Abstract
AIMS/HYPOTHESIS: Estimated GFRs utilising creatinine- (eGFR(creat)) or cystatin C-based (eGFR(cyst)) equations can generate discrepant results that are associated with clinical outcomes. A low eGFR(cyst)/eGFR(creat) ratio (<0.60), reflecting a pathological glomerular state termed shrunken pore syndrome (SPS), has been associated with excess mortality in some clinical situations including diabetes. The aim of the present study was to explore this association in a longitudinal observational study of type 2 diabetes with special reference to participants with normal renal function. METHODS: Of 1481 Fremantle Diabetes Study Phase II participants with type 2 diabetes, aged ≥17 years, 1466 had eGFR(creat) and eGFR(cyst) assessed as part of the baseline assessment and were followed for 10 years or until death, whichever came first. Cox regression modelling was used to determine independent associates of death excluding eGFR; eGFR(cyst)/eGFR(creat) ratio was then added to this model separately as a categorical or continuous variable. These analyses were also conducted in a subgroup (n=754) of participants with normal renal function (eGFR(creat) ≥60 ml/min per 1.73 m(2) and urinary albumin/creatinine ratio <3 mg/mmol) at baseline. RESULTS: At entry, the participants had a mean age of 65.9 years, 51.8% were male, the median diabetes duration was 9.0 years and 10.4% had eGFR(cyst)/eGFR(creat) ratio <0.60 (the definition of SPS). There were 384 deaths (26.2%) during follow-up. The eGFR(cyst)/eGFR(creat) ratio was independently, significantly and negatively associated with death (adjusted HR [95% CI] 0.91 [0.85, 0.97] for an increase of 0.1, p=0.004). Of eGFR(cyst)/eGFR(creat) ratio categories, only <0.60 added significantly to the most parsimonious Cox model of time to death (HR [95% CI] 1.56 [1.07, 2.29], p=0.021). In those with normal renal function, 123 (16.3%) died during follow-up. An eGFR(cyst)/eGFR(creat) ratio <0.60, observed in 57 (7.6%), was also independently associated with mortality (HR [95% CI] 2.55 [1.34, 4.84], p=0.004). CONCLUSIONS/INTERPRETATION: A low eGFR(cyst)/eGFR(creat) ratio is independently associated with mortality in type 2 diabetes, including in people without conventional markers of diabetic kidney disease. The presence of SPS may add clinical value to the risk assessment of people with type 2 diabetes regardless of renal status.