A 52-year-old man was admitted to the hospital with severe dyspnea. He had a history of mild chronic obstructive pulmonary disease, tertiary hyperparathyroidism, type II diabetes mellitus, and end-stage renal disease treated with hemodialysis for 4 years. He had stopped a 12-year habit of smoking 10 cigarettes per day 8 years previously. A living unrelated renal transplantation was performed 8 months before admission. It was complicated by massive intraoperative hemorrhage and required transfusion of approximately 40 U of packed red cells, and prolonged ventilatory and inotropic support. A thrombectomy to salvage a thrombosed arteriovenous fistula resulted in a large pulmonary embolus and cardiac arrest. He remained dialysis dependent throughout. Exertional dyspnea developed soon after discharge and 6 months before admission to our hospital. A chest radiograph and subsequent high-definition computed tomography scan of the thorax revealed focal calcification in the apices of both lungs. Laboratory data revealed a serum parathyroid hormone of 3373.33 pg/mL, phosphate of 5.14 mg/dL, and calcium of 10.56 mg/dL. Pulmonary function tests (PFTs) disclosed severe restrictive lung disease in association with severe reduction in oxygen diffusion capacity (Fig. 1). A transthoracic echocardiogram showed normal left ventricular systolic function. Nuclear bone scanning with single-photon emission computed tomography revealed advanced metabolic bone disease and large foci of uptake within the apices of both lungs. His dyspnea progressed despite therapy with home oxygen, corticosteroids, bronchodilators, and increased ultrafiltration at hemodialysis. He was admitted when rest-dyspnea ensued. He could speak in only one- or two-word sentences and was bed bound.FIGURE 1: Serial pulmonary function test results. STS, sodium thiosulfate; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; TLC, total lung capacity; DsbHb, diffusing capacity of the lung for carbon monoxide. The red line indicates the time when the patient was admitted to the hospital.Sodium thiosulfate (STS) 1250 mg administered intravenously after each thrice-weekly hemodialysis treatment was administered on admission. After 2 weeks, this was changed to STS 600 mg orally two times daily. Oral prednisone, cinacalcet, and lanthanum carbonate were continued. He began to notice improvement in his breathing and ability to weight-bear after 2 weeks. He then sustained a nontraumatic intratrochanteric fracture and required cemented bipolar hemiarthroplasty repair under spinal anesthesia. Two weeks later, he had a nontraumatic fracture of his contralateral intratronchanter and again required operative repair. STS was held when his fracture risk on bone scanning was found to be extreme (hip T score, –3.9; lumbar spine T score, –4.9), and resumed after a parathyroidectomy approximately 3 months later. One year later, he walked 252 m and maintained oxygen saturations of 97% during a 6-min walk test. Serial PFT results are shown in Figure 1. A follow-up computed tomography scan did not show evidence for radiographic improvement in the pulmonary calcification or nodules. Metastatic pulmonary calcification (MPC) occurs in 60% to 80% of patients receiving chronic hemodialysis and is usually asymptomatic being diagnosed incidentally on thoracic computed tomography or postmortem analysis (1). Occasionally, pulmonary calcification is associated with pulmonary restriction, respiratory failure, and death (1, 2). Risk factors for fulminant MPC-associated respiratory failure include recent renal transplantation (whether successful or not), corticosteroid use, elevated serum calcium and phosphate concentrations, and hyperparathyroidism (1–6). Outside of supportive care and attempts to improve these metabolic aberrations, there is no treatment currently available for respiratory failure in the setting of MPC. Pulmonary calciphylaxis is an exceedingly rare condition that is also characterized by abnormal alveolar septal wall deposits of calcium. It differs from MPC in that the deposits have been described as unstable, softer, and associated with diffuse infarcts (1–4). To our knowledge, all described cases were fatal. Our patient’s MPC-associated respiratory failure improved rapidly after administration of STS. STS is currently approved for the treatment of cyanide poisoning and to prophylax against cisplatin nephropathy. It is also increasingly used to treat patients with calcific uremic arteriolopathy (calciphylaxis), where it purportedly solubilizes tissue-bound calcium salts, scavenges local free oxygen radicals, and causes vasodilation by enhancing local nitric oxide formation (7, 8). We hypothesize that the use of STS solubilized unstable calcium deposits in the alveolar septal walls of our patient, leading to the improvement in lung compliance and volumes seen. The decline in PFT values when STS was held and the improvement when it was resumed support this (Fig. 1). However, without a lung biopsy, we are unable to comment on whether pulmonary calciphylaxis was present. Given its dismal prognosis, we propose to consider the use of STS in patients with MPC who develop otherwise unexplained progressive respiratory failure. Megan Christie 1 Janet Roscoe1,2 Jung Chee2 Miriam Inparajah2 Ted Vaughn-Neil2 Gordon Nagai1,2 Paul Ng1,2 Jason Fung1,2 Robert Ting1,2 Paul Tam1,2 Tabo Sikaneta1,2 1 Nephrology Associates, Scarborough Ontario, Canada 2 The Scarborough Hospital, Scarborough Ontario, Canada
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Jul 9, 2024
Shigenori Yamamoto + 14
Open Access
