Original Paper
Nephron 1992:61:187-191
Kazan Ota“ a Kidney Center, Tokyo Women's Medical College; b Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Key Words Hyaluronic acid Hemodialysis Amyloid-associated osteoarthropathy
Relationship between Plasma Levels of Hyaluronic Acid and Amyloid-Associated Osteoarthropathy in Chronic Hemodialysis Patients
Abstract Plasma levels of hyaluronic acid (HA) and acute-phase reactants were determined in chronic hemodialysis patients with or without carpal tunnel syndrome (CTS) an d /o r shoulder pain, which are characteristic symptoms of amyloid-as sociated osteoarthropathy. While levels of acute-phase reactants tended to be higher in the patients with CTS a n d /o r shoulder pain than in patients without these symptoms, the difference was not significant. However, plasma levels of HA were significantly higher in the patients with these symptoms. Analysis of plasma levels of HA in age-matched patients also demonstrated a significant correlation between elevated levels of HA and the presence of CTS and/or shoulder pain. Among the patients with CTS and/or shoulder pain, those patients with bone cysts in the carpal bone or humeral head had significantly higher plasma levels of HA than patients without bone cysts. Thus, there appears to be a relationship between elevated plasma HA and amyloid-associated osteoarthropathy in chronic hemodialysis patients that is more specific than any correlation with levels of acute-phase reactants.
Introduction Amyloid-associated osteoarthropathy is a new entity that develops in patients on long-term hemodialysis [1]. Characteristic symptoms of the amyloidosis are carpal tun nel syndrome (CTS), shoulder pain and cystic bone lesions [2] CTS is due to proliferative synovitis and amyloid depos its located in the synovium of the finger flexor tendon and carpal ligaments. Recently, it has been suggested that the
Accepted : September 3.1991
formation of cystic bone lesions is triggered by inflamma tion in the synovium [3]. It is noteworthy, in this context, that patients with rheu matoid arthritis (RA) have elevated levels of hyaluronic acid (HA) in their serum and synovial fluid [4]. Such elevat ed levels of HA in the serum of patients with RA may be associated with some aspects of the state of the hypermetaboiic and/or inflamed synovium that is mediated by in flammatory agents.
Hisashi Ozasa. MO Kidney Center, Tokyo Women’s Medical College Kawada-cho 8-1, Shinjuku-ku Tokyo 162(Japan)
© I992S. Kargcr AG, Basel 0028-2766/92/ 06I2-OI87S2.75/0
Downloaded by: King's College London 137.73.144.138 - 1/21/2019 1:48:22 AM
Hisashi Ozasaa Kenji Chichibuh Yo Tanakah Takashi Kondob Kumiko Kitajima*
Fig. 1. Relationships between CTS and/ or shoulder pain and plasma levels of HA and acute-phase reactants. + = Chronic hemodi alysis patients with CTS a n d /o r shoulder pain; - = chronic hemodialysis patients without CTS and/or shoulder pain; a r AT = ai-antitrypsin; a 2-MG = a:-macroglobulin; a r AG = ai-acid glycoprotein. Hatched areas show normal ranges.
Studying chronic hemodialysis patients, we have at tempted to determine whether a useful correlation exists between plasma levels of HA and amyloid-associated osteoarthropathy. Such a correlation might provide us with a tool for the objective evaluation of this disorder.
