Angiotensin-converting enzyme inhibitors and probucol suppress the time-dependent increase in urinary Type IV collagen excretion of Type II diabetes mellitus patients with early diabetic nephropathy.
BACKGROUND
A multicenter prospective clinical trial was carried out in 9 National Hospitals in Japan to elucidate the time-dependent change in urinary Type IV collagen excretion rate of Type II diabetes mellitus (DM) patients, and to investigate whether an angiotensin-converting enzyme inhibitor (ACE-I) or probucol is effective in preventing progression of renal involvement of diabetics by evaluating urinary Type IV collagen excretion.


METHODS
Normo- and microalbuminuric patients with Type II DM were recruited. Patients were assigned to either the control (n = 88), ACE-I (n = 43) or probucol (n = 37) group and treated for 24 months. Besides albumin excretion rate (AER), urinary Type IV collagen excretion rate was also measured.


RESULTS
Although, AER, urinary N-acetyl-beta-D-glucosaminidase and beta2-microglobulin excretion rates in the control group did not vary over 24 months, urinary Type IV collagen excretion rate in the control group increased time-dependently (p < 0.01 vs baseline at 18 months and p < 0.005 vs baseline at 24 months). In the ACE-I and probucol groups, time-dependent increases in urinary Type IV collagen excretion rates were not observed. In the ACE-I group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 24 months (p < 0.05). In the probucol group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 6 months (p < 0.05). In the ACE-I group, AER decreased significantly compared with baseline at 18 months (p < 0.05) and at 24 months (p < 0.005).


CONCLUSIONS
ACE-I has a beneficial effect and probucol may have a beneficial effect in preventing the progression of early diabetic nephropathy. Measurement of the urinary Type IV collagen excretion rate in combination with AER would be useful for the management of early renal involvement in Type II DM.
Nishimura
M
M
Department of Internal Medicine, Sakura National Hospital, Chiba, Japan. mnishi@snh.hosp.go.jp.
Sasaki
T
T
Ohishi
A
A
Oishi
M
M
Kono
S
S
Totani
Y
Y
Kato
Y
Y
Noto
Y
Y
Misaki
S
S
Higashi
K
K
Shimada
F
F
Wakasugi
H
H
Inoue
K
K
Hoshiyama
Y
Y
Yamada
K
K
D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D024141:Collagen Type IV / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000652:urine*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D013997:Time Factors
D000118:Acetylglucosaminidase; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D002784:Cholesterol; D024141:Collagen Type IV; D006442:Glycated Hemoglobin; D011341:Probucol