Sex related differences in glomerular ultrafiltration and proteinuria in Munich-Wistar rats

Munich-Wistar rats (MFW/Ztm), originally selected for high number of superficial glomeruli, were used to correlate abnormal urinary protein excretion with glomerular hemodynamics and glomerular morphology. Two animal groups were used, one of male and one of female rats. They were kept periodically in metabolic cages to determine urinary protein excretion. All animals were fed standard rat chow. In male animals protein excretion, evaluated at seven weeks of age, was already significantly higher than in females (17 ± 11 vs. 8 ± 3 mg/24 hr), and then progressively increased averaging 291 ± 51 mg/24 hr at week 21. In females urinary protein excretion was within the normal range up to week 18 and averaged 25 ± 13 mg/24 hr at week 21. Body and kidney weight at the end of the experimental period were significantly higher in males than in females. Whole kidney inulin clearance (C(In)) and single nephron glomerular filtration rate (SNGFR) were significantly higher in male than in female rats, while mean glomerular capillary hydraulic pressure (P̄(GC)) and transcapillary hydraulic pressure difference (Δ̄P̄) were comparable. Single nephron glomerular plasma flow (Q(A)) and afferent and efferent arteriolar resistance were comparable in male and female rats. The calculated glomerular ultrafiltration coefficient (K(f)) was significantly higher in male than in female MWF/Ztm rats. No significant differences were detected between the two groups in the total number of glomeruli, and in glomerular size. These findings indicate that male MWF/Ztm rats develop spontaneous proteinuria, which progressively increases with the age. This abnormal urinary protein excretion, not observed in female rats, is associated with higher SNGFR and elevation of K(f), without significant changes in the other determinants of glomerular ultrafiltration. These observations, together with the results of the morphometrical analysis, indicate that hydraulic membrane permeability is elevated in male rats when compared to females. It is speculated that the defects in membrane permeability to water and macromolecules are genetically determined rather than a consequence of glomerular hemodynamic changes.