Abstract
Objectives:
To investigate the incidence, etiological factors, predictors, and clinical outcomes of acute kidney injury (AKI) in patients with acute intracerebral hemorrhage (ICH).
Methods:
This retrospective cohort study included patients with ICH who were admitted to the ICU of Rashid Hospital, Dubai, between 2019 and 2024. Patients were grouped into AKI and non-AKI groups depending on the occurrence of AKI according to KDIGO clinical practice guidelines. Demographic characteristics, comorbidities, potential risk factors, and clinical outcomes were compared between both groups.
Results:
A total of 418 patients were included (median age: 44 years; males: 79.2%). Of these, 138 patients developed AKI (33%). AKI was more common in patients with spontaneous ICH (P = 0.016), males with hypertensive crisis, lower Glasgow Coma Scale (GCS) scores, and higher APACHE II scores (for all, P < 0.001). Significant etiological factors included hypertensive crisis (P = 0.005), hypotension (P = 0.024), high intracranial pressure (P = 0.004), blood transfusion (P = 0.002), diabetes insipidus (P < 0.001), and rhabdomyolysis (P = 0.017). Lower GCS scores on admission was associated with AKI (rpb: −0.23; P < 0.001). Factors that were independently associated with the development of early AKI were history of chronic kidney disease (OR: 4.79, 95% CI: 2.29–10.04; P < 0.001), diabetes insipidus (OR: 3.97, 95% CI: 1.95–8.10; P < 0.001), and hypertensive crisis (OR: 2.09, 95% CI: 1.21–3.61; P < 0.008). AKI was associated with lower GCS score at ICU discharge (P < 0.001) and increased length of ICU stay (P = 0.017), requirement for and duration of mechanical ventilation, incidence of brain death, 28-day mortality (for all, P < 0.001), and >28-day mortality (P = 0.004).
Conclusions:
Acute kidney injury (AKI) develops in about one third of patients with acute intracerebral hemorrhage (ICH). Lower GCS score, chronic kidney disease history, diabetes insipidus and hypertensive crisis are independently associated with increased odds of AKI. AKI is associated with an increase in morbidity and mortality in ICH patients.
Keywords: Acute kidney injury, chronic kidney diseases, hemorrhagic stroke, intracranial hypertension
INTRODUCTION
Acute intracerebral hemorrhage (ICH) is an important subtype of cerebrovascular event (CVE), accounting for 10%–20% of all CVE cases.[1,2] ICH patients present in emergencies with neurological deficits that may be paired with unconsciousness, airway compromise, or hemodynamic instability.[2,3,4] Acute management depends on the severity and cause of ICH.[2,3,4] The main aim of management is to prevent secondary brain damage.[2,3,4] The patients of ICH commonly require mechanical ventilation, hemodynamic management, contrast-enhanced radiological examinations, neurosurgical procedures, and medications with potential side effects.[2,3,4] Even with laborious intensive management, the mortality rate after severe ICH is around 35%–40%. In addition, in survivors, ICH contributes significantly to patient morbidity.[2,3,4]
Various neurological and non-neurological complications are observed in ICH patients.[5,6,7] These complications augment the morbidity and mortality after ICH.[5,6,7] Neurological complications can be hydrocephalus, brain infarction, intracranial infections, and brain death.[5,6,7] Common non-neurological complications are deep venous thrombosis, pressure sores, hospital-acquired infections, and acute kidney injury (AKI).[5,6,7] The reported incidence of AKI in ICH patients is 15%–30%, which is very high compared to other medical conditions.[8,9,10] The AKI after ICH is broadly categorized into early and late. The postulated pathophysiological process is different in early and late AKI.[8,9,10] Early AKI is often caused by hemodynamic instability and exposure to nephrotoxic medications. In contrast, late AKI is commonly caused by sepsis.[8,9,10]
Previous studies that have reported on AKI in ICH patients have had limitations such as incidence range being very wide (15%–30%), etiological factors being broadly defined, and the precise impact of AKI on the outcome of ICH patients being unclear. To address these limitations, the current retrospective study was conducted with the aim of 1) determining the incidence of AKI in the ICH patients, 2) studying etiological factors and predictors for AKI in the ICH patients, and 3) studying the impact of AKI on outcomes of ICH patients.
METHODS
Study design, setting, and patients
This retrospective study included adult non-traumatic ICH patients (aged 18–80 years) who were directly admitted to the intensive care unit (ICU) of Rashid Hospital, Dubai, between January 01, 2019, and December 31, 2024. Rashid Hospital is a 762-bed apex neuroscience center catering to Dubai, which has a population of about 4 million. This study was approved by the Dubai Scientific Research Ethics Committee.
Patients were excluded if they were potentially brain dead (Glasgow coma scale [GCS] of 3/15 and absent brain stem reflexes) upon presentation; had a history of stage 5 chronic kidney disease (CKD) or dialysis-dependent CKD; were renal transplant recipients; were receiving any nephrotoxic or immunosuppressive drug during the current episode of ICH; were admitted to another center before being admitted to our center; or were a brain-dead ICH patient who opted for either organ transplant or withdrawal of life support.
