Reduction in glomerular pore size is not restricted to pregnant women. Evidence for a new syndrome: ‘Shrunken pore syndrome’

Abstract

The plasma levels of cystatin C, β₂-microglobulin, beta-trace protein, retinol binding protein (RBP) and creatinine were determined in plasma samples from 111 randomly selected patients with eGFR_{cystatin C} ≤ 60% of eGFR_creatinine and from 55 control patients with 0.9eGFR_creatinine ≤ eGFR_{cystatin C} ≤ 1.1eGFR_creatinine (eGFR_{cystatin C} ≈ eGFR_creatinine). The concentration ratios of cystatin C/creatinine, β₂-microglobulin/creatinine, beta-trace protein/creatinine and RBP/creatinine were significantly higher in patients with eGFR_{cystatin C} ≤ 60% of eGFR_creatinine than in patients with eGFR_{cystatin C} ≈ eGFR_creatinine. When the patients were divided into three groups with different estimated GFR intervals (≤ 40, 40–60 and ≥ 60 mL/min/1.73m²) the concentration ratios of cystatin C/creatinine, β₂-microglobulin/creatinine, and beta-trace protein/creatinine were significantly higher in patients with eGFR_{cystatin C} ≤ 60% of eGFR_creatinine than in patients with eGFR_{cystatin C} ≈ eGFR_creatinine for all GFR intervals. Similar results were obtained when the population without pregnant women was studied as well as the subpopulations of men or of non-pregnant women. Populations of pre-eclamptic women and pregnant women in the third trimester display similar results. Since the production of these four proteins with sizes similar to that of cystatin C is not co-regulated, the most likely explanation for the simultaneous increase of their creatinine-ratios in patients with eGFR_{cystatin C} ≤ 60% of eGFR_creatinine is that their elimination by glomerular filtration is decreased. We suggest that this is due to a reduction in pore diameter of the glomerular membrane and propose the designation ‘Shrunken pore syndrome’ for this pathophysiological state.

Key Words::

• Beta-trace protein
• creatinine
• cystatin C
• glomerular filtration rate
• kidney diseases
• beta 2-microglobulin
• retinol-binding proteins

Acknowledgements

The investigation was supported by grants from the Alfred Österlund Foundation, Greta and Johan Kock Foundation, Medical Faculty of the University of Lund and from Region Skåne.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.