Abstract
Background. Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years’ detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon.
Methods. Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents’ consanguinity were recorded when feasible.
Results. The mean age at renal biopsy was 36.76 ± 20 years (range 1–84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001).
Conclusions. Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important implications for formulating renal health policies and designing research studies in this population.
Keywords: glomerular disease, kidney biopsy, nephrotic syndrome, proteinuria
Introduction
Knowledge of the epidemiology of renal disease along with clinico-pathological correlations provides important information in clinical practice. Current epidemiological data of renal diseases in Western countries are available from large national or regional renal biopsy registries. Information derived from these registries of renal biopsy shows comparable trends in incidence and prevalence of primary glomerular diseases. In contrast, few reports provide detailed epidemiological data for renal diseases in the region of the Middle East. For example, there is a complete lack of systematic data from Lebanon over a long period of time. Differences in epidemiology of kidney disease in this region may arise from variation in indication for biopsy, environmental exposure and socio-economic status. Moreover, the Lebanese population is composed of different ethnicities, with distinct ancestry, religion and customs, enabling comparison of the effect of these variables on the prevalence of kidney disease. Also, Lebanon is a small country on the eastern coast of the Mediterranean. Some religious communities in the country have been impacted more than others by different ‘invading’ or ‘visiting’ populations within recent historical times, mainly the Muslim expansion from the Arabian Peninsula and the Crusades [1]. Furthermore, religious sects have tended to marry within the group, thus preserving not only religious but ethnic characteristics. As a result, religious affiliation has become a substitute in some respects for ethnic affiliation. It is estimated that, of the current Lebanese population of almost four million people, 59% are Muslims, while 40% are Christians. The aim of this study is to report 5 years’ detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon representing a national series from a Middle-Eastern country. In addition to identifying clinico-pathological correlations, this series will be used as a platform for pursuing clinical and basic research and initiating a national Lebanese Registry for Renal Biopsies.
Materials and methods
Records of renal biopsies performed on patients at the American University of Beirut Medical Center (AUBMC) and Hotel Dieu de France Hospital (HDF) from January 2003 till December 2007 and records of renal biopsies performed in various other hospitals in Lebanon (see Appendix 1) and analysed in the Institut National de Pathologie (INP) during the same period were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Additional information on religious affiliation (Muslim or Christian) was inferred from data in most patients, whereas information on consanguinity in parents was obtained in the minority of patients whose contacts were available to us. Renal biopsy specimens were stained and analysed by light microscopy (LM) and immunohistochemistry/immunofluorescence (IF) using polyclonal antisera against human IgG, IgM, IgA, C3, C1q and, if necessary, kappa and lambda light chains. Electron microscopy (EM) was not uniformly performed in all biopsies. The indications for renal biopsy were categorized into five clinical syndromes: nephrotic syndrome (NS), haematuria and/or proteinuria (H/P), acute renal failure (ARF) and chronic renal failure (CRF). NS was defined as proteinuria >3.5 g/day. H/P encompassed isolated microscopic and/or non-nephrotic proteinuria. ARF was defined as a sudden and rapid deterioration of renal function, while CRF was considered when elevated serum creatinine persisted for >6 months. Histopathological diagnoses were classified into 14 pathologies: minimal change disease (MCD), diabetic nephropathy (DN), advanced nephropathy (ADV NEPH), mesangioproliferative glomerulonephritis (MesPGN), IgA nephropathy (IGAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), lupus nephritis (LN), benign nephroangiosclerosis (NAS), tubulointerstitial nephropathy (TIN), no significant pathological changes (NO SIGN), amyloidosis (AMYL). Miscellaneous pathology with <1% frequency in the series was classified as (OTHERS). Patients were divided into three groups according to age: a paediatric group, which consisted of patients 15 years old or younger, a young adult group that included patients aged from 16 to 60 and an elderly group with patients older than 60 years.
Data analysis
Data were stored on a database file (SPSS). 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. Qualitative variables were compared by Chi-square or by Fisher’s test as appropriate. P-values <0.05 were considered statistically significant. All analyses were performed using the SPSS statistical software package (Version 16).
Results
During the period of 5 years, 1327 renal biopsies were studied in three major centres in Lebanon; the AUBMC, HDF and the INP. AUBMC and HDF are the two largest tertiary medical centres in Lebanon. INP is the largest pathology centre in Lebanon and receives most kidney biopsies performed in the remaining hospitals located in various regions in Lebanon. Due to inadequate sample material in 87 biopsies (6.6%) and exclusion of 192 (14.5%) transplant kidney biopsies, we analysed in this study 1048 renal biopsies from native kidneys; 141 from AUBMC, 230 from HDF and 677 from INP. The average biopsy rate during the observed period was 66.35 p.m.p./year. The mean age at renal biopsy was 36.76 ± 20 years (range 1–84). One hundred and eighty-two (20%) fell within the paediatric age group, 612 (67.3%) in the young adult group and 116 (12.7%) in the elderly group. Males were slightly more prevalent (54.4%) than females.
The most common clinical syndrome as an indication for renal biopsy was H/P (46.8%), followed by NS (33.2%), CRF (10.7%) and ARF (9.4%) (Figure 1). The most common diagnosis was MesPGN (20%), followed by FSGS (13.2%), NO SIGN (9.4%), NAS (8.8%), IGAN (7.8%), TIN (7.7%), LN (6.2%) and MN (6.0%) (Figure 2). Listed under ‘OTHERS’, 5.3% constituted the so-called miscellaneous pathology and included (in order of decreasing frequency): acute tubular necrosis, microangiopathy, IgM nephropathy, vasculitis, thin basement membrane disease (TBM), oxalosis and atheroembolic disease. Over the period of 5 years there was a trend of decrease in MesPGN and of increase in FSGS diagnoses (Figure 3). In patients presenting with H/P, the most common cause was MesPGN (22.4%), the second was FSGS (14.7%) and the third was IGAN (13.3%). MesPGN was also the commonest diagnosis in patients presenting with NS (27.0%), followed by MN (14.1%) and FSGS (12.4%). TIN was the most common diagnosis in CRF (25.9%) and ARF (22.4%), followed by FSGS (18.8%) and NAS (14.3%) in CRF and CRESGN (15.3%) and MPGN (11.2%) in ARF (Table 1).
Fig. 1.
Frequency of different clinical indications for kidney biopsy.
Fig. 2.
Frequency of histopathological diagnoses in 1048 native kidney biopsies.
Fig. 3.
Change in frequency of MesPGN and FSGS over 5 years.
Table 1.
Frequency of various histopathological diagnoses according to clinical indications
| Diagnosis | Clinical indication |
||||
|---|---|---|---|---|---|
| ARF | CRF | H/P | NS | Total | |
| n = 98 (%) | n = 112 (%) | n = 490 (%) | n = 348 (%) | n = 1048 (%) | |
| ADV NEPH | 5.1 | 15.4 | 1.2 | 1.4 | 3 |
| AMYL | 1 | 0.9 | 0.2 | 3.4 | 1.4 |
| CRESGN | 15.3 | 0.0 | 0.6 | 0.6 | 1.9 |
| DN | 3.1 | 8 | 2.2 | 4 | 3.5 |
| FSGS | 2 | 18.8 | 14.7 | 12.4 | 13.2 |
| IGAN | 1 | 4.5 | 13.3 | 3.2 | 7.8 |
| LN | 7.1 | 0.9 | 8.8 | 4.3 | 6.3 |
| MCD | 1 | 0.0 | 0.4 | 3.2 | 1.3 |
| MesPGN | 2 | 3.6 | 22.4 | 27 | 20 |
| MN | 2 | 1.8 | 2 | 14.1 | 6 |
| MPGN | 11.2 | 2.7 | 3.5 | 4 | 4.3 |
| NO SIGN | 0 | 2.7 | 12 | 10.3 | 9.4 |
| NAS | 9.2 | 14.3 | 9.4 | 6.5 | 8.8 |
| OTHERS | 16.3 | 2.7 | 5.1 | 3.2 | 5.2 |
| TIN | 23.5 | 25.9 | 4.1 | 2.9 | 7.8 |
Nephrotic syndrome (NS), haematuria and/or proteinuria (H/P), acute renal failure (ARF), chronic renal failure (CRF), minimal change disease (MCD), diabetic nephropathy (DN), advanced nephropathy (ADV NEPH), mesangioproliferative glomerulonephritis (MesPGN), IgA nephropathy (IGAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), lupus nephritis (LN), benign nephroangiosclerosis (NAS), tubulointerstitial nephropathy (TIN), no significant pathological changes (NO SIGN), amyloidosis (AMYL), miscellaneous pathologies (OTHERS).
