An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients

被引:65
作者
Katz, A
Caramori, MLA
Sisson-Ross, S
Groppoli, T
Basgen, JM
Mauer, M
机构
[1] Univ Minnesota, Dept Pediat, MMC 491, Minneapolis, MN 55455 USA
[2] Bikur Holim Hosp, Dept Pediat & Nephrol, Jerusalem, Israel
关键词
diabetic nephropathy; renal interstitium; cell proliferation/hypertrophy; progressive kidney disease;
D O I
10.1046/j.1523-1755.2002.00370.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. Interstitial expansion is important in the progression of a variety of kidney diseases, including diabetic nephropathy (DN). However, the interstitial elements that constitute interstitial expansion in DN are unknown and are the subject of this report. Methods. Interstitial composition was analyzed in 15 long-standing type 1 diabetic patients, 8 with mild (approximate to1.5 x normal) and 7 with moderate (approximate to2 x normal) increases in cortical interstitial fractional volume [Vv(Int/cortex]. The mild group was 29 +/- 5 (mean +/- SD) years old with diabetes duration of 17 +/- 5 years. The moderate group was older (41 +/- 7 years; P < 0.03), had longer diabetes duration (28 +/- 7 years; P = 0.002), lower creatinine clearance (90 +/- 14 mL/min/1.73 m(2) vs. 109 +/- 18 mL/min/1.73 m(2) ; P = 0.05) and used antihypertensive medications more frequently (0/8 vs. 4/7; P < 0.03) compared to the mild group. Age- and gender-matched normal controls (N = 9) also were studied. Interstitial composition was evaluated by morphometric analysis of electron microscopic (EM) micrographs systematically obtained without bias at high (x7500) and low (x1500) magnification. Results. Mild interstitial expansion was associated with an approximate to50% increase in fractional volume of interstitial cells (P < 0.001) and approximate to70% increase in fractional volume of interstitial nuclei (P < 0.01). Numerical density of interstitial nuclei was normal in these patients, suggesting that the interstitial cells might be larger rather than simply more numerous. An increase over normal in the interstitial fractional volume of fibrillary collagen of approximate to50% was seen only with moderate expansion (P < 0.001), when creatinine clearance was already decreased. Interstitial expansion was associated with a decrease in volume and surface of peritubular capillaries as well as with a reduction in surface ratio of capillaries to tubules. Conclusions. In contrast to early mesangial expansion where matrix accumulation plays a dominant role, mild interstitial expansion in long-standing type 1 diabetic patients is largely due to an increase in the cell component of the interstitium. Increased fractional volume of interstitial fibrillary collagen is only seen at later stages of the disease, when the glomerular filtration rate is already reduced. Different pathogenetic processes may be operative in early diabetic glomerular and interstitial diseases.
引用
收藏
页码:2058 / 2065
页数:8
相关论文
共 34 条
[1]  
[Anonymous], 1997, ARCH INTERN MED, V157, P2413, DOI DOI 10.1001/ARCHINTE.1997.00440420033005
[2]   STRUCTURE AND FUNCTION OF THE KIDNEY IN DIABETIC GLOMERULOSCLEROSIS CORRELATIONS BETWEEN MORPHOLOGICAL AND FUNCTIONAL PARAMETERS [J].
BADER, R ;
BADER, H ;
GRUND, KE ;
MACKENSENHAEN, S ;
CHRIST, H ;
BOHLE, A .
PATHOLOGY RESEARCH AND PRACTICE, 1980, 167 (2-4) :204-216
[3]  
BOHLE A, 1991, PATHOL RES PRACT, V187, P251
[4]   Proximal tubular basement membrane width in insulin-dependent diabetes mellitus [J].
Brito, PL ;
Fioretto, P ;
Drummond, K ;
Kim, YK ;
Steffes, MW ;
Basgen, JM ;
Sisson-Ross, S ;
Mauer, M .
KIDNEY INTERNATIONAL, 1998, 53 (03) :754-761
[5]   Cellular basis of diabetic nephropathy 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes [J].
Caramori, ML ;
Kim, Y ;
Huang, CM ;
Fish, AJ ;
Rich, SS ;
Miller, ME ;
Russell, G ;
Mauer, M .
DIABETES, 2002, 51 (02) :506-513
[6]   Tubulointerstitium as predictor of progression of glomerular diseases [J].
D'Amico, G .
NEPHRON, 1999, 83 (04) :289-295
[8]  
DRUMMOND K, IN PRESS DIABETES, V51
[9]   GLOMERULAR-FILTRATION SURFACE IN TYPE-I DIABETES-MELLITUS [J].
ELLIS, EN ;
STEFFES, MW ;
GOETZ, FC ;
SUTHERLAND, DER ;
MAUER, SM .
KIDNEY INTERNATIONAL, 1986, 29 (04) :889-894
[10]   RELATIONSHIP OF RENAL SIZE TO NEPHROPATHY IN TYPE-1 (INSULIN-DEPENDENT) DIABETES [J].
ELLIS, EN ;
STEFFES, MW ;
GOETZ, FC ;
SUTHERLAND, DER ;
MAUER, SM .
DIABETOLOGIA, 1985, 28 (01) :12-15