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 Table of Contents  
ORIGINAL ARTICLES
Year : 2019  |  Volume : 19  |  Issue : 4  |  Page : 109-117

Renal biopsy registry in Alexandria area


1 Department of Nephrology and Transplantion, Alexandria University Hospital, Alexandria, Egypt
2 Department of Pathology, Alexandria University Hospital, Alexandria, Egypt

Date of Submission29-Jun-2019
Date of Decision12-Aug-2019
Date of Acceptance23-Aug-2019
Date of Web Publication25-Nov-2019

Correspondence Address:
Dr. Mahmoud S AbdElHady
Master Degree of Internal Medicine, Internal Medicine and Nephrology Department, Faculty of Medicine, Kafr ELSheikh University, Kafr el-Sheikh, 21648
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jesnt.jesnt_23_19

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  Abstract 


Background There is a paucity of registries on diseases found on renal biopsies, especially in Egypt. Therefore, in this study, we have attempted to identify the pattern of renal pathology among renal biopsy (RB) specimens and to study the clinicopathological correlation of RB in the Alexandria area, which is considered the biggest second city in Egypt after Cairo, with around six million inhabitants, as a step toward generating a national RB registry.
Methods We evaluated all the available adult native renal biopsies that were performed in the Alexandria area during the years 2012 and 2015 from the two main nephropathology centers. Clinical presentations were asymptomatic urinary abnormalities, nephrotic syndrome (NS), nephritic syndrome, and unexplained acute kidney injury. Renal diseases were divided into four major categories: (a) primary glomerulonephritides (GN); (b) secondary GN; (c) tubulointerstitial nephropathies (TIN); and (d) vascular nephropathies. The distinction between primary and secondary GN was not established by a single histological approach, but by association of the morphological findings and available clinical data. A RB forum was designed to collect the clinical and pathological data.
Results 861 native renal biopsies were included; the most common age interval during which RB was performed was 20–30 years (32.6%); female gender (51%) was slightly more prevalent than male sex (49%). The renal specimen was inadequate in 14.1% of the cases. Of all biopsies, primary GN was the most frequent (64.3%), followed by secondary GN (27.8%), TIN (4.2%), and vascular nephropathies (1.2%), where end stage renal disease (ESRD) cases represented 2.4%. The most common clinical syndrome as an indication for RB was NS (57.8%), followed by acute kidney injury (21.6%), chronic kidney disease (CKD) (9.3%), asymptomatic urinary abnormalities (8.9%), nephritic syndrome (1.2%), and nephritic nephrotic syndrome (1.2%). At the time of the biopsy, 53.2% of the patients presented with elevated kidney functions. Mesangioproliferative GN was the most common primary GN (24.8%), followed by membranoproliferative GN (23.7%), focal and segmental glomerulosclerosis (21.4%), membranous nephropathy (10.3%), IgA nephropathy (8.8%), minimal change disease (5.7%), and crescentic GN (5.3%). Lupus nephritis was the most common cause of secondary GN (56.3%), followed by amyloidosis (14.6%), diabetic nephropathy (12.6%), nodular GN (6.8%), cast nephropathy (4.4%), cryoglobulinemia (2.9%), gouty nephropathy (1.9%), and lymphomatous infiltration (0.5%). Acute TIN represented 65.5% of the TIN cases and chronic TIN represented 35.5%. Thrombotic microangiopathy represented 66.6% of the vascular diseases and hypertension (HTN) nephrosclerosis represented 33.3%.
Conclusion Our RB registry represents an important contribution toward understanding the epidemiology of renal diseases in Alexandria city. We are hoping that this registry will be the basis for developing a national registry. Establishment of a trusted national registry that will help in preventing and treating renal diseases requires good cooperation between nephrologists and pathologists, with collection of all clinical, serological, and pathological data.

