Abstract
Background:
Acute stroke patients often develop AKI. AKI is associated with poor clinical outcomes, but stroke incidence and outcomes data are scarce.
Aim:
The aim is to examine the prevalence of AKI in acute stroke patients, risk factors, and clinical outcomes of patients with and without AKI.
Methods:
This prospective observational study was carried out at a tertiary care center. The study examined 139 patients with acute ischemic stroke and intracerebral bleeding. AKI was defined as per the Kidney Disease: Improving Global Outcomes guidelines. The study measured acute stroke patients, AKI prevalence, cause of death, hospital stay duration, dialysis need, and outcome of ischemic versus hemorrhagic stroke outcomes. AKI and hospital mortality were outcomes in a multivariate logistic regression model with gender, age, ventilatory requirement, hospital stay duration, and NIHS scale at admission as covariates.
Results:
Out of 112 ischemic strokes, with 6 deaths (5.35%) and 27 intracranial hemorrhages (ICH) with 10 deaths (8.92%). The average age was 54 years, 68.34% were male, and AKI complicated 74.3% of ischemic stroke and 25.6% of ICH hospitalizations. In multivariate analysis, AKI and hospital mortality are the outcomes. Covariates include age, gender, ventilatory requirement, duration of hospital stay, and National Institute of Health Stroke Scales Score at admission. AKI was associated with hospital mortality from ischemic stroke (odds ratio (OR): 25.25, 95% confidence interval (CI): 4.4–225.21) and hemorrhagic stroke (OR: 5.20, 95% CI: 1.32–22.34).
Conclusions:
AKI complicates stroke and increases hospital mortality, requiring further research on a large scale to understand the causal relationship and whether preventing AKI could reduce mortality.
Keywords: Acute kidney injury, intracerebral hemorrhage, ischemic stroke, kidney disease
Résumé
Contexte:
Les patients victimes d’un accident vasculaire cérébral (AVC) aigu développent souvent une insuffisance rénale aiguë (IRA). L’IRA est associée à de mauvais pronostics cliniques, mais les données sur l’incidence et les conséquences de l’IRA chez les patients victimes d’AVC sont rares.
Objectif:
L’objectif est d’examiner la prévalence de l’IRA chez les patients victimes d’AVC aigu, les facteurs de risque et les résultats cliniques chez les patients avec et sans IRA.
Méthodes:
Cette étude observationnelle prospective a été menée dans un centre de soins tertiaires. L’étude a porté sur 139 patients atteints d’AVC ischémique aigu et d’hémorragie intracérébrale. L’IRA a été définie selon les recommandations de la Kidney Disease: Improving Global Outcomes (KDIGO). L’étude a mesuré la prévalence de l’IRA chez les patients victimes d’AVC aigu, la cause du décès, la durée du séjour hospitalier, le besoin de dialyse et les résultats des AVC ischémiques par rapport aux AVC hémorragiques. L’IRA et la mortalité hospitalière étaient les critères de jugement dans un modèle de régression logistique multivariée avec le sexe, l’âge, le besoin de ventilation, la durée du séjour hospitalier et le score NIHSS à l’admission comme covariables.
Résultats:
Sur 112 AVC ischémiques, on a dénombré 6 décès (5,35 %) et 27 hémorragies intracérébrales (HIC) avec 10 décès (8,92 %). L’âge moyen était de 54 ans, 68,34 % des patients étaient des hommes et l’IRA a compliqué 74,3 % des hospitalisations pour AVC ischémique et 25,6 % des hospitalisations pour HIC. Dans l’analyse multivariée, l’IRA et la mortalité hospitalière sont les critères de jugement. Les covariables comprennent l’âge, le sexe, le besoin de ventilation, la durée du séjour hospitalier et le score NIHSS à l’admission. L’IRA était associée à la mortalité hospitalière due à un AVC ischémique (rapport de cotes (OR) : 25,25, intervalle de confiance à 95 % (IC) : 4,4-225,21) et à un AVC hémorragique (OR : 5,20, IC à 95 % : 1,32-22,34).
Conclusions:
L’IRA complique les AVC et augmente la mortalité hospitalière, ce qui justifie des recherches plus approfondies à grande échelle afin de comprendre la relation de causalité et de déterminer si la prévention de l’IRA pourrait réduire la mortalité.
