The control of phosphate excretion in uremia.

Abstract

The patterns of phosphate excretion in man with advancing chronic renal disease are well established. Although phosphate clearance decreases with time, it falls proportionately less than glomerular filtration rate, and the ratio of phosphate clearance to GFR increases as the disease advances (1). Thus the average rate of phosphate excretion per residual nephron increases as the nephron population diminishes, and the onset of hyperphosphatemia thereby is delayed. The explanation for this sequence is of considerable theoretical interest. The major possibilities are two: 1) The change could reflect the operation of a control system geared either to maintain external phosphate balance or to maintain plasma phosphate concentrations constant; 2) the relative phosphaturia per nephron could be a consequence of uremia or of the abnormalities in residual nephrons or both. These studies represent an attempt to distinguish between these two interpretations using the dog with intrinsic renal disease as the experimental model. The experiments also were designed to delineate the general characteristics of a control system, should one exist. phate intake of at least 0.5 g. A preliminary bladdersplitting operation was performed to permit the quantitative collection of urine from the individual kidneys without recourse to ureteral catheterization (2). Thereafter, unilateral pyelonephritis was induced by a technique described previously (3). In five dogs, the diseased kidney was studied in the presence of the control kidney, and the functions of the two organs were compared. These experiments were similar in design to those described in a previous publication (4) and were performed to verify the previous results in the present animals. In 27 dogs, the control kidneys were removed to permit investigation of the diseased kidneys under environmental conditions varying from moderate azotemia to severe uremia. Methods

Mineral (Mal)Adaptation to Kidney Disease—Young Investigator Award Address

“…Because phosphate is freely filtered at the glomerulus, the total amount of filtered phosphate decreases in parallel to the reduction in GFR imposed by CKD. Modest increases in serum phosphate levels within the normal range help sustain the filtered load in CKD, but downregulation of phosphate reabsorption by the sodium-phosphate co-transporters, NPT2a and NPT2c, in the apical membrane of the proximal tubule appears to be the most important component of the adaptive response (11,12). Since individuals with normal GFR who consume typical Western diets excrete only 10%-20% of their filtered load of phosphate-the fractional excretion of phosphate-the kidney can readily respond to reduced filtration of phosphate by commensurately decreasing the percentage that NPT2a and NPT2c reabsorb.…”

Control of Hyperphosphatemia among Patients with ESRD

“…Hyperphosphatemia occurs as a consequence of diminished phosphorus filtration and excretion with the progression of CKD. Decreased phosphorus excretion can initially be overcome by increased secretion of parathyroid hormone (PTH), which decreases proximal phosphate reabsorption (2). Hence, phosphorus levels are usually within normal range until the GFR falls below approximately 30 ml/min, or stage IV.…”

FGF-23 and Hyperphosphatemia in Dialysis Dependent Chronic Kidney Disease Patients

“…Hyperphosphatemia develops as a consequence of diminished phosphorus filtration and excretion with the progression of CKD. Decreased phosphorus excretion can initially be overcome by increased secretion of parathyroid hormone (PTH), which decreases reabsorption of phosphate in the proximal tubules by regulating NaPi-2a and NaPi2c activities and thus induces an increase of urinary phosphate excretion [2] According to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) classification, phosphorus levels are usually within normal range until the GFR falls below approximately 30 ml/min, or CKD stage 4 [3]. In more advanced stages of CKD, the blunted urinary excretion of phosphorus can no longer keep pace with the obligatory intestinal phosphate absorption, resulting in hyperphosphatemia [4].…”