The three age groups differed in terms of frequency of clinical indications and diagnoses. MesPGN and NO SIGN were significantly more frequent in the paediatric age group (P = 0.001, P < 0.001, respectively), while FSGS and NAS were most prevalent among young adult and elderly groups (P = 0.031, P < 0.001, respectively) (Table 2, Figures 4 and 5). Male gender was significantly more frequent in patients presenting with CRF (12.6 vs 8.4%; P = 0.03), while female sex was significantly higher among patients presenting with H/P (51.5 vs 42.7%; P = 0.005). Among the different diagnoses, IGAN was significantly more prevalent in males (9.6 vs 5.7%; P = 0.02), while LN was significantly more diagnosed in females (11.4 vs 2.1%; P < 0.001) (Table 3, Figure 6).
Table 2.
Frequency of different gender, clinical indications and commonly encountered histopathological diagnoses according to age groups
| Age ≤15 | 15< Age ≤60 | Age >60 | P-value | |
|---|---|---|---|---|
| Sample size/percent | 182 (20.0%) | 612 (67.3%) | 116 (12.7%) | |
| Gender | 0.475 | |||
| Female | 77 (42.3%) | 285 (46.6%) | 46 (42.2%) | |
| Male | 105 (57.7%) | 327 (53.4%) | 67 (57.8%) | |
| Clinical indication | <0.001 | |||
| ARF | 14 (7.7%) | 55 (9.0%) | 13 (11.2%) | 0.586 |
| CRF | 10 (5.5%) | 67 (10.9%) | 18 (15.5%) | 0.017 |
| H/P | 71 (39.0%) | 319 (52.1%) | 41 (35.3%) | <0.001 |
| NS | 87 (47.8%) | 171 (27.9%) | 44 (37.9%) | <0.001 |
| Diagnosis | <0.001 | |||
| MesPGN | 49 (26.9%) | 115 (18.8%) | 11 (9.5%) | 0.001 |
| FSGS | 12 (6.6%) | 85 (13.9%) | 14 (12.1%) | 0.031 |
| NO SIGN | 37 (20.3%) | 45 (7.4%) | 7 (6.0%) | <0.001 |
| NAS | 3 (1.6%) | 58 (9.5%) | 22 (19.0%) | <0.001 |
| IGAN | 14 (7.7%) | 54 (8.8%) | 5 (4.3%) | 0.256 |
| TIN | 13 (7.1%) | 45 (7.4%) | 16 (13.8%) | 0.058 |
Nephrotic syndrome (NS), haematuria and/or proteinuria (H/P), acute renal failure (ARF), chronic renal failure (CRF), mesangioproliferative glomerulonephritis (MesPGN), IgA nephropathy (IGAN), focal segmental glomerulosclerosis (FSGS), lupus nephritis (LN), benign nephroangiosclerosis (NAS), tubulointerstitial nephropathy (TIN), no significant pathological changes (NO SIGN).
Fig. 4.
Frequency of various clinical indications according to age groups.
Fig. 5.
Frequency of the commonly encountered histopathological diagnoses according to age groups.
Table 3.
