Towards a definition of glomerulomegaly: clinical-pathological and methodological considerations

Abstract

Background: Glomerulomegaly, the abnormal enlargement of glomeruli, has been related to an increased risk of glomerulosclerosis, but the degree of enlargement that constitutes glomerulomegaly has not been defined.

Methods: The principal stereological methods for estimating glomerular volume are [1] the disector/Cavalieri method that is considered the 'gold standard' for measuring individual glomerular volume (IV(glom)) and [2] the disector/fractionator technique that estimates average glomerular volume (V(glom)) together with total glomerular number (N(glom)) for the entire kidney. The two methods produce different estimates with V(glom) consistently exceeding IV(glom). This study compares glomerular volumes obtained by the two methods in autopsy kidneys of 39 African American and 34 US white adult males, and correlates the values with N(glom), body mass index (BMI), hypertension, glomerulosclerosis and race, factors known or thought to influence glomerular volume.

Results: For the smallest glomeruli, V(glom) was 25% larger than IV(glom) with the difference increasing to over 50% for kidneys with the largest glomeruli. Both V(glom) and IV(glom) showed significant inverse correlations with N(glom) and significant direct correlations with BMI and hypertension. African Americans had larger IV(glom) and V(glom) than whites, but only IV(glom) was significant. The 90th percentile for IV(glom) was 6.81 μm(3) × 10(6) and 13.10 μm(3) × 10(6) for V(glom), but larger glomerular size did not separate hypertensive from non-hypertensive subjects nor did it show any significant relationship to glomerulosclerosis. While V(glom) overestimated glomerular size compared with IV(glom), both measurements demonstrated similar relationships to factors influencing glomerular volume.

Conclusions: With neither method could glomerulomegaly, the abnormal enlargement of glomerular size predisposing to glomerulosclerosis, be determined.

Fig. 1

Histogram of V_glom (m³ × 10⁶) for African American and white subjects with kernel density plots of non-hypertensive (blue line) and hypertensive subjects (red line). The volume estimates are skewed towards larger glomerular size.

Fig. 2

Histogram of IV_glom (m³ × 10⁶) for African American and white subjects with kernel density plots of non-hypertensive (blue line) and hypertensive subjects (red line). The volume estimates are more closely clustered around the median than in Figure 1 but are still skewed towards larger glomerular size.

Fig. 3

V_glom (m³ × 10⁶) plotted against MAP. There is no significant relationship between the two variables.

Fig. 4

IV_glom (m³ × 10⁶) plotted against MAP. There is a significant direct relationship between the two variables (adjusted r² = 0.130, P = 0.01). A MAP = 107 mmHg is hypertensive, and there is no level of IV_glom that separates hypertensive from non-hypertensive subjects.