Selectivity of renal injury and proteinuria in the spontaneously hypertensive rat

Selectivity of renal injury and proteinuria in the spontaneously hypertensive rat. We have followed the concentration and fractional composition of tubular fluid protein and urinary protein in spontaneously hypertensive rats (SHR) from 6 to 65 weeks of their age. At intervals these functional data were correlated with the morphologic changes read by light microscopy. Matched control animals were of the same genetic strain, Wistar-Kyoto (WKY). Proximal tubular fluid protein was measured by capillary polyacrylamide gel electrophoresis; urinary protein, by Lowry method; and fractionation, by gradient gel electrophoresis. Tubular fluid protein in superficial nephrons did not change, although protein excretion rose in the SHR group to six times the control value (4.3 to 26 mg/24 hr × 100g of body wt). The albumin fraction of urinary protein increased in the SHR from 10.5 ± 3.1% (SD) at week 6 to 72.3 ± 9.0% at week 65. No change occurred in WKY controls. Pathologic changes in SHR were strikingly limited to glomeruli and vessels of inner cortical nephrons, and progressed rapidly from 45 to 65 weeks. Glomeruli showed focal sclerosis with obliteration of the capillary tuft. Corresponding tubules were filled with protein casts. Small arteries and arterioles showed thickening and hyperplasia, particularly in the medial layer. Periglomerular fibrosis was moderate to marked. None of these changes were found in normotensive controls. The distinguishing pattern of proteinuria (albuminuria coincident with a decrease in low mol wt protein excretion) which evolved during the first year in SHR was temporally related to glomerular and arteriolarsclerotic changes. These changes mainly affected the deep cortical nephrons, which were less protected, perhaps, by autoregulation in the face of sustained hypertension. Superficial glomeruli were initially spared, and this is consistent with the finding of normal tubular fluid protein concentration in surface nephrons. Selectivite des lesions renales et de la proteinurie chez les rats spontanement hypertendus. Nous avons etudie le debit et la composition de la proteinurie chez les rats spontanement hypertendus (SHR) de la sixieme a la soixante cinquieme semaine de vie. Les resultats des etudes fonctionnelles ont ete correles, a intervalles reguliers, aux modificiations observees en microscopie photonique. Les controles ont ete des animaux de la meme souche genetique, Wistar-Kyoto (WKY). La concentration de proteine dans le liquide tubulaire proximal a ete mesuree par electrophorese sur gel de polyacrylamide, dans l'urine par la methode de Lowry et le fractionnement par electrophorese en gradient de gel. La concentration de proteine dans les nephrons superficiels n'augmente pas alors que l'excretion de proteine augmente pour atteindre six fois la valeur controle dans le groupe SHR (4,3 a 26 mg/24 hr × 100g poids corporel). La fraction d'albumine de la proteinurie augmente chez le SHR de 10,5 ± 3.1% (SD) a 6 semaines jusqu'a 72,3 ± 9,0% a 65 semaines. Aucune modification n'apparait chez les controles WKY. Les modifications histologiques chez les SHR sont limitees, de facon frappante, aux glomerules et aux vaisseaux des nephrons du cortex profond. Elles progressent rapidement de 45 a 65 semaines. Les glomerules ont une sclerose focale avec obliteration du capillaire. Les tubes correspondants sont remplis de cylindres proteiques. Les petites arteres et les arterioles sont epaissies et hyperplasiques, en particulier aux depends de la couche moyenne. La fibrose peri-glomerulaire est au moins moderee. Aucune de ces modifications n'est observee chez les controles a pression arterielle normale. La modalite particuliere de la proteinurie (albuminurie qui coand;ncide avec une diminution de l'excretion des proteines de faible PM) qui se developpe pendant la premiere annee chez les SHR est liee dans le temps aux modifications glomerulaires et vasculaires. Ces modifications interessent surtout les nephrons profonds, qui sont peut-etre moins proteges, par l'autoregulation, d'une hypertension prolongee. Les glomerules superficiels sont initialement epargnes et ceci explique que l'on trouve une concentration normale de proteine dans le liquide tubulaire des nephrons superficiels