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

Abstract

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.

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