Rationale & Objective

Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFR_cys) and creatinine (eGFR_cr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown.

Study Design

Prospective cohort study.

Setting & Participants

4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Exposure

Difference in GFR estimates (eGFR_diff; ie, eGFR_cys minus eGFR_cr).

Outcome

Incident HF hospitalization.

Analytical Approach

Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFR_diff with incident HF.

Results

Of 4,512 participants, one-third had eGFR_cys and eGFR_cr values that differed by over 15 mL/min/1.73 m². In multivariable-adjusted models, each 15 mL/min/1.73 m² lower baseline eGFR_diff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFR_diff less than −15 mL/min/1.73 m² had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFR_diff ≥15 mL/min/1.73 m² had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFR_cys and eGFR_cr. Participants with faster declines in eGFR_cys relative to eGFR_cr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFR_cys and eGFR_cr declined in parallel.

Limitations

Entry into the CRIC Study was determined by eGFR_cr, which constrained the range of baseline eGFR_cr—but not eGFR_cys—values.

Conclusions

Among persons with CKD who have large differences between eGFR_cys and eGFR_cr, risk for incident HF is more strongly associated with eGFR_cys. Diverging slopes between eGFR_cys and eGFR_cr over time are also independently associated with risk of incident HF.

中文翻译：

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肌酐与胱抑素 C 估计 GFR 的个体内差异与心力衰竭事件的关联

理由和目标

较低的估计肾小球滤过率 (eGFR) 与心力衰竭 (HF) 风险相关。然而，基于胱抑素 C (eGFR _cys ) 和肌酐 (eGFR _cr ) 的 eGFR 在个体中可能存在显着差异。这些差异对慢性肾脏病 (CKD) 患者 HF 风险的临床意义尚不清楚。

学习规划

前瞻性队列研究。

设置和参与者

4,512 名患有 CKD 但没有流行的 HF 的成年人参加了慢性肾功能不全队列 (CRIC) 研究。

接触

GFR 估计值的差异（eGFR _diff；即 eGFR _cys减去 eGFR _cr）。

结果

事件 HF 住院。

分析方法

Fine-Gray 比例子风险回归用于研究 eGFR_差异的基线、更新时间和斜率与事件 HF 的关联。

结果

在 4,512 名参与者中，三分之一的 eGFR _cys和 eGFR _cr值相差超过 15 mL/min/1.73 m ²。在多变量调整模型中，基线 eGFR_{差异每降低 15 mL/min/1.73 m} ²与更高的心衰住院风险相关（风险比 [HR]，1.20 [95% CI，1.07-1.34]）。在时间更新分析中，eGFR _diff小于 −15 mL/min/1.73 m ²的患者发生 HF 住院的风险更高（HR，1.99 [95% CI，1.39-2.86]），eGFR _diff  ≥15的患者与具有相似 eGFR 的参与者相比， mL/min/1.73 m ²发生 HF 住院的风险较低（HR，0.67 [95% CI，0.49-0.91]）_cys和 eGFR _cr。_{与 eGFR cys}和 eGFR _cr平行下降的参与者相比，eGFR _cys相对于 eGFR _cr下降更快的参与者发生 HF 的风险更高（HR，1.49 [95% CI，1.19-1.85]） 。

限制

进入 CRIC 研究由 eGFR _cr决定，它限制了基线 eGFR _cr的范围——但不是 eGFR _cys值。

结论

_{在 eGFR cys}和 eGFR _cr之间存在较大差异的 CKD 患者中，发生心衰的风险与 eGFR _cys的相关性更强。eGFR _cys和 eGFR _cr之间随时间的不同斜率也与发生 HF 的风险独立相关。