New insights on glomerular hyperfiltration: a Japanese autopsy study

Area of Science:

• Nephrology
• Pathology
• Stereology

Background:

• Low nephron number is implicated in progressive chronic kidney disease (CKD) pathogenesis.
• The high incidence of CKD in Japan necessitates understanding its underlying causes.
• Glomerular hypertension and hyperperfusion injury are potential consequences of reduced nephron count.

Purpose of the Study:

• To estimate nephron number and glomerular volume in Japanese individuals across normotensive, hypertensive, and CKD groups.
• To investigate the association between nephron count, glomerular volume, and estimated glomerular filtration rate (eGFR).
• To elucidate the compensatory mechanisms for maintaining GFR under conditions of low nephron number.

Main Methods:

• Stereological methods (disector/fractionator) were used to estimate total nephron number, nonsclerosed glomeruli, globally sclerosed glomeruli, and mean nonsclerosed glomerular volume in autopsy kidney samples.
• Age-matched Japanese men (n=27) were categorized into normotensive, hypertensive, and CKD groups (9 per group).
• Estimated glomerular filtration rate (eGFR), single-nephron eGFR (SNeGFR), and the SNeGFR/VglomNSG ratio were calculated.

Main Results:

• Nonsclerosed glomeruli number was significantly lower in hypertensive (392,108 ± 87,605) and CKD (268,043 ± 106,968) groups compared to normotensives (640,399 ± 160,016).
• eGFR directly correlated with nonsclerosed glomeruli number (r=0.70) and inversely with glomerular volume (r=-0.53).
• SNeGFR was elevated in hypertensives versus normotensives, but similar between normotensives and CKD. The SNeGFR/VglomNSG ratio was reduced in CKD patients.

Conclusions:

• Japanese individuals with hypertension or CKD exhibit a reduced nephron number.
• Glomerular hypertrophy, rather than glomerular hypertension, appears to be the primary mechanism for maintaining GFR when nephron number is low.
• These findings highlight the role of glomerular hypertrophy in compensating for reduced nephron count in kidney disease.