Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 143 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

Table of Contents   
BRIEF COMMUNICATION  
Year : 2018  |  Volume : 29  |  Issue : 2  |  Page : 386-391
Renal amyloidosis in ankylosing spondylitis: A monocentric study and review of literature


1 Department of Medicine A, Charles Nicolle Hospital; Laboratory of Renal Pathology - LR00S001, Charles Nicolle Hospital, Tunis, Tunisia
2 Department of Medicine A, Charles Nicolle Hospital, Tunis, Tunisia

Click here for correspondence address and email

Date of Web Publication10-Apr-2018
 

   Abstract 

Secondary renal amyloidosis (RA) is the most common type of renal involvement in ankylosing spondylitis (AS). We assessed the epidemiologic and clinico-biological profile of AS patients with RA, to analyze treatment modalities and prognostic aspects, and to determine predictive factors of RA during AS. This was a retrospective study including 13 cases of RA among 212 cases who presented with AS, during the period from 1978 to 2006. The median age of the patients at the time of diagnosing AS was 47 years (range: 19–67). There were 11 males and two females. RA onset was diagnosed after a mean follow-up of 144.6 months (range: 10–505) from the AS diagnosis. We noted erosive peripheral arthritis, lumbar stiffness with bamboo spine, and coxitis in 23.1%, 76.9%, and 30.8% of cases, respectively. Nephrotic syndrome was found in eight patients (61.5%). At the time of diagnosing RA, six patients had renal failure. Amyloid deposits were histologically proven by salivary gland biopsy in six cases (46.1%) and by renal biopsy in seven cases (53.8%). Four patients received a long-course treatment with colchicine but with a good outcome only in two cases. In our series, AS was more severe among patients with RA. Four predictive factors of RA were identified: smoking (P = 0.04), erosive peripheral arthritis (P = 0.002), bamboo spine (P = 0.001), and biologic indicators of inflammation (P = 0.0001). High erythrocyte sedimentation rate was identified as the only independent risk factor of RA during AS (P = 0.0001). Renal function as well as urinalysis should be monitored at regular intervals to detect early renal involvement during AS.

How to cite this article:
Barbouch S, Hajji M, Jaziri F, Aoudia R, Fellah E, Hedri H, Goucha R, Hamida FB, Taarit FB, Gorsane I, Abdallah TB. Renal amyloidosis in ankylosing spondylitis: A monocentric study and review of literature. Saudi J Kidney Dis Transpl 2018;29:386-91

How to cite this URL:
Barbouch S, Hajji M, Jaziri F, Aoudia R, Fellah E, Hedri H, Goucha R, Hamida FB, Taarit FB, Gorsane I, Abdallah TB. Renal amyloidosis in ankylosing spondylitis: A monocentric study and review of literature. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Nov 27];29:386-91. Available from: https://www.sjkdt.org/text.asp?2018/29/2/386/229291

   Introduction Top


Ankylosing spondylitis (AS) is a chronic, multisystemic inflammatory disease primarily involving the spine and the sacroiliac joints. Renal involvement is rare but often associated with a pejorative prognosis. Renal amyloidosis (RA) is the most common nephropathy complicating AS. Other nephropathies associated with RA include nonsteroidal anti-inflammatory drug nephropathy and glomerulonephritis such as IgA nephropathy, mesangioproliferative glomerulonephritis, membranous nephropathy, focal segmental glomerulosclerosis, and focal proliferative glomerulonephritis.[1] The purpose of this study was to highlight only secondary RA due to AS. Other forms of nephropathy were excluded. Thus, we conducted a retrospective study to evaluate the clinical course, treatment modalities as well as prognostic characteristics of AS associated with RA.


   Patients and Methods Top


Patients

In a retrospective case–control design, we reviewed the records of 13 patients with AS associated with RA from a total of 212 AS patients, in a single center, over a 20-year period (1986–2006). For each patient, we recorded clinical data, treatment modalities, and renal outcome. We included AS patients who fulfilled AMOR criteria.[2] We excluded patients with other forms of nephropathy secondary to AS. In all cases, amyloidosis was histologically proven.

Definitions

Glomerular filtration rate (GFR) was estimated by the formula of Modification of Diet in Renal Disease.[3] Renal failure was defined as estimated GFR (eGFR) <60 mL/min per 1.73 m2.[4] End-stage renal disease (ESRD) was defined as an eGFR <15 mL/min/m2 or the need to start dialysis.[4] Nephrotic syndrome was defined as proteinuria greater than 3 g in 24 h urine and serum albumin <30 g/L.[5]


   Statistical Analysis Top


The data on 13 patients with RA were analyzed. Prognostic analysis was performed using Statistical Package for the Social Sciences (SPSS) version 11.0 for Windows (SPSS Inc., Chicago, IL, USA). Chi-square test was used for categorical variables. Fisher's exact test was used for continuous variables. Univariate analysis using the Logrank test was used to investigate predictive factors of ESRD. P <0.05 was considered statistically significant. We used a logistic regression analysis to determine the independent risk factors for RA during AS.


   Results Top


Of 212 AS patients, there were 13 patients with RA. The prevalence of RA among AS patients was estimated at 6.1%. RA accounted for 40% of all nephropathies secondary to AS. The median patient age at diagnosis of AS was 47 years old (range: 19–67). There were 11 male and two female patients, with a male-to-female ratio of 5.5. RA diagnosis was made within a median duration of 144.6 months (range: 10–505) after the AS diagnosis. RA was revealed by edema in seven cases (53.8%) and renal failure in five cases (38.5%). Lumbar stiffness was noted in 10 patients (76.9%) and erosive arthritis in three patients (23.1%). Orthostatic hypotension was found in four patients (30.8%), whereas three patients presented initially with high blood pressure. Proteinuria was found in all patients. Microscopic hematuria was noted in seven cases, and it was associated with a renal stone passage (53.8%). Ten patients (76.9%) had bamboo spine radiologically. No further extra-articular signs of AS have been found, especially pulmonary or cardiovascular impairment. The mean proteinuria rate was at 5.7 ± 2.4 g/day. Eight patients had nephrotic syndrome (61.53%). Renal failure was noted in 10 cases (76.9%). The different stages of chronic kidney disease (CKD) at diagnosis of RA are illustrated in [Table 1]. Inflammatory biological syndrome (IBS) was noted in all cases. The mean erythrocyte sedimentation rate (ESR) was at 111.8 ± 32.7 mm and the mean C-reactive protein (CRP) rate (specified in 5 cases) was at 22.2 mg/L. Two patients had HLA typing, revealing HLA B27 (15.4%). Amyloid deposits were proven by salivary gland biopsy in six cases and by renal biopsy in seven cases. Optical microscopy showed glomerular and vascular amyloid deposits in all cases and tubular deposits in two cases [Figure 1]. Long-course treatment with col-chicine (1 mg/day) was initiated in four cases (30.8%) with a good tolerance. Nine patients had ESRD (69.2%), after a median follow-up of 20.9 months (range: 0–137). Among the three patients who had initially a normal renal function, only one developed chronic renal failure within 130 months, and then ESRD, seven months after. Fifty percent of patients initially with Stage 2 or 3 of CKD had ESRD and remained in the same stage after a median follow-up of 25.5 months (range: 19–32). We noted an improvement of proteinuria rate and in renal function in four cases after treatment with colchicine. The two remaining patients reached ESRD within 32 and 19 months of follow-up, respectively. [Table 2] shows the evolution of renal impairment in RA patients. Four predictive factors of RA were identified: smoking (P = 0.04), erosive peripheral arthritis (P = 0.002), bamboo spine (P = 0.001), and IBS (P = 0.0001). Hypergammaglobulinemia does not appear to be a predictive factor of RA in AS patients. On the other hand, high erythrocyte sedimentation rate was identified as the only independent risk factor of RA during AS (P = 0.0001) as shown in [Table 3]. The comparison of clinical and biological data between the two groups of AS patients with and without amyloidosis was summarized in [Table 4].
Table 1: Renal function at the time of the diagnosis of renal amyloidosis.

Click here to view
Figure 1: Glomerular accumulation of amyloidal deposits (Coloration of Trichrome de Masson ×250).

Click here to view
Table 2: Evolution of renal impairment in patients with renal amyloidosis.

