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Childhood nephrotic syndrome (NS) is defined by nephrotic-range proteinuria, generalized edema, hypoalbuminuria, and hyperlipidemia with normal renal function. Idiopathic nephrotic syndrome (INS) is the most frequent renal disease in children. Childhood NS typically follows a relapsing-remitting course, often requiring recurrent courses of myeloperoxidase (GC), but with low systemic inflammation during remission.
Bone mass deposition begins during fetal life and continues during infancy and adolescence, stabilizing at the beginning of adulthood. During childhood and adolescence, skeletal modeling results in sex- and maturation-specific increases in bone density. Metabolic bone disease (MBD) is characterized by changes in skeletal mineralization due to poor bone mineral content (BMC). Children may be especially vulnerable to the effects of GC on bone formation and peak bone mass.
Prednisone is the first-line treatment for INS to induce remission, to prevent relapses and to avoid side effects of the disease. Prolonged administration of prednisone interferes with growth and bone mineralization, and has deleterious effect on basic cellular mechanisms that are important in the development and maintenance of bone strength. Steroids are known to cause osteoporosis and affect BMC and bone mineral density (BMD) in children. Glucocorticoids have a suppressive effect on osteoblastogenesis in the bone marrow and promote the apoptosis of osteoblasts and osteocytes, thus leading to decreased bone formation. There is some evidence to suggest that GC may increase bone resorption by extending the lifespan of pre-existing osteoclasts. Glucocorticoids may also promote calcium loss through the kidneys and gut, and this negative calcium balance can itself lead to increased bone remodeling and osteoclastic activity due to secondary hyperparathyroidism.
Children with INS are at risk for MBD, accompanied by important alterations of mineral and bone metabolism.
Demographic and anthropometric characteristics of the participants with steroid-sensitive nephrotic syndrome (SSNS), steroid-resistant nephrotic syndrome (SRNS), and the control groups are summarized in Table 1. Weight and BMI Z-scores were significantly higher in the SSNS and SRNS patients than the controls, with no significant difference between them regarding the height Z-scores. In terms of serum markers of bone turnover, serum Ca (total and ionized) were significantly lower, while serum phosphorus and alkaline phosphatase were significantly higher in both SSNS and SRNS patients vs. the controls. Bone aches were found in eight patients (32%).
No significant statistical differences were found between SSNS and SRNS patients regarding the drugs received and DXA measurements (Table 2). Seventy-two percent of SSNS patients received immunosuppressive drugs, as follows: 48% were cyclosporine therapy, 4% on Mycophenolate Mofetil, 8% on cyclophosphamide, and 12% on mixed immunosuppressive therapy.
Bone mineral density (BMD) and fracture risk between nephrotic syndrome participants are given in Table 3. Osteopenia was documented by DXA scan in 11 patients (44%) (seven SDNS, four SRNS), and osteoporosis in two patients (8%) (two SDNS). Fracture risk was mild in six patients (24%) (one IFRNS, two SDNS, three SRNS), moderate in two (8%) (one SDNS, one SRNS), and marked in three (12%) (two SDNS, one SRNS).
A significant statistical correlation was observed between BMD Z-scores and age of patients (r=0.43; p<0.05), weight Z-score (r=0.56; p<0.001), height Z-score (r=0.57; p<0.05), BMI (r=0.34; p<0.05), duration (r=−0.46; p<0.05), and cumulative dose of GC therapy(r=−0.88; p<0.001). Linear regression analyses in Table 4 show that the steroid cumulative dose was the only significant independent risk factor.
Although GCs are the treatment of choice for children with idiopathic NS, obesity and bone mineralization side effects should be considered. In this study, the analyses clearly showed an impact of GCs on body weight and BMI in nephrotic syndrome participants. Not surprisingly, the SSNS and SDNS patients had significantly higher weight and BMI Z-scores than the controls, but with insignificant statistical difference between SSNS and SDNS. Similar results were reported by Lestari et al. and Ribeiro et al. in their analyses of obesity in SSNS and SDNS. The use of high-dose and long-term steroids leads to increased food intake and inhibited energy expenditure through stimulation of neuropeptide-Y and inhibited release of corticotrophin hormone. The process triggers an anabolic process and leads to obesity. Hypocalcemia in patients with NS reported in this study was in line with Koşan et al. GCs cause hypocalcemia by decreased Ca adsorption from gut and kidneys.
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