Outcome of IgA nephropathy in adults graded by chronic histological lesions

doi:10.1016/S0272-6386(00)70191-0

American Journal of Kidney Diseases

Volume 35, Issue 3, March 2000, Pages 392-400

https://doi.org/10.1016/S0272-6386(00)70191-0 Get rights and content

Abstract

This prognostic study of primary immunoglobulin A (IgA) nephropathy focused on chronic irreversible glomerular sclerosis and interstitial fibrosis, based on the premise that this disease is characterized by a protracted and, for many, progressive course. We used a chronicity-based histological grading system to assess the biopsy specimens of 126 adults with IgA nephropathy over a median follow-up of 10 years. Our grading system included a glomerular grading (GG) of 1 to 3 based on the extent of glomerular sclerosis, a tubulointerstitial grading (TIG) of 1 to 3 based on the degree of tubular loss or interstitial fibrosis, and the evaluation of hyaline arteriolosclerosis (HA). These three histological parameters were correlated with each other and with serum creatinine level, degree of proteinuria, and blood pressure at the time of renal biopsy. Univariate analysis showed that these three histological and three clinical parameters were significantly correlated with renal survival. By multivariate analysis using the Cox regression model, GG, serum creatinine level, and degree of proteinuria represented independent prognostic factors of renal survival. For a subset of patients at a relatively early stage of disease with a serum creatinine level less than 130 μmol/L at the time of biopsy, all three histological features and degree of proteinuria were significantly correlated with renal survival, and GG was the only independent prognostic factor for renal outcome. This study shows that glomerular sclerosis represents the most important prognostic factor in adult patients with primary IgA nephropathy and has a strong predictive value. Our chronicity-based histological grading system not only correlates well with the natural history of IgA nephropathy but is also reproducible and relatively simple to apply.

Section snippets

Patient selection and clinical parameters

The files of all adult patients with a renal biopsy diagnosis of IgA nephropathy in our institution between 1985 and 1991 were reviewed. The selection criteria included: (1) a diagnosis of IgA nephropathy based on predominant mesangial IgA-containing immune complexes detected by immunofluorescence study in ultrastructures, irrespective of light microscopic features, excluding patients with such systemic diseases as diabetes and systemic lupus erythematosus, chronic liver diseases, renal

Results

Of 126 adult patients, 74 were women and 52 were men, with a 1.4 woman-man ratio confirming the female preponderance of IgA nephropathy in our region.3, 6 Age ranged from 18 to 62 years, with a mean age of 32 years. Follow-up ranged from 8 to 14 years, with a median of 10 years. Among these 126 patients, 25 patients (20%) reached end-stage renal failure over a 10-year median follow-up. By univariate analysis using the Breslow test, the histological parameters of GG, TIG, and HA and degree of

Discussion

IgA nephropathy is the most common glomerulonephritis worldwide, currently with no specific effective therapy, and up to 30% of the patients progress to end-stage renal disease.2, 4, 5, 6 For such a chronic nephropathy, and for many patients a slowly progressive disease, it is thus imperative to identify factors permitting not only prediction of renal outcome, but also the detection of high-risk patients, which is important in planning the long-term management of these patients.

Although a

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Cited by (72)