Results
Plasma (EDTA, 1 mg/ml) before hemodialysis was obtained from 76 patients (36 males, 40 females), aged 27-85 years (mean 50.7), who had been treated by intermittent hemodialysis for 1-17 years (mean 11.2). None of these patients had liver disease, cancer, RA or other clinical evidence of inflammatory processes, and all were virtually anuric. Determination of levels of HA was performed by a sandwich protein-binding assay [5]. Levels of acute-phase reactants ( a r antitrypsin, n:-macroglobulin and ci|-acid glycoprotein) were measured by a commercially available nephelometric method [6]. Clinical symptoms of amyloid osteoarthropathy are diagnosed as follows [2, 7, 8]. CTS is diagnosed by swelling and/or stiffness of the hand, tingling and burning sensations, discomfort, and occasionally by loss of sensation from the palmar surface of the thumb, index and middle fingers and the radial aspect of the thumb, with atrophy of the thenar eminence. Shoulder pain includes scapulohumeral pain which occurs at night and during dialysis and may ultimately cause progres sive restriction of joint mobility. These pains often bring about morn ing stiffness and painful nocturnal awakening. Bone cysts of the carpal
Plasma Levels o f HA and Acute-Phase Reactants in Hemodialysis Patients with or without CTS a n d /o r Shoulder Pain
As shown in figure 1, levels of a r antitrypsin, «2-macroglobulin and a r acid glycoprotein, which are nonspecific markers of inflammation, tended to be higher in the patients with CTS and/or shoulder pain than in those without symptoms, but the difference was not significant. However, plasma levels of HA were significantly higher in the patients with those symptoms. S ex Difference
Plasma levels of HA were 261 ±167.3 ng/ml for male patients (n = 36) and 328.5 ±461.3 ng/ml for female pa tients (n = 40). The difference between the sexes was not significant.
O zasa/Chichibu/Tanaka/ Rondo/ Ritajima/Ota
Plasma HA and Amyloid-Associated Osteoarthropathy
Downloaded by: King's College London 137.73.144.138 - 1/21/2019 1:48:22 AM
Material and Methods
188
bone and humeral head are visualized as cystic radiolucencies of at least 5 mm in diameter in roentgenograms. Student’s t test for non-paired observations was used for statistical analysis. Correlation coefficients were obtained by linear regression analysis.
Fig. 2. Age and plasma levels of HA in chronic hemodial ysis patients (n = 76). 0 = Patients with CTS an d /o r shoul der pain.
Analysis o f Plasma Levels o f HA in Age-Matched Patients
Plasma levels of HA are correlated to a slight extent with age, not only in normal controls [9] but also in uremic patients [10]. To take into account any factors due to differ ences in age between the patients with or without CTS and/or shoulder pain, we performed an analysis of plasma levels of HA in age-matched, chronic hemodialysis pa tients. Plasma levels of HA showed a slight but significant correlation (r=0.338, p
Nephron 1992:61:187-191
Kazan Ota“ a Kidney Center, Tokyo Women's Medical College; b Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Key Words Hyaluronic acid Hemodialysis Amyloid-associated osteoarthropathy
Relationship between Plasma Levels of Hyaluronic Acid and Amyloid-Associated Osteoarthropathy in Chronic Hemodialysis Patients
Abstract Plasma levels of hyaluronic acid (HA) and acute-phase reactants were determined in chronic hemodialysis patients with or without carpal tunnel syndrome (CTS) an d /o r shoulder pain, which are characteristic symptoms of amyloid-as sociated osteoarthropathy. While levels of acute-phase reactants tended to be higher in the patients with CTS a n d /o r shoulder pain than in patients without these symptoms, the difference was not significant. However, plasma levels of HA were significantly higher in the patients with these symptoms. Analysis of plasma levels of HA in age-matched patients also demonstrated a significant correlation between elevated levels of HA and the presence of CTS and/or shoulder pain. Among the patients with CTS and/or shoulder pain, those patients with bone cysts in the carpal bone or humeral head had significantly higher plasma levels of HA than patients without bone cysts. Thus, there appears to be a relationship between elevated plasma HA and amyloid-associated osteoarthropathy in chronic hemodialysis patients that is more specific than any correlation with levels of acute-phase reactants.
Introduction Amyloid-associated osteoarthropathy is a new entity that develops in patients on long-term hemodialysis [1]. Characteristic symptoms of the amyloidosis are carpal tun nel syndrome (CTS), shoulder pain and cystic bone lesions [2] CTS is due to proliferative synovitis and amyloid depos its located in the synovium of the finger flexor tendon and carpal ligaments. Recently, it has been suggested that the
Accepted : September 3.1991
formation of cystic bone lesions is triggered by inflamma tion in the synovium [3]. It is noteworthy, in this context, that patients with rheu matoid arthritis (RA) have elevated levels of hyaluronic acid (HA) in their serum and synovial fluid [4]. Such elevat ed levels of HA in the serum of patients with RA may be associated with some aspects of the state of the hypermetaboiic and/or inflamed synovium that is mediated by in flammatory agents.
