Discussion
Our study found that there was an independent graded association between
eGFR levels and risks of both 1-month and 1-year mortalities in patients
with intracerebral hemorrhage after adjusting age, stroke severity and
comorbidities. The risk of mortality increased as the eGFR declined.
Renal dysfunction is a known independent risk factor for mortality after
stroke. A Scotland study followed 2042 stroke patients for 7-year and
found that reduced creatinine clearance (<51.27 ml/min) and
raised serum creatinine (≥1.35 mg/dL) could predict deaths in patients
with acute stroke8. But, the study failed to show
renal function as a significant predictor of mortality in hemorrhagic
stroke because of small size of fatal events.8 A
recent study from Taiwan found renal function could play a highly
significant role in predicting mortality among ischemic stroke
patients.11 An Israel study assessed risk factors
associated with deaths for patients with acute stroke during one-year
follow-up.7 Results demonstrated that eGFR was a
strong predictor of mortality and poor functional outcomes, such as
nursing home dwelling and Barthel index ≦75. Hao et al. reported that an
eGFR of < 60 ml/min/1.73 m2 was a strong
predictor of mortality and disability for hemorrhagic stroke but not for
ischemic stroke.18 Molshatzki revealed that presence
of moderate to severe reduction of eGFR (< 45 ml/min/1.73
m2) was associated larger, lobar hematomas and hence
higher one-year mortality in patients with intracerebral
hemorrhage.16 Data from the GET WITH The
Guidelines-Stroke (GWTG-Stroke) program showed that, after intracerebral
hemorrhage, patients had an increasing risk of in-hospital mortality
with declining eGFR.17 On the contrary, a study
analyzing China National Stroke Registry found that low eGFR
(< 45 ml/min/1.73 m2) was independently
associated with an increased risk of mortality in diabetic patients with
ischemic events, but not in those with hemorrhagic
stroke19. Our study focused on patients with
intracerebral hemorrhage and found that eGFR levels could predict the
risk of mortality in a graded relationship. This finding both confirms
the results of previous studies and provides new information on the
mortality prediction for intracerebral hemorrhage.
Decline in renal function is associated with anemia, increased oxidative
stress, abnormal apolipoprotein levels, inflammation, calcium-phosphate
derangement, elevated uremic toxins, hypercoagulability, and impaired
immunity.4,22-24 All these factors may contribute to
the increased risks of adverse outcomes such as cardiovascular events,
infection episodes, and deaths. These mechanisms may explain the graded
association between impaired renal function and the risk of death in
patients with hemorrhagic stroke. Our data also showed that most of the
baseline comorbidities were reversely associated with eGFR levels,
indicating that patients with low eGFR levels were more critically ill.
In addition, patients with a lower eGFR also had a higher NIHSS score,
indicating that impaired renal function could be associated with stroke
severity.
The strength of this study is using a large sample size from stroke
registry data with a representative group of stroke patients in Taiwan.
Thus, we could estimate the real world prognosis of patients with
intracerebral hemorrhage in Taiwan. In addition, we used the CKD-EPI
equation to estimate the eGFR as it is better than the MDRD equation for
Asian people.25 However, there are several limitations
in this study. First, there is no data regarding to the quantity of
proteinuria in the TSR database. We were unable to evaluate eGFR and
proteinuria simultaneously. Proteinuria is an important and independent
risk factor for cardiovascular disease.5,26 Second,
serum creatinine was measured and recorded once at the time of admission
and it was confounded by acute illness. Therefore, it is difficult to
determine the chronicity of renal dysfunction. Furthermore, some
patients were excluded from analysis because of missing information. The
precision of measurement might be affected. However, the demographic
characteristics, the prevalence of comorbidities, the values of
laboratory data, and the percentage of people using medication prior to
admission were similar between the selected and excluded patients (Table
S2). Moreover, although data on hematoma volume, location, and the type
of intracerebral hemorrhage were unavailable in this database, the NIHSS
score as stroke severity was adjusted in the multivariate analysis. In
addition, the use of direct oral anticoagulant was not recorded in this
database. This is a limitation for external validity.