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Potential relationship between eGFRcystatin C /eGFRcreatinine -ratio and glomerular basement membrane thickness in diabetic kidney disease
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- Öberg, Carl M. (author)
- Lund University,Lunds universitet,Njurfysiologi och peritonealdialys,Forskargrupper vid Lunds universitet,Renal physiology and peritoneal dialysis,Lund University Research Groups,Skåne University Hospital
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- Lindström, Martin (author)
- Lund University,Lunds universitet,Klinisk patologi, Malmö,Forskargrupper vid Lunds universitet,Clinical pathology, Malmö,Lund University Research Groups,Skåne University Hospital
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- Grubb, Anders (author)
- Lund University,Lunds universitet,Cystatin C, njursjukdom, amyloidos och antibiotika,Forskargrupper vid Lunds universitet,Cystatin C, renal disease, amyloidosis and antibiotics,Lund University Research Groups,Skåne University Hospital
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- Christensson, Anders (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2021-07-13
- 2021
- English.
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In: Physiological Reports. - : Wiley. - 2051-817X.
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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