Keywords: epidemiology, nephropathies, Registry, renal biopsy


How to cite this article:
AbdElHady MS, Koraei AF, Salem MA, Baddour NM, Nienaa YA. Renal biopsy registry in Alexandria area. J Egypt Soc Nephrol Transplant 2019;19:109-17

How to cite this URL:
AbdElHady MS, Koraei AF, Salem MA, Baddour NM, Nienaa YA. Renal biopsy registry in Alexandria area. J Egypt Soc Nephrol Transplant [serial online] 2019 [cited 2019 Dec 13];19:109-17. Available from: http://www.jesnt.eg.net/text.asp?2019/19/4/109/271561




  Introduction Top


The spectrum of diseases found on percutaneous renal biopsies varies considerably depending on multiple factors such as age, sex, race, geographical location, and the nature of biopsy indications. Moreover, there is evidence of change in many parts of the world in the spectrum of renal diseases recently. It is therefore imperative to accurately document the spectrum of renal diseases prevalent in a particular area over a particular period of time. Many countries now have their own databases on renal biopsy (RB) and the epidemiology of specific glomerular diseases in these countries such as the Italian renal biopsy registry database and the Japanese renal biopsy registry database and others. Therefore, in this study, we attempted to identify the pattern of renal pathology among RB specimens and to study the clinicopathological correlation of RB in Alexandria area in an effort to establish a national RB registry.


  Methods Top


We collected all the available data on native kidney biopsies in the Alexandria area between the years 2012 and 2015 that were performed on patients older than 14 years of age. The data gathering was performed in a retrospective and prospective arm. For the retrospective arm, all the possible archival materials from the pathology department for the past 2 years were retrieved and assessed by two independent pathologists blinded to the original report, together with all the possible available clinical data in the files of this cohort from the Nephrology and Transplantation Unit and treating physicians.

For the prospective arm, a new RB forum was created and the data collected were filled in this forum. All patients in this group underwent a thorough assessment of history, clinical examination, and routine laboratory investigations for the evaluation of the nephropathy type.

A final RB report from the pathological department should typically contain the following components: (a) identification of material submitted, proportion of cortex, proportion of medulla, and other tissues included, and number of glomeruli available. This was expressed as ‘at least’, meaning the largest number seen in any single section. (b) Changes in glomeruli. Cellularity, sclerosis, necrosis, crescents, numbers of glomeruli affected, segmental, or global changes. (c) Tubules: evidence of acute damage, extent of atrophy (as an estimated percentage), casts, crystals, inclusions, etc. (d) Interstitium: lymphocytic infiltrates, fibrosis, patchy, or diffuse changes. An estimate of these features yielded a more meaningful assessment of ‘activity’ and ‘chronicity’ than the glomerular changes. (e) Blood vessels: Number and size present, any age-related changes, any acute changes. (f) Immunohistochemical results. (g) Electron microscopic results. (h) Conclusions. In drawing conclusions, a differential diagnosis was provided, with arguments for and against each possibility.

Clinical presentations included were asymptomatic urinary abnormalities (AUA), nephrotic syndrome (NS), nephritic syndrome, and unexplained acute kidney injury (AKI). Renal diseases provided by the pathologists were divided into four major categories: (a) primary glomerulonephritides (GN); (b) secondary GN; (c) tubulointerstitial nephropathies (TIN); and (d) vascular nephropathies (VN).

Primary GN included mesangial GN (both IgA and non-IgA mesangial nephropathy), membranous GN, Focal and segmental glomerular sclerosis (FSGS), minimal change disease (MCD), mesangiocapillary GN, and crescentic GN. Secondary GN included autoimmune diseases such as lupus nephritis (LN), metabolic diseases such as diabetic nephropathy (DN) [both diabetic and nondiabetic renal diseases (NDRD)] and gouty nephropathy, infection-related GN (HCV-related GN and others), and malignant associated GN (lymphomatous nephropathy-myeloma kidney). TIN included acute tubulointerstitial nephritis (ATIN) and chronic tubulointerstitial nephritis (CTIN). VN included hypertensive nephrosclerosis and thrombotic microangiopathy. Data were fed into the computer and analyzed using IBM SPSS software package version 20.0 (IBM/Corp., Released 2011, IBM SPSS Statistics for Windows, Version 20.0, Armonk, NY: IBM Corp.). Qualitative data were described using number and percent. Quantitative data were described using range (minimum and maximum), mean, SD, and median. The significance of the obtained results was judged at the 5% level.


