The Effects Of Corticosteroid Therapy On Vitamin D And Bone Metabolism In Nephrotic Syndrome

The Effects of Corticosteroid Therapy on Vitamin D and Bone Metabolism in Nephrotic SyndromeNephrotic syndrome (NS) is believed to be a common clinical syndrome among the kidney diseases, usually associated with metabolic disorder of calcium (Ca), vitamin D, parathyroid hormone (PTH) and bone. Also, NS could be relieved by corticosteroid therapy(CT). The vitamin D metabolites and biochemical bone markers are considered as useful tools for evaluating the abnormalilies of vitamin D and bone metabolism in nephrotic syndrome.Objective: To evaluate the effects of long term high-dose corticosteroid therapy on vitamin D metabolism and bone turnover in NS. Serum osteocalcin (BGP) was applied as a specific marker for bone formation while urinary type 1 collagen peptides (Crosslaps) for bone resorption. Besides these, 1,25-dihydroxyvitamin D (1,25-(OH)2D) in the serum and renal tubule function were also investigated in the present study.Methods: 47 NS cases were involved in the current study. Among them there were 28 patients treated with predisone at the dosage of Img/Kg/day for 6 weeks and normal control were collected and serum 1,25-(OH)2D and BGP were measured by RIA while urinary Crosslaps by ELISA. Urinary NAG, GAL as the markers for the proximal renal tubule function, urinary acidification function and osmolality for the distal renal tubule function were also evaluated. All the data were analyzed by statistical software.Results: l.The result showed that the serum l^S-COH^D in NS group was lower than that in the normal control group,and positivelly correlated with serum Albumin, correlated with urinary NAG, GAL negatively instead. The serum BGP and urinary Crosslaps excretion hi NS group were elevated in comparison with that in the normal control. However, the urinary Crosslaps excretion was shown to3be a positive correlation with serum BGP. The serum Ca and Ca excretion in the urine in NS group were demonstrated to be lower than that in the normal group. Both of them showed a positive correlation with serum 1,25-(OH)2D. There was a positive correlation between serum Ca and urinary Ca excretion as well. As to the urinary NAG and GAL, the two parameters in NS group were shown to be elevated in comparison with the normal control. They were negativelly correlated with serum ALB while positivelly correlated with protein in the urine. 2. The serum 1,25-(OH)2D, Ca, ALB, urinary Ca excretion in the group treated with high-dose corticosteroid were significantly higher than that in NS group while the mean concentrations of BGP and iPTH in the serum as well as NAG ,GAL,Crosslaps and protein in the urine were significantly reduced than that in NS group.Conclusions: These findings indicate that reduction in serum 1,25-(OH)2D may be associated with direct urinary losses of 1 ,25-(OH)jD-DBP and 25-(OH)D-DBP, indicating an impairement to the poximal tubular function and 1 a -hydroxylase activity in the patients with NS. High bone turnover in NS is probably attributable to proteinuria and hypoalbuminemia. Both serum BGP and urinary crosslaps levels were elevated above the normal range in NS while the increase in BGP was less impressive, suggesting an imbalance between bone resorption and bone formation. Both serum Ca and urine Ca were significantly reduced in NS group than that in the normal control. The reduction in serum Ca was associated not only with the loss of Ca binding-protein from urine, but also with the decrease in Ca reabsorption at the impaired proximal tubule of the kidney. The amount of Ca excretion from urine was closely correlated with the Ca in the serum. It has been well known that hypocalcemia stimulates calcium reabsorption in the renal tubule, leading to the reduction in urine Ca excretion. As a hormone, 1,25-(OH)2D may have an indirect effect on urine Ca excretion by this way. Intestinal Ca absorption is increased and excretion is decreased in NS. Disturbance of proximal renal tubule function in NS is possibly mediated by largeand middle molecule protein in proteinuria i...