Click here to view
Table 3: Comparison of the clinical and biological characteristics between the groups: AS with and without renal amyloidosis.

Click here to view
Table 4: Comparison of clinical and biological data between the two groups of AS patients with and without amyloidosis.

Click here to view



   Discussion Top


Epidemiological data about RA during AS are very limited. The incidence of amyloidosis AA complicating chronic inflammatory diseases has decreased in Eastern countries.[6],[7],[8] In Tunisia, there are no epidemiological studies on amyloidosis complicating AS. RA is considered as a systemic disease, with a renal and an extra-renal involvement.[9],[10] RA is the most frequent nephropathy observed with AS, with a prevalence that varies from 4%–8.6%.[11],[12] The prevalence of RA, in our series, was at 6.1%. RA complicates more the adult form of AS.[12] Four among our patients (30.8%) were 16 years old at the time of AS diagnosis. In the literature, RA occurs among patients who had severe AS, beginning with peripheral arthritis.[13],[14] However, in our study, no extra-articular signs of AS beside renal involvement have been found, especially pulmonary or cardiovascular impairment. Since our data were not prospective, this could be explained as one limitation of this retrospective study. It was also reported that RA complicates often old AS.[15],[16],[17] In our study, the onset of RA was noted after a mean duration of 14.4 ± 10 years after diagnosing AS. RA is often discovered tardily, with massive proteinuria (70% of cases) and kidney impairment (18% of cases).[18],[19],[20] Orthostatic hypotension, noted in four patients in our study, is due to a low vascular reactivity by the amyloidal deposits causing an arterial wall infiltration. However, a high blood pressure is not uncommon during RA.[19],[21] Among our patients, It was observed in three cases. Hematuria is rare in RA (5–10%); it can result from an infiltration of the excretory ways by the amyloidal deposits. However, during RA complicating AS, it is more frequent (40%).[13] In our series, it was explained by the presence of urinary lithiasis in seven cases. The incidence of renal failure during AS was estimated at 18%–38% of cases,[15],[22] and initial renal failure was reported in 40%–60% of cases.[15],[17] Our data revealed that initial renal failure among AS patients was not a rare complication (76.9%). This high prevalence of renal failure in our study could be explained by the delay in diagnosis but also could be related to a selection bias, as renal involvement was the most common reason for consultation in a nephrology unit. Because amyloidosis is first of all a histologic diagnosis, all of our patients had a tissue biopsy; amyloid deposits were proven by salivary gland biopsy in six cases and by renal biopsy in seven cases. Noninvasive biopsies allow amyloidosis diagnosis in 80%–85% of the cases.[23] The abdominal sub-cutaneous fat aspiration has sensitivity bet-ween 55% and 75% and specificity of 100% for amyloidosis diag-nosis.[23] However, we did not use this diagnostic method in our study. Gratacos et al[13] practiced systematic abdominal subcutaneous fat aspiration among 137 patients having AS for more than five years and found amyloid deposits in 10 patients (7%). Half of them developed RA after a mean follow-up of 5.4 years (2–10 years). When these techniques fail to provide a proof of amyloidosis, a renal biopsy is required.[24],[25] Amyloid deposits can be found in all renal structures, but glomerular and vascular deposits are most frequently involved,[26] as in our study. The immuno-histochemistry is now the best method to classify the various types of amyloidosis. Wright technique was used to type amyloidal deposits in our study. The treatment of RA is based mainly on the control of the inflammatory process, which reduces availability of amyloidal protein pre-cursor.[27] Colchicine was successfully used in patients with AA amyloidosis secondary to certain chronic inflammatory diseases including AS.[28],[29] Geffriaud et al studied six cases of RA secondary to AS, two among them were unsuccessfully treated with colchicine and progressed to ESRD;[19] while our findings suggest that colchicine was more effective, since two among four patients treated by colchicine had a good outcome. However, these two patients had initially a normal renal function. Hence, we can speculate that colchicine will be effective only if started early. Tumor necrosis factor (TNF)-a blockers have been reported to be effective in the treatment of both arthritis and amyloidosis. However, there have been few reports concerning the alterations of renal tissue histology before and after long-term TNF-α blockers’ therapy in secondary RA.[30],[31] It was reported a patient who achieved complete remission of nephrotic syndrome after 17 months of etanercept treatment.[32] The five-year survival of AS patients with RA was estimated to 30%.[33],[34] Lance et al[16] showed that risk factors of RA during AS were duration of AS follow-up (>14 years), early onset of AS (<18 years old), and the presence of severe articular and spinal involvement. High gamma globulin level was described as a predictive factor of RA among AS patients,[35] which was not the case in our study. Erosive peripheral arthritis was the only common risk factor of RA during AS between Gratacos et al's study[13] and ours.


