) diffuse (involving >50% of glomeruli present, exclusive of globally sclerotic glomeruli) mesangial and/or endocapillary proliferative glomerulonephritis and (V) advanced chronic glomerulonephritis, characterized by ≥40% globally sclerotic glomeruli and/or ≥40% interstitial fibrosis/tubular atrophy in the cortical tissue present, regardless of other histologic features. Examples of each histologic subclass are shown in Figure 1, and the histologic grading schema is briefly summarized in Table 1. The following histologic findings were also evaluated: presence or absence or one or more cellular or fibrocellular crescents (on all slides from a given biopsy), and the fraction of cortical tissue present with interstitial fibrosis, estimated to the nearest 2.5%. For the latter, the average of the scores of the two observers was used except in seven cases where there was a difference of ≥10%; in these cases a consensus value was reached by viewing the slide together under a two-headed microscope. For those biopsies showing histologic subclass III or IV lesions only, the following additional histologic parameters were recorded: presence or absence of endocapillary cell proliferation in one or more glomeruli, fraction of globally sclerotic glomeruli and the fraction of segmentally sclerotic glomeruli. All histologic data were recorded on spreadsheets identifying each patient and biopsy only by a study number (1–224).


Figure 1
View larger version (222K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Photomicrographs illustrating examples of different histologic subclasses of IgA nephropathy. (A) Minimal histologic lesion (subclass I). The glomeruli are normocellular, without segmental sclerosis or extracapillary lesions. There is minimal tubular atrophy or interstitial fibrosis, which is typical of most subclass I lesions [periodic acid-Schiff (PAS) stain, original magnification 200x]. (B) Focal segmental glomerulosclerosis without proliferative change (subclass II). Both glomeruli shown are normocellular, although one shows segmental sclerosis (arrow) (PAS, 200x). (C) Focal proliferative glomerulonephritis (subclass III). The glomerulus at left is unremarkable, and is representative of the majority of glomeruli on this biopsy. The glomerulus at right shows segmental mesangial and endocapillary (arrow) hypercellularity [haematoxylin-eosin (H&E) stain, 200x]. (D) Diffuse proliferative glomerulonephritis (subclass IV). This biopsy shows prominent, diffuse mesangial hypercellularity, although there is no endocapillary hypercellularity or crescent formation (H&E, 200x). (E) Diffuse proliferative glomerulonephritis (subclass IV). Both glomeruli in this more severe subclass IV lesion show segmental fibrocellular crescents with mesangial and endocapillary hypercellularity. There is interstitial inflammation and fibrosis (PAS, 200x). (F) Advanced chronic glomerulonephritis (subclass V). There is severe tubular atrophy and interstitial fibrosis, well exceeding the 40% level required to assign a biopsy to subclass V. The glomerulus at the far right is globally sclerotic, while that near the center of the field shows residual hypercellularity (H&E, 200x).

 

View this table:
[in this window]
[in a new window]

  		Table 1 Brief summary of histologic grading schema

 
Clinical data
For each patient, the following information was compiled from review of written and/or electronic patient records: patient age at the time of the biopsy, sex and race; serum creatinine (mg/dL) and urinary protein excretion (g/24 h or protein/creatinine ratio) at the approximate time of the biopsy; presence or absence of gross and/or microscopic haematuria prior to the biopsy; presence or absence of hypertension (defined as systolic blood pressure ≥130 and diastolic blood pressure ≥90 for adults, ≥85 for children and adolescents or treatment with one or more anti-hypertensive drugs) prior to or at the time of the biopsy; treatment given for the patient's renal disease subsequent to the biopsy; the date of most recent follow-up and if and when the patient developed ESRD requiring dialysis or transplantation. When any of this information was not available from patient records, it was requested from the appropriate clinician via a written form and/or telephone inquiries. Such inquiries were used to obtain updated follow-up information on the 109 patients included in the prior study [3]. All clinical data was recorded on spreadsheets separate from those containing the pathologic data, also identifying each patient only by the study number.

Data analysis and statistics
The distributions of continuous data sets were initially examined using the Shapiro-Wilk test to determine if the data were normally or non-normally distributed. Normally distributed continuous data were compared across groups using independent sample t tests. Non-normally distributed continuous data were compared across groups using the Wilcoxon rank-sum test. Categorical data were compared using Pearson's chi-square test.

Renal survival was measured from the time of biopsy and was examined by the time to event analysis using the Kaplan–Meier method, and equality of survivor functions was examined by log-rank testing. Univariate and multivariate associations between clinical and pathologic parameters and renal survival were performed using the Cox regression analysis and Cox proportional hazards modeling. Patients who died with functioning kidneys were censored at the time of death. Analyses were performed using STATA statistical software, version 9 (Stata Corp., College Station, TX, USA).