Mots-clés: Insuffisance rénale aiguë, hémorragie intracérébrale, accident vasculaire cérébral ischémique, maladie rénale
INTRODUCTION
Stroke is a key contributor to long-term disability and globally the second-largest cause of mortality.[,2,3] Ischemic strokes account for approximately 68% of cases, whereas hemorrhagic strokes represent about 32%.[1,2] The absolute number of stroke cases and survivors is still rising, which adds to the growing global burden of disability, even if stroke-related mortality rates are falling in both high- and low-income nations.[4] According to estimates, the annual cumulative incidence of stroke in India is between 105 and 152 per 100,000 people.[5]
Hospitalized patients, especially critically unwell and those with comorbidities, often develop Acute Kidney Injury (AKI).[6,7] AKI is prevalent in acute stroke patients and related to poor clinical outcomes; however, data are scarce.[8,9] Lack of fluid intake, sepsis, nephrotoxic medicines, sympathetic nervous system overactivation, and contrast-based diagnostic tests contribute to its development in this population.[10] Importantly, AKI worsens stroke patients’ prognoses in several clinical situations.[8,11]
Stroke patients may have severe renal impairment due to systemic end-organ damage from atherosclerosis and vascular risk factors such as aging, smoking, hypertension, diabetes, and cardiovascular disease.[6,12] However, stroke-related acute kidney damage (AKI) mechanisms are unknown and need additional study.[12] Due to the similar anatomical and functional properties of the kidney, heart, and brain vascular beds, emerging data imply a substantial interplay between cardiovascular, cerebrovascular, and renal disease.[,14,15] Stroke and AKI may be linked by coincidence, bidirectional causality, or common risk factors and molecular pathways.[16,17] Brain damage can compromise kidney function through neuroinflammation, sympathetic nervous system activation, and hypothalamic–Pituitary axis dysregulation. CNS cells are rich in inflammatory mediators, and their production of proinflammatory cytokines and complement components recruits neutrophils and monocytes across the blood–brain barrier, exacerbating neuroinflammation.[16,18] Neuroendocrine mechanisms, including the hypothalamic pituitary adrenal axis and autonomic nervous system, modulate systemic effects of neuroinflammation.[,20,21] Recent studies show that acute kidney injury (AKI) independently predicts short-term stroke mortality.[8,22,23] Even after controlling for confounding factors, stroke survivors with high serum creatinine (SCr) levels have higher mortality rates.[,25,26] The estimated incidence of AKI in stroke is 4.63% across the studies. Hemorrhagic stroke (77.80%) has a greater AKI rate than ischemic stroke (54.5%).[10,25] AKI also prolongs hospital stays by 7–14 days, increasing patient and healthcare system costs.[22,26,27] This study examined the prevalence of AKI in acute stroke patients, its risk factors, and the clinical outcomes of patients with and without AKI.
METHODS
In this prospective observational study, we studied 145 adult acute stroke patients over a period of 1 year. During this period, six patients dropped out, so analysis was performed on 139 patients. Before commencement of the study, ethical approval was obtained from the institution’s ethics committee of KGMU (Ref code XXIII– PGTSC-IIA/P42). Patients consented in writing. We evaluated all consecutive acute stroke patients aged more than 18–70 years within 48 h of symptom onset. The study excluded participants with CKD, vascular disease, cancer, or nephrotoxic treatment for other disorders. Some causes of acute insult include sepsis, hypovolemia, medication toxicity, blockage, and parenchymal kidney disease.
The Kidney Disease: Improving Global Outcomes 2012 was used to determine if acute stroke patients have acute kidney injury (AKI) within 48 h.[28] The primary outcome was to measure the prevalence of AKI in stroke patients. All cause death, duration of hospital stay, dialysis requirement, and comparative outcome in ischemic versus hemorrhagic stroke were secondary outcomes. Risk variables for AKI were compared in patients with and without AKI. Age, gender, stroke subtype, severity, Glasgow Coma Scale, diabetes, hypertension, and computed tomography (CT) angiography were clinical variables. Patient parameters were recorded daily in hospitals. Results were compared between AKI and non-AKI patients.
Data collection and definition
The primary outcome of the study was the prevalence of AKI in acute stroke patients within 48 h of admission. Secondary outcome measures were all-cause mortality, length of hospital stay, dialysis requirement, and comparison of outcomes between ischemic and hemorrhagic stroke. Evaluation of risk factors causing AKI and comparison of outcomes in patients with and without AKI.