   Conclusion Top


In rare cases, patients with severe longstanding AS develop significant extra-articular manifestations such as RA. It is generally revealed by a glomerular nephropathy. The diagnosis of amyloidosis has to be histologically proven. The treatment aims to stabilize the inflammatory process to improve the longterm prognosis. Until now, treatment modalities are not well codified.

Conflict of interest: None declared.

 
   References Top

1.
Strobel ES, Fritschka E. Renal diseases in ankylosing spondylitis: Review of the literature illustrated by case reports. Clin Rheumatol 1998;17:524-30.  Back to cited text no. 1
[PUBMED]    
2.
Amor B, Dougados M, Mijiyawa M. Criteria of the classification of spondylarthropathies. Rev Rhum Mal Osteoartic 1990;57:85-9.  Back to cited text no. 2
[PUBMED]    
3.
KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 2013;3:1-150.  Back to cited text no. 3
    
4.
Lamb EJ, Levey AS, Stevens PE. The kidney disease improving global outcomes (KDIGO) guideline update for chronic kidney disease: Evolution not revolution. Clin Chem 2013;59: 462-5.  Back to cited text no. 4
[PUBMED]    
5.
Gupta K, Iskandar SS, Daeihagh P, Ratliff HL, Bleyer AJ. Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin. Nephrol Dial Transplant 2008;23:1595-9.  Back to cited text no. 5
[PUBMED]    
6.
Hazenberg BP, Van Rijswijk MH. Clinical aspects of Amyloidosis. Grateau G, Benson MD, Delpech M.. Les Amyloses. Paris: Flammarion, 2000:377-427  Back to cited text no. 6
    
7.
Ben Maiz H, Abderrahim E, Ben Moussa F, Goucha R, Karoui C. Epidemiology of glomerular diseases in Tunisia from 1975 to 2005. Influence of changes in healthcare and society. Bull Acad Natl Med 2006;190:403-16.  Back to cited text no. 7
    
8.
Rodríguez-Muguruza S, Martínez-Morillo M, Holgado S, et al. Amyloidosis complicating spondyloarthropathies: Study of 15 cases. Med Clin (Barc) 2015;145:327-31.  Back to cited text no. 8
    
9.
Real de Asúa D, Costa R, Contreras MM, et al. Clinical characteristics of the patients with systemic amyloidosis in 2000-2010. Rev Clin Esp (Barc) 2013;213:186-93.  Back to cited text no. 9
    
10.
Mercieca C, van der Horst-Bruinsma IE, Borg AA. Pulmonary, renal and neurological comorbidities in patients with ankylosing spondylitis; implications for clinical practice. Curr Rheumatol Rep 2014;16:434.  Back to cited text no. 10
[PUBMED]    
11.
Villiaumey J, Lejeune E, Avouac B, Horreard P. Spondylarthrite ankylosante et amylose. Ann Med Interne 1978;129:67-71.  Back to cited text no. 11
    
12.
Cristoph R, Genth E, Hartl W. Incidence of amyloidosis in ankylosing spondylitis. Scand J Rheumatol 1975;8:39.  Back to cited text no. 12
    