Frequency of different age groups, clinical indications and commonly encountered histopathological diagnoses according to gender
| Males | Females | P-value | |
|---|---|---|---|
| Sample size/percent | 565 (54.4%) | 474 (45.6%) | |
| Age group | 0.475 | ||
| Age ≤15 | 105 (21.0%) | 77 (18.7%) | |
| 15< age ≤60 | 327 (65.5%) | 285 (69.3%) | |
| Age >60 | 67 (13.4%) | 49 (11.9%) | |
| Clinical indication | 0.014 | ||
| ARF | 59 (10.4%) | 37 (7.8%) | 0.144 |
| CRF | 71 (12.6%) | 40 (8.4%) | 0.032 |
| H/P | 241 (42.7%) | 244 (51.5%) | 0.005 |
| NS | 194 (34.3%) | 153 (32.3%) | 0.484 |
| Diagnosis | <0.001 | ||
| MesPGN | 114 (20.2%) | 95 (20.0%) | 0.957 |
| FSGS | 83 (14.7%) | 55 (11.6%) | 0.144 |
| NO SIGN | 49 (8.7%) | 45 (9.5%) | 0.646 |
| NAS | 56 (9.9%) | 35 (7.4%) | 0.151 |
| IGAN | 54 (9.6%) | 27 (5.7%) | 0.021 |
| TIN | 41 (7.3%) | 40 (8.4%) | 0.479 |
| LN | 12 (2.1%) | 54 (11.4%) | <0.001 |
Nephrotic syndrome (NS), haematuria and/or proteinuria (H/P), acute renal failure (ARF), chronic renal failure (CRF), mesangioproliferative glomerulonephritis (MesPGN), IgA nephropathy (IGAN), focal segmental glomerulosclerosis (FSGS), lupus nephritis (LN), benign nephroangiosclerosis (NAS), tubulointerstitial nephropathy (TIN), no significant pathological changes (NO SIGN).
Fig. 6.
Frequency of the commonly encountered histopathological diagnoses according to gender.
Genetic variation within Lebanon was recently found to be more strongly structured by religious affiliation than by geography. Therefore, we looked at the distribution of various diagnoses between Muslims and Christians. We were able to infer information on religious affiliation in 909 cases, 557 Muslims (61.3%) and 352 Christians (38.7%). Since the distribution of religions among patients is comparable to the one estimated for the general Lebanese population (60% Muslims, 40% Christians), there is no apparent bias in biopsy rate among the two groups. Results showed that the most common diagnosis among Muslims was MesPGN (24.6%) while the most common diagnosis in Christians was FSGS (19%). Statistical analysis showed that there was no significant difference in age, gender or clinical indication by religion. However, overall, there was a significant difference in frequency of various diagnoses. In particular, MesPGN and LN were significantly higher among Muslims as compared to Christians (24.6 vs 18.8%; P = 0.039, 7.7 vs 3.1%; P = 0.004, respectively). On the other hand, FSGS was significantly higher in Christians (10.4 vs 19.0%; P < 0.001) (Table 4, Figure 7).
Table 4.
Frequency of different age groups, gender, clinical indications and commonly encountered histopathological diagnoses according to religion
| Muslim | Christian | P-value | |
|---|---|---|---|
| Sample size/percent | 557 (61.3%) | 352 (38.7%) | |
| Age | 0.765 | ||
| Age ≤15 | 102 (18.4%) | 59 (16.8%) | |
| 15< Age ≤60 | 390 (70.4%) | 250 (71.0%) | |
| Age >60 | 62 (11.2%) | 43 (12.2%) | |
| Gender | 0.735 | ||
| Female | 258 (46.3%) | 159 (45.2%) | |
| Male | 299 (53.7%) | 193 (54.8%) | |
| Clinical indication | 0.417 | ||
| ARF | 51 (9.2%) | 29 (8.2%) | 0.634 |
| CRF | 51 (9.2%) | 39 (11.1%) | 0.344 |
| H/P | 268 (48.1%) | 153 (43.5%) | 0.171 |
| NS | 187 (33.6%) | 131 (37.2%) | 0.262 |
| Diagnosis | 0.007 | ||
| MesPGN | 137 (24.6%) | 66 (18.8%) | 0.039 |
| FSGS | 58 (10.4%) | 67 (19.0%) | <0.001 |
| NO SIGN | 41 (7.6%) | 28 (8.0%) | 0.742 |
| NAS | 52 (9.3%) | 24 (6.8%) | 0.182 |
| IGAN | 43 (7.7%) | 37 (10.5%) | 0.148 |
| TIN | 33 (5.9%) | 31 (8.8%) | 0.098 |
| LN | 43 (7.7%) | 11 (3.1%) | 0.004 |
Mesangioproliferative glomerulonephritis (MesPGN), IgA nephropathy (IGAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), lupus nephritis (LN), benign nephroangiosclerosis (NAS), tubulointerstitial nephropathy (TIN), no significant pathological changes (NO SIGN).