  Results Top


A total of 861 native renal biopsies were included and the retrospective group constituted 600 RBs in the years 2012–2014, whereas the prospective group included 261 RBs in the year 2015. In this study, age was reported only in 818 patients, whereas for 43 patients, the age was not recorded. The most common age interval during which a RB was performed was 20–30 years (32.6%) ([Table 2]). Female gender (51%) was slightly more prevalent than male gender (49%).

The total percent of inadequate nephrology reports was 52.4%, whereas that of the adequate reports was 47.6%, and the percent of inadequate reports decreased over the years: it was 66.5% in 2013, 53.8% in 2014, and 42.9% in 2015 ([Table 1]).
Table 1 Distribution of renal biopsies according to the adequacy of the nephrology report

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Table 2 Percent of adequate and inadequate renal biopsy in 2012–2015

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The most common clinical syndrome as an indication for RB was NS (57.8%), followed by AKI (21.6%), chronic kidney disease (CKD) (9.3%), urinary abnormalities (8.9%), nephritic syndrome (1.2%), and nephritic NS (1.2%), as shown in [Table 3].
Table 3 Comparison between the studied groups according to the clinical presentation

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Of the 780 recorded biopsies about renal functions, a total of 415 (53.2%) patients had impaired renal functions at the time of biopsy, 365 (46.8%) had normal renalfunctions, and in 81 cases the renal functions were not reported. The cut-off value of serum creatinine was arbitrary (1.2 mg/dl), where the percent of patients who had abnormal serum creatinine was 50.4% in 2012, 50% in 2013, 57% in 2014, and 52.9% in 2015.

Hypertension (HTN) was not reported in 496 (57.6%) patients; out of the reported cases 365 (42.4%) more patients were presented by HTN 253 (29.4%) patients at time of RB than non-HTN 112 (13%) patients.

In our registry, the renal specimen was inadequate in 121 (14.1%) patients, whereas there were 740 (85.9%) adequate specimens during the years 2012–2015.

In this study, after exclusion of the 18 (2.4%) end stage renal disease (ESRD) cases proven by RBs, primary GN constituted 476 (64.3%) cases out of the 740 adequate RBs, whereas secondary GN was present in 206 (27.8%) cases out of the 740 adequate RBs. Tubulointerstitial diseases were present in 31 (4.2%) cases of the 740 adequate RBs and vascular diseases were present in nine (1.2%) cases of the 740 adequate RBs.

Mesangioproliferative glomerulonephritides (MesGN) was the most common primary GN, 118 (24.8) cases, followed by membranoproliferative glomerulonephritides (MPGN), 113 (23.7%), FSGS, 102 (21.4%), membranous nephropathy (MN), 49 (10.3%), IgA nephropathy, 42 (8.8%), MCD, 27 (5.7%), and crescentic GN, 25 (5.3%), as shown in [Table 4].
Table 4 Primary glomerulonephritides in the years 2012–2015 in the 740 adequate renal biopsy

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LN was the most common cause of secondary GN (56.3%), followed by amyloidosis (14.6%), DN (12.6%), nodular GN (6.8%), cast nephropathy (4.4%), cryoglobulinemia (2.9%), gouty nephropathy (1.9%), and lymphomatous infiltration (0.5%), as shown in [Table 5].
Table 5 Secondary glomerulonephritides in the years 2012–2015 in the 740 adequate biopsies

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ATIN represented 65.5% of the TIN and CTIN represented 35.5% as shown in [Table 6].
Table 6 Percent of tubulointerstitial diseases in the adequate 740 renal biopsy in the years 2012–2015

