Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study.

BACKGROUND: In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively. METHODS: In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias. RESULTS: Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 [75%]) than in those treated with FDI (1 out of 13 [8%]; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants. CONCLUSIONS: While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI. TRIAL REGISTRATION: Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).

Independent associations of vitamin D metabolites with anemia in patients referred to coronary angiography: the LURIC study.

PURPOSE: Anemia and vitamin D deficiency are both frequent in adult patients. Whether low vitamin D metabolite levels are an independent risk factor for different subtypes of anemia remains to be studied in detail. METHODS: In 3299 patients referred for coronary angiography, we investigated the association of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25(OH)2D] with anemia [hemoglobin (Hb) <12.5 g/dl] of specific subtypes. RESULTS: Compared with patients with 25OHD levels in the adequate range (50-125 nmol/l), patients with deficient 25OHD concentrations (<30 nmol/l; 33.6 % of patients) had 0.6 g/dl lower Hb levels. Hb values were 1.3 g/dl lower in patients with 1,25(OH)2D levels <40 pmol/l (5.4 % of patients), compared with patients in the highest 1,25(OH)2D category (>70 pmol/l). Of the participants, 16.7 % met the criteria for anemia. In multivariate-adjusted regression analyses, the odds ratios for anemia in the lowest 25OHD and 1,25(OH)2D categories were 1.52 (95 % CI 1.15-2.02) and 3.59 (95 % CI 2.33-5.52), compared with patients with 25OHD levels in the adequate range and patients with 1,25(OH)2D levels >70 pmol/l. The probability of anemia was highest in patients with combined 25OHD and 1,25(OH)2D deficiency [multivariable-adjusted odds ratio 5.11 (95 % CI 2.66-9.81)]. Patients with anemia of chronic kidney disease had the highest prevalence of 25OHD deficiency and 1,25(OH)2D concentrations of <40 pmol/l. CONCLUSIONS: Low 25OHD and 1,25(OH)2D concentrations are independently associated with anemia. Patients with poor kidney function are most affected. Interventional trials are warranted to prove whether administration of plain or activated vitamin D can prevent anemia.

[Calciphylaxis. A call for interdisciplinary cooperation]. / Kalziphylaxie. Eine nephrologisch-dermatologische Herausforderung.

Calciphylaxis is a rare, often very painful and potentially life-threatening disorder at the interface between nephrology and dermatology. It is characterized by skin lesions and ulcerations following calcification and occlusion of cutaneous arterioles. Most patients have chronic kidney disease or are on dialysis. A concert of various, still incompletely understood local and systemic risk factors is necessary to cause the development of calciphylaxis. Since randomized prospective trials are missing, interdisciplinary treatment is based on pathophysiological considerations as well as evidence derived from case reports or case series. Normalization of mineral metabolism, intensifying dialysis and avoidance of coumarins, as well as administration of calcimimetics, bisphosphonates and sodium thiosulfate and hyperbaric oxygen therapy are often used. Supportive measures include analgesics, antibiotics and local wound care. We have initiated an internet-based registry for patients with calciphylaxis in order to collect data for improved patient care (with support from Amgen) (www.calciphylaxie.de).

Review: update on the management of calciphylaxis.

Calciphylaxis is a disease of significant morbidity and mortality, predominantly affecting dialysis patients. The term 'calciphylaxis' was coined by Seyle et al. in 1961 to describe calcium deposition in the skin and subcutaneous soft tissue of uremic rats in response to 'triggers' (e.g. trauma, metallic salts) after exposure to 'sensitizing agents' (e.g. vitamin D and parathyroid hormone). In humans, calciphylaxis, however, is not a disorder of induced hypersensitivity. Instead, it is a disorder of cutaneous microvascular occlusion caused by thrombosis and calcification. Progressive, excruciatingly painful, non-healing wounds develop in these patients, pre-disposing them to high risk of sepsis and death. Calciphylaxis has no approved therapies. Increased awareness and research in this field have facilitated identification of risk factors and causation pathways. Development of therapeutic options and wound care management, however, are still at a nascent stage. Certain therapies have shown a promise that needs evaluation in prospective clinical trials. It is hoped that ongoing research will help us better understand the pathogenesis of this complex disease and develop efficacious treatment options. In this review, we outline the components involved in calciphylaxis diagnosis and treatment.

IgA nephropathy in a young man with primary hyperparathyroidism.

We report the first documented case of IgA nephropathy occurring after treatment of primary hyperparathyroidism. A 29-year-old man with a history of kidney stones and primary hyperparathyroidism underwent kidney biopsy for persistent proteinuria and microhematuria 18 months after resection of an ectopic parathyroid adenoma with subsequent normalization of serum calcium and parathyroid hormone levels. On ultrasound, renal intraparenchymal calcifications were noted. Renal biopsy revealed IgA nephropathy in addition to tubulointerstitial microcalcifications. The development of IgA nephropathy may have been influenced by hyperparathyroidism and/or its treatment. The case highlights the role of renal biopsy in patients with a history of kidney stones and abnormal urinary findings.

Color-coded duplex sonography study of arteriovenous fistulae and pseudoaneurysms complicating percutaneous renal allograft biopsy.