At the time of admission, we have evaluated for the National Institute of Health Stroke Scale (NIHSS). Modified Rankin scale, a noncontrast computed tomography of the head, and if necessary, computed tomography with angiography of the brain and neck vessels were done. Treatment of patients was done as per our hospital protocol. Wherever necessary interventions suchas thrombolysis, mechanical thromboectomy or decompressive craniotomy were done in case of hemorrhagic stroke, or conservative treatment as per recent guidelines.
Baseline investigations such as complete hemogram, liver function test, renal function test, and urine examination, were done in all patients. Clinical variables including age, gender, types of stroke, severity of stroke (NIHSS at admission), Glasgow coma scale (GCS), history of diabetes mellitus, hypertension, and CT angiography, were recorded. Daily monitoring of vitals, input, and urine output was done during hospital stay. All patients were divided into two groups: Group A – Stroke patients with AKI, and Group B – stroke patients without AKI. Outcomes were measured between two groups and Ischemic versus hemorrhagic strokes.
Statistical analysis
Data were analyzed using SPSS (Statistical Package for the Social Sciences) 25th IBM Corporation, Armonk, New York, United States software. Categorical data were depicted as numbers and percentages and were compared using Chi-square test. Continuous data were depicted as mean ± standard deviation. Comparison of continuous data was done using an independent sample ‘t’-test. When comparison was made between two groups and ANOVA was used when comparison was being made among more than two groups. Logistic regression was used for multivariable regression analysis with stepwise risk estimation and 95% confidence intervals (CIs) ‘P’ < 0.05 was considered statistically significant. The Kaplan–Meier curve was used to express the mortality during hospital stay in both groups.
RESULTS
A total of 139 stroke patients were included, 112 ischemic and 27 hemorrhagic. Men dominated (71.4%) with a 2.66:1 male-to-female ratio. Hemorrhagic stroke patients had higher median systolic and diastolic blood pressures (P = 0.001). Ischemic stroke patients had higher rates of hypertension, diabetes, smoking, and heart disease (P = 0.03, 0.086, 0.46, and 0.001). Hemorrhagic stroke patients presented later (median 10 vs. 5 h, P = 0.001), had lower GCS scores, and had higher NIHSS scores upon admission (15 vs. 8, P = 0.001). They also had longer hospital stays (mean 14 vs. 7 days, P = 0.001) and more tracheostomy and ventilator support (P = 0.001). Initial lab tests showed hemorrhagic stroke patients had higher total leukocyte counts and blood urea (P = 0.001). Hemorrhagic stroke patients had a greater rate of acute kidney damage (AKI) than ischemic stroke patients (77.8% vs. 54.5%, P = 0.001. AKI patients had significantly worse GCS scores at presentation, increased requirement for tracheostomy and ventilatory assistance (P = 0.001), and longer hospital admissions (median 9 vs. 8 days, P = 0.001). They showed greater leukocyte and lower platelet counts (P = 0.002 and 0.004), suggesting sepsis. All 10 (12.1%) AKI patients who needed dialysis died. A total of 16 patients expired, out of which 6 (5.35%) patients belonged to Group A and 10 (8.92%) belonged to Group B [Table 1]. A total of 16 patients died, with mortality markedly rising with AKI severity (P = 0.001) [Table 2]. Mean survival among patients without AKI and varying severity of AKI was not significantly different during the study duration [Figure 1].
Table 1.
