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 (IVglom) and [2] the disector/fractionator technique that estimates average glomerular volume (Vglom) together with total glomerular number (Nglom) for the entire kidney. The two methods produce different estimates with Vglom consistently exceeding IVglom. 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 Nglom, body mass index (BMI), hypertension, glomerulosclerosis and race, factors known or thought to influence glomerular volume.Results. For the smallest glomeruli, Vglom was 25% larger than IVglom with the difference increasing to over 50% for kidneys with the largest glomeruli. Both Vglom and IVglom showed significant inverse correlations with Nglom and significant direct correlations with BMI and hypertension. African Americans had larger IVglom and Vglom than whites, but only IVglom was significant. The 90th percentile for IVglom was 6.81 μm3 × 106 and 13.10 μm3 × 106 for Vglom, but larger glomerular size did not separate hypertensive from non-hypertensive subjects nor did it show any significant relationship to glomerulosclerosis. While Vglom overestimated glomerular size compared with IVglom, 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.