   Results
Top
 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 References
 
Tables 2 and 3 summarize clinical and histologic findings in paediatric and adult patients, respectively, with IgA nephropathy. In both groups, focal proliferative glomerulonephritis (subclass III) was the most commonly seen histologic type, accounting for >40% of cases in each. Diffuse proliferative glomerulonephritis (subclass IV) and focal segmental glomerular sclerosis without proliferation (subclass II) accounted for ~20% and ~10%, respectively, of cases in both paediatric and adult populations. The frequency of normal histology (subclass I) was more common in the paediatric group, while that of advanced chronic glomerulonephritis (subclass V) accounted for 17% of adult cases but only 3% of paediatric cases. Not unexpectedly, mean serum creatinine levels at the time of biopsy were highest with subclass IV and V lesions. Mean levels of proteinuria were similarly associated with histology in both patient populations (II > IV, V > III > I). Gross haematuria was seen more commonly in children and adolescents than in adults (particularly in individuals with subclass I, III and IV lesions). Hypertension was far more common in adults (particularly with subclasses III and IV), although it is possible that part of this difference may be attributable to the criteria used to define hypertension, which were only mildly different for adult and paediatric patients (see the ‘Materials and methods’ section). Adult biopsies in all subclasses (except V, where there were only three paediatric cases) showed greater mean levels of interstitial fibrosis than corresponding biopsies in paediatric patients. Both adult and paediatric cohorts had a similar composition with respect to gender (68% and 63% male, respectively) and race (78% white, 9% black and 77% white, 10% black, respectively). In adults, but not children, there was a significantly higher fraction of males among patients with more severe histologic lesions (subclasses IV and V) than among those with less severe lesions (P = 0.009 by Pearson's chi-square test).


View this table:
[in this window]
[in a new window]

  		Table 2 Clinical and histologic findings in paediatric patients with IgA nephropathy

 

View this table:
[in this window]
[in a new window]

  		Table 3 Clinical and histologic findings in adult patients with IgA nephropathy

 
Table 4 compares additional histologic features of biopsies in the adult versus paediatric populations, focusing on those biopsies with proliferative lesions (subclasses III and IV). Within subclass III, but not subclass IV, biopsies of adult patients were significantly more likely to show endocapillary hypercellularity in at least one glomerulus, and also showed significantly higher fractions of globally and segmentally sclerotic glomeruli than biopsies of paediatric patients. All of these are consistent with previous findings [19], and the greater fractions of globally and segmentally sclerotic glomeruli in adults with subclass III lesions is also consistent with the higher mean level of interstitial fibrosis in adult compared with paediatric biopsies (Tables 2 and 3).


View this table:
[in this window]
[in a new window]

  		Table 4 Additional histologic features of proliferative IgA nephropathy in paediatric and adult patients

 
Mean follow-up for paediatric patients was 73 ± 45 (SD) months (median 66 months, range 18–215) and for adults was 65 ± 41 months (median 62 months, range 18–201). Only 1 of 61 patients with a subclass I or II lesion developed ESRD over a mean follow-up interval of 90 months (an adult with a subclass II lesion, 74 months post-biopsy). Figure 2 shows that in both paediatric and adult cohorts, patients with subclass IV and V lesions had the poorest renal survival, with subclass III being intermediate.


Figure 2
View larger version (18K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Renal survival in patients with IgA nephropathy diagnosed as children or adolescents (top) and as adults (bottom), according to histologic subclass. These subclasses are (I) minimal histologic lesion, (II) focal segmental glomerulosclerosis without proliferative change, (III) focal proliferative glomerulonephritis (GN), (IV) diffuse proliferative GN and (V) advanced chronic lesion. The number of patients in each subclass is listed in Table 2 (for paediatric patients) and Table 3 (for adults).

 
However, both overall and among patients with subclass III and IV lesions, renal survival among individuals diagnosed with IgA nephropathy as children was clearly superior to that in patients diagnosed as adults (Figure 3). Overall actuarial 10-year renal survival in children and adolescents was 87% [95% confidence interval (CI) 72–94%], whereas in adults this was 48% (95% CI 35–60%) (Figure 3a). In paediatric patients with subclass III lesions, 10-year renal survival was 91% (95% CI 51–99%), compared with 60% (95% CI 36–78%) in adults (Figure 3b). In paediatric patients with subclass IV lesions, 10-year renal survival was 63% (95% CI 28–83%), compared with 0% in adults (Figure 3c). Combining subclasses III and IV, 10-year renal survival in children and adolescents was 80% (95% CI 57–92%), compared with 35% (95% CI 17–54%) in adults (Figure 3d).


Figure 3
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Comparison of renal survival in cohorts of patients with IgA nephropathy diagnosed as children or adolescents and as adults. Upper left: all histologic subclasses combined. Upper right: histologic subclass III (focal proliferative glomerulonephritis) only. Lower left: histologic subclass IV (diffuse proliferative glomerulonephritis) only. Lower right: subclasses III and IV combined. The number of patients in each subclass is listed in Table 2 (for paediatric patients) and Table 3 (for adults). In each instance, renal survival was significantly better in patients diagnosed as children or adolescents than as adults by both long-rank and Wilcoxon tests: all subclasses, P < 0.0001; subclass III, P < 0.01; subclass IV, P < 0.01; subclasses III and IV, P < 0.001. Actuarial 10-year renal survival numbers associated with each curve are listed in the text.

 
Multivariate analysis
Renal survival data in patients with subclass III and IV lesions were subjected to multivariate analysis including the following parameters: age group (adult or paediatric), sex, race, treatment with corticosteroids and/or other immunosuppressive agent(s) (Table 5), estimated percent interstitial fibrosis, percent globally sclerotic glomeruli, percent segmentally sclerotic glomeruli, presence or absence of endocapillary hypercellularity and presence of one or more cellular or fibrocellular crescents. Because we did not have the appropriate data to calculate an estimated GFR for many of the study patients (particularly those used in the previous study [3]) and as serum creatinine values cannot be compared between children and adults, estimated renal function at the time of biopsy could not be included in this analysis. Hypertension was not included because of the single, somewhat arbitrary cutoff in blood pressure used to define hypertension in the paediatric group that is probably not appropriate across the full range of patient ages represented in this group, and because of limited available data regarding use of anti-hypertensive medications. Finally, as urinary protein excretion levels for the majority of study patients were obtained in g/24 h, which like serum creatinine levels cannot be compared between children and adults, and not protein/creatinine ratios (the use of which has become widespread only during the past decade), we could not include the level of protein excretion in this analysis. Within subclass III, only the percent interstitial fibrosis [hazard ratio (HR) 1.15 per additional 1% estimated fibrosis, P = 0.004] was a significant, independent predictor of development of ESRD (Table 6). However, in patients with subclass IV lesions, age group was the strongest and only significant independent predictor of renal survival, with the risk of developing ESRD (HR) being seven times greater in adults than in children and adolescents. With combined subclasses III and IV, percent interstitial fibrosis, subclass IV histology and patient age group were each significantly and independently associated with development of ESRD (Table 6). Diffuse proliferative lesions (versus focal proliferative) were associated with a nearly three-fold greater risk of ESRD, and adult age group (versus paediatric) was associated with more than a five-fold greater risk of ESRD (Table 6). Demographic parameters other than age group, histologic parameters other than percent interstitial fibrosis and histologic subclass, and treatment with corticosteroids and/or other immunosuppressive agent(s) were not independent predictors of renal survival in subclass III or subclass IV alone, or combined.


View this table:
[in this window]
[in a new window]

  		Table 5 Treatment of IgA nephropathy in paediatric and adult patients

 

View this table:
[in this window]
[in a new window]

  		Table 6 Multivariate analysis of potential predictors of renal survival in patients with IgA nephropathy

 


   Discussion
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
References
 
The major objectives of this study were (1) to compare renal outcomes of patients with IgA nephropathy diagnosed as children and adolescents versus those diagnosed as adults, focusing on patients with active proliferative lesions, and (2) to determine if any differences observed could be accounted for by known histopathologic risk factors for progression of IgA nephropathy [3–9,11–16], or whether there are apparently intrinsic differences in the clinical courses of paediatric and adult IgA nephropathy.

Previous studies of patients from Japan [12] and from Kentucky and Tennessee [13,17] found better long-term outcomes in patients diagnosed with IgA nephropathy as children or adolescents than as adults, and our results are consistent with these studies. Furthermore, in considering only patients with focal or diffuse proliferative lesions of IgA nephropathy, we found that patients diagnosed as children or adolescents had a 10-year actuarial renal survival of 80%, compared to 35% in patients diagnosed as adults. In patients with diffuse proliferative glomerulonephritis, 10-year renal survival of patients diagnosed before age 18 was 63%, compared with 0% in those diagnosed as adults.