Baseline characteristics of ischemic and hemorrhage stroke patients
| Baseline characteristic | Ischemic (112) | hemorrhage stroke (27) | P |
|---|---|---|---|
| Age, mean±SD | 54.14±12.35 | 57.14±15.46 | 0.254 |
| Males, n (%) | 80 (71.4) | 15 (55.5) | 0.871 |
| eGFR (mL/min/1.73 m2), mean±SD | 97.21±12.5 | 92.15±14.35 | 0.767 |
| BP (mmHg), median (IQR) | |||
| SBP | 145 (140.2–160.5) | 186 (165.8–185.20) | 0.001 |
| DBP | 85 (80.9–91.7) | 104 (95.6–106.2) | 0.001 |
| Risk factors prevalence, n (%) | |||
| HTN | 55 (49.1) | 20 (74.07) | 0.03 |
| DM | 53 (47.3) | 8 (36.3) | 0.086 |
| Smoking | 40 (35.7) | 10 (37.03) | 0.466 |
| Alcohol intake | 20 (17.8) | 5 (18.5) | 0.890 |
| Dyslipidemia | 8 (7.14) | 4 (14.8) | 0.765 |
| Heart disease | 34 (30.3) | 8 (29.6) | 0.001 |
| Previous stroke | 10 (8.9) | 3 (11.1) | 0.386 |
| Family history | 2 (1.7) | 1 (3.7) | 0.253 |
| Use of antiplatelets | 11 (9.8) | 4 (14.8) | 0.455 |
| Ventilatory requirement | 20 (17.8) | 10 (37.3) | 0.001 |
| Tracheostomy | 8 (7.14) | 12 (14.4) | 0.001 |
| GCS at presentation, median (IQR) | 15 (10.0–15.0) | 10 (7.50–10.0) | 0.001 |
| GCS <8, n (%) | 7 (6.3) | 8 (29.6) | 0.001 |
| GCS 9–15, n (%) | 105 (93.7) | 19 (70.3) | 0.001 |
| eGFR (mL/min/1.73 m²), n (%) | |||
| G2 | 32 (28.6) | 10 (37.3) | 0.230 |
| G1 | 80 (71.4) | 17 (62.7) | |
| NIHSS, median (IQR) | 8 (7.5–10.5) | 15 (14.50–16.50) | 0.001 |
| AKI, n=82, n (%) | 61 (54.40) | 21 (77.7) | 0.001 |
| Time frames, median (IQR) | |||
| Onset to hospitalization (h) | 5 (4.50–6.0) | 10 (8.50–11.30) | 0.001 |
| Hospital stay (days) | 7 (4.5–10.0) | 14 (12.50–16.0) | 0.001 |
| Numbers of death | 6 (5.35) | 10 (8.92) | 0.046 |
| Baseline investigations (mean±SD) | |||
| Hemoglobin (g/dL) | 12.6±2.5 | 13.6±2.7 | 0.393 |
| TLC (/µL) | 8567±3227 | 10,245±2897 | 0.001 |
| Platelet count (lakhs/mm3) | 2.10±0.68 | 1.80±0.76 | 0.968 |
| Serum creatinine (mg/dL) | 0.80±0.18 | 0.84±0.19 | 0.196 |
| Blood urea (mg/dL) | 32.16±15.63 | 45.19±17.12 | 0.001 |
| HbA1c | 6.65±2.15 | 5.85±1.20 | 0.052 |
| Total bilirubin | 0.85±0.45 | 0.90±0.54 | 0.989 |
| SGOT (U/L) | 40.25±25.65 | 70.26±36.25 | 0.054 |
| SGPT (U/L) | 30.12±52 | 52.8±142±34 | 0.918 |
| Total cholesterol (mg/dL) | 165±42.37 | 167±36.80 | 0.997 |
| LDL (mg/dL) | 110±34.65 | 108±40.34 | 0.42 |
AKI=Acute kidney injury, BP=Blood pressure, DBP=Diastolic blood pressure, eGFR=Estimated glomerular filtration rate, GCS=Glasgow Coma Scale, GFR=Glomerular filtration rate, G1=GFR 90 mL/min/1.73 m2 and above, G2=GFR 60–89 mL/min per 1.73 m2, HbA1c=Glycated hemoglobin, LDL=Low-density lipoprotein, NIHSS=National Institutes of Health Stroke Scale, SBP=Systolic blood pressure, SD=Standard deviation, SGOT=Serum glutamic oxaloacetic transaminase, SGPT=Serum glutamic pyruvic transaminase, TLC=Total leukocyte count, DM=Diabetes mellitus, HTN=Hypertension, IQR=Interquartile range
Table 2.