Definitions
ICH was defined as pathological bleeding in the brain parenchyma documented on computed tomography (CT) of the brain. Isolated subarachnoid hemorrhage, isolated intraventricular hemorrhage, and spontaneous subdural hemorrhage without involvement of brain parenchyma were not included in this study.[11] AKI and CKD (and their stages) were defined according to KDIGO 2023-24 clinical practice guidelines.[12,13] According to KDIGO clinical practice guidelines, an AKI event was defined if any of the following were noted in the ICH patients: an increase in serum creatinine by ≥0.3 mg/dL within 48 hours, an increase in serum creatinine to ≥1.5 times the baseline, or urine output <0.5 ml/kg/h for 6 hours.[12] Early AKI was defined as an AKI that was evident within 7 days of the ICH event.[12] In this study, only patients with early AKI were considered as having AKI, while patients with no AKI event within the first 7 days of ICH were classified as not having AKI
Hypertensive crisis and hypotension were defined as a mean arterial pressure of >110 mmHg and <65 mmHg, respectively. Single radiological contrast exposure was defined as when iohexol was administered only one time, either for CT angiography or digital subtraction angiography (DSA), while additional radiological contrast exposure was defined iohexol being administered more than one time, either for CT angiography or DSA. High intracranial pressure (ICP) was defined as a constant increase of ICP >20 mmHg for a period of >30 minutes.[14] Rhabdomyolysis was defined as serum creatinine phosphokinase >1000 U/L.[15]
Diabetes insipidus was defined as hypernatremia (>145 mmol/L) with urine specific gravity ≤1.005 and a urine osmolality ≤ 200 mosm/kg.[16] Nephrotoxic drug exposure was defined as the administration of any of the following drugs: aminoglycosides, amphotericin-B, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, non-steroidal anti-inflammatory drugs, and/or diuretics. Renal recovery was defined as the event of the patient’s serum creatinine returning to its normal level or baseline.[12] Renal replacement therapy (RRT) was defined as when dialysis was performed for either volume overload, metabolic acidosis, hyperkalemia, uremia, or persistent/progressive renal dysfunction.[12] Brain death was considered positive when a patient was declared brain dead according to neurological criteria.[17]
Variables
Demographic and baseline characteristics data of the ICH patients included age, sex, nationality, body mass index, history of hypertension, history of CKD (and its stage), Carlson comorbidity index,[18] GCS on presentation,[19] structural etiology of ICH (spontaneous, aneurysmal rupture, or arteriovenous malformation [AVM] rupture), location of ICH in the CT scan (basal ganglia/thalamus, cortex, midbrain/pons, or cerebellum), and acute physiology and chronic health evaluation (APACHE) II[20] scores (calculated within 24 hours following admission to ICU). Etiological factors for AKI in the ICH patients included hypertensive crisis, hypotension, exposure to radiological contrast (iohexol, single/subsequent), events of neurosurgical procedure (single/subsequent), receipts of blood transfusion, incidents of high ICP, occurrence of rhabdomyolysis, occurrence of diabetes insipidus, exposure to mannitol (20%), exposure to hypertonic saline (3%–5.8%), and exposure to nephrotoxic drugs. Outcome of patients after the ICH included length of stay (LOS)-hospital, LOS-ICU, requirement of ventilators, days spent on a ventilator, GCS at ICU discharge, incidents of brain death, 28-day mortality, and >28-day mortality.
Statistical analysis
Statistical analysis was done using SPSS version 24.0 (IBM Corp., Armonk, NY, United States). The categorical variables were represented by frequency. Quantitative variables with normal distribution were presented as mean ± standard deviation, while quantitative variables with skewed distribution were represented by median (interquartile range). ICH patients were grouped based on the event of AKI into the AKI group and the non-AKI group. Within the groups, the presence of each data variable was statistically compared using either the Pearson Chi-square test, Fisher’s exact test, the independent sample t-test, or the Mann–Whitney U-test. A P < 0.05 was considered as statistically significant. Point-biserial correlation and multivariate logistic regression was calculated using variables with a P < 0.05 to predict AKI in the ICH patients.
RESULTS
A total of 418 patients with ICH were included in this study (median age: 44 years; males: 79.2%). Of these, 138 patients had AKI (33%), and most had stage-1 AKI (42.6%). Among AKI patients, 3.4% of the patients required RRT, 68.1% had complete renal recovery, and 21.0% patients progressed to brain death. In terms of mortality, the 28-day and >28-day mortality was 23.9% and 10.5%, respectively [Table 1].
Table 1.
