Phosphate Metabolism in Cardiorenal Metabolic Disease

Abstract

Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the 'normal laboratory range' by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease.

A Case of Carcinoid Tumor-Associated Hypercalcemia

“…We posit that the most likely factor to explain the hypercalcemia in the current case of carcinoid was the increased tumor production of FGF-23, a phosphaturic hormone that normally buffers rising phosphate levels in early renal failure [17]. Indeed, the serum FGF-23 was borderline elevated despite low serum phosphate levels suggesting dysregulation of its production, likely via the carcinoid tumor.…”

“…Indeed, the serum FGF-23 was borderline elevated despite low serum phosphate levels suggesting dysregulation of its production, likely via the carcinoid tumor. FGF-23, which is a normal osteocyte product, is now known to be an important phosphatonin, augmenting renal phosphate excretion by decreasing the expression of type 2a sodium-dependent phosphate co-transporters in proximal tubular cells [17]. FGF-23 also inhibits the activation of vitamin D, by decreasing the expression of renal 1-alpha-hydroxylase.…”

“…An overexpression of FGF-23 is now known to be associated with and possibly causative of autosomal-dominant and X-linked hypophosphatemic rickets and oncogenic osteomalacia [9]. A heightened expression of FGF-23 is observed progressively as chronic renal failure evolves, buffering against hyperphosphatemia and mineralization of vascular and soft tissues [17]. As measured by enzyme-linked immunosorbent assay (ELISA), increased serum FGF-23 has been associated with humoral hypercalcemia of several different malignancies, possibly including carcinoid tumors [9].…”

Fibroblast Growth Factor 23 and Hypophosphatemia: A Case of Hypophosphatemia along the Rickets-Osteomalacia Spectrum

“…Recently, information acquired through the research of bone and renal physiology has added evidence for the complexity of mineral metabolism and the role of phosphorus in bone mineralization [13,14]. The cross talk of the bone, kidney and parathyroid is increasingly recognized as being critical for maintaining normal calcium and phosphorus homeostasis in bone mineralization and structural integrity.…”

Медикаментозная Коррекция Нарушений Фосфатно-Кальциевого Обмена У Пациентов С Хронической Болезнью Почек И Минерально-Костной Болезнью

“…К примеру, гиперфосфатемия сама по себе обу-словливает повышенный уровень смертности у па-циентов на диализе [3] и пациентов -реципиентов донорской почки [4], а также ускоряет прогрессиро-вание и усугубляет течение тубулоинтерстициаль-ных поражений почек, почечной остеодистрофии, кардиоваскулярных заболеваний [5].…”