Sequential Bone Scintigraphy and the Evolution of Warfarin-Mediated Calcific Uremic Arteriolopathy.

Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a complex syndrome of deranged mineral metabolism and vascular calcification leading to tissue ischemia that primarily occurs in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). We report a case illustrating a temporal relationship between long-term warfarin anticoagulation and development of CUA in a patient with pre-dialysis chronic kidney disease (CKD) who progressed to ESRD. Serial 99mTc-methylene diphosphonate bone scintigraphy documented the evolution of metastatic CUA over a 5-month period following HD initiation. Given the temporality demonstrated here via imaging, we speculate that warfarin's influence on vitamin K-dependent matrix Gla protein function coupled with risk factors associated with ESRD led to the development of metastatic CUA.

Clinical characteristics and risk factors associated with mortality in calcific uremic arteriolopathy.

BACKGROUND: Calcific uremic arteriolopathy (CUA) is an often-fatal condition in dialysis patients. The clinical descriptions and treatments of CUA patients have been confined mostly to case reports. We report a comprehensive characterization of CUA and its associated diagnosis, treatment patterns, and outcome. METHODS: An internet-based registry collected information about CUA in dialysis patients. Univariate analysis using Cox proportional hazards models estimated hazard ratios of the association between clinical characteristics, laboratory values, and treatments with all-cause mortality. RESULTS: A total of 117 CUA patients had adequate information for analysis. The majority of patients (56.7%) were diagnosed clinically, with only 32.5% biopsied. Debridement was undertaken in 42.6% of cases. Intravenous sodium thiosulfate (STS) was initiated in 54.7% of patients; most received ≥ 12.5 g of STS (98.3%) for < 3 months (79.7%). Mean parathyroid hormone (PTH) and phosphorus (P) were 459 ± 492 pg/mL and 6.3 ± 2.1 mg/dL, respectively. A total of 24 patients (21.6%, of 111 with information) died, with a median survival time of 2.9 months. In univariate analysis, higher mortality was observed in patients with cardiovascular disease (CVD; HR = 10.47; 95% CI 1.40-78.38), those taking warfarin at time of diagnosis (HR = 2.74; 95% CI 1.16-6.51), and those who had both diabetes (DM) and CVD and who were taking warfarin (HR = 13.41; 95% CI 1.66-109.29). CONCLUSIONS: In real-world clinical practice, there is substantial variability in the diagnosis and treatment of CUA. There is usually only modest derangement of bone and mineral parameters at the time of diagnosis. Death is common. The presence of CVD and use of warfarin may influence clinical outcome after diagnosis of CUA.

Elevated FGF23 levels are associated with impaired calcium-mediated suppression of PTH in ESRD.

CONTEXT: The positive association of elevated fibroblast growth factor-23 (FGF23) with PTH levels in the setting of secondary hyperparathyroidism is paradoxical to the purported effects of FGF23 to suppress PTH secretion. OBJECTIVE: We used dynamic calcium-mediated suppression of PTH levels in hemodialysis (HD) patients to determine the relationship between FGF23 levels and parathyroid gland function. DESIGN: HD patients with elevated PTH were washed out of vitamin D analogs and/or calcimimetics and then exposed them to a high-calcium dialysate bath designed to suppress PTH. SETTING: The study was conducted at an outpatient HD unit of an academic medical center. PARTICIPANTS: Eighteen maintenance HD patients with elevated PTH levels participated in the study. MAIN OUTCOME MEASURES: Ionized calcium (iCa), PTH, and FGF23 levels were measured during HD. The slope of the relationship between iCa and PTH (a marker of parathyroid gland mass) and the iCa level required for a 50% reduction in PTH were determined, and the association of these with FGF23 levels was determined. RESULTS: Increased baseline log FGF23 levels were associated with putative alterations in gland mass as estimated by significantly shallower slopes of the iCa/PTH suppression curves (P = 0.0004), but there was no association between FGF23 and calcium sensing as measured by ionized Ca associated with a 50% suppression of PTH (P = 0.38). FGF23 levels decreased significantly during HD, but this change was not correlated with decrements in either renal phosphate or PTH. CONCLUSIONS: High FGF23 levels may be a marker for parathyroid gland hyperplasia in HD patients. Acute reductions in neither PTH nor renal phosphate during dialysis correlated with PTH suppression.

Resolution of SLE-related soft-tissue calcification following haematopoietic stem cell transplantation.

BACKGROUND: Calciphylaxis and calcinosis can both cause severe morbidity and mortality in patients with systemic lupus erythematosus (SLE). Haematopoietic stem cell transplantation (HSCT) has been successfully used to treat patients with refractory SLE. It was hypothesized that in calciphylaxis and calcinosis, ongoing inflammatory activity contributes to the calcium deposition in the media of small arteries, as well as perivascular and periarticular tissues. We report three patients whose soft-tissue calcification syndromes dramatically resolved after undergoing HSCT. METHODS: Three patients referred for refractory SLE underwent HSCT at a tertiary care medical center. SLE serologies and clinical features before and after HSCT were recorded. RESULTS: Despite receiving >6 months of intravenous cyclophosphamide (CYC), three SLE patients showed signs of persistent lupus activity, including severe soft-tissue calcification. The first patient was on haemodialysis and developed severe calciphylaxis with large ulcers and tissue necrosis. The second patient had calcinosis, with palpable crystals extruding from ulcers. The third patient had calcinosis characterized by subcutaneous nodules and plaques. Because prior conventional therapies had failed, the three were treated with high-dose CYC, anti-thymocyte globulin and HSCT. They have been followed post-HSCT for 26-38 months, with excellent clinical responses, including sustained resolution of skin abnormalities. CONCLUSIONS: The successful treatment of advanced calcium deposition by aggressive immune ablation underscores the contribution of SLE-mediated inflammation to soft-tissue calcification syndromes.