Descriptive statistics of patients with acute kidney injury
| Variable | AKI on CKD n (%) | Stage 1 n (%) | Stage 2 n (%) | Stage 3 n (%) |
|---|---|---|---|---|
| Number of patients (n=138) | 23 (16.7) | 59 (42.8) | 26 (18.8) | 30 (21.7) |
| RRT (n=16, 3.9%) | 5 (3.6) | 0 | 0 | 11 (8) |
| Full renal recovery (n=94, 68.1%) | 20 (14.5) | 43 (31.2) | 20 (14.5) | 11 (8) |
| Brain death (n=29, 21.0%) | 1 (0.7) | 8 (5.8) | 5 (3.6) | 15 (10.9) |
| 28-day mortality (n=33, 23.9%) | 3 (2.2) | 13 (9.4) | 3 (2.8) | 14 (10.1) |
| >28-day mortality (n=11, 10.5%) | 0 | 3 (2.9) | 3 (2.9) | 5 (4.8) |
AKI – Acute kidney injury; CKD – Chronic kidney disease; RRT – Renal replacement therapy
The median age was not significantly different between the AKI and non-AKI groups. However, the proportion of males was significantly higher in the AKI group compared with the non-AKI group (89.1% vs. 74.3%; P < 0.001). Overall, most patients were Asian (84%), and there was no difference in nationality distribution between both groups. In terms of comorbidities, CKD was significantly more common among AKI than among non-AKI patients (18.2% vs. 4.6%; P < 0.001) [Table 2].
Table 2.
Demographic, health-related, and baseline clinical characteristics of the study population
| Variable | Non-AKI group (n=280) n (%) | AKI group (n=138) n (%) | P |
|---|---|---|---|
| Age (years), median (IQR) | 44 (37.8–51) | 43.5(38–53) | 0.589a |
| Age-groups (years) | |||
| 18–30 | 32 (11.4) | 6 (4.6) | 0.069b |
| 31–40 | 70 (25) | 47 (34.1) | |
| 41–50 | 104 (37.1) | 45 (32.6) | |
| 51–60 | 45 (16.1) | 23 (16.7) | |
| >60 | 29 (10.4) | 17 (12.3) | |
| Sex | |||
| Male | 208 (74.3) | 123 (89.1) | <0.001b |
| Female | 72 (25.7) | 15 (10.9) | |
| Nationality | |||
| Emirati | 5 (1.8) | 8 (5.8) | 0.084b |
| Non-Emirati | |||
| Asian | 237 (84.6) | 114 (82.6) | |
| Middle Eastern | 17 (6.1) | 5 (3.6) | |
| African | 14 (5) | 10 (7.3) | |
| European-American | 7 (2.5) | 1 (0.7) | |
| BMI (kg/m2), median (IQR) | 25.2 (22.4–28.1) | 25 (23.2–27.9) | 0.871a |
| History of hypertension | 114 (40.7) | 60 (43.4) | 0.59b |
| History of CKD* | 13 (4.6) | 25 (18.1) | <0.001b |
| CKD stages | n=13 | n=25 | |
| Stage 2 | 1 (7.7) | 2 (8) | 0.63b |
| Stage 3a | 5 (38.5) | 7 (28) | |
| Stage 3b | 4 (30.8) | 5 (20) | |
| Stage 4 | 3 (23.1) | 11 (44) | |
| Charlson Comorbidity Index, mean±SD | 0.7±1.14 | 0.89±1.58 | 0.167c |
| GCS on admission to hospital**, median (IQR) | 11 (8–14) | 9 (6–12) | <0.001a |
| Structural etiology of ICH | |||
| Spontaneous | 218 (77.9) | 121 (87.7) | 0.016b |
| Aneurysm rupture | 32 (11.4) | 11 (8) | 0.274b |
| AVM rupture | 30 (10.7) | 6 (4.4) | 0.029b |
| Location of ICH | |||
| Basal ganglia/thalamus | 165 (58.9) | 91 (65.9) | 0.166b |
| Cortex | 72 (25.7) | 26 (18.8) | 0.119b |
| Midbrain/pons | 9 (3.2) | 5 (3.6) | 0.827b |
| Cerebellum | 34 (12.1) | 16 (11.6) | 0.871b |
| APACHE II score on admission to ICU, median (IQR) | 11 (6–15) | 14 (9–19.7) | <0.001a |
*included in the multivariate regression analysis; ** included in the point serial correlation to predict AKI in the ICH patients. aMann–Whitney test; bPearson Chi-square test; cIndependent sample test. SD – Standard deviation; CKD – Chronic kidney disease; GCS – Glasgow Coma Scale; ICH – Intracerebral hemorrhage; AVM – Arteriovenous malformation; AKI – Acute kidney injury; APACHE – Acute Physiology and Chronic Health Evaluation; ICU – Intensive care unit; BMI – Body mass index; IQR – Interquartile range
In terms of etiology, the proportion of patients with spontaneous ICH patients due to hypertensive crisis was higher in the AKI group than the non-AKI group (87.7% vs. 77.9%, respectively, P = 0.016). On admission, in the AKI group, the median GCS score was lower than the non-AKI group (9 vs. 11, P < 0.001), while the APACHE II score was higher (14 vs. 11; P < 0.001) [Table 2].
Etiological factors associated with acute kidney injury in intracerebral hemorrhage patients
Compared with the non-AKI group, the AKI group had significantly greater proportion of patients with hypertensive crisis (82.6% vs. 69.64%; P = 0.005) and hypotension (5.8% vs. 1.4%, P = 0.024). Similarly, the AKI group had a significantly higher incidence of high ICP (39.1% vs. 25.4%; P = 0.004) and prevalence of diabetes insipidus (18.8% vs. 6.1%; P < 0.001). In addition, patients from the AKI group more frequently required blood transfusion than the non-AKI group (44.2% vs. 29.3%, P = 0.002). Finally, although rare, a significant higher proportion of patients from the AKI group had rhabdomyolysis after ICH compared with the non-AKI group (5.1% vs. 1.1, P = 0.017) [Table 3].
Table 3.
Etiological factors for acute kidney injury after intracerebral hemorrhage
| Variable | Non-AKI group (n=280) n (%) | AKI group (n=138) n (%) | P |
|---|---|---|---|
| Hypertensive crisis* | 195 (69.6) | 114 (82.6) | 0.005a |
| Hypotension | 4 (1.4) | 8 (5.8) | 0.024b |
| Single radiological contrast exposure | 266 (95) | 126 (91.3) | 0.141a |
| Additional radiological contrast exposure | 65 (23.2) | 35 (25.4) | 0.628a |
| Neurosurgical procedure | 201 (71.8) | 101 (73.2) | 0.763a |
| Redo neurosurgical procedure | 71 (25.4) | 37 (26.8) | 0.749a |
| Blood transfusion* | 82 (29.3) | 61 (44.2) | 0.002a |
| ICP monitored | 164 (58.6) | 95 (68.8) | 0.042a |
| High ICP* | 71 (25.4) | 54 (39.1) | 0.004a |
| Rhabdomyolysis | 3 (1.1) | 7 (5.1) | 0.017b |
| Mannitol exposure | 66 (23.6) | 40 (29) | 0.232a |
| Hypertonic saline exposure | 66 (23.6) | 26 (18.8) | 0.272a |
| Diabetes insipidus* | 17 (6.1) | 26 (18.8) | <0.001a |
| Nephrotoxic drug exposure | 38 (13.6) | 28 (20.3) | 0.076a |
*Included in the multivariate regression analysis. aPearson Chi-square test; bFisher’s exact test. AKI – Acute kidney injury; ICH: Intracerebral hemorrhage; ICP – Intracranial pressure
Predictors of acute kidney injury in the intracerebral hemorrhage patients
From the univariate analysis, male sex, history of CKD, low GCS score, high APACHE II score, hypertensive crisis, hypotension, blood transfusion, high ICP, diabetes insipidus, and rhabdomyolysis were found to be associated with AKI. Of these, GCS was selected for point biserial correlation. Point biserial correlation analysis showed that low GCS scores on admission was associated with AKI (rpb: −0.23; P < 0.001) [Figure 1]. The following variables were not included in final multivariate regression: Male sex, because most of our study population was male; APACHE II score, to avoid multicollinearity; and hypotension and rhabdomyolysis, as the number of patients in both these groups were very small. In the multivariate regression analysis, factors that were independently associated with the development of early AKI were history of CKD (odds ratio [OR]: 4.79, 95% confidence interval [CI]: 2.29–10.04, P < 0.001), diabetes insipidus (OR: 3.97, 95% CI: 1.95–8.10; P < 0.001), and hypertensive crisis (OR: 2.09, 95% CI 1.21–3.61; P < 0.008) [Table 4].
Figure 1.
Point biserial correlation between Glasgow Coma Scale and development of acute kidney injury
Table 4.
Multivariate regression analysis of etiological factors associated with acute kidney injury in patients with acute intracerebral hemorrhage
| Variable | Coefficient B | SE | Z | P | OR | 95% CI |
|---|---|---|---|---|---|---|
| Constant | −1.85 | 0.27 | 6.86 | <0.001 | 0.16 | 0.09–0.27 |
| History of CKD | 1.57 | 0.38 | 4.16 | <0.001 | 4.79 | 2.29–10.04 |
| Hypertensive crisis | 0.74 | 0.28 | 2.63 | 0.008 | 2.09 | 1.21–3.61 |
| High ICP | 0.47 | 0.26 | 1.83 | 0.067 | 1.60 | 0.97–2.63 |
| Blood transfusion | 0.33 | 0.25 | 1.34 | 0.179 | 1.39 | 0.86–2.25 |
| Diabetes insipidus | 1.38 | 0.36 | 3.79 | <0.001 | 3.97 | 1.95–8.10 |
AKI – Acute kidney injury; CKD – Chronic kidney disease; ICP – Intracranial pressure; SE – Standard error; OR – Odds ratio; CI – Confidence interval; GCS – Glasgow Coma Scale; APACHE – Acute Physiology and Chronic Health Evaluation
Outcome of intracerebral hemorrhage patients with acute kidney injury
In ICH patients with or without AKI, the LOS in the hospital was similar. However, ICH patients with AKI spent more days in the ICU as compared to those without AKI (16 [IQR: 12–23.8] days vs. 15 [IQR: 9–21] days; P = 0.017). Similarly, ICH patients after AKI had a higher requirement of ventilators (95.7% vs. 75.7; P < 0.001) and longer days spent on ventilators (11 [IQR: 8–18] days vs. 9 [IQR: 1–15.25] days; P < 0.001). GCS at the time of discharge from ICU was low in ICH patients after the event of AKI (10 [IQR: 3–12.8] vs. 11.5 [IQR: 10–15]; P < 0.001). Yet, the need for tracheostomy was similar in both groups. ICH patients with AKI more frequently progressed to brain death (21.0% vs. 6.1%; P < 0.001). Resultantly, compared with the non-AKI group, the AKI group had higher 28-day mortality (23.9% vs. 7.1%; P < 0.001) and >28-day mortality (10.5% 3.1%; P = 0.004) [Table 5].
