Bone mineral density and urinary N-acetyl-beta-D-glucosaminidase activity in paediatric patients with idiopathic hypercalciuria

BACKGROUND: Idiopathic hypercalciuria (IH) is defined as hypercalciuria that persists after correction of dietary inbalances and has no detectable causes. Patients with IH have a higher prevalence of osteoporosis. Defective reabsorption of calcium by the renal tubule is considered a likely mechanism of IH. N-acetyl-beta-D-glucosaminidase (NAG) is a lysosomal enzyme that is a very sensitive marker of renal tubular impairment. METHODS: Fifteen patients (nine boys and six girls, mean age 12.4 +/- 4.0 years) with IH (urinary calcium excretion >0.1 mmol/kg per 24 h) had their bodyweight, height, body mass index (BMI), urinary NAG/creatinine ratio (U-NAG/Cr) and 24-h urinary calcium excretion (U-Ca/24 h) assessed. L1-L4 bone mineral density (BMD) was measured by dual energy X-ray absorptiometry and volumetric BMD (BMDvol) was calculated. The obtained results were expressed as Z-scores. RESULTS: The values of basic anthropometric parameters did not differ significantly from the values of the reference population and there was a tendency to short stature, which did not reach statistical significance (P = 0.08). The values of calciuria and U-NAG/Cr were significantly higher while BMD was significantly lower when compared to the reference values (P < 0.0006, P < 0.006 and P < 0.001, respectively). Inverse and significant correlations were found between U-Ca/24 h and BMD, U-Ca/24 h and body height, and U-Ca/24 h and BMDvol (r = -0.64 and -0.70, respectively, P < 0.01; r = -0.55, P < 0.05), while there was no correlation between U-NAG/Cr and U-Ca/24 h, nor between BMD and weight or BMD and BMI. CONCLUSION: Tubular impairment is highly probable in children with IH, but there is a poor relationship with the degree of calcium leakage. Idiopathic hypercalciuria should be considered as a risk factor for stunted growth and low bone mass.     

Renal expression of CD44 correlates with acute renal allograft rejection

As CD44 is involved in the activation, proliferation, adhesion, and extravasation of lymphocytes, we hypothesized that CD44 could be involved in the pathogenesis of acute renal allograft rejection. Renal biopsies and plasma were collected from patients suffering an episode of acute renal allograft rejection. CD44 and its ligands, hyaluronic acid (HA) and osteopontin, were analyzed retrospectively by immunohistochemistry and, computer-aided, morphometric analysis. Soluble CD44 (sCD44) and osteopontin in the plasma were determined by enzyme-linked immunosorbent assay. During acute rejection episodes, CD44 and its ligands, HA and osteopontin, were upregulated in the renal allograft. Also, increased sCD44 plasma levels were observed, which correlated with both tubular expression of CD44 and the extent of infiltrate. No differences could be detected between the different pathologic grades of rejection. Upregulation of tubular CD44 and increased levels of circulating sCD44 may reflect a common pathogenic mechanism during acute renal rejection and could be useful markers in the diagnosis of acute renal rejection.     

The diagnostic role of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in the detection of renal tubular impairment

The kidney function can be assessed by a number of methods. The urinary excretion of enzymes, in particular N-acetyl-beta-D-glucosaminidase (NAG), is considered a relatively simple, cheap, fast and non-invasive method in the detection and follow-up of renal tubular function under various conditions. The determination of urinary NAG provides a very sensitive and reliable indicator of renal damage, such as injury or dysfunction due to diabetes mellitus, nephrotic syndrome, inflammation, vesicoureteral reflux, urinary tract infection, hypercalciuria, urolithiasis, nephrocalcinosis, perinatal asphyxia, hypoxia, hypertension, heavy metals poisoning, treatment with aminoglycosides, valproate, or other nephrotoxic drugs. This paper gives an overview of the current use of urinary NAG in the detection of renal injury.     

