CHRONOLOGY OF RENAL SCARRING IN MALES WITH ALPORT-SYNDROME

We investigated the onset of renal scarring in 62 males (aged 4-26 yea rs) with Alport syndrome by measuring cortical interstitial volume fra ction [Vv (interstitium/cortex)] and percentage global glomerular scle rosis in kidney biopsies. Male pediatric (n = 9) and adult (n = 7) don or kidneys served as controls. Creatinine clearance at the time of bio psy was available for 43 Alport patients. A statistically insignifican t correlation between age and Vv (interstitium/cortex) was observed in normal subjects (r = +0.47, slope = 0.0009, P = 0.07). In the Alport patients, age was significantly correlated with Vv (interstitium/corte x) (r = +0.49, slope = 0.01, P = 0.001) and global glomerular sclerosi s (r = +0.41, P = 0.01), and inversely cor related with creatinine cle arance (r = -0.33, P = 0.04). Creatinine clearance was inversely corre lated with Vv (interstitium/cortex) (r = -0.78, P = 0.001) and global glomerular sclerosis (r = -0.74, P = 0.001). The correlation with crea tinine clearance was especially strong for Vv (interstitium/cortex) va lues above the normal range, i.e., >0.2 (r = -0.82, P = 0.001), and wa s absent for Vv (interstitium/cortex) <0.2 (r = -0.119, P = 0.55). Cre atinine clearance values less than 80 ml/min per 1.73 m(2) occurred mo re frequently in patients with Vv (interstitium/cortex) values >0.2 (P < 0.0001) and in patients with >10% globally sclerosed glomeruli (P < 0.001). Patients r or > 10 years of age differed in Vv (interstitium/ cortex) [0.13 +/- 0.09 (mean +/- SD) vs. 0.24 +/- 0.026, P < 0.001], t he frequency of Vv (interstitium/cortex) > 0.2 (3/32 vs. 15/31, P < 0. 0001), the frequency of >10% globally sclerosed glomeruli (3/33 vs. 11 /30, P < 0.05), mean creatinine clearance (113 +/- 7 vs. 84 +/- 10 ml/ min per 1.73 m(2) P = 0.057), and the frequency of creatinine clearanc e < 80 ml/min per 1.73 m(2) (1/20 vs. 11/23, P < 0.01). Thus, reduced creatinine clearance in males with Alport syndrome is associated with Vv (interstitium/cortex) > 0.2 and > 10% globally sclerosed glomeruli. These are frequently detectable in the 2nd decade. We hypothesize tha t most Alport males will require intervention during the 1st decade fo r optimal preservation of kidney function.