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Thrombotic microangiopathy represented 66.6% of the vascular diseases and HTN nephrosclerosis represented 33.3% as shown in [Table 7].
Table 7 Percent of vascular diseases in the years 2012–2015 in the 740 adequate biopsies

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The 861 renal biopsies were mainly evaluated by light microscopy, where the percent of immunohistochemistry was 18.2% from 740 adequate specimens and electron microscopy was used much less frequently by 2.3% as shown in [Table 8],[Table 9],[Table 10].
Table 8 Comparison between the studied groups according to the histopathological diagnosis

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Table 9 Comparison between the studied groups according to immunohistochemistry

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Table 10 Relation between histopathological diagnosis with clinical presentation in the adequate biopsies

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Histopathological diagnosis on the basis of light microscopy and percent of inadequate renal biopsy

In our registry, the renal specimen was inadequate in 121 (14%) patients during the years 2012–2015.

[Table 8] shows that MesGN was the most frequent pattern 37%, followed by MPGN 23.7%, FSGS 14.3%, membranous 7.7%, and MCD 3.6%. TIN represented 4.18%, whereas VN represented 1.2%.

[Table 9] shows that IgA nephropathy represented the most common pathology (31.1%) in all specimens proceeded to immunohistochemistry.

Only 17 specimens from the adequate 740 RBs were examined by EM, where fibrillary GN represented 70% and immunotactoid represented 5.8% of the cases.

The most common pathological pattern in patients who presented with AKI was MPGN (21.1%) and MesGN (21.1), followed by crescentic GN (15.1%), FSGS (25.%) was the most common pathological pattern in patients presenting with CKD, MesGN was the most common pathological pattern in patients with NS (28.2%) and in patients presented with urinary abnormalities (51.5%), MPGN was the most common pathological pattern in patients with nephritic syndrome (66.7%) and in (50%) of patients presented by nephritic nephrotic syndrome [Table 10].

MesGN was the most common pathological pattern in patients in most age groups, where the most common clinical presentation in various pathological types was NS. Female sex was more common than males in all pathological types except in patients diagnosed as MCD and FSGS, as shown in [Table 11].
Table 11 Relation between histopathological diagnoses with age, sex, and clinical presentation in the entire sample

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In this study, 28 hepatitis C virus (HCV) patients were reported; NS was the most common clinical presentation (50%), followed by AKI/rapidly progressive glomerulonephritis (RPGN) (32.2%), nephritic-NS (7.1%), CKD (7.1%), and urinary abnormalities (3.6%), as shown in [Table 12].
Table 12 Distribution of the studied cases according to the clinical presentation in HCV-positive patients (n=28)

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Distribution of HCV-positive patients according to histopathological patterns

In this study, in 28 (3.3%) HCV-positive patients, seven (25%) RBs were inadequate. Cryoglobulinemic MPGN was the most common histopathological pattern (21.4%), followed by MPGN (14.3%), MesGN (14.3%), FSGS (10.7%), and amyloidosis (10.7%), as shown in [Table 13].
Table 13 Distribution of the studied cases according to histopathological patterns in HCV-positive patients (n=28)

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Distribution of diabetic nephropathy and nondiabetic kidney diseases among diabetic patients who underwent renal biopsy in the years 2012–2015

In this study, 43 (5%) cases with DM underwent a RB, of which four (9.3%) cases were inadequate. Of the 39 adequate cases, 10 (23.3%) cases were DN IIa, eight cases were DN IIa, five cases were DN III, three cases were DN IV, and two cases were DN I. Other NDRD were found among diabetic cases; the most common pathology was MPGN in three (7%) cases and others were MN (2.3%), FSGS (2.3%), amyloidosis (2.3%), fibrillary GN (2.3%), ATIN (2.3%), and crescentic GN (2.3%), as shown in [Table 14].
Table 14 Distribution of histopathological patterns among diabetic patients who underwent renal biopsy in the years 2012–2015

