Dialysis-related amyloidosis.

Abstract

A 38-year-old male required the initiation of regular hemodialysis treatment 19 years ago because of end-stage renal disease due to mesangioproliferative glomerulonephritis. After an initial 3 months of center dialysis, during which an arteriovenous fistula was created in the left forearm, the patient was trained for home dialysis. At home, he was dialyzed overnight 3 x 10 hours/week at a blood flow of 250 mI/mm and a dialysate flow of 500 mi/mm using the Klll dialyzer with cellulosic membranes and a 1 m2 surface area; a given dialyzer was used three times before being rebuilt. After 5 years, reuse KiiI dialysis was replaced by single-use dialysis employing a 1 m2 commercial plate dialyzer with cellulosic membranes; dialysis time was reduced to 3 x 8 hours/week but blood and dialysate flow rates were unchanged. At that time the patient was totally anuric. His predialysis (first dialysis of the week) serum urea and creatinine concentrations with the new dialysis regime ranged from 2 1—25 mmol/ liter (120—150 mg/dl) and 1000—1100 mol/liter (11—12 mg/dl), respectively. The patient was unemployed but physically well; he refused to be placed on the walting list for cadaveric transplantation. Ten years after the start of hemodialysis, radiologic examination of the skeleton showed general osteoporosis without specific lesions attributable to renal osteodystrophy. The serum levels of C-terminal PTH were moderately elevated. The patient was normocalcemic and had intermittent mild hyperphosphatemia (< 6 mg/dl). Bone histology from an iliac crest biopsy revealed only slight osteitis fibrosa, as well as minor evidence of defective mineralization. The dose of oral phosphate binders and oral calcium carbonate was increased, and treatment with calcitriol (0.25 pg/day) was initiated. In the following years, clinical and neurophysiologic signs of carpaltunnel syndrome developed and increased in intensity; 13 years after the start of hemodialysis, bilateral carpal-tunnel release procedures were required for relief of symptoms. Light and electron microscopy examination of the excised tissue showed synovial amyloid deposits with positive immunoperoxidase staining for J2 microglobulin in the right carpal tunnel. Histologic search for amyloid in tissue obtained from the left carpal tunnel was negative. In both carpal tunnels, synovial collagen was massively increased. Skeletal radiography performed at the time of the operation showed small cystic lesions in both radial heads, a single cyst in the left navicular bone, several cystic trnnslucencies with a maximal diameter of 1.5 cm in both femoral heads, and one juxtaarticular cyst in the right os acetabulum. Subsequently, increasing pain and limitation of movement in both hip joints developed; 16 years after the start of hemodialysis, the patient could walk only with the help of crutches because of severe pain in the left hip. Radiography revealed fractures of both femoral necks (left side, complete; right side, incomplete) in areas of cystic transformation. Bilateral total hip replacement was performed. Histologic examination disclosed masses of $2 microglobulin-related amyloid within the synovia as well as in cystic bone lesions. In comparison with the histologic findings on an iliac crest biopsy obtained 6 years earlier, the extent of osteitis fibrosa had increased; staining for aluminum was negative. Postoperatively, the daily calcitriol dose was increased to 0.5 jig. Dialysis was performed with a 1.2 m2 polysulfone capillary membrane at a weekly dialysis prescription of 3 x 6 hours. The j32-microglobulin concentrations decreased from an average predialysis level of 45 mg/liter (during dialysis with the cellulosic membrane) to an average of 30 mg/liter. One year later, the patient developed hypercalcemia, which persisted after calcitriol therapy was stopped. At the same time, serum alkaline phosphatase activity started to rise and C-terminal PTH was found to be extremely high; subtotal parathyroidectomy was performed. During his 19th year of hemodialysis, the patient began to experience severe pain in the upper cervical vertebrae, which was induced by movements of the neck and which spread to both shoulders and upper arms. Radiography showed massive destruction of the arcus of the second cervical vertebra and cystic lesions of the third cervical vertebra (Fig, I). A nuclear magnetic resonance scan revealed nodular masses with reduced signal intensity overlying destroyed areas of the right lateral pnrts of the second and third cervical vertebrae (Fig. 2). These findings were interpreted as consistent with amyloid deposits. There was no indication of spinal cord compression. The risks of cord damage from neurosurgical intervention were unacceptable to the patient so that no operative procedure to stabilize the cervical vertebrae was performed. He was provided with an external stabilizing cravatte to prevent palnful and dangerous movements. Now in his 19th year after hemodialysis, the patient has expressed willingness to receive a renal transplant and has been placed on a wailing list for a cadaveric graft.