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

Avi Katz, Luiza Caramori, Susan Sisson-Ross, Thomas Groppoli, John M. Basgen, Michael Mauer

Research output: Contribution to journalArticle

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Abstract

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 longstanding type 1 diabetic patients, 8 with mild (≈1.5 × normal) and 7 with moderate (≈2 × 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 m2 vs. 109 ± 18 mL/min/1.73 m2; 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 (×7500) and low (×1500) magnification. Results. Mild interstitial expansion was associated with an ≈50% increase in fractional volume of interstitial cells (P < 0.001) and ≈70% 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 ≈50% 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.

Original languageEnglish (US)
Pages (from-to)2058-2065
Number of pages8
JournalKidney International
Volume61
Issue number6
DOIs
StatePublished - Jan 1 2002

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Cellular Structures
Fibrosis
Diabetic Nephropathies
Creatinine
Collagen
Kidney Diseases
Glomerular Filtration Rate
Cell Size
Antihypertensive Agents
Electrons

Keywords

  • Cell proliferation/hypertrophy
  • Diabetic nephropathy
  • Progressive kidney disease
  • Renal interstitium

Cite this

An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients. / Katz, Avi; Caramori, Luiza; Sisson-Ross, Susan; Groppoli, Thomas; Basgen, John M.; Mauer, Michael.

In: Kidney International, Vol. 61, No. 6, 01.01.2002, p. 2058-2065.

Research output: Contribution to journalArticle

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abstract = "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 longstanding type 1 diabetic patients, 8 with mild (≈1.5 × normal) and 7 with moderate (≈2 × 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 m2 vs. 109 ± 18 mL/min/1.73 m2; 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 (×7500) and low (×1500) magnification. Results. Mild interstitial expansion was associated with an ≈50{\%} increase in fractional volume of interstitial cells (P < 0.001) and ≈70{\%} 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 ≈50{\%} 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.",
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T1 - An increase in the cell component of the cortical interstitium antedates interstitial fibrosis in type 1 diabetic patients

AU - Katz, Avi

AU - Caramori, Luiza

AU - Sisson-Ross, Susan

AU - Groppoli, Thomas

AU - Basgen, John M.

AU - Mauer, Michael

PY - 2002/1/1

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N2 - 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 longstanding type 1 diabetic patients, 8 with mild (≈1.5 × normal) and 7 with moderate (≈2 × 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 m2 vs. 109 ± 18 mL/min/1.73 m2; 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 (×7500) and low (×1500) magnification. Results. Mild interstitial expansion was associated with an ≈50% increase in fractional volume of interstitial cells (P < 0.001) and ≈70% 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 ≈50% 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.

AB - 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 longstanding type 1 diabetic patients, 8 with mild (≈1.5 × normal) and 7 with moderate (≈2 × 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 m2 vs. 109 ± 18 mL/min/1.73 m2; 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 (×7500) and low (×1500) magnification. Results. Mild interstitial expansion was associated with an ≈50% increase in fractional volume of interstitial cells (P < 0.001) and ≈70% 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 ≈50% 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.

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KW - Diabetic nephropathy

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