Fig. 7.
Frequency of the commonly encountered histopathological diagnoses according to religion.
To see the effect of consanguinity on the frequency of different diagnoses, we were able to collect information on the presence of consanguinity in parents from 110 patients. Parents’ consanguinity was reported by 29 (26.4%) patients. Degree of consanguinity was reported as first cousins by 14 patients, almost in half of related parents. Analysis showed no significant difference in the distribution of patients among the different age groups, gender, religion or clinical indications between patients born to consanguineous parents and non-consanguineous parents. Regarding diagnosis, however, MesPGN was significantly more frequent in patients with reported parents’ consanguinity (20.7 vs 6.2%; P < 0.05) (Table 5, Figure 8).
Table 5.
Frequency of different age groups, gender, religion, clinical indications and commonly encountered histopathological diagnoses according to parents’ consanguinity
| Consanguinity | No consanguinity | P-value | |
|---|---|---|---|
| Sample size/percent | n = 29 | n = 81 | |
| Age | 0.769 | ||
| Age ≤15 | 2 (6.9%) | 7 (8.6%) | |
| 15< Age ≤60 | 20 (69.0%) | 59 (72.8%) | |
| Age >60 | 7 (24.1%) | 15 (18.5%) | |
| Gender | 0.459 | ||
| Female | 17 (58.6%) | 41 (50.6%) | |
| Male | 12 (41.4%) | 40 (49.4%) | |
| Religion | 0.230 | ||
| Muslim | 27 (93.1%) | 66 (81.5%) | |
| Christian | 2 (6.9%) | 15 (18.5%) | |
| Clinical indication | 0.521 | ||
| ARF | 2 (6.9%) | 8 (9.9%) | 0.480 |
| CRF | 4 (13.8%) | 4 (4.9%) | 0.125 |
| H/P | 12 (41.4%) | 41 (50.6%) | 0.393 |
| INS | 1 (3.4%) | 5 (6.2%) | 0.498 |
| NS | 10 (34.5%) | 23 (28.4%) | 0.539 |
| Diagnosis | 0.492 | ||
| MesPGN | 6 (20.7%) | 5 (6.2%) | 0.036 |
| FSGS | 4 (13.8%) | 14 (17.3%) | 0.456 |
| NO SIGN | 2 (6.9%) | 13 (16.0%) | 0.182 |
| NAS | 6 (20.7%) | 10 (12.3%) | 0.212 |
| IGAN | 3 (10.3%) | 5 (6.2%) | 0.354 |
| TIN | 1 (3.4%) | 1 (1.2%) | 0.460 |
| LN | 1 (3.4%) | 6 (7.4%) | 0.405 |
Mesangioproliferative glomerulonephritis (MesPGN), IgA nephropathy (IGAN), focal segmental glomerulosclerosis (FSGS), lupus nephritis (LN), benign nephroangiosclerosis (NAS), tubulointerstitial nephropathy (TIN), no significant pathological changes (NO SIGN).
Fig. 8.
Frequency of commonly encountered histopathological diagnoses according to parents’ consanguinity.
Discussion
This is the first series to determine the prevalence rate and the frequency of different glomerulonephritis (GN) in Lebanon. Data were collected from three centres covering most kidney biopsies performed in Lebanon during the period of 2003–2008. The incidence rate of renal biopsy (66.35 p.m.p./year) approaches that of some national registries in Europe like in Spain [2] and the Czech Republic [3], but remains lower than that reported in countries like France [4], USA [5] and Australia [6].
