Bruce David G, Davis Wendy A, Chubb S A Paul, Davis Timothy M E
Medical School, University of Western Australia, Fremantle, WA, Australia.
Diabetologia. 2025 Apr 21. doi: 10.1007/s00125-025-06430-6.
AIMS/HYPOTHESIS: Estimated GFRs utilising creatinine- (eGFR) or cystatin C-based (eGFR) equations can generate discrepant results that are associated with clinical outcomes. A low eGFR/eGFR 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.
Of 1481 Fremantle Diabetes Study Phase II participants with type 2 diabetes, aged ≥17 years, 1466 had eGFR and eGFR 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/eGFR 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 ≥60 ml/min per 1.73 m and urinary albumin/creatinine ratio <3 mg/mmol) at baseline.
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/eGFR ratio <0.60 (the definition of SPS). There were 384 deaths (26.2%) during follow-up. The eGFR/eGFR 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/eGFR 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/eGFR 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/eGFR 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.
目的/假设：利用基于肌酐的估算肾小球滤过率（eGFR）或基于胱抑素C的估算肾小球滤过率（eGFR）方程可能会产生与临床结局相关的不一致结果。低eGFR/eGFR比值（<0.60）反映了一种称为收缩孔综合征（SPS）的病理性肾小球状态，在包括糖尿病在内的一些临床情况下与过高死亡率相关。本研究的目的是在一项2型糖尿病纵向观察性研究中探讨这种关联，特别关注肾功能正常的参与者。
在1481名年龄≥17岁的弗里曼特尔糖尿病研究二期2型糖尿病参与者中，1466人在基线评估时进行了eGFR和eGFR评估，并随访10年或直至死亡，以先到者为准。采用Cox回归模型确定排除eGFR后的死亡独立相关因素；然后将eGFR/eGFR比值作为分类变量或连续变量分别添加到该模型中。这些分析也在基线时肾功能正常（eGFR≥60 ml/min per 1.73 m且尿白蛋白/肌酐比值<3 mg/mmol）的参与者亚组（n = 754）中进行。
入组时，参与者的平均年龄为65.9岁，51.8%为男性，糖尿病中位病程为9.0年，10.4%的eGFR/eGFR比值<0.60（SPS的定义）。随访期间有384人死亡（26.2%）。eGFR/eGFR比值与死亡独立、显著且呈负相关（每增加0.1，调整后HR [95% CI] 为0.91 [0.85, 0.97]，p = 0.004）。在eGFR/eGFR比值类别中，只有<0.60显著增加了最简约的死亡时间Cox模型（HR [95% CI] 为1.56 [1.07, 2.29]，p = 0.021）。在肾功能正常的参与者中，随访期间有123人（16.3%）死亡。57人（7.6%）的eGFR/eGFR比值<0.60也与死亡率独立相关（HR [95% CI] 为2.55 [1.34, 4.84]，p = 0.004）。
结论/解读：低eGFR/eGFR比值与2型糖尿病患者的死亡率独立相关，包括无糖尿病肾病传统标志物的人群。无论肾脏状态如何，SPS的存在可能会增加2型糖尿病患者风险评估的临床价值。