13.
Gratacos J, Orellana C, Sanmarti R, et al. Secondary amyloidosis in ankylosing spondylitis. A systematic survey of 137 patients using abdominal fat aspiration. J Rheumatol 1997;24:912-5.  Back to cited text no. 13
[PUBMED]    
14.
Hajjaj-Hassouni N, Laghrissi S, Khalil A, et al. Ankylosing spondylitis and amyloidosis. Apropos of 2 cases. Rev Rhum 1982;49:687-91.  Back to cited text no. 14
[PUBMED]    
15.
Kovacsovics-Bankowski M, Zufferey P, So AK, Gerster JC. Secondary amyloidosis: A severe complication of ankylosing spondylitis. Two case-reports. Joint Bone Spine 2000;67:129-33.  Back to cited text no. 15
[PUBMED]    
16.
Lance NJ, Curran JJ. Amyloidosis in a case of ankylosing spondylitis with a review of the literature. J Rheumatol 1991;18:100-3.  Back to cited text no. 16
[PUBMED]    
17.
Etaouil N, Ben Yahya EO, Janani S, et al. Ankylosing spondylitis and amyloidosis. Apropos of 1 case. Ann Med Int 2002;153:543.  Back to cited text no. 17
    
18.
Hazenberg BP, van Rijswijk MH. Clinical and therapeutic aspects of AA amyloidosis. Baillieres Clin Rheumatol 1994;8:661-90.  Back to cited text no. 18
[PUBMED]    
19.
Geffriaud C, Noël LH, Blanche P, et al. Ankylosing spondylitis with type AA amyloiddosis 6 cases. Presse Med 1988;17:2344-7.  Back to cited text no. 19
    
20.
Dönmez S, Pamuk ÖN, Pamuk GE, Aydoğdu E, Inman R. Secondary amyloidosis in ankylosing spondylitis. Rheumatol Int 2013;33:1725-9.  Back to cited text no. 20
    
21.
Saba M, Tohmé A, Abadjian G, Haddad F, Ghayad E. Multisystemic amyloidosis. Clinical study of 39 patients in Lebanon. Presse Med 2005;34:640-6.  Back to cited text no. 21
    
22.
Hachulla E, Janin A, Flipo RM, et al. Labial salivary gland biopsy is a reliable test for the diagnosis of primary and secondary amyloidosis. A prospective clinical and immunohistologic study in 59 patients. Arthritis Rheum 1993;36:691-7.  Back to cited text no. 22
[PUBMED]    
23.
Duston MA, Skinner M, Meenan RF, Cohen AS. Sensitivity, specificity, and predictive value of abdominal fat aspiration for the diagnosis of amyloidosis. Arthritis Rheum 1989;32:82-5.  Back to cited text no. 23
[PUBMED]    
24.
Hachulla E, Grateau G. Paraclinical means of diagnosis of amyloidosis. Rev Rhum 2002;69: 1172-80.  Back to cited text no. 24
    
25.
Gillmore JD, Hawkins PN, Pepys MB. Amyloidosis: A review of recent diagnostic and therapeutic developments. Br J Haematol 1997;99: 245-56.  Back to cited text no. 25
[PUBMED]    
26.
Westmark P. Diagnosing amyloidosis. Scand J Rheumatol 1995;24:327-9.  Back to cited text no. 26
    
27.
Pamuk ÖN, Kalyoncu U, Aksu K, et al. A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients. Rheumatol Int 2016;36:945-53.  Back to cited text no. 27
    
28.
Ravid M, Shapira J, Kedar I, Feigl D. Regression of amyloidosis secondary to granulomatous ileitis following surgical resection and colchicine administration. Acta Hepatogastroenterol (Stuttg) 1979;26:513-5.  Back to cited text no. 28
[PUBMED]    
29.
Fak AS, Ozener C, Akoglu E. Colchicine and secondary amyloidosis. Ann Intern Med 1992; 117:795-6.  Back to cited text no. 29
[PUBMED]    
30.
Drewe E, Huggins ML, Morgan AG, Cassidy MJ, Powell RJ. Treatment of renal amyloidosis with etanercept in tumour necrosis factor receptor-associated periodic syndrome. Rheumatology (Oxford) 2004;43:1405-8.  Back to cited text no. 30
[PUBMED]    
31.
Gottenberg JE, Merle-Vincent F, Bentaberry F, et al. Anti-tumor necrosis factor alpha therapy in fifteen patients with AA amyloidosis secondary to inflammatory arthritides: A followup report of tolerability and efficacy. Arthritis Rheum 2003; 48:2019-24.  Back to cited text no. 31
[PUBMED]    
32.
Lee YH, Kim EY, Jeong DW, et al. Complete remission of nephrotic syndrome without resolution of amyloid deposit after anti-tumor necrosis factor α therapy in a patient with ankylosing spondylitis. J Clin Rheumatol 2016;22:86-8.  Back to cited text no. 32
[PUBMED]    
33.
Joss N, McLaughlin K, Simpson K, Boulton- Jones JM. Presentation, survival and prognostic markers in AA amyloidosis. QJM 2000;93:535-42.  Back to cited text no. 33
    
