NDT Advance Access originally published online on October 25, 2005
Nephrology Dialysis Transplantation 2006 21(2):419-424; doi:10.1093/ndt/gfi207
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Epidemiology of renal disease in Romania: a 10 year review of two regional renal biopsy databases
1 Dialysis and Transplantation Center, ‘C.I. Parhon’ University Hospital, Ia
i and 2 Dialysis and Transplantation Center, Timisoara, Romania
Correspondence and offprint requests to: Adrian Covic, MD PhD, Professor of Nephrology, C.I. Parhon University Hospital, Blvd. Carol 1st No. 50, Iasi 6600, Romania. Email: acovic{at}xnet.ro
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Abstract |
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Background. Epidemiological data of renal disease are available from large national renal biopsy registries from Central and Western European countries; in contrast, detailed epidemiological data from Eastern European countries are missing. This report is the first review of histological data, over a period of 10 years (1995–2004), covering a population of over 6 million inhabitants and two distinct regions from an East European country – Romania.
Methods. 635 eco-guided kidney biopsies from the Moldova (North-Eastern Romania, 8 counties, 4 754 048 inhabitants) and Banat (Western Romania, 3 counties, 1 454 747 inhabitants) regions were analysed. Data on serum creatinine concentration (sCr), 24 h proteinuria, haematuria, clinical diagnosis, histological diagnosis and complications after renal biopsy were collected.
Results. The number of biopsies performed varied between 10.9 p.m.p./year in 1995 and 11.3 p.m.p./year in 2004. The most common clinical syndromes – as indication for performing the renal biopsy – were: nephrotic syndrome (52.3%), followed by nephritic syndrome (21.9%), acute renal failure (ARF) (12.4%), chronic kidney disease (CKD) (10.2%) and asymptomatic urinary abnormalities (AUA) (3.3% of the cases). The major histological groups identified were: primary glomerulonephritis (GN) (66.2%), secondary GN (26.4%), vascular nephropathies (2.3%), and tubulointerstitial nephropathies (TIN) (1.5%) of the cases. Among primary GN's, the most frequent diagnoses were: membranoproliferative GN (MPGN) (29.4%, incidence in 2004 – 9.3 p.m.p./year), mesangioproliferative GN (MesGN) (28.9%, incidence – 10 p.m.p./year), membranous GN (MGN) (11.2%, incidence – 5.3 p.m.p./year), minimal change disease (MCD) (8.5%, incidence – 7.3 p.m.p./year), focal and segmental glomerulosclerosis (FSGS) (11.5%, incidence – 3.3 p.m.p./year) and crescentic GN (CGN) (7.9%, incidence – 3.3 p.m.p./year). The prevalence of membranoproliferative GN significantly decreased from 1995 to 2004. The prevalence of different types of secondary GN was similar to Western and Central European countries, with the particular difference of higher infectious diseases associated GN.
Conclusion. The present data are an important contribution to the epidemiology of renal diseases in Europe, highlighting not only numerous similarities but also significant epidemiological differences in Western and Central European countries, particularly a higher, albeit declining, incidence and prevalence of membranoproliferative GN. This report represents the basis for the future of Romanian Registry of Renal Biopsies and is intended to serve as a source of information for nephrologists concerned with East European renal pathology.
Keywords: chronic kidney disease; parenchymal diseases; renal biopsy; renal biopsy registry
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Introduction |
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Knowledge of the epidemiology of renal disease along with clinico-pathological correlations provides important information in clinical practice. Current epidemiological data of renal disease in Western Europe are available from large national renal biopsy registries from Italy [1,2], Denmark [3,4] and Spain [5]. Information derived from local regional registries of renal biopsy has also been reported from other Western European countries – France, Holland [6,7] – showing comparable trends in incidence and prevalence of primary glomerular diseases. In contrast, only one large report [8] provides detailed epidemiological data for renal disease in Central Europe. Moreover, there is a complete lack of systematic data from Eastern Europe, over a long period of time. There are two main reasons to suspect significant epidemiological differences for this region: a higher prevalence of infectious diseases (hepatitis B and C, streptococcal infections, etc.) [www.who.int] and differences in social and economic status that may translate into differences in the epidemiological pattern, as recently suggested by the concept of transitional epidemiology [9].
The aim of this study was to report long-term, detailed epidemiology of renal disease, based on histological diagnosis, in a large representative sample from an Eastern European Country, to identify clinico-pathological correlations and to provide the embryo for the national Romanian Registry for Renal Biopsies.