Hisashi Ozasa. MO Kidney Center, Tokyo Women’s Medical College Kawada-cho 8-1, Shinjuku-ku Tokyo 162(Japan)
© I992S. Kargcr AG, Basel 0028-2766/92/ 06I2-OI87S2.75/0
Downloaded by: King's College London 137.73.144.138 - 1/21/2019 1:48:22 AM
Hisashi Ozasaa Kenji Chichibuh Yo Tanakah Takashi Kondob Kumiko Kitajima*
Fig. 1. Relationships between CTS and/ or shoulder pain and plasma levels of HA and acute-phase reactants. + = Chronic hemodi alysis patients with CTS a n d /o r shoulder pain; - = chronic hemodialysis patients without CTS and/or shoulder pain; a r AT = ai-antitrypsin; a 2-MG = a:-macroglobulin; a r AG = ai-acid glycoprotein. Hatched areas show normal ranges.
Studying chronic hemodialysis patients, we have at tempted to determine whether a useful correlation exists between plasma levels of HA and amyloid-associated osteoarthropathy. Such a correlation might provide us with a tool for the objective evaluation of this disorder.
Results
Plasma (EDTA, 1 mg/ml) before hemodialysis was obtained from 76 patients (36 males, 40 females), aged 27-85 years (mean 50.7), who had been treated by intermittent hemodialysis for 1-17 years (mean 11.2). None of these patients had liver disease, cancer, RA or other clinical evidence of inflammatory processes, and all were virtually anuric. Determination of levels of HA was performed by a sandwich protein-binding assay [5]. Levels of acute-phase reactants ( a r antitrypsin, n:-macroglobulin and ci|-acid glycoprotein) were measured by a commercially available nephelometric method [6]. Clinical symptoms of amyloid osteoarthropathy are diagnosed as follows [2, 7, 8]. CTS is diagnosed by swelling and/or stiffness of the hand, tingling and burning sensations, discomfort, and occasionally by loss of sensation from the palmar surface of the thumb, index and middle fingers and the radial aspect of the thumb, with atrophy of the thenar eminence. Shoulder pain includes scapulohumeral pain which occurs at night and during dialysis and may ultimately cause progres sive restriction of joint mobility. These pains often bring about morn ing stiffness and painful nocturnal awakening. Bone cysts of the carpal
Plasma Levels o f HA and Acute-Phase Reactants in Hemodialysis Patients with or without CTS a n d /o r Shoulder Pain
As shown in figure 1, levels of a r antitrypsin, «2-macroglobulin and a r acid glycoprotein, which are nonspecific markers of inflammation, tended to be higher in the patients with CTS and/or shoulder pain than in those without symptoms, but the difference was not significant. However, plasma levels of HA were significantly higher in the patients with those symptoms. S ex Difference
Plasma levels of HA were 261 ±167.3 ng/ml for male patients (n = 36) and 328.5 ±461.3 ng/ml for female pa tients (n = 40). The difference between the sexes was not significant.
O zasa/Chichibu/Tanaka/ Rondo/ Ritajima/Ota
Plasma HA and Amyloid-Associated Osteoarthropathy
Downloaded by: King's College London 137.73.144.138 - 1/21/2019 1:48:22 AM
Material and Methods
188
bone and humeral head are visualized as cystic radiolucencies of at least 5 mm in diameter in roentgenograms. Student’s t test for non-paired observations was used for statistical analysis. Correlation coefficients were obtained by linear regression analysis.
Fig. 2. Age and plasma levels of HA in chronic hemodial ysis patients (n = 76). 0 = Patients with CTS an d /o r shoul der pain.
Analysis o f Plasma Levels o f HA in Age-Matched Patients
Plasma levels of HA are correlated to a slight extent with age, not only in normal controls [9] but also in uremic patients [10]. To take into account any factors due to differ ences in age between the patients with or without CTS and/or shoulder pain, we performed an analysis of plasma levels of HA in age-matched, chronic hemodialysis pa tients. Plasma levels of HA showed a slight but significant correlation (r=0.338, p