34.
Immonen K, Finne P, Hakala M, et al. No improvement in survival of patients with amyloidosis associated with inflammatory rheumatic diseases-data from the Finnish national registry for kidney diseases. J Rheumatol 2008;35:1334-8.  Back to cited text no. 34
[PUBMED]    
35.
Lehtinen K. The mortality and causes of death of patients with “hypergamma type” of ankylosing spondylitis. Scand J Rheumatol 1983;12:3-4.  Back to cited text no. 35
[PUBMED]    

Top
Correspondence Address:
Dr. Meriam Hajji
Department of Medicine A, Charles Nicolle Hospital, Tunis
Tunisia
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.229291

Rights and Permissions


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

This article has been cited by
1 Pauci-immune necrotizing glomerulonephritis in a patient with ankylosing spondylitis
Beyhan Güvercin, Kubra Kaynar, Hasibe Bilge Gür, Sevdegül Mungan, Emre Selim, Muammer Cansiz, Sükrü Ulusoy
Nefrología. 2021;
[Pubmed] | [DOI]
2 The risk, predictors and outcomes of amyloidosis in ankylosing spondylitis: a longitudinal population-based cohort study
Mouhammad Kridin, Khalaf Kridin, Arnon D Cohen, Howard Amital, Abdulla Watad
Rheumatology. 2021;
[Pubmed] | [DOI]
3 Trends in amyloidosis in spondyloarthritis: results from the Spanish National Inpatient Registry over a 17-year period (1999–2015)—TREND-EspA study
Ramon Mazzucchelli, Raquel Almodovar-González, Elisa Dieguez-Costa, Natalia Crespí-Villarías, Elia Pérez-Fernández, Elena García-Zamora, Alberto Garcia Vadillo
RMD Open. 2021; 7(3): e001782
[Pubmed] | [DOI]
4 Clinical features of ankylosing spondylitis in patients with secondary AA amyloidosis
D. G. Rumyantseva, E. M. Agafonova, S. O. Krasnenko, A. S. Starkova, M. M. Urumova, Sh. Erdes
Modern Rheumatology Journal. 2020; 14(3): 45
[Pubmed] | [DOI]
5 Membranous nephropathy and thymoma in a patient with ankylosing spondylitis
Lirong Lin, Lei Zhao, Bengang Huo, Luquan Zheng, Rongjie Yu, Weibing Li, Jurong Yang
Medicine. 2020; 99(18): e20111
[Pubmed] | [DOI]
6 Renal amyloidosis in ankylosing spondylitis: A case report
Juan David Romero-Marín, Yeison Cantor, Esteban Prieto-Bravo, Reinaldo Sierra-Rosales, Adriana Flórez-Vargas, Miguel Antonio Mesa-Navas, Carlos Jaime Velásquez-Franco
Revista Colombiana de Reumatología. 2020; 27(1): 46
[Pubmed] | [DOI]
7 Renal amyloidosis in ankylosing spondylitis: A case report
Juan David Romero-Marín, Yeison Cantor, Esteban Prieto-Bravo, Reinaldo Sierra-Rosales, Adriana Flórez-Vargas, Miguel Antonio Mesa-Navas, Carlos Jaime Velásquez-Franco
Revista Colombiana de Reumatología (English Edition). 2020; 27(1): 46
[Pubmed] | [DOI]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
   Patients and Methods
   Statistical Analysis
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables
 

 Article Access Statistics
    Viewed6065    
    Printed38    
    Emailed0    
    PDF Downloaded463    
    Comments [Add]    
    Cited by others 7    

Recommend this journal