The urea-creatinine ratio on the seventh day predicts the short-term prognosis of spontaneous intracerebral hemorrhage: a retrospective study

Introduction

Spontaneous intracerebral hemorrhage (SICH), defined as non-traumatic bleeding into the brain parenchyma from rupture of cerebral vessels, such as capillaries, internal cerebral veins, and arteries, represents a critical neurological emergency with substantial morbidity and mortality (Greenberg et al., 2022). Hypertension constitutes the primary etiology, responsible for 70–80% of cases, with an annual incidence of 12–15 individuals per 100,000. The clinical course is often severe, with approximately 75% of patients experiencing acute-phase disability and the overall mortality ranges from 30% to 50% (Greenberg et al., 2022; Sheth, 2022). Notably, lobar hemorrhages demonstrate distinct pathophysiological characteristics and worse early outcomes compared to deep subcortical hemorrhages, primarily due to their association with cerebral amyloid angiopathy rather than hypertensive vasculopathy (De Mendiola et al., 2023).

The role of hydration status in SICH management remains controversial. While some evidence suggests potential benefits of controlled dehydration, including reduced cerebral perfusion pressure, decreased perihematomal edema, and lower intracranial pressure through induced hypovolemia and hypernatremia (Frey et al., 1994; Koenig et al., 2008; Diringer et al., 2011; Schrock, Glasenapp & Drogell, 2012), these advantages must be weighed against significant risks. Excessive dehydration may compromise cerebral perfusion during the critical acute phase, exacerbate patient fatigue, impair neurological recovery mechanisms, and increase thromboembolic complications (Bhalla et al., 2000; Kelly et al., 2004; Font, Arboix & Krupinski, 2010; Acciarresi, Bogousslavsky & Paciaroni, 2014).

Clinical assessment of dehydration in stroke patients presents unique challenges due to nonspecific symptoms, necessitating reliance on objective biomarkers (Bahouth, Gottesman & Szanton, 2018). The blood urea nitrogen-to-creatinine ratio (UCR) has emerged as a particularly valuable indicator, with values ≥15 demonstrating reliable correlation with dehydration status in patients with preserved renal function (Schrock, Glasenapp & Drogell, 2012; Liu et al., 2014; Shi et al., 2019). Elevated UCR has been consistently associated with worse outcomes in stroke populations (Schrock, Glasenapp & Drogell, 2012; Cortés-Vicente et al., 2019; Deng et al., 2019) and serves as an important prognostic marker in other acute conditions (Rowat, Graham & Dennis, 2012; Schrock, Glasenapp & Drogell, 2012; Liu et al., 2014; Lacey et al., 2019; Liu et al., 2019). However, current evidence regarding hydration status in SICH remains limited, with few studies examining its impact on short-term mortality and none investigating optimal dehydration thresholds (Lehmann et al., 2021).

The study aims to elucidate the relationship between the hydration status (quantified by UCR) and 90-day functional outcomes in SICH patients, and establish evidence-based thresholds for dehydration management to guide clinical decision making.

Materials and Methods

Outcome measures

Neurological outcomes were assessed at 90 days post-discharge through either clinic follow-up or structured telephone interviews using the modified Rankin Scale (mRS) (Sulter, Steen & De Keyser, 1999). Patients were stratified into good (mRS ≤ 2) and poor (mRS > 2) outcome groups for comparative analysis (Fig. 1).

Results

Predictive value of UCR

An ROC curve analysis was conducted to evaluate the predictive effectiveness of day-7 UCR in determining clinical outcomes of SICH patients. The day-7 UCR had an area under the curve (AUC) of 0.72 (95% CI [0.643 ∼ 0.789]), sensitivity of 0.48 (95% CI [0.367–0.593]), specificity of 0.843 (95% CI [0.783–0.903]), positive predictive value (PPV) of 0.621, negative predictive value (NPV) of 0.752, and diagnostic accuracy of 0.707, with an optimal cutoff value of 30.68 (Fig. 2).

Discussion

Our study demonstrates that a blood UCR > 30.68 on day seven post-SICH independently predicts poor 90-day functional outcomes (mRS > 2). This finding carries significant clinical relevance, as excessive dehydration indicated by elevated UCR, may compromise cerebral perfusion through multiple mechanisms: plasma volume contraction, reduced cardiac output, and impaired collateral circulation (González-Alonso et al., 1995).