Table 5.
Outcomes of patient after intracerebral hemorrhage
| Variable | Non-AKI group (n=280) n (%) | AKI group (n=138) n (%) | P |
|---|---|---|---|
| LOS-hospital | 46.5 (23–84.3) | 45 (21–81) | 0.962a |
| LOS-ICU | 15 (9–21) | 16 (12–23.75) | 0.017a |
| Mechanical ventilation | 212 (75.7) | 132 (95.65) | <0.001b |
| Ventilator days | 9 (1–15.3) | 11 (8–18) | <0.001a |
| GCS at ICU discharge | 11.5 (10–15) | 10 (3–12.75) | <0.001a |
| Tracheostomy | 101 (36.1) | 62 (44.93) | 0.081b |
| Brain death | 17 (6.1) | 29 (21.01) | <0.001b |
| 28-day mortality | 20 (7.1) | 33 (23.91) | <0.001b |
| >28 day mortality | (n=260) 8 (3.08) |
(n=105) 11 (10.48) |
0.004b |
aMann–Whitney U-test, bPearson’s chi-square test. Values are presented as n (%) or median (interquartile difference). ICH – Intracerebral hemorrhage; LOS – Length of stay; ICU – Intensive care unit; GCS – Glasgow Coma Scale
DISCUSSION
In this study, the incidence of AKI in the ICH patients was about 33%. Stage 1 was the most common stage of AKI. AKI was common after spontaneous ICH due to hypertensive crisis in male patients with low GCS and high APACHE II scores. Further, AKI in ICH patients was associated with low GCS score at ICU discharge and increased LOS-ICU, need for mechanical ventilation, days spent on ventilators, incidents of brain death, 28-day mortality, and >28-day mortality. Nonetheless, ICH patients with AKI had a good likeliness of recovery in terms of renal function (68.1%). History of CKD, diabetes insipidus, and hypertensive crisis were independently associated with increased odds of AKI following ICH (ORs: 4.79, 3.97, and 2.09, respectively). Furthermore, lower GCS scores at admission were significantly associated with the development of AKI.
The renal system is particularly at risk of dysfunction following diverse transients or prolonged diseases.[21] Hemorrhage in the brain often disrupts the autonomic, neuroendocrine, and renin–angiotensin–aldosterone systems.[9] Due to these pathophysiological changes, patients’ clinical presentation, and management interventions, the incidence of AKI is noticeable in patients with ICH.[9] In coherence with the incidence reported in the current study, a recent study that analyzed patients’ data over a 10-year duration reported a 29.3% incidence of AKI in ICH patients.[22] In another similar large-scale study, the incidence of AKI in ICH patients was found to increase from 10.7% in 2010 to 19.6% in 2019.[23] Collectively, these findings highlight that AKI is common in patients with ICH.
ICH, while commonly labeled as “spontaneous,” is usually a result of prolonged exposure to cardiovascular risk factors and underlying comorbidities.[1] Hypertension, CKD, prior stroke, chronic heart disease, and diabetes mellitus are some of the comorbidities implicated in the causality of ICH.[1] The same comorbidities can concurrently affect the kidneys.[24] According to one study, AKI was more common in older ICH patients.[25] In contrast, in our study, most ICH patients with AKI were aged 41–50 years, and only about 10% were aged >60 years, and there was no relation between age and AKI. In terms of gender, Tian et al. found that female gender is protective against AKI after ICH.[23] Similarly, we also found that AKI was more common in males. Several studies have reported that patients with multiple comorbidities are more likely to experience AKI after ICH, with CKD being among the reported comorbidities.[25,26,27] In coherence, we found that among comorbidities, only CKD was independently associated with increased odds of AKI.
The majority of ICH cases occur spontaneously, while some patients have an intracranial vascular aneurysm or AVM.[1] Spontaneous ICH is commonly caused by a hypertensive crisis.[1] Blood pressure is elevated in ICH patients as a response to higher ICP.[1] An abrupt increase in blood pressure can result in vasoconstriction, endothelial damage, and microvascular thrombosis in the kidney.[9] Consequently, AKI is more common after spontaneous ICH.[23] Our study confirmed this observation; AKI was more common among spontaneous ICH patients. In our study, ICH patients due to AVM rupture had statistically lower rates of AKI events. The probable reason for these observations is that patients with AVM were young and did not have any comorbidities. The location of ICH and the size of ICH also play a role in the pathophysiology of AKI.[28] Previous studies indicated that large volumes of ICH in the basal ganglia and functional areas of the brain (right insular cortex, amygdala, and hypothalamus) increase the odds of AKI.[25,29] In this study, we did not find any such association.
