The incidence of biopsy-proven glomerulonephritis in Australia

Esther M. Briganti1, John Dowling2,3, Moira Finlay4, Prue A. Hill5, Colin L. Jones6, Priscilla S. Kincaid-Smith7, Roger Sinclair8, John J. McNeil1 and Robert C. Atkins9,

1 Department of Epidemiology and Preventive Medicine, Monash University, 2 Department of Pathology, Monash Medical Centre, 3 Department of Pathology, Alfred Hospital, 4 Department of Pathology, Royal Melbourne Hospital, 5 Department of Pathology, St Vincent's Hospital, 6 Department of Nephrology, Royal Children's Hospital, 7 Department of Medicine, Epworth Hospital, 8 Department of Pathology, Austin and Repatriation Medical Centre 9 Department of Nephrology, Monash Medical Centre, Australia



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. There is limited population-based epidemiological data on renal disease. An insight into the spectrum of clinically significant glomerulonephritis can be obtained from renal biopsy diagnoses. This is a descriptive report of biopsy-proven glomerulonephritis within a defined population.

Methods. A retrospective review of the pathology reports of all native renal biopsies performed in the Australian state of Victoria in 1995 and 1997 was undertaken. Trends in the average annual age- and sex-specific incidence rates for biopsy-proven glomerulonephritis were calculated. Comparisons were made with the incidence of end-stage renal disease due to glomerulonephritis confirmed on renal biopsy.

Results. The most common glomerulonephritides in adults are IgA disease, focal glomerulosclerosis, lupus nephritis and vasculitis, and in children are lupus nephritis, focal glomerulosclerosis, IgA disease and minimal change disease. A male predominance is seen for all glomerulonephritides, except lupus nephritis, in both adults and children. An increase in incidence of disease with age, particularly in males, is seen for vasculitis and focal glomerulosclerosis. The most common glomerulonephritides on renal biopsy are reflected in the most common causes of end-stage renal disease due to glomerulonephritis.

Conclusions. This review has provided population-based descriptive epidemiological data on clinically significant glomerulonephritis. This data provides important clues for further studies relating to the identification of risk factors for the various types of glomerulonephritis.

Keywords: epidemiology; glomerulonephritis; renal biopsy



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Detailed registry data exists for end-stage renal disease in Australia, as well as in several other countries around the world. However, basic epidemiological data on less advanced renal disease is generally lacking. A review of renal biopsy data can give some insight into the spectrum of clinically significant renal disease in the community. This can provide an important foundation for further epidemiological studies aimed at identifying relevant risk factors in the development and progression of renal diseases through case-control and cohort study designs. This review reports primarily on the frequency of renal biopsy and of biopsy-proven glomerulonephritis for both children and adults in Australia, and compares them with the incidence of end-stage renal disease due to glomerulonephritis.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
A retrospective review was undertaken of the pathology reports of all renal biopsies performed on native kidneys in Victoria, Australia, in 1995 and 1997. Renal biopsy reports were obtained from seven centres. Six were based at primarily adult hospitals, one of these also being a major paediatric hospital. The remaining centre was based at a paediatric hospital. Biopsies were evaluated by light microscopy and immunofluorescence or immunohistochemistry. The majority was also assessed by electron microscopy. No clinical details were available in relation to associated clinical findings or indication for renal biopsy. The study area is the second largest state of Australia, with an estimated 4560155 inhabitants (947 358 children and 3 612 797 adults) in 1996. This represents 25% of the total Australian population. The age and sex distribution for all of the population in Victoria is representative of that of the rest of Australia.

A total of 2030 renal biopsies were performed. The age or sex of patients was not known for 13 (0.6%) of the biopsies. A total of 12 (0.6%) biopsies included no renal tissue and 18 (0.9%) biopsies were reported as normal, all from adults. Reports of the remaining 1987 biopsies—104 from children (<15 years of age) and 1883 from adults (>=15 years of age)—were reviewed and categorized by histological diagnosis. Of these, a total of 1147 renal biopsies had a histological diagnosis of glomerulonephritis and were included in this analysis. Categories included anti-glomerular basement membrane disease, cryoglobulinaemia, focal glomerulosclerosis, IgA disease, lupus nephritis, membranoproliferative glomerulonephritis, membranous nephropathy, minimal change disease, post-infectious glomerulonephritis, thrombotic microangiopathy and vasculitis.

