Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle

Abstract

The disector method, a stereologic procedure unbiased by feature size, shape, or tissue-processing methods, for the estimation of total glomerular number was performed on pairs of human kidneys from 11 normal spontaneous second trimester abortions and stillbirths (15 to 40 weeks gestation). In addition, gestational age-dependent patterns of change in the average volume of the nephron and its cortical and medullary segments were analyzed. Mean glomerular number, plateauing at 36 weeks, increased from 15,000 at 15 weeks to 740,000 at 40 weeks. Average volume of the medullary nephron segment (Henle's loop) increased throughout pregnancy. Average volume of the cortical nephron segment (Tubuli Contorti) decreased from 15 weeks to 25 weeks, then increased after 36 weeks. Fractional volume of the renal cortex decreased from 15 weeks to 40 weeks. Three to 4 hours of microscopic analysis time were required per kidney on routinely processed 5-microns hematoxylin and eosin-stained paraffin sections. Average coefficient of error for number estimation was 8.02%. Average intra- and interobserver reproducibilities were 96.8 and 93.7%, respectively. The demonstrated temporal differences in the development of the cortical and medullary nephron components may result in a dissociation of function, which may explain the increased incidence of fetal hydrops in the second trimester of pregnancy, and which must be taken into account in the treatment of (very) premature infants. Although the number of kidneys included in this study is limited, as they reflect the whole period of antenatal development relevant to neonatal intensive care, the disector method of glomerular number estimation shows significant potential for the analysis and increased understanding of the development of renal function. The method appears to be more sensitive in detecting small and early deviations from normal renal growth and development than previously available parameters e.g., renal weight and (cortical) volume.