Patients with IgA nephropathy diagnosed as adults tend to have more advanced lesions, is manifested by more frequent and severe renal insufficiency, a greater incidence of hypertension and more chronic morphologic changes [12,14,17–19]. The more advanced chronic changes in adults are manifested in part by a much higher fraction of patients with advanced chronic lesions (histologic subclass V), but importantly are also present among patients with lesions of histologic subclasses III and IV, which together account for ~60% of total cases of IgA nephropathy in both paediatric and adult populations. Still, even considering the differences in the fractions of globally and segmentally sclerotic glomeruli and in the severity of interstitial fibrosis and excluding those patients with advanced chronic lesions (subclass V), children and adolescents with proliferative forms of IgA nephropathy (subclasses III + IV, combined) had a significantly (more than fivefold) lower risk of developing ESRD than adults with focal or diffuse proliferative IgA nephropathy. In this regard, it is worth noting that Ronkainen et al. [15] found that the poorer outcomes of children or adolescents diagnosed with IgA nephropathy at older (16–17 years) as compared with younger (7–15) ages were also not accounted for by a difference in histologic activity or chronicity.

It is also noteworthy that none of the 42 patients in this study with minimal histologic lesions (subclass I) developed ESRD. Similar findings have been reported elsewhere [20–23]. As such, transformation from very mild to severe lesions appears to be extremely rare in IgA nephropathy, although the reverse has been documented, particularly following immunosuppressive treatment [24,25].

As a retrospective study, ours has limitations with regard to selection bias, and we were further limited in our analysis because a subset of biopsies came from multiple different referring hospitals. Of particular note, we were not able to include measures of renal function and of hypertension and proteinuria in our multivariate analysis, because the data available to us for many of the study patients (e.g. serum creatinine and 24-h urine protein levels) were not suitable for an analysis comparing children and adults. In nearly all studies of adults and children with IgA nephropathy reviewed by D’Amico [9], impaired renal function, hypertension and severe proteinuria (most often defined as ≥1 g/day) were found to be independent predictors of disease progression, with urine protein excretion during follow-up being a more accurate predictor of the rate of decline of renal function than proteinuria at baseline [10]. Additionally, as patients diagnosed over a 23-year time interval (1980–2003) and at four different centres were included, there was clearly considerable variability with respect to treatment, both with respect to immunosuppressive agents as well as angiotensin-converting enzyme inhibitiors (ACEi), the latter having been shown to be effective in reducing proteinuria in adults and children with IgA nephropathy and slowing the progression of adult-onset IgA nephropathy [26–28]. However, by multivariate analysis we did not find a significant correlation between treatment with corticosteroids and/or other immunosuppressive agents and renal survival in patients with proliferative forms of IgA nephropathy. Furthermore, among patients with such lesions for whom treatment data could be obtained, similar fractions of children and adolescents (38/66; 58%) and adults (40/65; 62%) received an ACEi and/or angiotensin receptor blocker (ARB). Finally, as we included only patients with a minimum post-biopsy follow-up of 18 months (or until ESRD), there was likely to be a bias toward more severe lesions, with a higher fraction of patients having mild lesions becoming lost to renal follow-up, particularly among adults. While much of this bias was eliminated by excluding patients with nonproliferative lesions from the analyses of renal survival, a subset of patients with proliferative IgA nephropathy (particularly focal proliferative) have normal renal function, no hypertension and only mild proteinuria. As such, it cannot be ruled out that this possible selection bias may account in part for the poorer outcomes in patients diagnosed during adulthood compared with during childhood and adolescence.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