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Distribution of lupus nephritis cases according to classes in this study

In this study, 124 LN RBs were reported, eight (6.5%) RBs were inadequate. Of the adequate 116 RBs (93.5%), LN class IV+V represented the most common histopathological pattern (43.1%), followed by pure class IV (22.4%), class III (13.8%), class III+V (7.8%), class V (6.9%), and class II (6%), as shown in [Table 15].
Table 15 Distribution of the lupus nephritis cases studied according to classes (n=124)

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  Discussion Top


In this study, a total of 861 RBs were collected over the years 2012–2015 in the Alexandria area. This number in our study is significantly lower in comparison with most registries worldwide: 13 835 in Italy [1], 9617 in Brazil [2], 4004 in the Czech Republic [3], 2126 in Japan [4], and 2362 in the Serbian registry. This lower incidence of renal biopsies might be attributed to different factors:

First, the time frame considered by each report was different. In some reports such as the Olmsted County, the RB study [5] encompassed a 30-year observation (1974–2003), whereas in our report, it was only 4 years.

Second, many nephrologists adopted a conservative approach. This was a consequence of the opinion of most physicians to perform a biopsy only when they believed that the pathology could alter the therapy or when patients had signs of progressive renal disease.

Third, the economic factor plays a role in this lower incidence in Egypt. Even though we observed a steadily increasing biopsy rate that was seen over this 4-year survey, this was also the pattern in some countries [6].

In this study, the 861 renal biopsies were mainly evaluated by light microscopy where the percentage of immunohistochemistry was 18.2% from 740 adequate specimens and electron microscopy was used much less frequently by 2.3%. This is probably because of many reasons: first is the unavailability of resources and second, insufficient tissue did not always allow complete evaluation, especially by immunohistochemistry (IHC) or EM.

NS was the most frequent indication for RB in our study, which is similar to the majority of published RB registers [3],[7],[8]. On the contrary, some studies noted AUA as the most frequent indication for RB [1].

AKI was the second most common indication for RB in our study, which was not in agreement with some studies that noted AKI as the least indication partly because they grouped more than one clinical syndrome in one patient; also, the Czech series explained this as the etiology of AKI is detected earlier by clinical examination and that renal functions recover fast after the induction of therapy and also because of the policy of some clinics [3],[9].

In our registry, the renal specimen was inadequate in 121 (14%) patients during the years 2012–2015 and this was much higher than the reported incidence from other registries. In the Italian registry, only 3% inadequate samples were reported and in the Czech registry it was 4.6%, but a decreased pattern was observed over the 4-year study, which was explained by increasing experience over time and the emerging specialty of interventional nephrology [1].

MesGN was the most common pathological pattern among the primary GN, followed by MPGN and FSGs, whereas IgA nephropathy represented (8.8%) of this cases.

Similar results was found in the Serbian registry, where non-IgA MesGN was the most frequent primary GN (25.1%) [9].

Our results were considerably different from those of many other registries, where IgA nephropathy was the most common disease in eight national registries (Scotland, Japan, Italy, Czech Republic, Australia, France, Denmark, Spain) [1],[3],[4],[5]. The lower prevalence of IgA nephropathy (IgAN) in our series might be attributed to the lower rate of renal biopsies in patients with AUA and the incomplete evaluation by IHC in most of the cases [1],[11].

In this study, tubulointerstitial diseases were recorded only in 31 (3.6%) cases. Of these, 65% were ATIN and 35% were CTIN. Similar to our results, the Czech registry showed only 4.4% incidence of TIN, whereas in the Serbian registry, it was 5.2% [1],[9].

In contrast to our results,CTIN was more common than ATIN in the Serbian registry and IRBR; this could be attributed to the decreased percentage of RB in patients with AKI suspected to have ATIN as the diagnosis of ATIN is mainly made on the basis of clinical backgrounds and procedures less invasive than RB.

