Recent education known fibroblasts progress factor (FGF)-23 while the a special protein that have phosphaturic activity. It is mostly released by osteocytes which will be today thought to be the most important factor to own control regarding phosphorus homeostasis.
Whenever GFR falls, the new phosphorus approval minimizes somewhat, leading to phosphorus preservation. Which hyperphosphatemia, subclinical when projected GFR are >29 mL/min, is assumed is the primary cause for additional hyperparathyroidism (Fig. 2). Phosphorus induces PTH hormonal because of the 3 systems:
Induction of mild hypocalcemia by precipitating with calcium as CaHPOcuatro. Hypocalcemia also results from decreased calcium release from bone pools.
Pleasure out-of FGF-23, which biggercity slevový kód leads to serious inhibition of just one-? hydroxylase and you can depressed amount of step one,25 dihydroxyvitamin D. 9 The brand new downregulation of the supplement D receptors towards the parathyroid glands contributes to supplement D resistance. Losing negative opinions towards parathyroid glands reasons a highest PTH peak.
PTH secretion is appropriate in this case and, along with FGF-23, can decrease the tubular reabsorption of phosphorus to <15%. This is a relatively steady state: the phosphorus and calcium levels are back to normal but at the expense of high PTH and FGF-23. When GFR falls below 30 mL/min (CKD stage IV), the tubular reabsorption of phosphorus cannot be further lowered, causing more PTH and FGF-23 secretion. Even though tubular reabsorption of phosphorus is maximally suppressed, there are too few nephrons left to balance the continuing phosphorus intake. Although PTH is no more active on the kidney, its action on the bone is maintained and continues to promote calcium and phosphorus release. The end result is a vicious cycle in which high phosphorus causes PTH secretion and PTH causes more hyperphosphatemia.
Outcomes
Secondary hyperparathyroidism is a very early disease and its diagnosis and treatment is crucial in the management of patients with CKD. Levin et al 10 demonstrated that the PTH starts to increase as early as the beginning of CKD stage III (estimated GFR, <60 mL/min), along with normal levels of serum calcium and phosphorus.
The effect of secondary hyperparathyroidism on mortality was thought to be mainly caused by hyperphosphatemia. The last phase of the Dialysis Outcomes and Practice Patterns Study identified hyperphosphatemia (PO4 > 6.1 mg/dL), hypercalcemia (Ca > 10 mg/dL), and high PTH (>600 pg/mL) as 3 independent risk factors for all-cause and cardiovascular mortality, with hazard ratios of 1.18, 1.16, and 1.21, respectively. 11 Moreover, it is known that a calcium-phosphorus product >72 mg 2 /dL 2 is associated with a 34% increased risk of mortality and metastatic calcification. This risk further increases by 11% for every 10 points of elevation of the calcium-phosphorus product. 12
Up until now, it had been thought that new phosphorus homeostasis are primarily attained by PTH and you will vitamin D
Concurrently, additional hyperparathyroidism ‘s the leading reason behind kidney osteodystrophy and bones condition. Kidney osteodystrophy is usually called “the newest quiet crippler”; affected patients can be completely asymptomatic. Symptoms, in addition to limbs and you may joint pain and you may bone deformation and fractures, be more repeated when you look at the later degrees of problem. Osteitis fibrosa cystica, new classic and you will former most commonly known osteodystrophy, is usually considering higher limbs turnover secondary so you’re able to highest levels off circulating PTH. The unnecessary suppression out-of PTH can lead to adynamic bone disease (the common osteodystrophy), simply because of lower bones return. 13 In fact, inside late grade out-of CKD, exactly how many PTH receptors throughout the bones try downregulated, resulting in what is actually called skeletal opposition, an organic procedure to your bones to defend itself against the high amounts of PTH. For that reason the modern Renal Condition Outcomes Top quality Initiative (K/DOQI) testimonial will be to continue PTH anywhere between 150 and 300 pg/mL to eliminate a complete suppression of osteoclasts and avoid adynamic limbs condition. Some other less frequent bones illness due to lowest bones turin D deficiency was osteomalacia, that’s mainly characterized by an increased number of unmineralized limbs. Mixed osteodystrophy is additionally named having parts of one another higher and lower limbs turnovers. Although clients possess a prevalent sorts of bones disease, really patients features several types which get into new blended classification.