Quantitative bone histology in children with chronic renal failure
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In children with reduced kidney function, significant bone disease primarily appears when glomerular filtration rate (GFR) drops below 30 ml/min/1.73m2. Bone histology is crucial for early detection, though GFR levels often predict disease presence.
Area of Science:
- Pediatric Nephrology
- Bone Histology
- Renal Osteodystrophy
Background:
- Chronic kidney disease (CKD) in children can lead to significant bone abnormalities.
- Assessing bone disease in pediatric CKD patients is challenging.
- Early detection of renal osteodystrophy is critical for patient management.
Purpose of the Study:
- To investigate the relationship between glomerular filtration rate (GFR) and bone histology in children.
- To evaluate the effectiveness of noninvasive methods in diagnosing bone disease in pediatric CKD.
- To determine the threshold of GFR for the development of significant bone disease.
Main Methods:
- Quantitative bone histology using undecalcified sections and double tetracycline labeling.
- Radiographic assessment.
- Biochemical analysis including parathyroid hormone and alkaline phosphatase.
- Study included 47 children aged 1-17 years with GFR < 80 ml/min/1.73m2.
Main Results:
- Earliest histologic changes included increased osteoid and osteoblast surfaces.
- Significant bone disease (osteoclastic surface, fibrosis, mineralization lag time) occurred only at GFR < 30 ml/min/1.73m2.
- Radiographs and alkaline phosphatase were normal in 25% of affected children; PTH was elevated in 48% of unaffected children.
- GFR was the most sensitive indicator, with bone disease present in all children with GFR < 20 ml/min/1.73m2.
Conclusions:
- Bone histology is essential for early detection of renal osteodystrophy in children.
- Noninvasive investigations are unreliable predictors of bone disease in this population.
- GFR is a sensitive indicator, and bone biopsy can often be avoided in clinical practice based on GFR levels.
Abstract:
Quantitative bone histology (on undecalcified sections following double tetracycline labeling), radiographs, and biochemistry were studied in 47 children, ages 1 to 17 years, with glomerular filtration rates (GFR) below 80 ml/min/1.73m2. The earliest histologic change was an increased osteoid surface accompanied by increased osteoblast and tetracycline surfaces. However, significant bone disease (increased osteoclastic surface, fibrosis, increased osteoid area, increased mineralization lag time, and reduced tetracycline uptake at osteoid surfaces) occurred only at GFR below 30 ml/min/1.73m2. Radiographs and alkaline phosphatase were normal in 25% of children with significant bone disease; parathyroid hormone was increased in 48% of children without bone disease. Thus, these noninvasive investigations were poor predictors of disease presence. GFR was the most sensitive indicator because bone disease occurred only at GFR below 30 ml/min/1.73m2 and was present in all children with GFR below 20 ml/min/1.73m2. It was concluded that bone histology is required for early detection of bone disease and is an essential tool in experimental studies of renal osteodystrophy. However, because the level of GFR will indicate the presence or absence of bone disease in most children, bone biopsy can be avoided generally in clinical practice.