Chronology of renal scarring in males with Alport syndrome

Clifford Kashtan, Marie Claire Gubler, Susan Sisson-Ross, Michael Mauer

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

We investigated the onset of renal scarring in 62 males (aged 4-26 years) with Alport syndrome by measuring cortical interstitial volume fraction [Vv (interstitium/cortex)] and percentage global glomerular sclerosis in kidney biopsies. Male pediatric (n = 9) and adult (n = 7) donor kidneys served as controls. Creatinine clearance at the time of biopsy was available for 43 Alport patients. A statistically insignificant 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/cortex (r = +0.49, slope = 0.01, P = 0.001) and global glomerular sclerosis (r = +0.41, P = 0.01), and inversely correlated with creatinine clearance (r = -0.33, P = 0.04). Creatinine clearance was inversely correlated with Vv (interstitium/cortex) (r = -0.78, P = 0.001) and global glomerular sclerosis (r = -0.74, P = 0.001). The correlation with creatinine clearance was especially strong for Vv (interstitium/cortex) values above the normal range, i.e., > 0.2 (r = -0.82, P = 0.001), and was absent for Vv (interstitium/cortex) < 0.2 (r = -0.119, P = 0.55). Creatinine clearance values less than 80 ml/min per 1.73 m2 occurred more 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 ≤ or > 10 years of age differed in Vv (interstitium/cortex) [0.13 ± 0.09 (mean ± SD) vs. 0.24 ± 0.026, P < 0.001], the 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 m2, P = 0.057), and the frequency of creatinine clearance < 80 ml/min per 1.73 m2 (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 that most Alport males will require intervention during the 1st decade for optimal preservation of kidney function.

Original languageEnglish (US)
Pages (from-to)269-274
Number of pages6
JournalPediatric Nephrology
Volume12
Issue number4
DOIs
StatePublished - Jan 1 1998

Fingerprint

Hereditary Nephritis
Chronology
Cicatrix
Creatinine
Sclerosis
Kidney
Biopsy
Reference Values
Tissue Donors
Pediatrics

Keywords

  • Alport syndrome
  • Cortical interstitial volume fraction
  • Global glomerular sclerosis
  • Renal scarring

Cite this

Chronology of renal scarring in males with Alport syndrome. / Kashtan, Clifford; Gubler, Marie Claire; Sisson-Ross, Susan; Mauer, Michael.

In: Pediatric Nephrology, Vol. 12, No. 4, 01.01.1998, p. 269-274.

Research output: Contribution to journalArticle

Kashtan, Clifford ; Gubler, Marie Claire ; Sisson-Ross, Susan ; Mauer, Michael. / Chronology of renal scarring in males with Alport syndrome. In: Pediatric Nephrology. 1998 ; Vol. 12, No. 4. pp. 269-274.
@article{ae909afbb19d48999374d11b8f0bd6f5,
title = "Chronology of renal scarring in males with Alport syndrome",
abstract = "We investigated the onset of renal scarring in 62 males (aged 4-26 years) with Alport syndrome by measuring cortical interstitial volume fraction [Vv (interstitium/cortex)] and percentage global glomerular sclerosis in kidney biopsies. Male pediatric (n = 9) and adult (n = 7) donor kidneys served as controls. Creatinine clearance at the time of biopsy was available for 43 Alport patients. A statistically insignificant 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/cortex (r = +0.49, slope = 0.01, P = 0.001) and global glomerular sclerosis (r = +0.41, P = 0.01), and inversely correlated with creatinine clearance (r = -0.33, P = 0.04). Creatinine clearance was inversely correlated with Vv (interstitium/cortex) (r = -0.78, P = 0.001) and global glomerular sclerosis (r = -0.74, P = 0.001). The correlation with creatinine clearance was especially strong for Vv (interstitium/cortex) values above the normal range, i.e., > 0.2 (r = -0.82, P = 0.001), and was absent for Vv (interstitium/cortex) < 0.2 (r = -0.119, P = 0.55). Creatinine clearance values less than 80 ml/min per 1.73 m2 occurred more 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 ≤ or > 10 years of age differed in Vv (interstitium/cortex) [0.13 ± 0.09 (mean ± SD) vs. 0.24 ± 0.026, P < 0.001], the 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 m2, P = 0.057), and the frequency of creatinine clearance < 80 ml/min per 1.73 m2 (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 that most Alport males will require intervention during the 1st decade for optimal preservation of kidney function.",
keywords = "Alport syndrome, Cortical interstitial volume fraction, Global glomerular sclerosis, Renal scarring",
author = "Clifford Kashtan and Gubler, {Marie Claire} and Susan Sisson-Ross and Michael Mauer",
year = "1998",
month = "1",
day = "1",
doi = "10.1007/s004670050451",
language = "English (US)",
volume = "12",
pages = "269--274",
journal = "Pediatric nephrology (Berlin, Germany)",
issn = "0931-041X",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - Chronology of renal scarring in males with Alport syndrome

