UNDERSTANDING FELINE CKD: MINERAL AND BONE DISORDER

摘要

Chronic kidney disease (CKD) is a common condition in both feline and canine medicine and the concept of secondary renal hyperparathyroidism (SRHP) is well recognised. However, phosphorus homeostasis and the pathophysiology of SRHP has been, and remains, incompletely understood. In recent years, the discovery of phosphotonins (a factor responsible for inhibition of renal tubular reabsorption of phosphorus) and in particular Fibroblast Growth Factor 23 (FGF23) has revolutionised our understanding of the control of phosphorus and the changes that occur in phosphorus homeostasis during CKD. Based on the realisation that PTH is not the only player in the regulation of phosphorus and calcium homeostasis in CKD the term secondary renal hyperparathyroidism, in human medicine, has largely been superceded by the term mineral and bone disorder. In the last 2-3 years, studies have begun to investigate the role that FGF23 may play in our veterinary patients.Regulation of phosphorus is intrinsically linked to the regulation of calcium with both electrolytes being under the influence of parathyroid hormone (PTH) and calcitriol (1, 25 dihydroxycholecalciferol). Calcitriol increases calcium and phosphorus absorption from the gastrointestinal tract whilst PTH increases calcium and phosphorus resorption from bone, increases calcium reabsorption and decreases phosphorus reabsorption from the tubular filtrate in the kidney. For many decades we have widely acceptedthe 'trade off hypothesis'. Reduction in the number of functioning nephrons leads to a reduced capacity to excrete various solutes in the urine including phosphorus with resulting hyperphosphatemia. This retention of phosphorus, by the law of mass action, results in a relative decline in free calcium concentration. A combination of reduced free calcium and increased phosphorus concentration contribute to stimulating production of PTH (Figure 1). Simlutaneously, increasing phosphorus concentrations havean inhibitory action on the production of calcitriol, which also has a stimulatory action on PTH production. As PTH inhibits reabsorption of phosphorus in the proximal tubules, increased PTH production serves to try and increase phosphorus excretion. Atthe same time increased PTH concentrations will also stimulate release of calcium and phosphorus from bone and increase production of calcitriol, which will increase absorption of both calcium and phosphorus from the small intestine. However, with continually declining renal function phosphorus retention continues to occur such that the body becomes phosphorus loaded and the SRHP develops. The 'trade-off for increasing phosphorus excretion by remaining functioning nephrons is therefore the gradual butpersistent increase in PTH concentration.Chronically increased PTH production can ultimately result in bone demineralization (renal osteodystrophy) and complex of phosphorus and calcium can result in dystrophic mineralisation of soft tissues. When this mineralisation occurs within the kidney concern is raised that it can contribute to progressive renal injury.