Clinical assessment of phosphorus status, balance and renal handling in normal individuals and in patients with chronic kidney disease.

PURPOSE OF REVIEW: The concepts of steady state, external balance, total body status and internal distribution are not always appreciated or even considered in clinical practice. The current tests available for clinical assessment of phosphorus physiology and pathophysiology are valid in some aspects, but also have many limitations. The purpose of this review is to clarify the above concepts and discuss the utility of the currently available tests to assess phosphorus disorders. RECENT FINDINGS: Both epidemiologic and preclinical data have shown that disturbances in mineral metabolism contribute significantly to the morbidity and mortality in chronic kidney disease. There are also emerging data supporting the notion that phosphotoxicity may exist even in individuals with normal renal function. In chronic kidney disease (CKD), hyperphosphatemia is a relative late event and is a suboptimal indicator of phosphorus balance and status. The judicious use of plasma and urine chemistry and hormonal biomarkers such as fibroblast growth factor 23 should be considered. SUMMARY: There is a dire need to increase awareness of what physiologic parameters should be monitored in terms of phosphorus pathophysiology. Although the current available tests in the clinical armamentarium are not ideal, understanding their implications and limitations will improve patient care and motivate practitioners and investigators to develop better tests.

Phosphate metabolism in the setting of chronic kidney disease: significance and recommendations for treatment.

Phosphorus is an essential mineral that plays a crucial role in cell structure and metabolism. In living organisms, phosphorus exists surrounded by four oxygen atoms to form phosphate (PO(4)). Within cells, PO(4) regulates enzymatic activity and serves as an essential component of nucleic acids, adenosine triphosphate, and phospholipid membranes. Outside cells, PO(4) primarily resides in bone and teeth as hydroxyapatite. A small amount of inorganic PO(4) circulates in serum, with levels balanced by gastrointestinal intake, renal excretion, and a set of specific hormones. Under normal conditions, PO(4) is excreted through the kidneys. Among patients with end stage renal disease (ESRD) receiving chronic dialysis, circulating PO(4) levels typically rise to levels well above the normal laboratory range. Higher serum PO(4) levels are strongly associated with arterial calcification and mortality in this setting. Among predialysis patients with chronic kidney disease (CKD), phosphaturic hormones enhance renal PO(4) excretion to maintain serum PO(4) levels within the high-normal laboratory range. Recently, high-normal serum PO(4) levels have been associated with cardiovascular (CV) events and mortality among individuals who have CKD and among those who have normal kidney function. This review discusses PO(4) metabolism in the context of CKD, examines associations of PO(4) levels with adverse outcomes in the CKD setting, and suggests treatment strategies for moderating serum PO(4) levels.

Factors for increased morbidity and mortality in uremia: hyperphosphatemia.

Hyperphosphatemia is a metabolic abnormality present in the majority of patients treated by dialysis. Inorganic phosphorus (iP) can be categorized as a true uremic toxin given its known in vivo and in vitro effects and the ability to reduce these effects by normalizing iP levels. However, despite regular and adequate dialysis treatment, the goal of normalization of phosphorus levels rarely is achieved. This article briefly evaluates the significance of hyperphosphatemia in hemodialysis patients, current therapeutic approaches, and describes a new model for evaluating the dialysis prescription for iP balance.

Consequences of hyperphosphatemia in patients with end-stage renal disease (ESRD).

Hyperphosphatemia is invariably present among patients with end-stage renal disease (ESRD) and is becoming an increasingly important clinical entity. Despite concerted efforts by patients, dietitians, and nephrologists to control serum phosphorus, a recent study by Block et al found that more than 60% of patients on hemodialysis in the United States have serum phosphorus levels above the recommended goal of 5.5 mg/dL. Historically, nephrologists have been concerned about the central role of elevated serum phosphorus in the pathogenesis of secondary hyperparathyroidism and extraosseous calcification. However, the consequences of untreated hyperphosphatemia have assumed more importance in the last few years, largely due to recent clinical studies that revealed a more sinister role of elevated serum phosphorus in increasing the mortality risk among patients with ESRD. Hemodialysis patients with serum phosphorus greater than 6.5 mg/dL were reported to have a 27% higher mortality risk than patients with serum phosphorus between 2.4 and 6.5 mg/dL. The pathophysiologic mechanisms by which persistent hyperphosphatemia enhances the mortality risk in dialysis patients are not yet completely understood. However, given that inadequate control of serum phosphorus contributes to elevated calcium-phosphorus product (Ca x P), untreated hyperphosphatemia may play a key role in cardiovascular calcification. In response to these findings, the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease have recently recommended more stringent levels for controlling serum phosphorus and Ca x P product in order to improve patients' quality of life and longevity.