Peter E. Gower

Serum amyloid P component in chronic renal failure and dialysis

A normal reference interval for serum amyloid P component (SAP) concentration in the serum was established in 500 healthy adult individuals (274 women, 226 men), by electroimmunoassay calibrated with standards of highly purified, isolated SAP. The mass of SAP in these was determined from the extinction coefficient of SAP at 280 nm measured here precisely for the first time by spectrophotometry and cryogenic drying. The mean (SD, range) SAP concentration was significantly lower in women: 24 mg/l (8, 8-55), compared to 32 mg/l (7, 12-50) in men (P less than 0.001). In renal insufficiency patients, 38 with chronic renal failure, 79 on hemodialysis and 66 on continuous ambulatory peritoneal dialysis, the mean values for SAP concentration were all significantly higher than normal (range of means, 39-59 mg/l in men and 35-42 mg/l in women), but did not correlate with serum creatinine, duration of dialysis or the presence of an acute phase response. The metabolism of SAP is thus altered in renal failure and is not normalized by dialysis, but it is not clear whether this is relevant to the pathogenesis of dialysis related arthropathy and amyloidosis.

Clearance of beta-2-microglobulin using continuous ambulatory peritoneal dialysis.

In the 9 continuous ambulatory peritoneal dialysis (CAPD) patients studied, the mean clearance of beta 2-microglobulin was significantly higher using hypertonic as opposed to isotonic exchanges (1 ml/min and 0.75 ml/min, respectively). Clearance of beta 2-microglobulin correlated with the clearance of albumin. The daily mass transfer of beta 2-microglobulin ranged from 19 to 62 mg. Although all the daily production of beta 2-microglobulin is not eliminated in patients on CAPD their serum beta 2-microglobulin levels would be expected to be lower than in patients on haemodialysis. Long-term prospective studies are needed to determine whether lower serum beta 2-microglobulin levels lead to a lower incidence of dialysis amyloid.

CAPD, Protective against Developing Dialysis-Associated Amyloid?

Dr. Dinesh Sethi, MB, Department of Medicine, Charing Cross and Westminster Medical School, GB-London W 6 8RF (UK) Dear Sir, Recent reports suggest that raised levels of ß2-micro-globulin (ß2M) in long-term haemodialysis patients lead to the deposition of dialysis-associated amyloid (DAA) [1]. Amyloid derived from this precursor molecule is of importance because of its implication in the development of dialysis arthropathy, recurrent carpal tunnel syndrome and bone amyloidosis [2, 3]. However, the question as to whether patients on continuous ambulatory peritoneal dialysis (CAPD) have an equal predisposition to developing DAA remains unanswered. Although there have been reports which suggest that elevated levels of ß2M in CAPD patients may predispose them to developing DAA [4], histological confirmation of this has not yet been published. In this letter we present results which suggest that CAPD may be protective against this form of amyloidosis. Between March 1986 and January 1987, 6 patients on maintenance haemodialysis using cuprophane membranes have changed to CAPD because of problems with vascular access. Their mean length of time on haemodialysis was 6 years (range 1.5–13). Samples for ß2M were taken whilst they were on haemodialysis and then after they had been established on CAPD for a mean of 3 months. Samples were taken before dialysis whilst patients were undergoing haemodialysis. Laboratory measurement was with the Pharmacia ß2M radioimmunoas-say kit. There was a significant difference in ß2M concentration between the two treatment modalities (p < 0.02, paired t test) and all 6 patients demonstrated a lowering in the concentration of ß2M. The mean ( ± SD) ß2M level in the patients whilst on haemodialysis was 59.4+17.2 mg/l, and after changing to CAPD, 35.5 ± 4.5 mg/l (normal range 1–3 mg/l). These results demonstrate a significant lowering in ß2M concentration during treatment with CAPD in patients who have previously been on maintenance haemodialysis. This suggests that CAPD is less likely to result in elevation of serum ß2M levels. It has been shown that the in vitro formation of amyloid fibrils from intact ß2M is dependent upon increasing the concentration of ß2M [5]. If a comparable process can occur in vivo then amyloi-dogenesis in dialysis patients would be dependent upon exceeding a threshold concentration of ß2M. Should this be the case then CAPD patients would be less likely to develop DAA. This assertion is supported by the fact that there have been no reports in the literature of the development of DAA in CAPD patients [6]. 2 of these 6 patients also had dialysis arthropathy at rheumatological assessment. On conversion to CAPD they both showed a significant improvement in severity of pain and range of movement of affected joints. The possible relationship between a fall in ß2M level and relief of shoulder

Technetium-99-Labelled Methylene Diphosphonate Uptake Scans in Patients with Dialysis Arthropathy

Patients on long-term haemodialysis suffer from dialysis arthropathy due to the deposition of dialysis amyloid. We investigated the use of 99Tc-labelled methylene diphosphonate bone scans in 17 patients as a possible in vivo diagnostic technique. In most clinically affected joints, with the exception of shoulders and hands, there was increased radioisotope uptake consistent with uptake by periarticular bone. In addition, we describe intense soft-tissue uptake around some clinically affected large joints. In contrast, control groups of patients on haemodialysis without arthropathy and patients without renal failure did not have increased uptake. A semi-quantitative scale of uptake was devised, and the following correlations were significant: pain perception and isotope uptake score in the ankles and feet, and the number of radiological lesions and isotope uptake scores in the wrists and knees. The following sites where the radioisotope might bind in the affected joints are proposed: amyloid deposits, areas of soft-tissue calcification, or areas of increased bone turnover. It is concluded that whereas the scanning technique cannot make a definite diagnosis of amyloid and, therefore, cannot be expected to supersede histological diagnosis, it is a useful adjuvant investigation, of particular importance in those patients unable or unwilling to undergo biopsy.