Role of calcium-phosphorous disorders in the progression of renal failure

Abstract

Among factors related to disturbed calcium-phosphate metabolism in chronic kidney disease, the following must be mainly considered as potential culprits in the progression of renal dysfunction: hyperphosphatemia, hyperparathyroidism, lack of active vitamin D, and possibly excess of the phosphaturic hormone FGF 23. Early experimental work suggested a parathyroid hormone (PTH)-independent beneficial role of phosphate restriction on progression in rats (animals with physiologic hyperphosphatemia), so that the generalization of the data is uncertain. Recent observational studies also found a correlation between S-phosphate and progression, but it remains uncertain whether the relationship is causal. There is very little direct experimental or clinical evidence for a role of PTH in accelerating progression, although the PTH1 receptor is expressed in podocytes and PTH affects podocyte function (i.e., Kf). It is undoubtedly a candidate that requires more sophisticated investigation. Recently, it has been shown that progression is significantly attenuated by calcimimetics (and equally by parathyroidectomy), but it is currently impossible to exclude a confounding effect of lower blood pressure values. The most solid evidence for an impact on progression exists for active vitamin D. In the past, it was widely assumed that vitamin D was "nephrotoxic." In retrospect, nephrotoxicity was the result of hypercalcemia. Recent evidence is overwhelming that 1,25(OH)2D3 and its analogues attenuate progression in noninflammatory and inflammatory models of chronic kidney disease. The main target cells identified so far are podocytes and mesangial cells. It is currently unknown whether the novel phosphaturic hormones have an impact on progression.

Risk of Kidney Injury Following Oral Phosphosoda Bowel Preparations

“…16 Similarly, in humans, acute rises in serum phosphate on the basis of tumor lysis results in acute kidney injury [17][18][19][20] from renal parenchymal calcification, alterations in renal hemodynamics, and direct tubular cell cytotoxicity. [21][22][23] Multiple case reports and controlled human studies 5-7,24 -26 demonstrated that receipt of a standard regimen of OPS (which contains approximately six times the average daily phosphate intake) results in acute rises in serum phosphate. Moreover, data in rat models of CKD (remnant kidney and nephrotoxic serum nephritis) demonstrate that higher levels of dietary phosphate accelerate loss of kidney function 10,11 and that this effect is attenuated by administration of phosphate binders.…”

Acute Effects of Very-Low-Protein Diet on FGF23 Levels

“…Potential culprits for progression are hyperphosphatemia, secondary hyperparathyroidism (sHPT), lack of active vitamin D, and high levels of fibroblast growth factor 23 (FGF23) (3)(4)(5). This hormone is primarily secreted by osteocytes in response to dietary phosphorus overload or increase in 1,25-dihydroxyvitamin D , and it stimulates renal excretion of P, downregulates the production of 1,25-dihydroxyvitamin D, and reduces parathyroid hormone (PTH) levels (6,7).…”

Fibroblast Growth Factor 23 (FGF23) Predicts Progression of Chronic Kidney Disease

“…Although in the past it was assumed that vitamin D therapy is "nephrotoxic," probably as a result of vitamin D-induced hypercalcemia in patients with CKD, 7 recent experimental evidence clearly revealed that 1,25-OH 2 D 3 and its analogues attenuate progression in various CKD models. 3,8,9 Finally, the role of FGF23 in CKD progression is unknown.…”

“…Among factors that are related to calciumphosphate metabolism in patients with CKD, potential culprits for progression are hyperphosphatemia, hyperparathyroidism, lack of active vitamin D, and possibly excess of the recently discovered phosphaturic hormone fibroblast growth factor 23 (FGF23). 3,4 Early experimental work suggested a parathyroid hormone (PTH)-independent beneficial role of phosphate restriction on progres-sion in rats, 5 but it has to be pointed out that these animals have physiologic hyperphosphatemia. Furthermore, there is also little direct experimental or clinical evidence for a role of PTH in accelerating progression, 3 although results from recent experimental studies documented that progression is significantly attenuated by administration of calcimimetics or by parathyroidectomy.…”

“…3,4 Early experimental work suggested a parathyroid hormone (PTH)-independent beneficial role of phosphate restriction on progres-sion in rats, 5 but it has to be pointed out that these animals have physiologic hyperphosphatemia. Furthermore, there is also little direct experimental or clinical evidence for a role of PTH in accelerating progression, 3 although results from recent experimental studies documented that progression is significantly attenuated by administration of calcimimetics or by parathyroidectomy. 6 However, a confounding effect of lower BP values in these experimental settings cannot be excluded.…”