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Methods |
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We evaluated all renal biopsies performed during the 1995–2004 period in patients >18 years old; data were provided by two large regional referral centres – Iasi and Timisoara. These centers were selected for the following reasons: (1) each unit performed all the renal biopsies for a homogenous (historical, geographical, social, cultural) but different area from Romania: Moldova (North-eastern Romania, 8 counties, 4 754 048 inhabitants), and Banat (Western Romania, 3 counties, 1 454 747 inhabitants); (2) comparable technical expertise, previously reported in the literature [10], (3) similar indications for performing the renal biopsy, (4) for the reported study period, this sample represents more than 50% of all renal biopsies performed in Romania.
The following data were collected for each case: clinical and histological diagnosis, serum creatinine concentration (sCr), 24 h proteinuria, presence of haematuria, presence of arterial hypertension defined as a blood pressure >140/90 mmHg and/or antihypertensive medication, clinical complications after renal biopsy (with serious complications defined as: clinically symptomatic subcapsular or perirenal haematoma, gross haematuria, presence of hypovolaemic shock and/or need for blood transfusion).
In order to enable comparisons of the biopsy and clinical results from our database with current epidemiological data of renal disease from Western Europe and from the single Central and Eastern European national registry available – the Czech Registry of Renal Biopsies (CRRB), and for the histological classification of renal diseases, we used the scheme described by Gesualdo et al. in the Italian Registry of Renal Biopsies (IRRB) [1], and subsequently also followed by Rychlik et al. [8] in their registry reports – see Methods section of [1], [2] and [8].
Data analysis
Data were stored on a standard EXCEL database; an SPSS 13.0 statistics package was used. The annual incidence was defined as the number of new cases per year related to the mean total population, expressed as per million populations (p.m.p.) per year.
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Results |
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The total population of the two regions reported, for the 1995–2004 period was 6.4 (1995) to 6.2 (2004) million inhabitants, with a male/female ratio of 0.97 and an urban–rural distribution ratio of 2 : 1. Median age increased from 69.2 years in 1995 to 71.4 years in 2004.
Over the 10-year study, a total of 635 renal biopsies were performed (all native kidneys, 51.5% males, mean age = 38.5±15.2, range 18–80 years). The number of renal biopsies performed was stable year by year, being 10.9 p.m.p./year in 1995 and 11.3 p.m.p./year in 2004 (compared with 44.1 p.m.p./year in 1994 and 69.3 p.m.p./year in 2000 for the CRRB [8]).
The distribution of clinical syndromes according to age and gender is presented in Table 1. Nephrotic syndrome was more frequently recorded as an indication for performing a renal biopsy in the age group 18 to 60 years (compared with the 
60 years age-group), while ARF was significantly more frequent in the older (60 years) age group. There were no differences for other indications between the two age groups. The only gender-related differences were seen in the 18 to 60 years age group, again for the nephrotic syndrome (more frequent in males), and also for CKD (more frequent in females).
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An adequate renal fragment was obtained in 606 cases (95.4%). The mean number of glomeruli/fragment was 9.1±4.9. These 606 cases were included in the analysis. The distribution of major histological groups of renal disease is shown in Table 2, comparatively with data from the largest Western European registry (the Italian Registry of Renal Biopsies – IRRB) and with data from a Central European country (CRRB). Of all diseases, primary GN was the most frequent – 66.2%; but overall, the relative distribution of the major groups was similar between the three registries. The incidence (number/per million) of various histologic forms in 2004, is presented in Table 3. The overall incidence of primary GN was 38.5 p.m.p./year.
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Table 4 shows the frequency of different forms of primary GN, again in comparison with similar data from IRRB and CRRB. Clearly, membranoproliferative and crescentic GN were more frequently encountered in Romania; mesangial GN was less frequent, while FSGS, minimal change disease and membranous GN had a similar prevalence with IRRB and particularly with CRRB. The prevalence of MPGN significantly decreased from 1995 to 2004 (Figure 1). Correlations between the histologic diagnosis and the clinical presentation are presented in Table 5. Nephropathies which most frequently presented as a nephrotic syndrome were: membranoproliferative GN (35.1%) and MesGN (19.8%) (compared with MGN (44.1%) and FSGS (16.9%) in Italy).
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Table 6 shows the frequency of different types of secondary GN, also in comparison with similar data from IRRB and CRRB. Immune-mediated GN and dysgammaglobulinaemia associated GN had similar prevalences in all three registries. More infectious disease associated GN were present in both Romanian regions, while metabolic and hereditary associated GN were less frequent. Among secondary GN, dysgammaglobulinaemia associated GN (39.7%) were the type of nephropathies which most frequently presented as a nephrotic syndrome, very similar to the Italian Registry: 30.4%.
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Ultrasound needle guidance and the biopsy gun were used for all biopsies. Fifty-seven clinically serious complications were recorded (8.9% of all biopsies) (Table 7), a rate similar to Ref. [11]. Serious complications were observed most frequently when a large fragment was harvested (>20 glomeruli, data not shown); 14/15 patients with hypotension following biopsy had concomitant severe renal insufficiency and were on antihypertensive therapy.