Studies have reported that ICH patients who present with low GCS scores have a high possibility of developing AKI,[27,29] which is similar to the findings of the current study. In addition, we found that AKI was commonly observed in ICH patients with high APACHE II scores, consistent with the observation is correlated with the results of a previous study.[26]
AKI in ICH patients is caused by pre-renal (common), intrinsic renal (less common), and post-renal (rare) etiological factors.[9] Pre-renal factors can be hypertensive crisis, hypotension, anesthesia/surgery related, diabetes insipidus, mannitol, and high ICP. Intrinsic renal factors can be radiological contrast, rhabdomyolysis, nephrotoxic drugs, etc.[9] Some factors may have mixed pre-renal and intrinsic renal mechanisms.[9] Several etiological findings of our study correlated with that of a previous study.[26] However, our study did not demonstrate a significant association between neurosurgical intervention and AKI, which in contrast to a previous observation.[30] Further, Sorimachi et al. observed that exposure to radiological contrast was associated with AKI in ICH patients;[31] however, our study’s results contrast this observation.[31] Our study also did not find any association between AKI in ICH patients and mannitol, hypertonic saline, and nephrotoxic drugs, in contrast to the findings from previous studies.[8,26,29]
In this study, we found that high ICP in ICH patients was associated with the development of AKI. Following neurosurgical interventions, ICP monitoring is a standard of care. ICP monitoring aids in the diagnosis of hematoma expansion, cerebral edema, and brain herniation,[32] and also provides a guide to target proper cerebral perfusion pressure. Additionally, studies indicate that the event of high ICP in ICH patients increases the risk of cardiac arrhythmias (Cushing’s triad), neurogenic pulmonary edema, syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus, stress hyperglycemia, systemic inflammatory response syndrome, and gastrointestinal hemorrhage.[32] Theoretically, an event of ICP can cause AKI due to neuro-humoral stress, hemodynamic alterations, and renal hypoperfusion.[14] The risk of AKI is further increased by osmotic therapy after a high ICP event.[33] The relationship between high ICP and the event of AKI has been less frequently studied in the past. Accordingly, the study on the behavior of ICP in ICH patients and its relation to AKI is relatively unique in our study.
Findings of this and previous studies indicate that very few ICH patients with AKI require RRT, and recovery of renal function is good even without RRT.[26] In our study, the most common stage of AKI was stage 1, followed by stage 3, stage-2, and AKI on CKD. This finding is consistent with those reported by Dai et al.[26] Studies indicate that the event of AKI in ICH patients is associated with a delay in neurological recovery and increased mortality.[22,23,29,34]
Strength and limitations
A major strength of this study is that it assessed the association between high ICP and AKI in patients with ICH, which is relatively unique for this study. A limitation of this study is that it is a single-center retrospective study with a relatively small sample size, thereby limiting generalizability. Further, the study did not assess the adequacy of resuscitation/management of ICH patients. It should also be noted that although AKI was associated with poorer patient outcomes, patients who developed AKI also presented with lower GCS scores and higher APACHE II scores, and thus the adverse outcome could also be attributed to the greater disease severity in these patients. There is need for multicenter prospective studies with larger sample sizes to validate the findings of the current study.
CONCLUSIONS
This study found that about one-third of patients with acute intracerebral hemorrhage (ICH) are at risk of an acute kidney injury (AKI), with stage 1 being the most common stage. AKI occurs commonly after spontaneous ICH, and is more common among male patients with hypertensive crisis, lower GCS scores, and higher APACHE II. Factors such as hypertension crises, hypotension, high ICP, blood transfusion, rhabdomyolysis, and diabetes insipidus may contribute to the development of AKI following ICH. Further, independent predictors of AKI in patients with ICH were history of CKD, diabetes insipidus, and hypertensive crisis, while lower GCS scores at admission were significantly associated with the development of AKI. The majority of patients with AKI demonstrated recovery of renal function, and only a small proportion required RRT. However, AKI in ICH patients was associated with increased length of ICU stay, requirement of ventilators, days spent on ventilators, incidence of brain death, and mortality.
Ethical considerations
This study was done after approval by Dubai Scientific Research Ethics Committee (DSREC-02/2025_35; dated March 03, 2025). Requirement for patient consent was waived owing to the study design. The study adhered to the principles of the Declaration of Helsinki, 2024.
Peer review
This article was peer-reviewed by two independent and anonymous reviewers.
Data availability statement
Deidentified data and study materials are available upon reasonable request from the corresponding author.
Author contributions
Conceptualization: B.S.W., Z.F.A., M.M.B., and A.M.H.; Methodology: B.S.W., Z.F.A., M.M.B., A.M.H., M.M.T., N.G.M., S.K.B., A.A.S., I.M., M.N., S.B.A., and M.H.E.; Data analysis: B.S.W., Z.F.A., M.M.B., A.M.H., M.M.T., N.G.M., S.K.B., A.A.S., I.M., M.N., S.B.A., and M.H.E.; Writing–original draft preparation: B.S.W., Z.F.A., M.M.B., A.M.H., M.M.T., N.G.M., S.K.B., A.A.S., I.M., M.N., S.B.A., and M.H.E.; Writing – review and editing: B.S.W., Z.F.A., M.M.B., A.M.H., M.M.T., N.G.M., S.K.B., A.A.S., I.M., M.N., S.B.A., and M.H.E.; Supervision: B.S.W., Z.F.A., M.M.B., and A.M.H.
