STRUCTURAL-FUNCTIONAL RELATIONSHIPS IN ALPORT SYNDROME

Renal morphometric analysis was performed in 15 (13 male) Alport syndr ome patients ages 4 to 26 years, along with 10 controls ages 3 to 26 y ears, to better understand the structural basis of renal dysfunction i n Alport syndrome. The glomerular basement membrane (GEM) width class frequencies of controls were normally distributed; those of Alport syn drome patients were slightly skewed, especially toward thicker classes , although there was also an increase in the proportion of thinner cla sses. Mesangial volume fraction was not different between Alport syndr ome patients (0.21 +/- 0.09) and controls (0.19 +/- 0.04). There was a n inverse correlation between mesangial volume fraction and creatinine clearance in Alport syndrome patients (r = -0.72, P < 0.01); however, the creatinine clearances in Alport syndrome patients were far less t han in insulin-dependent diabetic patients with similar mesangial volu me fraction. Similarly, there was no significant difference in the sur face density of the peripheral GEM (in square micrometers per cubic mi crometer) in Alport syndrome patients (0.12 +/- 0.04) versus controls (0.13 +/- 0.02). The surface density of the peripheral GEM correlated with creatinine clearance in Alport syndrome patients (r = 0.71, P < 0 .01). However, there was a greater reduction in creatinine clearance a s related to declining the surface density of the peripheral GEM in Al port syndrome than in diabetic patients. The cortical interstitial vol ume fraction was highly inversely correlated with creatinine clearance in Alport syndrome patients (r = -0.85, P < 0.01). Global glomerular sclerosis was 0% in five and 5 to 61% in nine Alport syndrome patients and correlated inversely with creatinine clearance (r = -0.74, P < 0. 01). However, the creatinine clearance was lower in Alport syndrome th an in diabetic patients with similar cortical interstitial volume frac tion and percent glomerular sclerosis. There was no significant differ ence in an index of glomerular number between Alport syndrome patients and controls. Thus, changes in mesangial volume fraction, cortical in terstitial volume fraction, percent glomerular sclerosis, and surface density of the peripheral GEM in Alport syndrome patients only partial ly account for the reduction in creatinine clearance. It was speculate d that decreased glomerular capillary wall hydraulic conductivity in A lport syndrome could explain many of these observations.