Phosphorus and Calcium Metabolism Disorders Associated with Chronic Kidney Disease Stage III-IV (Systematic Review and Meta-Analysis)

Kidneys play an important role in maintenance of the calcium and phosphorus balance. Renal failure is associated with disorders of all phases of the phosphorus and calcium turnover. The decrease of glomerular filtration rate (GFR) under 60 ml/min/1.73 m2 is associated with phosphorus filtration rate decrease with further elevation of its serum level that results in parathyroid hormone (PTH) secretion stimulation. PTH suppresses phosphorus reabsorption; therefore, it returns its serum level to normal. However, when the GFR falls below the 30 ml/min/1.73 m2 level, this mechanism becomes ineffective and persistent hyperphosphatemia develops. The latter enhances the PTH secretion. Hyperphosphatemia is associated with inhibition of 1┙-hydroxylase effect in proximal renal tubules and the decrease of serum 1,25(OH)2D3 (calcitriol) level. Calcitriol deficiency results in calcium absorption disorders in small intestine; as a result, hypocalcemia develops. Persistent hypocalcemia results in parathyroid glands hyperplasia (PTGH) that is associated with excessive PTH production and secretion. PTH hyper-production and hyperphosphatemia are the manifestations of secondary hyper-parathyroidism (SHPT). Hypocalcemia, vitamin D deficiency and hyperphosphatemia are the main factors responsible for secondary hyperparathyroidism. Hypocalcemia, vitamin D deficiency and hyperphosphatemia develop at the initial stage or renal dysfunction – Chronic Kidney Disease (CKD) III (GFR 60-30 ml/min/1.73 m2); they progress with the increasing severity of renal failure (GFR 29-15 ml/min/1.73 m2, CKD IV-V). Disorders of calcium and phosphorus balance associated with CKD result in bone diseases, generally called renal osteodystrophy. At the same time numerous cohort studies have broadened the focus of CKD-related mineral and bone disorders to include cardiovascular disease ( which is the leading cause of death in patients at all stages of CKD). All three of these processes (abnormal mineral metabolism, abnormal bone and extra skeletal calcification) are closely interrelated and together make a major contribution to the morbidity and mortality of patients with CKD. Since the publication of the 2003 K/DOQI guidelines for bone and mineral metabolism, there has been tremendous advancement in our understanding of mineral metabolism in CKD patients. Major modifications of K/DOQI bone guidelines are essential and should