Calcium Metabolism in Early Chronic Renal Failure: Implications for the Pathogenesis of Hyperparathyroidism

Abstract

Studies in the past showed elevated immunoreactive parathyroid hormone (PTH) serum values in early renal failure, but the assays used in these studies could not discriminate between bioinactive fragments of the PTH peptide and biologically active hormone. The availability of a sensitive PTH assay, which quantitates intact hormone, now allows the analysis of biologically active PTH in renal failure. To characterise more precisely the point of onset of hyperparathyroidism in the course of chronic renal failure and its relation to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], we measured plasma intact PTH and vitamin D metabolite serum values in 63 non-nephrotic uraemic patients (male n = 35, female n = 28, age 31-78 years) with incipient (GFR 60-90 ml/min per 1.73 m3, n = 19) mild (GFR 40-60, n = 22) and moderate (GFR 20-40, n = 22) renal failure, and in 22 age-matched healthy control subjects. Intact PTH concentrations were negatively correlated with GFR (r = -0.57, P less than 0.001). Median plasma intact PTH values (normal range 1.2-6 pmol/l) were 5.6 (range 2.2-13.0) in incipient, 8.1 (2.9-24.0) in mild, and 13.0 (5.4-59.0) in moderate renal failure. Intact PTH values in incipient renal failure were significantly greater than in 22 age-matched control subjects (P less than 0.01). The decline of GFR was paralleled by a progressive decrease in 1,25(OH)2D3 serum values (r = 0.44, P = 0.001). Median values of the hormone (normal range 35-90 pg/ml) were 32 (range 20-66) in incipient (P less than 0.01 vs. age-matched control subjects), 34 (22-74) in mild, and 26 (17-39) in moderate renal failure. In all three groups, mean serum phosphate and total calcium concentrations (corrected for serum protein) were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

A new significant and independent risk factor for falls in elderly men and women: a low creatinine clearance of less than 65�ml/min

“…The conversion of calcidiol (25(OH)D 3 ) to the metabolically most active form of vitamin D, the D-hormone (calcitriol/1.25(OH) 2 D 3 ), is highly dependent on the creatinine clearance [18,19]. It is hypothesized that below a creatinine clearance of 60 ml/min [20] or 50 ml/ min [21], the renal conversion of 25(OH)D 3 to 1.25(OH) 2 D 3 becomes insufficient [20,21].…”

Insuficiência e deficiência de vitamina D em pacientes portadores de doença renal crônica

“…However, this factor should not be the only one, since many patients who did not have nephrotic proteinuria also presented with vitamin D deficiency. 24 However, it is important to observe that the high frequency of vitamin D deficiency in our sample of patients with CKD (73.6%) is not different from that recently demonstrated in healthy people living in São Paulo, in which 77.4% of the people presented serum levels of 25(OH)D < 30 ng/mL. 13 The consequences of vitamin D deficiency in patients with CKD are not established yet.…”

“…24,25 Likewise, it is a known fact that the presence of nephrotic proteinuria is associated with vitamin D deficiency, possibly due to the urinary loss of vitamin D bound to its plasma carrier protein. 26 As to the patients analyzed in this study, those who had the nephrotic syndrome presented serum levels of 25(OH)D ≤ 30 ng/mL.…”

Three-year outcome of alendronate treatment in older Japanese women with osteoporosis

“…31 The conversion of calcidol (25-hydroxyvitamin D) to the most active metabolic form of vitamin D, calcitriol (1,25-dihydroxyvitamin D), is highly dependent on the renal function. 32,33 Thus, one possible explanation of the higher incidence of falls in the older group may be attributable to an agerelated increase in the prevalence of renal dysfunction, although a secondary data analysis of women participating in the FIT demonstrated that ALN treatment increased BMD and decreased the relative risk, but not the absolute risk, of clinical fractures to a similar degree among women with and without reduced renal function. 34 Impairment of muscle strength and muscle power of the lower extremities, balance/postural control, and walking ability has been recognized as important risk factors for falls.…”