Níveis séricos de homocisteína em crianças e adolescentes com comprometimento da saúde óssea

IntroductionAssociation between high serum homocysteine (S-Hcy) levels and low bone mineral density (BMD) and increased fracture risk in postmenopausal women has been documented. Data concerning S-Hcy and bone health in children are scarce.ObjectiveOur aim was to evaluate S-Hcy in children and adolescents with impaired bone health and look for correlations with clinical and laboratory data.Patients and methodsWe assessed S-Hcy levels in 37 children and adolescents (22 boys and 15 girls; mean age 13.9 ± 3.5 years) with prevalent low-energy trauma fractures (mean 3.3 ± 2.3 per patient) and/or low spinal L1-L4 BMD (below -2SD Z-score; DXA Lunar GE). We also evaluated S-ALP, serum CrossLaps, osteocalcin (S-OC), body height, weight, body mass index (BMI) and serum levels of folate and vitamin B12. At the time of assessment, the chil- dren were not taking any drugs known to influence bone metabolism. The age-dependent parameters were expressed as Z-scores ± SD.ResultsS-Hcy Z-score was significantly higher (1.3 ± 1.5; P < 0.0001) and L1-L4 BMD Z-score was significantly lower (-1.7 ± 1.3; P < 0.0001), respectively, in comparison with reference values. S-ALP did not differ from reference values (P = 0.88), while S-CrossLaps and S-osteo- calcin were higher (1.2 ± 1.8 and 0.4 ± 0.5; P = 0.0001 and P = 0.001, respectively). S-Hcy was inversely correlated to L1-L4 BMD (r = -0.33; P = 0.05) and S-ALP (r = -0.36; P = 0.04) and not related to number of prevalent fractures (r = 0.01), S-osteocalcin (r = -0.22) or S-CrossLaps (r = 0.003).ConclusionThese results suggest increased bone turnover and negative influence of elevat- ed S-Hcy on bone formation and BMD in children and adolescents with recurrent fractures.     

Modified orthostatic load for spectral analysis of short-term heart rate variability improves the sensitivity of autonomic dysfunction assessment

AimTo evaluate the impact of orthostatic load for sensitivity of short-term spectral analysis of heart rate variability (HRV) assessment of potential early autonomic dysfunction in diabetes mellitus.MethodsComparison of results of short-term time- and frequency-domain analysis of HRV during single positions and during modified orthostatic load (supine 1–standing–supine 2, each position 300 s) in diabetic subjects with good glycemic control (n=80, age 38±14, diabetes duration 16±10 years) and without autonomic neuropathy as assessed by a standard bedside reflex test battery, and in nondiabetic controls (n=150, age 40±13 years).ResultsNone of the short-term frequency-domain parameters [absolute and logarithmic (LN) values of spectral powers in total- (TF), low- (LF), and high-frequency (HF) bands and its centroid frequencies] as obtained in single positions “supine” or “standing” revealed a significant difference between well-controlled patients and healthy controls (P>.3). However, during modified orthostatic load, significant differences in ΔLN TF_{(supine 1–supine 2)} and in ΔLN LF_{(supine 1–supine 2)} as well as in ΔLN LF_{(standing–supine 2)} values between diabetic and healthy subjects were recorded [?0.2±0.5 vs. ?0.1±0.4 LN (ms²), P=.05; ?0.3±0.8 vs. 0.1±0.7 LN (ms²), P=.001 and 0.2±1.0 vs. 0.4±0.9 LN (ms²), P=.05, respectively] with insignificant intergroup differences in related centroid frequencies. This finding suggests a delayed recovery of LF spectral power in diabetic subjects after orthostatic challenge.ConclusionsWhen compared with single position measurements, the modified orthostatic load protocol improves the sensitivity of short-term HRV examination. In well-controlled diabetic subjects without cardiovascular autonomic neuropathy (as excluded by standard cardiovascular reflex testing), the delayed recovery of LF band spectral power after orthostatic load with standing up indicates diminished parasympathetic activation.