Different ways of diagnosing selective glomerular hypofiltration syndromes such as shrunken pore syndrome and the associated increase in mortality.

Abstract

Background: In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed "Shrunken pore syndrome." Numerous studies have thereafter found an association between this syndrome (defined by a low eGFR_{cystatin C} to eGFR_creatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFR_{cystatin C} and eGFR_creatinine to describe a similar disorder, and this investigation compares the two measures.

Methods: Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFR_difference and the eGFR_ratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated.

Results: Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 "healthy" individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria.

Conclusion: The eGFR_difference is not superior to the eGFR_ratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification.