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Potential relationship between eGFRcystatin C /eGFRcreatinine -ratio and glomerular basement membrane thickness in diabetic kidney disease

Öberg, Carl M. LU ; Lindström, Martin LU ; Grubb, Anders LU orcid and Christensson, Anders LU (2021) In Physiological Reports
Abstract
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomeru- lar basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle-molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine. Here we test the hypothesis that thickening of the glomerular filter leads to an increased diffusion length, and lower clearance, of cystatin C. Twenty- nine patients with a kidney biopsy diagnosis of either DKD (n = 17) or MCD (n = 12) were... (More)
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomeru- lar basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle-molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine. Here we test the hypothesis that thickening of the glomerular filter leads to an increased diffusion length, and lower clearance, of cystatin C. Twenty- nine patients with a kidney biopsy diagnosis of either DKD (n = 17) or MCD (n = 12) were retrospectively included in the study. GBM thickness was measured at 20 sepa- rate locations in the biopsy specimen and plasma levels of cystatin C and creatinine were retrieved from health records. A modified two-pore model was used to simulate the effects of a thicker GBM on glomerular water and solute transport. The mean age of the patients was 52 years, and 38% were women. The mean eGFRcystatin C/ eGFRcreatinine-ratio was 74% in DKD compared to 98% in MCD (p < 0.001). Average GBM thickness was strongly inversely correlated to the eGFRcystatin C/eGFRcreatinine- ratio (Pearson's r = −0.61, p < 0.01). Two-pore modeling predicted a eGFRcystatin C/ eGFRcreatinine-ratio of 78% in DKD. We provide clinical and theoretical evidence sug- gesting that thickening of the glomerular filter, increasing the diffusion length of cys- tatin C, lowers the eGFRcystatin C/eGFRcreatinine-ratio in DKD. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physiological Reports
article number
e14939
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:34254743
  • scopus:85109954932
ISSN
2051-817X
DOI
10.14814/phy2.14939
language
English
LU publication?
yes
id
9b514900-af3b-4f1a-8ca7-df4c2f9f2394
date added to LUP
2021-08-11 15:09:31
date last changed
2023-03-24 20:59:18
@article{9b514900-af3b-4f1a-8ca7-df4c2f9f2394,
  abstract     = {{Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomeru- lar basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle-molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine. Here we test the hypothesis that thickening of the glomerular filter leads to an increased diffusion length, and lower clearance, of cystatin C. Twenty- nine patients with a kidney biopsy diagnosis of either DKD (n = 17) or MCD (n = 12) were retrospectively included in the study. GBM thickness was measured at 20 sepa- rate locations in the biopsy specimen and plasma levels of cystatin C and creatinine were retrieved from health records. A modified two-pore model was used to simulate the effects of a thicker GBM on glomerular water and solute transport. The mean age of the patients was 52 years, and 38% were women. The mean eGFRcystatin C/ eGFRcreatinine-ratio was 74% in DKD compared to 98% in MCD (p &lt; 0.001). Average GBM thickness was strongly inversely correlated to the eGFRcystatin C/eGFRcreatinine- ratio (Pearson's r = −0.61, p &lt; 0.01). Two-pore modeling predicted a eGFRcystatin C/ eGFRcreatinine-ratio of 78% in DKD. We provide clinical and theoretical evidence sug- gesting that thickening of the glomerular filter, increasing the diffusion length of cys- tatin C, lowers the eGFRcystatin C/eGFRcreatinine-ratio in DKD.}},
  author       = {{Öberg, Carl M. and Lindström, Martin and Grubb, Anders and Christensson, Anders}},
  issn         = {{2051-817X}},
  language     = {{eng}},
  month        = {{07}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Physiological Reports}},
  title        = {{Potential relationship between eGFRcystatin C /eGFRcreatinine -ratio and glomerular basement membrane thickness in diabetic kidney disease}},
  url          = {{http://dx.doi.org/10.14814/phy2.14939}},
  doi          = {{10.14814/phy2.14939}},
  year         = {{2021}},
}