All authors have read and agreed to the published version of the manuscript.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
REFERENCES
- 1.Lee TH. Intracerebral hemorrhage. Cerebrovasc Dis Extra. 2025;15:1–8. doi: 10.1159/000542566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Parry-Jones AR, Krishnamurthi R, Ziai WC, Shoamanesh A, Wu S, Martins SO, et al. World Stroke Organization (WSO): Global intracerebral hemorrhage factsheet 2025. Int J Stroke. 2025;20:145–50. doi: 10.1177/17474930241307876. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Steiner T, Purrucker JC, Aguiar de Sousa D, Apostolaki-Hansson T, Beck J, Christensen H, et al. European Stroke Organisation (ESO) and European Association of Neurosurgical Societies (EANS) guideline on stroke due to spontaneous intracerebral haemorrhage. Eur Stroke J. 2025;10:1007–86. doi: 10.1177/23969873251340815. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Gil-Garcia CA, Flores-Alvarez E, Cebrian-Garcia R, Mendoza-Lopez AC, Gonzalez-Hermosillo LM, Garcia-Blanco MD, et al. Essential topics about the imaging diagnosis and treatment of hemorrhagic stroke: A comprehensive review of the 2022 AHA guidelines. Curr Probl Cardiol. 2022;47:101328. doi: 10.1016/j.cpcardiol.2022.101328. [DOI] [PubMed] [Google Scholar]
- 5.Zhang Y, Wang Y, Ji R, Wang A, Wang Y, Yang Z, et al. In-hospital complications affect short-term and long-term mortality in ICH: A prospective cohort study. Stroke Vasc Neurol. 2021;6:201–6. doi: 10.1136/svn-2020-000386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Lord AS, Gilmore E, Choi HA, Mayer SA. VISTA-ICH Collaboration. Time course and predictors of neurological deterioration after intracerebral hemorrhage. Stroke. 2015;46:647–52. doi: 10.1161/STROKEAHA.114.007704. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Naidech AM, Bendok BR, Tamul P, Bassin SL, Watts CM, Batjer HH, et al. Medical complications drive length of stay after brain hemorrhage: A cohort study. Neurocrit Care. 2009;10:11–9. doi: 10.1007/s12028-008-9148-x. [DOI] [PubMed] [Google Scholar]
- 8.Husain-Syed F, Takeuchi T, Neyra JA, Ramírez-Guerrero G, Rosner MH, Ronco C, et al. Acute kidney injury in neurocritical care. Crit Care. 2023;27:341. doi: 10.1186/s13054-023-04632-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Chen Y, Zhao G, Xia X. Acute kidney injury after intracerebral hemorrhage: A mini review. Front Med (Lausanne) 2024;11:1422081. doi: 10.3389/fmed.2024.1422081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Zorrilla-Vaca A, Ziai W, Connolly ES, Jr, Geocadin R, Thompson R, Rivera-Lara L. Acute kidney injury following acute ischemic stroke and intracerebral hemorrhage: A meta-analysis of prevalence rate and mortality risk. Cerebrovasc Dis. 2018;45:1–9. doi: 10.1159/000479338. [DOI] [PubMed] [Google Scholar]
- 11.Penckofer M, Kazmi KS, Thon J, Tonetti DA, Ries C, Rajagopalan S. Neuro-imaging in intracerebral hemorrhage: Updates and knowledge gaps. Front Neurosci. 2024;18:1408288. doi: 10.3389/fnins.2024.1408288. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Kung CW, Chou YH. Acute kidney disease: An overview of the epidemiology, pathophysiology, and management. Kidney Res Clin Pract. 2023;42:686–99. doi: 10.23876/j.krcp.23.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105:S117–314. doi: 10.1016/j.kint.2023.10.018. [DOI] [PubMed] [Google Scholar]
- 14.Canac N, Jalaleddini K, Thorpe SG, Thibeault CM, Hamilton RB. Review: pathophysiology of intracranial hypertension and noninvasive intracranial pressure monitoring. Fluids Barriers CNS. 2020;17:40. doi: 10.1186/s12987-020-00201-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Cabral BM, Edding SN, Portocarrero JP, Lerma EV. Rhabdomyolysis. Dis Mon. 2020;66:101015. doi: 10.1016/j.disamonth.2020.101015. [DOI] [PubMed] [Google Scholar]
- 16.Tomkins M, Lawless S, Martin-Grace J, Sherlock M, Thompson CJ. Diagnosis and management of central diabetes insipidus in adults. J Clin Endocrinol Metab. 2022;107:2701–15. doi: 10.1210/clinem/dgac381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Drost G, Absalom AR, Kuiper MA. Brain death/death by neurologic criteria determination: An update. Curr Opin Anaesthesiol. 2022;35:570–6. doi: 10.1097/ACO.0000000000001173. [DOI] [PubMed] [Google Scholar]
