Preservation of Function in Experimental Renal Disease by Dietary Restriction of Phosphate

Abstract

We sought to determine the importance of calcium phosphate deposition in the functional deterioration of damaged or diseased kidneys. Using the remnant-kidney model in rats, we found that dietary phosphate restriction prevented proteinuria, renal calcification, histologic changes, functional deterioration and death in uremia. Histologic examination of the remnant kidney in the nonrestricted animals showed calcium and phosphorus deposits in the cortical tubular cells, basement membranes and interstitium. A similar degree and pattern of calcification have been found in preliminary studies of human end-stage kidneys. Our results suggest that the calcification produced by the altered phosphorus metabolism present in the uremic state incites an inflammatory and fibrotic reaction leading to destruction of the remnant kidney. Phosphate restriction prevents this response in the remnant kidney. The potential applicability of these findings to other forms of experimental renal disease and to clinical uremia remains to be explored.

Fibroblast Growth Factor-23 in Early Chronic Kidney Disease

“…Low calcitriol levels are hypothesized to decrease cardiac contractility and to contribute to arteriosclerosis and endothelial dysfunction (51,52). In addition, clinical and experimental data indicate that high serum phosphate levels and phosphate loading may accelerate the progression of CKD (12,53,54).…”

Risk of Kidney Injury Following Oral Phosphosoda Bowel Preparations

“…[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. 12,13 Despite this plausible link, our data do not support an association between receipt of OPS and kidney injury.…”

Phosphorus and the Kidney: What Is Known and What Is Needed

“…Experimentally, high dietary phosphorus has been shown to initiate and/or worsen progression of kidney dysfunction (26), whereas dietary phosphate restriction reverses and/or restricts the dysfunction (27). Although the most common explanation has been phosphorus-induced calcification, there are other potential proposed mechanisms including phosphorus-dependent podocyte injury due to overexpression of pituitary-specific positive transcription factor 1 (Pit-1) transporter in rats (28).…”