The clinical detection of dehydration presents notable challenges, particularly in patients with SICH. Traditional physical signs such as dry mucous membranes, decreased skin turgor, and subjective thirst may prove unreliable, as they are often influenced by patient perception and clinical context. This diagnostic difficulty is further compounded in elderly patients, who frequently exhibit both diminished thirst perception and age-related declines in renal concentrating ability, making them particularly vulnerable to inadequate hydration. In clinical practice, objective biomarkers including the blood UCR (Schrock, Glasenapp & Drogell, 2012; Crary et al., 2013; Liu et al., 2014) and plasma osmolarity (Bhalla et al., 2000) have emerged as valuable tools for assessing hydration status. The UCR offers particular advantages in stroke populations, as serum urea and creatinine measurements are routinely obtained, cost-effective, and provide rapid results. Our study specifically highlights the clinical value of day-7 UCR measurements, which demonstrate superior reliability compared to admission values. By this timepoint, patients have typically stabilized from acute resuscitation, and confounding factors such as pre-hospital dietary intake, stress responses, and medication effects are minimized. This allows for a more accurate reflection of true hydration status under standardized hospital care. However, several practical limitations of UCR monitoring warrant consideration. Serial blood sampling may cause patient discomfort, while the inherent delay in laboratory processing could potentially delay therapeutic adjustments. These limitations highlight the need for technological advances in real-time hydration monitoring to better guide fluid management decisions. Despite these challenges, the UCR remains a pragmatic and clinically relevant biomarker for hydration assessment in stroke patients, supported by its widespread use in existing literature and consistent performance in prognostic studies (Bahouth, Gottesman & Szanton, 2018).

Our univariate analysis identified three clinically significant prognostic indicators: advanced age, lower GCS scores, and elevated day-7 UCR. These factors demonstrated strong associations with poorer 90-day functional outcomes, suggesting their potential utility in clinical risk stratification. The relationship between advanced age and worse outcomes likely reflects the cumulative impact of age-related physiological decline. Elderly patients typically present with multiple comorbidities, including renal impairment and reduced physiological reserve, which may compromise recovery potential (Fried et al., 2001; Radholm et al., 2015). Neurological status at admission, as measured by GCS, proved to be another powerful prognostic indicator. The GCS provides a standardized assessment of consciousness through evaluation of eye opening, verbal response, and motor function (scores 3–15), with lower scores indicating more severe neurological impairment (Mehta et al., 2019). On the 7th day post-admission, the UCR effectively reflects the patient’s hydration status following standardized treatment protocols. Patients in the adverse prognosis group exhibited higher UCR levels compared to those with favorable prognoses, suggesting that excessive dehydration is not conducive to favorable outcomes in cerebral hemorrhage patients. This finding represents a significant and novel discovery of this study. As stated above, patients with spontaneous intracerebral hemorrhage often present with advanced age and poor consciousness. This group of patients requires objective indicators for the dynamic follow-up of dehydration treatment after admission, rather than continuous dehydration treatment during the acute phase. For such patients, if dehydration treatment is necessary due to significant mass effect after admission, UCR monitoring should be carried out on the seventh day. If the value is >30.68, adjusting the dehydration treatment plan may be safer for the patient’s prognosis.

Dehydration—a recognized care quality indicator—was unassessed. It may impact outcomes via physiological (e.g., prerenal injury) or care-related (e.g., fluid management) pathways, especially for post-first-week non-neurological deaths. This study represents the investigation into the prognostic value of blood UCR for 90-day outcomes in SICH patients, with external validation enhancing the credibility of our findings. The identification of UCR as a potential biomarker for guiding dehydration therapy endpoints constitutes a significant contribution to clinical practice. However, several important limitations must be acknowledged. The relatively small sample size and exclusion of patients with severe hemorrhage or those requiring surgical intervention may affect the generalizability of our results. Notably, we did not assess intraventricular extension (IVE) of hematoma (Arboix et al., 2007), a well-established poor prognostic factor that could confound the observed association between UCR and outcomes. We also did not assess the process of care, like late hospital arrival, ≥24 h in the Emergency Department and Stroke Unit admission (Fernandes et al., 2022), which have strong impact on mortality of SICH. Other unmeasured confounders including comorbidities (e.g., infections, dysphagia), alternative causes of elevated UCR (e.g., renal insufficiency, medication effects), and direct measures of hydration status limit our ability to definitively establish dehydration as the primary driver of poor outcomes. The 90-day follow-up period precludes evaluation of long-term prognosis, while the absence of data on specific dehydration management interventions represents another important knowledge gap. Future multicenter studies incorporating detailed neuroimaging for IVE assessment, comprehensive comorbidity documentation, direct hydration metrics, and standardized treatment protocols will be essential to validate and extend our findings, ultimately improving risk stratification and fluid management in SICH patients.

Conclusions

Our study demonstrates that a blood UCR exceeding 30.68 on day seven post-admission is a significant predictor of poor 90-day outcome in SICH patients, suggesting its potential utility in guiding dehydration therapy. While these findings provide a promising biomarker for clinical decision-making, further large-scale validation studies are needed to confirm the optimal UCR threshold and establish evidence-based protocols for its application in routine patient management. This research direction could lead to more precise and individualized treatment strategies for SICH patients.

Supplemental Information