A comparison of types of biopsy-proven glomerulonephritis in the general population and in patients with end-stage renal disease was made using data from the Australia and New Zealand Dialysis and Transplant Registry for 1995 and 1997 [1,2]. Of all patients with end-stage renal disease attributed to glomerulonephritis, a biopsy diagnosis was available for 77% of patients in 1995 and 74% of patients in 1997. The incidence of end-stage renal disease due to glomerulonephritis confirmed on biopsy was calculated for the total population of Australia and compared with the incidence of biopsy-proven glomerulonephritis in Victoria for the same time periods.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Frequency of renal biopsy
The rate of renal biopsy was 21.5 per 100 000 people per year (23.0 and 19.6 per 100 000 per year for males and females, respectively). The rate in children was 5.5 per 100 000 per year (the same value of 5.5 per 100 000 per year for males and females) and in adults 26.1 per 100 000 per year (28.5 and 23.7 per 100 000 per year for males and females, respectively).

The rate of renal biopsy was significantly more in females compared with males in the 25–34 year age group (odds ratio (OR): 1.53; 95% confidence interval (CI): 1.21, 1.94). It was significantly more in males compared with females in the 55–64 year age group (OR: 1.50; 95% CI: 1.19, 1.88), the 65–74 year age group (OR: 2.03; 95% CI: 1.62, 2.55), and the 75+ year age group (OR: 2.75; 95% CI: 1.91, 3.95).

Incidence of biopsy-proven glomerulonephritis in children (see Tables 1Go and Table 2Go)
The most common glomerulonephritis in children under the age of 5 years was focal glomerulosclerosis (0.5 per 100 000 per year), followed by minimal change disease and IgA disease. In children of 5–14 years of age, the most common diagnosis was lupus nephritis (1.7 per 100 000 per year), followed by IgA disease and focal glomerulosclerosis.


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Table 1. Age- and sex-specific incidence for major histological categories of biopsy-proven glomerulonephritis, per 100 000 per year

 

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Table 2. Age- and sex-specific incidence for minor histological categories of biopsy-proven glomerulonephritis, per 100 000 per year

 
The diagnosis of lupus nephritis was significantly more common in females than males (OR: 9.97; 95% CI: 2.32, 42.79).

Incidence of biopsy-proven glomerulonephritis in adults (see Table 1Go and Table 2Go)
In adults, the most common glomerulonephritis was IgA disease (10.5 per 100 000), followed by focal glomerulosclerosis and vasculitis. IgA disease was the most common diagnosis in patients up to 65 years of age (15–24 years: 3.9 per 100 000 per year; 25–34 years: 5.7 per 100 000 per year; 35–44 years: 5.0 per 100 000 per year; 45–54 years: 6.1 per 100 000 per year; and 55–64 years: 6.8 per 100 000 per year). The most common diagnosis was vasculitis in the 65–74 year age group (5.8 per 100 000 per year) and in those 75 years and over (4.0 per 100 000 per year).

In adults, the following diagnoses were significantly more common in males than females: anti-glomerular basement membrane disease (OR: 8.35; 95% CI: 1.04, 66.77), post-infective glomerulonephritis (OR: 3.65; 95% CI: 1.20, 11.10), membranous glomerulonephritis (OR: 2.23; 95% CI: 1.51, 3.29), IgA disease (OR: 1.95; 95% CI: 1.57, 2.40), vasculitis (OR: 1.69; 95% CI: 1.20, 2.39) and focal glomerulosclerosis (OR: 1.60; 95% CI: 1.19, 2.16). Lupus nephritis was significantly more common in females compared with males (OR: 2.75; 95% CI: 1.89, 3.84).

Incidence of end-stage renal disease (see Table 3Go )
For the most common types of glomerulonephritis, i.e. IgA disease and focal glomerulosclerosis, the incidence of biopsy-proven disease was about six times that of end-stage renal disease (OR: 6.5 (95% CI: 5.5, 7.6) and OR: 6.0 (95% CI: 4.8, 7.5), respectively). The incidence of biopsy-proven lupus nephritis and membranous nephropathy was 16 times greater than their incidence of end-stage renal disease, while vasculitis was about eight times greater (OR: 16.0 (95% CI: 11.3, 22.5), OR: 13.5 (95% CI: 9.3, 19.5) and OR: 8.5 (95% CI: 6.3, 11.3), respectively). For the more uncommon causes of biopsy-proven glomerulonephritis, a marked disparity was seen for thrombotic microangiopathy, less so with anti-glomerular basement membrane disease, and minimal disparity for membranoproliferative glomerulonephritis (OR: 116.4 (95% CI: 16.0, 854.1), OR: 9.0 (95% CI: 3.0, 27.6) and OR: 3.2 (95% CI: 1.9, 5.5), respectively).


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Table 3. Comparison of the incidence of biopsy-proven glomerulonephritis and end-stage renal disease due to glomerulonephritis, per 1 million person-years

 

Other renal biopsy diagnoses
The only other significant category of renal disease diagnosed on renal biopsy in children was interstitial nephritis, with an incidence of 0.3 per 100 000 per year. In adults, other renal diseases included thin basement membrane disease (2.5 per 100 000 per year), diabetic nephropathy (1.7 per 100 000 per year), nephrosclerosis (1.7 per 100 000 per year), interstitial nephritis (1.4 per 100 000 per year), amyloidosis (0.3 per 100 000 per year) and cholesterol emboli (0.2 per 100 000 per year).