Endothelial cell injury in acute and chronic glomerular lesions in patients with IgA nephropathy
2016, Human Pathology
Citation Excerpt :
Renal insufficiency and proteinuria are known to be strong risk factors in terms of the prognosis of IgAN [20–23]. Chronic glomerular lesions, particularly those with glomerular sclerosis and fibrous crescent formation, have also been emphasized to be valuable prognostic lesions of ESRD in cases of IgAN [22–28]. In the present study, the loss of CD34+ glomerular capillaries was accompanied by segmental and global glomerular sclerosis with or without fibrous crescents.
Endothelial cell injury may contribute to the progression of various glomerular diseases. In the present study, we examined glomerular capillary injury in acute and chronic glomerular lesions in patients with Immunoglobulin A nephropathy (IgAN). We selected renal biopsy samples of IgAN (n = 200), and glomerular capillary injury in the acute and chronic glomerular lesions was assessed using immunohistochemistry for CD34 and electron microscopy. We examined the correlations between acute and chronic glomerular lesions and proteinuria, hematuria, and the renal function. The injured glomerular capillaries in the acute glomerular lesions were characterized morphologically by the separation of CD34+ endothelial cells from the glomerular basement membrane and the loss of glomerular endothelial cells and capillaries, together with inflammatory cell infiltration, fibrin exudation, rupture of the glomerular basement membrane, and/or crescent formation. In addition, the injured capillaries in the chronic glomerular lesions were characterized by the loss of CD34+ glomerular endothelial cells and capillaries exhibiting segmental and global glomerular sclerosis with or without fibrous crescents. In the acute glomerular lesions, the presence of endocapillary hypercellularity, fibrinoid necrosis, and cellular and fibrocellular crescents correlated significantly with hematuria, with or without proteinuria. In the chronic glomerular lesions, a significant relationship was evident between segmental or global sclerosis and proteinuria and/or the serum creatinine level. In conclusion, injuries of glomerular capillaries and the loss of endothelial cells occurred in the acute and chronic glomerular lesions in IgAN and may contribute to the development of hematuria, proteinuria, and renal dysfunction.
Treatment of early immunoglobulin A nephropathy by angiotensin-converting enzyme inhibitor
2013, American Journal of Medicine
The treatment of immunoglobulin A (IgA) nephropathy with normal renal function and minimal proteinuria is unknown.
We randomly assigned 60 patients with IgA nephropathy, proteinuria <0.5 g/day, normal blood pressure and renal function to ramipril 2.5 mg daily or no treatment. Patients were followed for 5 years for the development of hypertension, proteinuria, or impaired renal function.
The blood pressure of the treatment group was marginally lower than the control group throughout the study period. At 60 months, the event-free survival was marginally higher for the treatment group as compared with the control group (81.1% vs 70.5%, P = .27). The proteinuria-free survival was similar at 82.9% and 79.3% for the treatment and control groups, respectively (P = .6); hypertension-free survival was 86.4% and 79.3% (P = .2). After 60 months of follow-up, the estimated glomerular filtration rate (GFR) was 108.1 ± 29.0 mL/min/1.73 m² for the treatment group and 105.7 ± 17.7 mL/min/1.73 m² for the control group (P = .7), but the difference was not statistically significant. None of the patients developed impaired renal function. The rate of GFR decline was similar between the treatment and control groups (−0.39 ± 2.57 vs −0.59 ± 1.63 mL/min/1.73 m² per year, respectively, P = .7). In general, the study medication was well tolerated. Two patients needed to stop prematurely because of cough and dizziness.
For early IgA nephropathy patients with minimal proteinuria, normal blood pressure, and normal renal function, treatment with 2.5 mg/daily of ramipril for 5 years does not offer any benefit.
Long-term study of mycophenolate mofetil treatment in IgA nephropathy
2010, Kidney International
Since the efficacy of mycophenolate mofetil (MMF) to treat immunoglobulin A (IgA) nephropathy is controversial, we extended our original study by following 40 Chinese patients with established IgA nephropathy for 6 years. All patients were maintained on their angiotensin blockade medication and half were randomized to receive MMF for 6 months. After 6 years, 11 patients required dialysis (2 from the MMF and 9 from the control group). Significantly, only 3 treated (as compared to 10 control) patients reached the composite end point of serum creatinine doubling or end-stage renal disease. Linear regression showed the annualized decline in the estimated glomerular filtration rate was significantly less in the MMF-treated group. Urinary protein excretion and the albumin-to-creatinine ratio were lower with MMF treatment during the first 24 months, beyond which there was no difference between groups. Multivariable Cox regression analysis showed that the baseline estimated glomerular filtration rate and proteinuria, and change in the urine albumin-to-creatinine ratio at 1 year to be important predictors of progression to end-stage renal disease. We found that among Chinese patients with IgA nephropathy who had mild histologic lesions and persistent proteinuria despite maximal angiotensin blockade, MMF treatment may result in transient and partial remission of proteinuria in the short-term and renoprotection in the long-term.
The Oxford classification of IgA nephropathy: Pathology definitions, correlations, and reproducibility
2009, Kidney International
Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/fibrocellular crescents; (5) percentage of interstitial fibrosis/tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease.
Inhibition of RNA-binding protein HuR reduces glomerulosclerosis in experimental nephritis
2020, Clinical Science
Association between native T1 mapping of the kidney and renal fibrosis in patients with IgA nephropathy
2019, BMC Nephrology

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: Address reprint requests to Fernand Mac-Moune Lai, FRCPA, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Room 34055, Shatin, Hong Kong, China SAR. E-mail: [email protected]

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Original InvestigationsOutcome of IgA nephropathy in adults graded by chronic histological lesions

Abstract

Section snippets

Patient selection and clinical parameters

Results

Discussion

Pathology

Kidney Int

Kidney Int

Hum Pathol

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Original Investigations
Outcome of IgA nephropathy in adults graded by chronic histological lesions