Scintigraphy for Abeta2m with 111In-labeled rhbeta2m provides a homogenous and safe recombinant protein source and leads to enhanced sensitivity and lower radiation exposure.

beta2-Microglobulin-derived amyloidosis (Abeta2m) represents a major cause or morbidity in patients with end-stage renal disease. Symptoms of Abeta2m amyloid are mainly related to (peri-) articular amyloid deposition. Conventional non-invasive diagnostic techniques, i.e. clinical evaluation, joint ultrasonography or X-ray, computed tomography or magnetic resonance imaging findings, as well as conventional bone scans, suffer from relative non-specificity and/or low sensitivity. Two recent methods, namely scintigraphy with radiolabelled serum amyloid P component (SAP) or with the radiolabelled Abeta2m-precursor protein, beta2-microglobulin (beta2m), yield more specific information. Using (123)I-labelled SAP, Abeta2m deposits have been visualized in several long-term haemodialysis (HD) patients. However, this scan did not show tracer accumulation in other frequently involved sites, such as hips or shoulders, but did frequently label the spleen, which is usually spared from Abeta2m deposits. Scanning with (131)I-labelled beta2m, in contrast, yielded tracer accumulations corresponding to the typical distribution pattern of Abeta2m. Specificity of this method was shown by several methods, and the sensitivity was found to markedly exceed that of combined clinical and radiological investigations. Recently, both the radiation exposure and the optical resolution of this latter scan have been further refined by substituting (131)I with (111)In. In a final step we generated recombinant human beta2m (rhbeta2m). (111)In-rhbeta2m again failed to show significant tracer accumulation over joint regions in patients on short-term HD without evidence of Abeta2m amyloidosis. In contrast, local tracer accumulations similar to those observed with natural, (111)In-labelled beta2m could be demonstrated in long-term HD patients with evidence of Abeta2m amyloidosis. In conclusion, scintigraphy for Abeta2m with (111)In-labelled rhbeta2m provides a homogenous and safe recombinant protein source, and allows for the sensitive and specific non-invasive detection of Abeta2m-amyloid deposits in dialysis patients.

Abstract. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Its concentration is elevated in patients with end-stage renal disease (ESRD), in part because it is excreted via the kidneys. In this study, the plasma concentrations of ADMA, symmetric dimethylarginine, and L-arginine were determined in relation to plasma nitrate levels (as an index of NO formation) for a group of 80 patients with ESRD. The effects of two treatment methods, i.e., hemodialysis (HD) and peritoneal dialysis (PD), and the role of the presence of atherosclerotic disease were evaluated. Forty-three patients receiving HD and 37 patients receiving PD were compared with healthy control subjects. Plasma L-arginine and dimethylarginine levels were determined by HPLC, using precolumn derivatization with o-phthaldialdehyde. Plasma nitrate levels were determined by gas chromatography-mass spectrometry. Predialysis ADMA concentrations in HD-treated patients were approximately sixfold higher than those in the control group (6.0 ± 0.5 versus 1.0 ± 0.1 μmol/L; P < 0.05). Plasma nitrate concentrations were significantly lower in HD-treated patients, which suggests that ADMA may inhibit NO synthase. In contrast, plasma ADMA levels and nitrate concentrations in PD-treated patients were similar to those in control subjects. Plasma L-arginine concentrations were not significantly decreased in patients with ESRD. ADMA concentrations were significantly decreased 5 h after HD, compared with baseline values. ADMA levels were significantly higher in HD-treated patients with manifest atherosclerotic disease than in HD-treated patients without atherosclerotic disease (7.31 ± 0.70 versus 3.95 ± 0.52 μmol/L; P < 0.05). This study confirms that ADMA is accumulated in ESRD. PD-treated patients exhibit significantly lower ADMA levels than do HD-treated patients. Accumulation of ADMA may be a risk factor for the development of endothelial dysfunction and cardiovascular disease in patients with ESRD.

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