Hypokinetic azotemic osteodystrophy

Abstract

CASE PRESENTATION A 61-year-old male dialysis patient was referred from another center to the Bone and Mineral Research Unit of the Hospital Central de Asturias for evaluation. At age 24, renal tuberculosis had necessitated a left nephrectomy; at age 42 nephrolithiasis in the right kidney had prompted surgical intervention. Four years later, moderate renal failure presumably due to chronic interstitial nephritis was diagnosed; 7 years later, at age 53, he entered the dialysis program. He received treatment in a dialysis unit equipped with a reverse osmosis (RO) system for water treatment. Renal osteodystrophy had been present since the beginning of dialysis, and the thoracic and lumbar spine showed demineralization. During the first 5 years of hemodialysis, symptoms and radiologic signs of hyperparathyroidism, including multiple vascular calcifications, worsened. The serum calcium (Ca+) level progressively increased, reaching 10.5 mg/dl. The serum phosphorus (P) level was high, although the patient had received long-term treatment with aluminum hydroxide. During that period, parathyroid hormone (PTH) levels (carboxy terminal) had remained 40 to 50 times higher than the upper limit of normal. Total alkaline phosphatase measurements had stayed in the low-normal range. The patient needed frequent red cell transfusions to avoid symptoms of anemia. Five years after beginning dialysis, he had a non-traumatic radial fracture coincident with worsening of the radiologic signs and his symptoms. A subtotal parathyroidectomy was performed. During the 2 years after the subtotal parathyroidectomy, his symptoms mildly improved, and the carboxy terminal PTH level decreased, stabilizing in the upper limit of normal. Total alkaline phosphatase fell to lower than normal, and the serum P was kept at acceptable values by aluminum hydroxide and calcium carbonate. Oral calcitriol (1.5–3.5 μg/week) maintained serum Ca+ levels in the range of 10.0 mg/dl–10.5 mg/dl. Two years after the parathyroidectomy, bilateral carpal tunnel syndrome was detected and surgically relieved. Amyloid was detected in the surrounding fat tissue, serum beta-2 microglobulin was elevated; dialysis with highly permeable membranes (PAN) was prescribed. Three years after the parathyroidectomy, PTH levels, measured several times using a PTH intact assay, revealed very low values (from undetectable to 13.5 pg/ml) and total alkaline phosphatase had returned to pre-surgery values (in the low-normal range). Basal serum aluminum (Al) was 96 μg/liter, increasing to 234 μg/liter after the infusion of 40 mg/kg of deferoxamine. Because Al-induced bone disease was suspected, a bone biopsy with tetracycline labeling was performed. The main histologic and histomorphometric findings of the bone biopsy were reduction in trabecular bone volume (11%), a slight increase in relative osteoid surface (20%), a decrease in osteoid volume (1.3%), low osteoblast surface (0.12%), low osteoclast surface (0.59%), positive Al surface staining (aluminum 16%; solochrome of azurine, 47%), and negative iron (Fe) staining (Perls). Bone Al and Fe concentration, measured by atomic absorption spectrometry, were 28 μg/g and 405 μg/g, respectively (normal, 3 μg/g and 300 μg/g, respectively). The tetracycline study showed only a single and diffuse labeling. Aluminum-induced adynamic bone disease was diagnosed. After the bone biopsy, therapy with deferoxamine (40 mg/kg/week) was prescribed (18 months of intermittent treatment over 3 years). During deferoxamine therapy, repeated basal serum Al levels were 50–85 μg/liter; these values doubled after the deferoxamine tests performed during that period. At the end of deferoxamine treatment, the serum Al remained at the same level, but intact PTH and alkaline phosphatase levels progressively increased, reaching 150 pg/ml and 219 U/liter, respectively (normal, 10–65 pg/ml and 70–280 U/liter). Before and after the deferoxamine treatment, serum transferrin, serum Fe, and Fe-transferrin saturation were always in the normal range. Two years after the bone biopsy, when the patient was 62 years old, he suffered a fracture of the right femoral neck; one year later, he fractured the left femoral neck. Both were treated with standard surgical techniques. During the following 4 years, the patient was admitted to the hospital several times with diagnoses of diabetes mellitus type II, diverticulitis, ventricular tachycardia, and congestive cardiac failure. Also, severe vascular obstruction of the left leg necessitated amputation of the second toe of the left foot. During the last year (7 years after the bone biopsy), he has maintained a serum calcium ranging between 9.0–9.5 mg/dl; serum phosphorus, 4.7–6.5 mg/dl; serum aluminum, 73.0–90.8 μg/liter; normal serum iron parameters; intact PTH levels of 314–415 pg/ml; and an alkaline phosphatase of 125–139 U/liter.