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
We report on the age- and sex-specific incidence of biopsy-proven glomerulonephritis and compare it with the incidence of end-stage renal disease due to glomerulonephritis in Australia for 1995 and 1997. The participation of all centres that report renal biopsies in the study area ensured complete ascertainment of renal biopsy records. While the rates for biopsy-proven renal disease underestimates the true rate of disease, as only those above a certain level of disease severity are likely to be biopsied, the figures presented probably do reflect the minimum incidence of moderate to severe disease.

The average annual rate of renal biopsy found in this review was considerably greater than that reported in other studies. The observed biopsy rate for all ages was seven times as frequent as that reported from Italy, which was 3.3 per 100 000 in 1993 [3]. It was more comparable to that reported in France, which was 16.2 per 100 000 per year in those aged 10–80 years for the period 1986 to 1990 [4]. In children, the biopsy rate was four times as frequent as that from Italy, which was ~1.7 per 100 000 per year for the period 1992–1994 [5]. In Australia there has been a liberal renal biopsy policy. Indicators for renal biopsy include non-urological haematuria, proteinuria and renal impairment, as well as the more specific presentations of glomerulonephritis such as nephrotic or nephritic syndrome.

In adults, the annual incidence of IgA disease has been reported to be between 0.4 and 3.1 per 100 000, and that of focal glomerulosclerosis between 0.1 and 0.9 per 100 000, in several studies [3,4,68]. The annual incidence of lupus nephritis has been reported at 0.3 per 100 000 in Italy; however, this included children and adults together [3]. These rates are all lower than that found in this review for adults. The annual incidence of primary renal vasculitis in adults was very similar to that reported from a population-based registry in the UK, at 1.8 per 100 000 for the period 1992–1997 [9]. The male to female ratio was identical, at 1.7. These rates are higher than those previously reported in European studies [3,1013], but are not as high as those reported in Kuwait [14].

In children, the annual incidence of IgA disease or Henoch-Schonlein purpura nephritis has been reported at 0.5 per 100 000, minimal change disease at 0.2 per 100 000, focal glomerulosclerosis at 0.1 per 100 000 and lupus nephritis at 0.1 per 100 000, from the Italian Registry of Renal Biopsies [5]. Again, these rates are all lower than that found in this review for children. In addition, unlike the Italian registry data, this review found that lupus nephritis and focal glomerulosclerosis were the most common diseases diagnosed by renal biopsy in children.

Notable patterns of disease identified in this review included the male predominance of biopsy-proven glomerulonephritis for all histological categories, with the exception of lupus nephritis in both adults and children. In addition, an increase in the incidence of disease with age, particularly in males, was seen for vasculitis and focal glomerulosclerosis. The peak age-specific incidence is similar in males and females for lupus nephritis (25–34 years), focal glomerulosclerosis (55–64 years), membranous nephropathy (55–64 years) and vasculitis (65–74 years). For IgA disease, however, the age-specific incidence peaks at a younger age in females (25–34 years) compared with males (55–64 years). These findings suggest the potential role of age- and gender-specific environmental exposures, such as infective, dietary or occupational exposures, in the aetiology of these renal diseases.

The most common causes of biopsy-proven glomerulonephritis (IgA disease, focal glomerulosclerosis, lupus nephritis, vasculitis and membranous nephropathy) were also the most common causes of end-stage renal disease due to glomerulonephritis. Although non-concurrent, with biopsy-based data reflecting relatively newly diagnosed renal disease, and the registry-based data of uptake onto the end-stage renal disease programme reflecting renal disease which is more progressed in its natural history, the similar proportions of the glomerulonephritides indicates the clinical and public health importance of the renal disease identified on biopsy.

While true variation may exist between populations, differences in biopsy rate, referral patterns, indications for renal biopsy and classification criteria for histological diagnosis of renal biopsies may at least in part explain the observed geographical variations. The absence of this information in this study, due to its retrospective nature, limit comparisons with data from other countries. However, the data collected in this review in relation to age and sex distribution provides important insights into potential risk factors for the various glomerulonephritides for further study, an area of research which to date has been limited.



   Acknowledgments
 
Data relating to end-stage renal disease have been supplied by the Australia and New Zealand Dialysis and Transplant Registry. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the Australia and New Zealand Dialysis and Transplant Registry. This review was supported by the Australian Kidney Foundation.



   Notes
 
Correspondence and offprint requests to: Robert Atkins, Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia. Back



   References
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
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Received for publication: 29.11.00
Revision received 19. 2.01.