In this study, the percent of HCV-related GN was 3.3% (28 cases), despite HCV endemicity in Egypt. The low incidence of HCV-related GN in our series can be explained by the reluctance of many nephrologists to recommend biopsy for HCV-positive patients with the full-blown clinical picture of HCV-related GN (proteinuria, hematuria, renal insufficiency, and hypocomplementemia with or without a positive cryoglobulin test), and this might be related to the believe at the RB would not alter the management plane in most patients with HCV-related nephropatheis.

In this study, 5% of the patients (43 cases) had DM at the time of RB; among these, pathological characteristics of DN were found in 65.1%, whereas NDRD were diagnosed in the remaining 34.9%. MPGN was the most common pathological pattern among these NDRD. Other pathological patterns were FSGS, MN, amyloidosis, and crescentic GN.

Diabetic patients are usually not biopsied unless there are doubts about the role of diabetes in the causation of renal disease, as in the case of the absence of DR, rapidly progressive renal failure, and significant proteinuria in the setting of short duration of diabetes.

In a retrospective analysis from China, among diabetic patients who had undergone RB during a 6-year period, there was a high prevalence of NDRD in the diabetic population. Sixty-nine patients were investigated, 52.2% were diagnosed with NDRD and 47.8% with DN. Focal segmental glomerulosclerosis was the most common lesion found in patients with NDRD. It was determined that the absence of DR and a lower fasting blood glucose level are useful in differentiating NDRD from DN in diabetic patients with overt proteinuria [12].

In Europe, similar results were obtained. In Poland, from the data of 76 patients with type 2 diabetes who underwent RB and were diagnosed in the Department of Nephropathology, NDRD was found in 38 (50%) patients, NDRD in addition to underlying DN was diagnosed in 11 (14.5%) patients, and isolated DN was diagnosed in 27 (35.5%) patients. The most common glomerular lesion found in NDRD and the mixed group was FSGS [13].

Also in the Czech registry, 12.2% of the patients were diabetic; of these, DN was found in 42.4% and NDRD were found in 47.5%, where 10.1% of samples were nondiagnostic. Among NDRD, the most frequent diagnoses were IgAN and membranous GN [3],[14].

In this study, LN was the most common cause of secondary GN (56.3%); 124 LN RBs were reported. The most common histopathological pattern was LN class IV+V (43.1%), followed by pure class IV, representing (22.4%).

Similar data were found in almost all registries worldwide, where LN was the most common cause of secondary GN; in IRBR, Serbia, Czech as well as in many Arabian countries; Bahrain, Saudi Arabia andUnited Arab Emirates [3],[9],[15],[16].

A slight difference was reported in a recent USA study, where they reported LN class III as the most common pathological type, followed by class II and finally class IV in their series of LN cases [17].

It is rather difficult to report definitive epidemiological data on the frequency of the various forms of GN for several reasons. First, the RB indication policy varies from center to center. Second, RB is often not performed when the likelihood of a therapeutic consequence is low (e.g. steroid-sensitive NS in children, intermittent hematuria without proteinuria, bilateral small kidneys, and postinfection GN). For this reason, the true incidence of MCD, PEGN, and IgAN will be under-represented; thus, the lack of clear guidelines on indications for RB may hamper the epidemiological classification of renal diseases.

Third, insufficient tissue did not always allow complete evaluation, that is, by immunohistochemistry, so that a correct histological diagnosis could not be established (e.g. IgAN, only); only 18.2% of all adequate specimens were examined by IHC. Other reports are similarly incomplete; for example, only 78% out of all samples were evaluated by immunofluorescence in a Danish study [7] and 56.5% in Japan [4], and in the Czech report, they observed a ‘cross-over’ phenomenon with decreasing incidence of non-IgA MesGN and increasing incidence of IgA nephropathy, suggesting increasingly complete evaluation by IHC [3].

Fourth, the lack of financial resources makes the application of expensive tools such as immunoflourscence (IF) and electron microscopy (EM) on all biopsies difficult.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14], [Table 15]



 

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