BACKGROUND: The exact incidence and clinical impact of arteriovenous fistulae (AVF) and pseudoaneurysms as complications emerging from renal allograft biopsy are not well established. We therefore conducted a prospective study using color-coded duplex sonography (CCDS) to determine the frequency, clinical presentation and spontaneous occlusion rate of biopsy-related AVF and pseudoaneurysms in kidney transplant recipients. METHODS: We investigated 72 consecutive patients undergoing renal allograft biopsy using an automated biopsy technique. CCDS was performed before, immediately after and up to more than 6 months after biopsy. The diagnosis of AVF was based on the presence of perivascular vibration artifacts and detection of typical Doppler curves. Pseudoaneurysms were diagnosed based on the presence of"to-and-fro" signals. RESULTS: In 5 patients (6.9%), an AVF was detectable before biopsy. Post-biopsy AVF were found in 12 additional patients (16.7%) with a spontaneous occlusion rate of 50% within 48 hours and 75% after 4 weeks. Three (25%) AVF persisted longer than 1 year. Four patients (5.6%) were found to have pseudoaneurysms. All pseudoaneurysms were located closely to AVF and closed spontaneously. None of the post-biopsy AVF and pseudoaneurysms required specific therapy. In 2 patients (2.8%), allograft biopsy lead to significant hemorrhage independent of AVF or pseudoaneurysms. CONCLUSION: These results indicate that post-biopsy AVF and pseudoaneurysms are a frequent finding after automated renal allograft biopsy. The natural history of these lesions shows a high rate of early occlusion. The present data fail to demonstrate significant clinical impact of AVF and pseudoaneurysms after renal allograft biopsy.

Urinary bone resorption markers (deoxypyridinoline and C-terminal telopeptide of type I collagen) in healthy persons, postmenopausal osteoporosis and patients with type I diabetes.

PURPOSE: Deoxypyridinoline (DPD) is a derivative of hydroxypyridinium, which is released during bone resorption into the blood stream and is eliminated unmodified with urine. A further collagen-derived marker of bone resorption is the C-terminal telopeptide of type I collagen (beta-CTX-I, here abbreviated as CTX), which is released in bone resorption and almost entirely excreted by the kidneys. The aim of our study was to investigate different well-described patient groups as well as normal probands in view of differences and expected correlations of these two parameters: patients with insulin-dependent diabetes mellitus, postmenopausal women with osteoporosis and healthy control persons. MATERIALS AND METHODS: We used a solid-phase chemiluminescence enzyme immunoassay (Pyrilinks D-IMMULITE) for urinary DPD measurement and for the assessment of urinary CTX we used a quantitative ELISA (Osteometer Biotec A-S, CrossLaps ELISA). RESULTS: We found a highly significant correlation between both parameters in the group of healthy persons (r = 0.75, p < 0.05, n = 28) as well as in the group of patients with diabetes mellitus type I (r = 0.79, p < 0.05, n = 65). Also, a significant correlation was observed between DPD and CTX (r = 0.583, p < 0.05, n = 88) in the group of female osteoporotic patients. CONCLUSIONS: Despite good correlations between DPD and CTX in all of the investigated groups, these urinary markers were of limited diagnostic significance in the group of postmenopausal osteoporosis due to a wide spread (few patients showed concentrations above the range of healthy persons) in this newly diagnosed drug-naïve patient collective.

[Therapy and prophylaxis of renal failure]. / Therapie und Prophylaxe von Endorganschäden der Niere.

The number of patients with end-stage renal disease is constantly growing. If patients at risk are identified early enough, currently available therapeutic options allow a potent primary and secondary prevention of progressive renal failure. If the underlying disease can not be eliminated, the mainstay of the therapy are supportive measures such as antihypertensive and, in case of an underlying diabetes mellitus, antidiabetic therapy, dietary restrictions as well as avoidance of additional nephrotoxic agents. Furthermore, even a mild renal insufficiency has been identified as a potent cardiovascular risk factor. The second major goal of supportive therapy therefore is a reduction of the markedly increased cardiovascular morbidity of these patients. This can be achieved through treatment of various consequences of renal failure, such as hyperparathyroidism, renal anemia etc. Supportive therapy thus represents a highly complex and interdisciplinary treatment, which should prompt an early inclusion of a nephrologist into the therapeutic strategy.

[Immobilization hypercalcemia as a complication of polyneuropathy]. / Immobilisations-Hyperkalzämie als Komplikation einer Polyneuropathie.

Prolonged immobilization or physical inactivity has been shown to produce increased bone resorption due to enhanced osteoclastic activity and diminished bone formation. These skeletal changes are a typical complication in tetraplegic patients, who are at risk of developing hypocalcemia. Hypercalciuria is the most characteristic symptom. However, some patients develop hypercalcemia, which is infrequent in these patients, and the hypercalcemia can become a life-threatening complication. Until now, it has been unclear why a small percentage of immobilized patients develop hypercalcemia. Here we present a case of symptomatic hypercalcemia (serum calcium: 3.5 mM/l) following immobilization due to a critical illness polyneuropathy. The diagnosis could be established after malignant hypercalcemia, primary hyperparathyroidism, and other causes of hypercalcemia were excluded. Treatment with intravenous saline, furosemide, and calcitonin was not effective in lowering serum calcium. Treatment with pamidronate (Aredia) was successful and reduced the serum calcium to normal values.

[Hypokalemic paralysis with thyrotoxicosis]. / Hypokaliämische Lähmung bei Hyperthyreose.

Hypokalemic periodic paralysis as a complication of thyrotoxicosis (thyrotoxic periodic paralysis) most often occurs in east Asian men. It is characterised by recurrent episodes of flaccid paralysis, hypokalemia, and underlying hyperthyroidism. It needs to be distinguished from sporadic and familial forms of periodic hypokalemic paralysis. No disturbances in the acid-base state and no extracorporal potassium loss are present. We report on the typical case of a young Chinese man presenting with hypokalemic periodic paralysis associated with yet unknown Graves' disease. Intravenous substitution of potassium and oral propranolol were administered. Complete remission was achieved after 10 hours. After medical therapy had normalised thyroid hormone levels, no further hypokalemic paralytic attacks occurred.