The results showed that MesPGN is the most common encountered diagnosis. This result was in agreement with reports from other countries in the region where MesPGN was reported as the first or second most common primary GN [7,8]. What makes MesPGN that frequent in our series may have more than one explanation. Focal or diffuse mesangial cell proliferation is a relatively non-specific response to glomerular injury. This pattern can be seen in a variety of diseases including LN, IGAN, mild post-infectious GN, vasculitis, FSGS, Alport’s syndrome and IgM nephropathy [9–11]. This makes mesangial changes as common background for more specific pathological changes that can be further delineated in IF study and/or EM study. Although some of the reports from the region included series without IF analysis, our series includes performing IF on all cases. Moreover, it has been suggested that MesPGN is a more severe form of MCD in which the initial injury is greater, leading to mesangial dysfunction and a slower rate of recovery [12,13]. In the absence of routine EM study, these patients may contribute to the increased diagnosis of MesPGN in our series. The younger age and high prevalence of NS, both characteristics of MCD patients, among this group may support this possibility. On the other hand, in reports from Saudi Arabia including ones with routine EM analysis [14], MesPGN was the second most common primary GN after FSGS which suggests that additional causes beside the lack of EM study also contribute to the high prevalence of MesPGN in this region.
The second highest cause of renal disease in the present series was FSGS. The difference in frequencies of FSGS reported from different parts of the world is difficult to explain, but this could either be genuinely related to genetic and environmental influences or a result of differences in biopsy policy, adequacy and endeavour on the part of reporting pathologists to find this lesion in a given material. In a recent report from Brazil, FSGS was the most common primary glomerular disease [15]. In our study, there is a trend in increasing in the frequency of FSGS diagnosis over the past 5 years along with a decrease in MesPGN diagnosis. This trend may eventually result in making FSGS the leading diagnosis in the coming years.
The third cause of renal disease of the present series was NO SIGN. Among patients presenting with NS, this diagnosis suggests that most of these cases are MCD that could not be diagnosed without EM analysis. The possibility of a high prevalence of MCD is further supported by the higher prevalence of the diagnosis in the younger age group. In addition, among patients presenting with isolated haematuria, beside the possibility that a non-glomerular lesion may be behind the urinary abnormality, this diagnosis suggests that these cases may be unidentified TBM. Therefore, TBM and MCD were certainly under-diagnosed in this series due to the lack of routine performance of EM study on the kidney biopsy specimens. This represents a shortcoming of current renal biopsy practice.
There was a relatively high prevalence in the present series of NAS, a pattern different from those found in other countries. This result may be related to the applied biopsy policy as more patients with CRF and older age were noted in this group. Also, vascular lesions are commonly reported in patients with idiopathic GN [16], and may lead to the diagnosis of NAS in patients with conspicuous renal vascular lesions and global sclerosis from unidentified specific glomerular disease such as MCD, MN and IGAN due to lack of EM and/or inadequate IF studies.
Results indicate that IGAN is not a common primary GN in Lebanon, and apparently it is also not common in neighbouring countries such as Saudi Arabia [14] and Egypt [8]. This is in contrast to the higher frequencies of IGAN in reports from Europe and Far East. This could be due to lower threshold of obtaining biopsies from patients with isolated haematuria. In the Italian registry [17], asymptomatic urinary abnormalities are more common than NS, perhaps expressing a tendency to biopsy asymptomatic haematuria or proteinuria. IGAN was the disease diagnosed predominantly in this group (29.8%). Conversely, FSGS is the most common primary glomerular disease in Brazilian registry and among African Americans [15, 18]. The most frequent clinical syndrome at any age was the NS. The pattern of primary glomerular diseases occurring in China is unique in its high prevalence of IGAN and non-IgA mesangial proliferative lesion. Among 9278 cases of primary glomerular diseases examined, the most frequent histopathologic lesion was IGAN (45.26%) [19]. Whether their high prevalence is related to genetic background, environmental factors or frequent infections (either bacterial or viral) is uncertain.
