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Saudi Journal of Kidney Diseases and Transplantation
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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

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Date of Web Publication10-Apr-2018


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


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.


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.

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

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Table 2: Evolution of renal impairment in patients with renal amyloidosis.

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

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

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   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

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Correspondence Address:
Dr. Meriam Hajji
Department of Medicine A, Charles Nicolle Hospital, Tunis
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.229291

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  [Figure 1]

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

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