Glomerular Density and Volume in Renal Biopsy Specimens of Children with Proteinuria Relative to Preterm Birth and Gestational Age

Abstract

Background and objectives: A low total nephron number, which is associated with low birth weight (LBW), may indicate increased susceptibility to early-onset renal diseases in children. However, few studies have assessed renal biopsy findings in LBW children. We examined the relationship between LBW and glomerular density (GD) and/or glomerular volume (GV) in renal biopsy samples as a surrogate for total nephron number.

Design, setting, participants, & measurements: Renal biopsy findings of children of LBW were compared with those of age-matched control subjects of normal birth weight (NBW) who were histopathologically diagnosed with FSGS or minimal change nephrotic syndrome (MCNS) from 1995 to 2011. The GD and GV were estimated on the basis of measurements obtained by computerized image analysis.

Results: A total of 31 subjects (mean age 11 years; eight with low birth weight-FSGS [LBW-FSGS], 10 with normal birth weight-FSGS [NBW-FSGS], and 13 with normal birth weight-minimal change nephrotic syndrome [NBW-MCNS]) were analyzed. The mean birth weight of each group was 777 g (629-1000), 3110 g (2888-3358), and 3120 g (2748-3398), respectively (median [25th-75th percentile]). Age, body mass index, BP, and degrees of globally sclerotic glomeruli at biopsy were comparable between the groups. The GD was lower (LBW-FSGS, 1.4±0.6/mm²; NBW-FSGS, 3.3±1.2/mm²; and NBW-MCNS, 3.6±1.1/mm²; P<0.05) and the GV was greater (LBW-FSGS, 4.1 [3.1-5.1]×10⁶µm³; NBW-FSGS, 1.6 [1.5-2.1]×10⁶µm³; and NBW-MCNS, 1.3 [1.1-1.8]×10⁶µm³ [median, (25th-75th percentile)]; P<0.05) in patients with LBW-FSGS than in the other patient groups. The GD showed close positive correlations with birth weight (r=0.48) and gestational age (r=0.54), independent of renal function and degree of global glomerular sclerosis.

Conclusions: A low GD together with marked glomerular enlargement characterizes renal biopsy samples of children born with a LBW at an early stage of gestation.

Keywords: biopsy; birth weight; blood pressure; body mass index; child; female; gestational age; glomerulosclerosis, focal segmental; humans; infant, low birth weight; infant, newborn; kidney; kidney glomerulus; nephrons; nephrosis, lipoid; pregnancy; premature birth; proteinuria; sclerosis; segmental glomerulosclerosis.

Figure 1.

Representative light micrographs of renal biopsy findings. Representative renal biopsy findings in cases of (A) LBW-FSGS (13-year-old boy with an eGFR of 68.4 ml/min per 1.73 m²), (B) NBW-FSGS (8-year-old boy with an eGFR of 170.7 ml/min per 1.73 m²), and (C) NBW-MCNS (14-year-old girl with an eGFR of 123.1 ml/min per 1.73 m²). Periodic acid–methenamine silver stain was used (original magnification, ×50). All glomeruli are indicated with a circle. LBW-FSGS, low birth weight–FSGS; NBW-FSGS, normal birth weight–FSGS; NBW-MCNS, normal birth weight–minimal change nephrotic syndrome.

Figure 2.

Relationship between GD and mean GV/gestational age. GD showed a close inverse correlation with mean GV (A). GD showed close correlations with gestational age (B). Closed circle, LBW-FSGS; open circle, NBW-FSGS; open triangle, NBW-MCNS. The distributions are represented by a curve-fitting. GD, glomerular density; GS, globally sclerotic glomeruli; GV, glomerular volume; LBW-FSGS, low birth weight–FSGS; NBW-FSGS, normal birth weight–FSGS; NBW-MCNS, normal birth weight–minimal change nephrotic syndrome.