The difference in the distribution of various diagnoses according to religion is an interesting finding in our study. The religious communities are interspersed throughout Lebanon with no apparent difference in biopsy rate, and there were no significant differences in age, gender or indications for biopsy based on religious affiliation, suggesting that variation in clinical practice, demographics or environmental variables is unlikely to contribute to these distinct patterns. Recently, genetic variation within Lebanon was found to be more strongly structured by religious affiliation than by geography [20]. The Muslim and Christian populations show increased prevalence of Y-chromosome haplogroups of Arabian and European lineage, respectively, reflecting differences in ancestry. These Y-chromosome signatures are attributable to introduction of population of different ancestry during the Islamic expansion and the Crusades. Variation in ancestry may therefore explain the differing distribution of glomerular disorders according to religion. The distribution of disease among the Muslim group is similar to the pattern reported among other countries in the Middle East [7], while the distribution among the Christians resembles the pattern reported from Brazil and young Caucasians in the USA [15,18]. However, consanguineous marriage is prevalent in Lebanon as in other countries in the region with reported rate of 25–35% [21,22] and is seemingly favoured by Muslim religion and low socio-economic status. In the surveyed patients group, the consanguinity rate among the parents was 26% with MesPGN significantly more frequent among patients born to consanguineous parents. The overrepresentation of MesPGN in offspring of consanguineous union suggests a recessive genetic contribution to this trait among the Lebanese. A hereditary contribution is further supported by the higher prevalence of MesPGN in younger patients. This suggests an opportunity to apply homozygosity mapping, which relies on identification of segments of genome that are inherited by homozygous-by-descent to localize and, ultimately, identify genes that contribute to this trait in the Lebanese population.
The study raises the importance of routinely performing EM evaluation to avoid incomplete diagnosis in a number of entities. There were 9.4% cases that had no significant findings on LM and IF. Additionally, the absence of routine EM study may have contributed to the increased diagnosis of MesPGN in our series. Recent reviews [23–25] showed that EM was absolutely necessary to make a correct diagnosis in 21% of cases, while EM evaluation resulted in clinically relevant refinement of or addition to the diagnosis in another 24%. Diagnoses most frequently requiring EM included MCD, early DN, membranous LN, MPGN, post-infectious GN and TBM nephropathy. Therefore, a future study including EM analysis of the available paraffin blocks from cases diagnosed with NO SIGN or MesPGN may be performed to further refine the initial diagnosis. This will also help identify the robust MesPGN phenotype for a subsequent study to explore any underlying genetic cause. Less than a complete workup for the kidney biopsy should be a rare exception, usually resulting from an inadequate specimen for one of the studies, LM, IF or EM. If EM cannot be performed routinely on all such biopsies, it is recommended that tissue for ultrastructural studies be set aside in each case.
In conclusion, this study shows the prevalence of glomerular disease in Lebanon based on reports of 1048 renal biopsies and includes material from all regions of the country. It demonstrates that the two major primary glomerular diseases are currently MesPGN and FSGS. The observed distinct patterns of glomerular disease among Muslim and Christian groups likely reflect differences in population structure and ancestry. The increased prevalence of MesPGN among offspring of consanguineous unions points to a previously unrecognized recessive genetic component to this disease which may be revealed via homozygosity mapping. This is an initial step in the understanding of the epidemiology of renal diseases in Lebanon providing data for comparison with other countries.
Conflict of interest statement. None declared.
Appendix 1
Hospitals that contributed to the renal biopsy collection analysed in Institut National de Pathologie (INP)
Hopital Notre Dame de Secours-Jbeil, Hopital Islamique-Tripoli, Centre du Nord Medical-Zgharta, Ain Wazein Hospital-Chouf, Hopital Ste. Therese-Hadath, Hopital Notre Dame du Liban-Jounieh, Hopital St Charles-Fiyadieh, Hopital Mont Liban-Chiyah, Hopital Sacre Coeur-Hazmieh, Bahman Hospital-Beirut, Zahra Hospital-Beirut, Sahel Hospital-Beirut, Makassed Hospital-Beirut, Hopital Rizk-Beirut, Hotel Dieu de France-Beirut, Hopital Libanais-Beirut, Hopital St. Georges-Beirut, Hopital Hayek-Beirut, Hopital Khoury-Zahle, Hopital Tal Chiha-Zahle, Hopital Rayan-Baalbeck, Hopital Dar Al Amal-Baalbeck, Labib Medical Center-Saida, Hopital Hammoud-Saida, Jabal Amel Hospital-Sour.
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