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Fibroblast growth factor 23 (FGF23) is a relatively new phosphatonin, which is produced mainly by bone cells. It is responsible for the regulation of calcium- phosphate homeostasis in the body. FGF23 is one of hormones with phosphaturic effect. It inhibits renal reabsorbtion of phosphate and increases its urinary excretion. Moreover, FGF23 decreases serum concentration of 1,25(OH)2D by inhibition of lα-hydroxylase and stimulation of 24-hydroxylase. The current knowledge on FGF23 and its cofactor-Klotho protein in disturbances of calcium-phosphate balance or in Chronic Kidney Disease is quite obvious. Still we need to know more about the influence of FGF23 on the cardiovascular system and its role in the pathogenesis of hypertension thus this will be the main aspect of our study.

Disorders of calcium and phosphate metabolism are among the major problems in patients with chronic kidney disease (CKD), especially undergoing chronic dialysis. Besides the classic parathyroid-kidney axis, in recent years the existence of an endocrinological bone-kidney axis has been established, which allows better explanation of calcium and phosphate metabolism pathophysiology and secondary hyperparathyroidism in CKD. Fibroblast growth factor 23 (FGF-23) and its co-factor alpha-Klotho protein are the most important factors in the axis. The role of FGF-23 and Klotho protein, their mechanisms of action and significance in CKD have been presented. In ealy stages of CKD the increase of FGF-23 level precedes the decline in vitamin 1.25 (OH)2D3 and the increase of PTH level. Some studies showed correlation between the elevated FGF-23 level and increased mortality from cardiovascular disease in patients with chronic kidney disease. Clinical usefulness of determinations of FGF-23 and Klotho protein in chronic kidney disease is currently investigated.

In the last few years cytokines have been shown to be the most important local cell signaling molecules, strongly involved in the pathogenesis of the overactive bladder symptoms. Proper bladder function is dependent on gap junction activity The main gap junction proteins which can be found in bladder smooth muscle are Connexin 43 (Cx43) and Connexin 45 (Cx45). Experimental studies focused on the influence of Basic Fibroblast Growth Factor on Connexin expression in bladder smooth muscle cells have shown an increased expression of Cx43, contrary to Cx45. Elevated level of Connexin 43 leads to overactivity of muscle fibers. It was also proved that expression of these proteins in tissues is modulated by cytokines. Regulation of the Cx43 promoter depends on an activating factor 1 (AP-1), cyclic monophosphate (cAMP) and retinoid concentration as well. AP-1 is induced by extracellular-signal-regulated kinases (ERK 1/2) through the activation of basic fibroblast growth factor (bFGF). Recent studies revealed that cytokine-induced modulation of gap junction plays an important role in the pathogenesis of OAB, whereas activation of sympathetic fibers via beta adrenoreceptors (beta-AR) causes relaxation of the bladder The beta-3 adrenoreceptors are divided into beta-1, beta-2, beta-3 subtypes. beta-3 adrenoreceptors have been found in fat and smooth muscle tissue. Density of beta-3 AR is very high in urinary bladder detrusor Activation of beta-3 AR leads to the relaxation of smooth muscle fibers during the filling phase and is cAMP-dependent. Missense mutation of this receptor subtype in the human bladder leading to the substitution of Tryptophan (Trp) by Arginine (Arg), occurs in about one-third of the world's population. Studies have shown that about 50% of women with Trp 64 Arg polymorphism have OAB symptoms. Higher concentration of beta3-AR with Trp 64 Arg polymorphism in bladders of women with diagnosed OAB is probably associated with a lower level of cAMP and weaker relaxation of the bladder smooth muscle. The role of the muscarinic receptors (M1-M5) in the pathogenesis of OAB has been widely described. Unfortunately due to lack of selective muscarinic ligands, the function of each subtype of the receptor has not been fully elucidated yet. A mouse model lacking one or more muscarinic receptors types has been constructed recently Animals were used to assess the real influence of various muscarinic receptors on bladder function. Studies have confirmed the importance of these receptors in the function of the urinary tract, offering a new insight in their mutual interactions and pathogenesis of OAB. Better understanding of these and new mechanisms may improve the process of diagnosis and treatment of the disease in the near future.

Oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome induced by tumor produced phosphaturic factors, i.e. phosphatonins. The disorder is characterized by renal tubular phosphate loss, secondary to this process hypophosphatemia and defective production of active form of vitamin D. The clinical course of oncogenic osteomalacia is characterized by bone pain, pathological fractures, muscle weakness and general fatigue. Osteomalacia-associated tumors are usually located in the upper and lower limbs, with half of the lesions primarily situated in the bones. Most of them are small, slow-growing tumors. Their insignificant size and various location coupled with rare occurrence of the disease and non-specificity of clinical symptoms lead to difficulties in reaching a diagnosis, which is often time-consuming and requires a number of additional tests. The average time between the appearance of the first symptoms and the establishment of an accurate diagnosis and the beginning of treatment is over 2.5 years. The aim of this study is to discuss the pathophysiology of disease symptoms, pathomorphology of tumors, diagnostic methods and treatment of oncogenic osteomalacia.

Fibroblast growth factor-23 (FGF-23) discovered in the last years, produced by osteocytes and osteoblast is hormone that lowers plasma phosphate level due to inhibition of renal tubule phosphate reabsorption (phosphaturic effect). It diminishes gut absorption of phosphate as a result of lowered kidney 1alpha-hydroxylase activity and respective decreased active vitamin D1,25(OH)2D synthesis. FGF-23 acts in the presence of the co-receptor Klotho protein which stabilizes its binding with receptor. The pathological states that are associated with increased FGF-23 synthesis in normal renal function lead to hypophosphatemia, while its deficiency may lead to severe hyperphosphatemia. The increased FGF-23 synthesis in patients with chronic kidney disease (CKD) allow to maintain phosphate concentration in spite of severe kidney dysfunction. This problem will be discussed in the II-nd part of this review.

Research on the regulation of mineral homeostasis have been continuing for the decades, with an effect of establishing the impression that the governing mechanisms are already fairly well known and understood. Revealing of the molecular mechanism of action of the Klotho protein, forced us to revise this knowledge. It is known already that Kloto is a unique regulatory efector playing key role in reversing the imbalanced extracellular Ca(++) concentrations, by affecting the intensity of the transepithelial transport and modulation of the parathormone excretion. In cooperation with the phosphaturic hormone - Fgf23 it regulates calcium concentration by suppression of 1,25(OH)(2)D synthesis, and reabsorption of phosphate in a distal convoluted part of nephron. Acting through these mechanisms Klotho takes part in the regulation of the mineral homeostasis of cerebrospinal fluid, blood and body fluids acting on the choroid plexus, parathyroid glands and distal convoluted nephrons. In that way Klotho becomes one of the main players in a complex and multilevel system of maintaining the mineral homeostasis of the organism.

The paper presents recent data on the angiogenesis and the angiogenic and angiostatic mediators in rheumatoid arthritis.

Growing factors influenced on proliferation of follicular cekks of thyroid and probability influence upon a rising of recurrent goitre were presented. Effect of growing factors depending on TSH, specially IGF-1, EGF, FGF and thyroid growth immunoglobulins (TGI) are analysed.