PROGRESSIVE GLOMERULAR INJURY IN THE MWF RAT IS PREDICTED BY INBORN NEPHRON DEFICIT

It has been suggested that a reduced number of nephrons may predispose to systemic hypertension and glomerular injury. Compensatory hemodyna mic changes, due to a low number of glomeruli, might be responsible fo r glomerular functional and structural changes. It is difficult to eva luate this hypothesis in humans because of limitations in estimating t he number of nephrons in the living kidney. The aim of the present stu dy was to estimate nephron number, single glomerular hemodynamics, and glomerular volume in male and female MWF rats, a strain that spontane ously develops systemic hypertension, proteinuria, and glomerulosclero sis. Male and female Wister rats were used as controls. At 12 to 14 wk of age, male MWF rats developed proteinuria, whereas female MWF and W istar rats showed normal urinary protein excretion rate. Glomerular nu mber was significantly reduced in male and female MWF rats (13,690 +/- 1,489 and 12,855 +/- 1,781 gl/kidney, respectively) compared with Wis tar rats (26,955 +/- 2,171 and 27,166 +/- 1,754 gl/kidney, respectivel y). The mean number of nephrons per unit of body weight was also lower in MWF males (88 +/- 10) compared with MWF females (139 +/-. 20) and compared with male and female Wistar animals (142 +/- 14 and 221 +/- 2 2 gl/g body wt). Whole-kidney hemodynamic parameters and the number of nephrons were used to calculate single-nephron filtration rate and pl asma flow. Both measures were markedly elevated in male MWF rats relat ive to values obtained in the ocher three groups. Similarly, glomerula r volume was significantly greater in MWF males than in other animals. These results suggest that an inborn deficit of nephrons may be respo nsible for spontaneous development of later-in-life hypertension and r enal dysfunction. The data also indicate the need to investigate the r ole of this potential pathogenetic factor for human hypertension and k idney disease in humans.