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 μm³ × 10⁶ and 13.10 μm³ × 10⁶ 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.