AU - Kashtan, Clifford

AU - Gubler, Marie Claire

AU - Sisson-Ross, Susan

AU - Mauer, Michael

PY - 1998/1/1

Y1 - 1998/1/1

N2 - We investigated the onset of renal scarring in 62 males (aged 4-26 years) with Alport syndrome by measuring cortical interstitial volume fraction [Vv (interstitium/cortex)] and percentage global glomerular sclerosis in kidney biopsies. Male pediatric (n = 9) and adult (n = 7) donor kidneys served as controls. Creatinine clearance at the time of biopsy was available for 43 Alport patients. A statistically insignificant 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/cortex (r = +0.49, slope = 0.01, P = 0.001) and global glomerular sclerosis (r = +0.41, P = 0.01), and inversely correlated with creatinine clearance (r = -0.33, P = 0.04). Creatinine clearance was inversely correlated with Vv (interstitium/cortex) (r = -0.78, P = 0.001) and global glomerular sclerosis (r = -0.74, P = 0.001). The correlation with creatinine clearance was especially strong for Vv (interstitium/cortex) values above the normal range, i.e., > 0.2 (r = -0.82, P = 0.001), and was absent for Vv (interstitium/cortex) < 0.2 (r = -0.119, P = 0.55). Creatinine clearance values less than 80 ml/min per 1.73 m2 occurred more 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 ≤ or > 10 years of age differed in Vv (interstitium/cortex) [0.13 ± 0.09 (mean ± SD) vs. 0.24 ± 0.026, P < 0.001], the 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 m2, P = 0.057), and the frequency of creatinine clearance < 80 ml/min per 1.73 m2 (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 that most Alport males will require intervention during the 1st decade for optimal preservation of kidney function.

AB - We investigated the onset of renal scarring in 62 males (aged 4-26 years) with Alport syndrome by measuring cortical interstitial volume fraction [Vv (interstitium/cortex)] and percentage global glomerular sclerosis in kidney biopsies. Male pediatric (n = 9) and adult (n = 7) donor kidneys served as controls. Creatinine clearance at the time of biopsy was available for 43 Alport patients. A statistically insignificant 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/cortex (r = +0.49, slope = 0.01, P = 0.001) and global glomerular sclerosis (r = +0.41, P = 0.01), and inversely correlated with creatinine clearance (r = -0.33, P = 0.04). Creatinine clearance was inversely correlated with Vv (interstitium/cortex) (r = -0.78, P = 0.001) and global glomerular sclerosis (r = -0.74, P = 0.001). The correlation with creatinine clearance was especially strong for Vv (interstitium/cortex) values above the normal range, i.e., > 0.2 (r = -0.82, P = 0.001), and was absent for Vv (interstitium/cortex) < 0.2 (r = -0.119, P = 0.55). Creatinine clearance values less than 80 ml/min per 1.73 m2 occurred more 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 ≤ or > 10 years of age differed in Vv (interstitium/cortex) [0.13 ± 0.09 (mean ± SD) vs. 0.24 ± 0.026, P < 0.001], the 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 m2, P = 0.057), and the frequency of creatinine clearance < 80 ml/min per 1.73 m2 (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 that most Alport males will require intervention during the 1st decade for optimal preservation of kidney function.

KW - Alport syndrome

KW - Cortical interstitial volume fraction

KW - Global glomerular sclerosis

KW - Renal scarring

UR - http://www.scopus.com/inward/record.url?scp=0031801487&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031801487&partnerID=8YFLogxK

U2 - 10.1007/s004670050451

DO - 10.1007/s004670050451

M3 - Article

VL - 12

SP - 269

EP - 274

JO - Pediatric nephrology (Berlin, Germany)

JF - Pediatric nephrology (Berlin, Germany)

SN - 0931-041X

IS - 4

ER -