Elevated FGF23 and disordered renal mineral handling with reduced bone mineralization in chronically erythropoietin over-expressing transgenic mice

Fibroblast Growth Factor 23 (FGF23) is a phosphaturic factor causing increased renal phosphate excretion as well as suppression of 1,25 (OH)2-vitamin D3. Highly elevated FGF23 can promote development of rickets and osteomalacia. We and others previously reported that acute application of erythropoietin (EPO) stimulates FGF23 production. Considering that EPO is clinically used as chronic treatment against anemia, we used here the Tg6 mouse model that constitutively overexpresses human EPO in an oxygen-independent manner, to examine the consequences of long-term EPO therapy on mineral and bone metabolism. Six to eight weeks old female Tg6 mice showed elevated intact and C-terminal fragment of FGF23 but normal plasma levels of PTH, calcitriol, calcium and phosphate. Renal function showed moderate alterations with higher urea and creatinine clearance and mild albuminuria. Renal phosphate excretion was normal whereas mild hypercalciuria was found. Renal expression of the key proteins TRPV5 and calbindin D28k involved in active calcium reabsorption was reduced in Tg6 mice. Plasma levels of the bone turnover marker osteocalcin were comparable between groups. However, urinary excretion of deoxypyridinoline (DPD) was lower in Tg6 mice. MicroCT analysis showed reduced total, cortical, and trabecular bone mineral density in femora from Tg6 mice. Our data reveal that chronic elevation of EPO is associated with high FGF23 levels and disturbed mineral homeostasis resulting in reduced bone mineral density. These observations imply the need to study the impact of therapeutically applied EPO on bone mineralization in patients, especially those suffering from chronic kidney disease.

Disorders of phosphate in the critically ill

Phosphorus plays an important role in many cellular processes and hypophosphataemia can result from a number of causes. Critically-ill patients are at increased risk for developing hypophosphataemia due to the presence of multiple causal factors. Hypophosphataemia may lead to a multitude of symptoms and frequent monitoring of serum phosphate is advised in critically-ill patients is recommended and should be corrected in patients with associated symptoms. It is uncertain whether correction in apparently asymptomatic patients affects outcome, although treatment is generally recommended for severe hypophosphataemia. Multiple strategies of intravenous phosphate administration have been described, but it is unknown which strategy is superior. Hyperphosphataemia is most often caused by renal insufficiency, but can also be caused by increased intake or release from damaged cells. Symptoms are mainly associated with subsequent hypocalcaemia and correction of hyperphosphataemia can be achieved by minimizing the intake of phosphate, increasing renal phosphate excretion, and renal replacement therapy.

Two Cases of Hypophosphatemia with Increased Renal Phosphate Excretion in Legionella Pneumonia

We encountered 2 cases of hypophosphatemia due to Legionella pneumonia. Both cases showed increased urinary phosphate excretion and renal tubular dysfunction, which ameliorated with recovery from Legionella pneumonia. Serum fibroblast growth factor-23 level was suppressed, whereas serum 1,25(OH)2 vitamin D and parathyroid hormone levels were normal. Delayed elevation of serum 1,25(OH)2 vitamin D levels was observed with improvement in renal tubular function. These findings suggested hypophosphatemia might be mediated by renal tubular dysfunction.

Phosphate homeostasis and the renal-gastrointestinal axis

Transport of phosphate across intestinal and renal epithelia is essential for normal phosphate balance, yet we know less about the mechanisms and regulation of intestinal phosphate absorption than we do about phosphate handling by the kidney. Recent studies have provided strong evidence that the sodium-phosphate cotransporter NaPi-IIb is responsible for sodium-dependent phosphate absorption by the small intestine, and it might be that this protein can link changes in dietary phosphate to altered renal phosphate excretion to maintain phosphate balance. Evidence is also emerging that specific regions of the small intestine adapt differently to acute or chronic changes in dietary phosphate load and that phosphatonins inhibit both renal and intestinal phosphate transport. This review summarizes our current understanding of the mechanisms and control of intestinal phosphate absorption and how it may be related to renal phosphate reabsorption; it also considers the ways in which the gut could be targeted to prevent, or limit, hyperphosphatemia in chronic and end-stage renal failure.

Oncogenic osteomalacia from pterygopalatine fossa mass

Introduction:Oncogenic osteomalacia, or tumour-induced osteomalacia, is an uncommon cause of osteomalacia. It has been reported to occur in patients with hypophosphataemia due to excess renal phosphate excretion secondary to mesenchymal tumours. Occurrence of this pathological process in the head and neck is extremely rare.Methods:Case report and literature review.Results:We present a case of a 73-year-old woman with tumour-induced osteomalacia. She was initially followed by the endocrinologists for osteomalacia and pathological fractures. An indium-111 pentetreotide scan showed activity in the left pterygopalatine fossa. A mass was endoscopically resected, and the histopathological appearance was consistent with a haemangiopericytoma. Following surgery, the patient's hypophosphataemia and vitamin D deficiency corrected and her symptoms resolved.Conclusions:Oncogenic osteomalacia, or tumour-induced osteomalacia, is a rare entity in the head and neck. Current research is elucidating the mechanism by which phosphaturic wasting occurs. In most patients, symptoms resolve once the offending tumour is removed.