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Discussion |
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This report provides information about the occurrence of renal diseases diagnosed by renal biopsy, during a period of 10 years, in a population of over 6 million, from two distinct regions from Romania: Moldova (North-eastern Romania) and Banat (Western Romania). To our knowledge, this is the first systematic review of histological data from Eastern Europe and the Balkan area. The main findings of this large regional database are: (a) similar incidence of primary and secondary GN, and a similar distribution of major histological groups of renal disease to Western and Central European countries, (b) a higher incidence and prevalence of MPGN, although this form of primary GN is steadily declining over the 10 years interval and, (c) similar prevalence of different types of secondary GN to Western and Central European countries, with the particular difference of a higher infectious diseases associated GN (including hepatitis B and C).
Nephrotic and nephritic syndromes were the most frequent clinical presentations, accounting for approximately 75% of all cases, at the time of the biopsy. The incidence of GN (38.5 p.m.p./year) was comparable with that seen in other European countries: 34, 47, 39 p.m.p./year [4,8,12]. The distribution pattern of major histological groups of renal disease also corresponded to other European series. Furthermore, a very similar proportion of nephrotic patients with FSGS, MGN and MCD were seen in the Czech Registry of Renal Biopsies (10.3%, 12.7% and 9.4% respectively), compared with our series (12.1%, 14.5% and 10.9% respectively). However, there are also significant differences compared with other registries. First, both in Italy [1] and in Spain [5] MCD and specially MGN, in nephrotic cases, are observed with a higher frequency. Second, both MPGN (35.1%) – as a primary GN – and infectious diseases associated GN (30.8%) – as a secondary GN – are the most frequent causes of nephrotic syndrome in Romania, in sharp contrast with published European series [1,5,6].
The issue of MPGN deserves special attention. It is interesting to point out that the annual prevalence has constantly decreased in our study from 1995 to 2004. In fact, in 2004 MPGN we report close figures to the Italian registry (Figure 1). Such a trend can hardly be exclusively explained by improvements in technique [13], and has been reported elsewhere – for example in France, where a decline in rheumatic fever was associated with a parallel decline in MPGN and post-streptococcal GN [6]. We hypothesize that the epidemiology of MPGN is strongly related to socio-economic conditions. Improvement in income, sanitation, social and medical infrastructure are followed by a decrease in MPGN. These improvements were evident in Romania following 1989, as in all Eastern European countries [14]. Further arguments to support our hypothesis are epidemiology gradients seen in Europe (see above) and in Romania (higher prevalence in Moldova, region with a lower income per capita and infrastructure than the Banat region). Finally, it is important to underline the high prevalence of streptococcal and hepatitis infections in the general population in Romania [www.who.int]. What we describe is probably another excellent example of the concept of transitional epidemiology described by La Porte [9].
IgAN is the most frequent disease among patients with primary GN, ranging from 7.9 p.m.p./year in Spain [5] to 8.4 p.m.p./year in Italy [1], to the very high 25–31 p.m.p./year in France [6] (11.2 p.m.p./year in the CRRB [8]). In reality, the true incidence of IgAN is unknown, but probably higher since an important proportion of primary GN, diagnosed as MesGN, is not always evaluated by immunofluorescence [3,15]. In our study MesGN, including IgA was the second most frequent cause of nephrotic syndrome and the first cause of nephritic syndrome/AUA.
In this (morphologic) series, ARF was mainly due to vasculitis and crescentic GN; furthermore, there was a high prevalence of CGN (8%) among primary GN. Overall, one-third of the cases presenting with ARF had crescentic GN (data not shown) – similar to a recent Italian survey [2] and to large series from Spain and Baltimore [12,16].
This report shares clear limitations common to all disease registries based on diagnostic manoeuvres. Analysis is based on retrospective data collected from different centres with different referral patterns, local expertise and changing indications. However, this report represents the embrion for the Romanian Registry of Renal Biopsies (RRRB), which will include prospective collected data from Transylvania, Bucuresti and Southern Romania, providing the basis for the design of regional protocols for preventive medicine.
In conclusion, we show that while primary and secondary GN have a similar incidence and a similar distribution of major histological groups to other European countries, a higher (but declining) incidence and prevalence of MPGN is recorded in Romania. Present data represent an important contribution to the epidemiology of renal diseases in Europe, providing a valuable comparison with other renal biopsy registries worldwide, as a basis for nephrologists and health care providers to stimulate new analysis and improve treatment of renal diseases.
Conflict of interest. None declared.
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Accepted in revised form: 12. 9.05
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