  1. D’Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med (1987) 245:709–727.
  2. Jennette JC. The immunohistology of IgA nephropathy. Am J Kidney Dis (1988) 12:348–352.[Web of Science][Medline]
  3. Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis (1997) 29:829–842.[Web of Science][Medline]
  4. Lee SMK, Rao VM, Franklin WA, et al. IgA nephropathy: morphologic predictors of progressive renal disease. Hum Pathol (1982) 13:314–322.[Web of Science][Medline]
  5. Ibels LS, Gyory AZ. IgA nephropathy: analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. Medicine (1994) 73:79–102.[Medline]
  6. Radford MG, Donadio JV Jr, Bergstralh EJ, et al. Predicting renal outcome in IgA nephropathy. J Am Soc Nephrol (1997) 8:199–207.[Abstract]
  7. Alamartine E, Sabatier JC, Guerin C, et al. Prognostic factors in mesangial IgA glomerulonephritis: an extensive study with univariate and multivariate analyses. Am J Kidney Dis (1991) 18:12–19.[Web of Science][Medline]
  8. Bogenschutz O, Bohle A, Batz C, et al. IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients. Nephron (1990) 10:137–147.
  9. D’Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol (2004) 24:179–196.[CrossRef][Web of Science][Medline]
  10. Bartosik LP, Lajoie J, Sugar L, et al. Predicting progression in IgA nephropathy. Am J Kidney Dis (2001) 38:728–735.[Web of Science][Medline]
  11. Hogg RJ, Silva FG, Wyatt RJ, et al. Prognostic indicators in children with IgA nephropathy—report of the Southwest Paediatric Nephrology Study Group. Pediatr Nephrol (1994) 8:15–20.[CrossRef][Web of Science][Medline]
  12. Kusumoto Y, Takebayashi S, Taguchi T, et al. Long-term prognosis and prognostic indices of IgA nephropathy in juvenile and in adult Japanese. Clin Nephrol (1987) 28:118–124.[Web of Science][Medline]
  13. Wyatt RJ, Kritchevsky SB, Woodford SY, et al. IgA nephropathy: long-term prognosis for paediatric patients. J Pediatr (1995) 127:913–919.[CrossRef][Web of Science][Medline]
  14. Okada K, Funai M, Kawakami K, et al. IgA nephropathy in Japanese children and adults: a comparative study of clinicopathologic features. Am J Nephrol (1990) 10:191–197.[Web of Science][Medline]
  15. Ronkainen J, Ala-Houhala M, Autio-Harmainen H, et al. Long-term outcome 19 years after childhood IgA nephritis: a retrospective cohort study. Pediatr Nephrol (2006) 21:1266–1273.[CrossRef][Web of Science][Medline]
  16. Linne T, Berg U, Sohman SO, et al. Course and long-term outcome of idiopathic IgA nephropathy in children. Pediatr Nephrol (1991) 5:383–386.[CrossRef][Web of Science][Medline]
  17. Wyatt RJ, Julian BA, Bhathena DB, et al. IgA nephropathy: presentation, clinical course, and prognosis in children and adults. Am J Kidney Dis (1984) 4:192–200.[Web of Science][Medline]
  18. Mina SN, Murphy WM. IgA nephropathy. A comparative study of the clinicopathologic features in children and adults. Am J Clin Pathol (1985) 83:669–675.[Web of Science][Medline]
  19. Ikezumi Y, Suzuki T, Imai N, et al. Histological differences in new-onset IgA nephropathy between children and adults. Nephrol Dial Transplant (2006) 21:3466–3474.[Abstract/Free Full Text]
  20. D’Amico G, Minetti L, Ponticelli C, et al. Prognostic indicators in idiopathic IgA mesangial nephropathy. Q J Med (1986) 228:363–378.
  21. Katafuchi R, Kiyoshi Y, Oh Y, et al. Glomerular score as a prognosticator in IgA nephropathy: its usefulness and limitation. Clin Nephrol (1998) 49:1–8.[Web of Science][Medline]
  22. Daniel L, Saingra Y, Giorgi R, et al. Tubular lesions determine prognosis of IgA nephropathy. Am J Kidney Dis (2000) 35:13–20.[Web of Science][Medline]
  23. Lee HS, Lee MS, Lee SM, et al. Histological grading of IgA nephropathy predicting renal outcome: revisiting H.S. Lee's glomerular grading system. Nephrol Dial Transplant (2005) 20:342–348.[Abstract/Free Full Text]
  24. Hotta O, Furuta T, Chiba S, et al. Regression of IgA nephropathy: a repeat biopsy study. Am J Kidney Dis (2002) 39:493–502.[Web of Science][Medline]
  25. Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide. Nephrol Dial Transplant (2003) 18:1321–1329.[Abstract/Free Full Text]
  26. Cattran DC, Greenwood C, Ritchie S. Long-term benefits of angiotensin-converting enzyme inhibitor therapy in patients with severe immunoglobulin A nephropathy: a comparison to patients receiving treatment with other antihypertensive agents and to patients receiving no therapy. Am J Kidney Dis (1994) 23:247–254.[Web of Science][Medline]
  27. Praga M, Gutierrez E, Gonzalez E, et al. Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol (2003) 14:1578–1583.[Abstract/Free Full Text]
  28. Coppo R, Peruzzi L, Amore A, et al. IgACE: a placebo-controlled, randomized trial of angiotensin-converting enzyme inhibitors in children and young people with IgA nephropathy and moderate proteinuria. J Am Soc Nephrol (2007) 18:1880–1888.[Abstract/Free Full Text]
Received for publication: 6. 8.07
Accepted in revised form: 8. 1.08


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
23/8/2537    most recent
gfn014v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Haas, M.
Right arrow Articles by Bartosh, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Haas, M.
Right arrow Articles by Bartosh, S. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?