- 18.Drosdowsky A, Gough K. The Charlson comorbidity index: Problems with use in epidemiological research. J Clin Epidemiol. 2022;148:174–7. doi: 10.1016/j.jclinepi.2022.03.022. [DOI] [PubMed] [Google Scholar]
- 19.Mehta R, Trainee GP, Chinthapalli K. Consultant Neurologist. Glasgow coma scale explained. BMJ. 2019;365:l1296. doi: 10.1136/bmj.l1296. [DOI] [PubMed] [Google Scholar]
- 20.Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med. 1985;13:818–29. [PubMed] [Google Scholar]
- 21.Adiyeke E, Ren Y, Guan Z, Ruppert MM, Rashidi P, Bihorac A, et al. Clinical courses of acute kidney injury in hospitalized patients: A multistate analysis. Sci Rep. 2023;13:17781. doi: 10.1038/s41598-023-45006-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.She S, Shen Y, Luo K, Zhang X, Luo C. Prediction of acute kidney injury in intracerebral hemorrhage patients using machine learning. Neuropsychiatr Dis Treat. 2023;19:2765–73. doi: 10.2147/NDT.S439549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Tian B, Tang X, He L, Cheng J, Wang J, Liang S, et al. Predictors and outcomes of acute kidney injury in intracerebral hemorrhage patients: Evidence from a large-scale national database analysis. Shock. 2025;63:878–84. doi: 10.1097/SHK.0000000000002577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Obrador GT, Levin A. CKD hotspots: Challenges and areas of opportunity. Semin Nephrol. 2019;39:308–14. doi: 10.1016/j.semnephrol.2019.02.009. [DOI] [PubMed] [Google Scholar]
- 25.Zhang C, Xia J, Ge H, Zhong J, Chen W, Lan C, et al. Long-term mortality related to acute kidney injury following intracerebral hemorrhage: A 10-Year (2010-2019) retrospective study. J Stroke Cerebrovasc Dis. 2021;30:105688. doi: 10.1016/j.jstrokecerebrovasdis.2021.105688. [DOI] [PubMed] [Google Scholar]
- 26.Dai H, Ding F, Ma J, Zhao S. Risk factors for acute kidney injury after intracranial hemorrhage. Neuro Endocrinol Lett. 2022;43:257–64. [PubMed] [Google Scholar]
- 27.Ansaritoroghi M, Nagaraju SP, Nair RP, Kumar V, Kongwad LI, Attur RP, et al. Study on acute kidney injury in patients with spontaneous intracerebral hemorrhage: An overview from a tertiary care hospital in South India. World Neurosurg. 2019;123:e740–6. doi: 10.1016/j.wneu.2018.12.018. [DOI] [PubMed] [Google Scholar]
- 28.Teo KC, Fong SM, Leung WC, Leung IY, Wong YK, Choi OM, et al. Location-specific hematoma volume cutoff and clinical outcomes in intracerebral hemorrhage. Stroke. 2023;54:1548–57. doi: 10.1161/STROKEAHA.122.041246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Ludwiniak K, Maciejewska O, Olejnik P, Opuchlik A, Małyszko J, Golenia A. Acute kidney injury in patients with spontaneous intracerebral hemorrhage – Is it a real problem? Neurol Neurochir Pol. 2025;59:460–8. doi: 10.5603/pjnns.104530. [DOI] [PubMed] [Google Scholar]
- 30.Deng Y, Yuan J, Chi R, Ye H, Zhou D, Wang S, et al. The incidence, risk factors and outcomes of postoperative acute kidney injury in neurosurgical critically ill patients. Sci Rep. 2017;7:4245. doi: 10.1038/s41598-017-04627-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Sorimachi T, Atsumi H, Yonemochi T, Hirayama A, Shigematsu H, Srivatanakul K, et al. Benefits and risks of CT angiography immediately after emergency arrival for patients with intracerebral hematoma. Neurol Med Chir (Tokyo) 2020;60:45–52. doi: 10.2176/nmc.oa.2019-0152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Duan S, Yuan Q, Wang M, Li R, Yuan H, Yao H, et al. Intracranial pressure monitoring in patients with spontaneous intracerebral hemorrhage: A systematic review with meta-analysis. World Neurosurg. 2024;189:447–55.e4. doi: 10.1016/j.wneu.2024.07.007. [DOI] [PubMed] [Google Scholar]
- 33.Nau R. Osmotherapy for elevated intracranial pressure: A critical reappraisal. Clin Pharmacokinet. 2000;38:23–40. doi: 10.2165/00003088-200038010-00002. [DOI] [PubMed] [Google Scholar]
- 34.Qureshi AI, Huang W, Lobanova I, Hanley DF, Hsu CY, Malhotra K, et al. Systolic blood pressure reduction and acute kidney injury in intracerebral hemorrhage. Stroke. 2020;51:3030–8. doi: 10.1161/STROKEAHA.120.030272. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Deidentified data and study materials are available upon reasonable request from the corresponding author.