Comparison of baseline characteristics between acute kidney injury and non-acute kidney injury subgroups of patients
| AKI (n=61) | No AKI (n=21) | P | |
|---|---|---|---|
| Age, mean±SD | 54.57±15.7 | 57.12±14.7 | 0.226 |
| Males, n (%) | 52 (85.25) | 11 (52.40) | 0.876 |
| eGFR (mL/min/1.73 m2), mean±SD | 98.34±15.32 | 97.25±16.41 | 0.811 |
| BP (mmHg), median (IQR) | |||
| SBP | 155 (140.2–158.9) | 152 (145.4–165.6) | 0.001 |
| DBP | 85 (81.5–92.6) | 90 (86.7–92.40) | 0.001 |
| Risk factors prevalence, n (%) | |||
| HTN | 40 (65.5) | 18 (85.7) | 0.100 |
| DM | 21 (34.4) | 7 (33.34) | 0.890 |
| Smoking | 22 (36.06) | 7 (33.34) | 0.540 |
| Alcohol intake | 8 (13.1) | 6 (28.6) | 0.180 |
| Dyslipidemia | 7 (11.5) | 6 ( 28.6) | 0.620 |
| Heart disease | 10 (16.40) | 5 (23.8) | 0.050 |
| Previous stroke | 5 (8.2) | 3 (14.2) | 0.989 |
| Family history | 2 (3.2) | 1 (4.76) | 0.401 |
| GCS at presentation, median (IQR) | 12 (19.7) | 15 (71.4) | 0.001 |
| GCS <8, n (%) | 21 (34.4) | 4 (19.04) | 0.001 |
| GCS 9–15, n (%) | 40 (65.60) | 17 (80.95) | 0.050 |
| NIHSS, median (IQR) | 12 (19.67) | 10 (47.6) | 1.240 |
| Factors in hospital, n (%) | |||
| Ventilatory requirement | 45 (73.7) | 4 (19.04) | 0.001 |
| Tracheostomized | 17 (27.86) | 3 (14.3) | 0.001 |
| eGFR G2 | 20 (32.8) | 10 (47.6) | 0.230 |
| eGFR G1 | 41 ( 67.2) | 11 (52.40) | 0.510 |
| eGFR (mL/min/1.73 m2), mean±SD | 96.53±16.59 | 99.55±16.80 | 0.09 |
| Time frames, median (IQR) | |||
| Onset to hospitalization (h) | 8 (13.1) | 7 (33.3) | 0.868 |
| Hospital stay (days) | 9 (14.8) | 8 (38.1) | 0.001 |
| No of death | 13 (15.85) | 3 (5.2) | 0.723 |
AKI=Acute kidney injury, NIHSS=National Institute of Health Stroke Scale, eGFR=Estimated glomerular filtration rate, DM=Diabetes mellitus, HTN=Hypertension, BP=Blood pressure, DBP=Diastolic blood pressure, GCS=Glasgow Coma Scale, GFR=Glomerular filtration rate, G1=GFR 90 mL/min/1.73 m2, G2= GFR 60–89 mL/min/1.73 m2, LDL=low-density lipoprotein, SBP=Systolic blood pressure, SD=Standard deviation, IQR=Interquartile range
Figure 1.
Kaplan–Meier survival analysis during hospital stay
A comparison of characteristics between ischemic and hemorrhagic stroke patients after stratification into AKI and non-AKI subgroups is shown in Table 3. Three logistic regression models were created after stratifying by stroke type: one to assess AKI and in-hospital mortality, and two to identify ischemic and hemorrhagic stroke AKI predictors. Hypertension and diabetes mellitus were the best predictors of AKI in hemorrhagic stroke (P = 0.05 and P = 0.001, respectively), while ventilatory support was the strongest predictor in ischemic stroke (P = 0.001) [Table 4].
Table 3.
Comparison of characteristics between ischemic and hemorrhage stroke subgroups (stratifies by acute kidney injury)
| Characteristics | Ischemic (112) | Hemorrhagic (27) | ||
|---|---|---|---|---|
|
|
|
|||
| AKI | No AKI | AKI | No AKI | |
| Age, mean±SD | 55.10±15.1 | 54.5±14.5 | 58.5±13.5 | 58.6±13.8 |
| Males, n (%) | 20 (32.8) | 21 (34.4) | 10 (47.6) | 11 (52.4) |
| BP (mmHg), median (IQR) | ||||
| SBP | 156 (154.5–165.4) | 152 (146.0–155.5) | 188 (170.56–190.2) | 165 (148.7–175.2) |
| DBP | 90 (88.4–96.2) | 88 (82.5–92.5) | 98 (95.5–104.5) | 100 (86.8–105.6) |
| Risk factors prevalence, n (%) | ||||
| HTN | 20 (17.85) | 30 (26.8) | 8 (29.6) | 5 (18.5) |
| DM | 12 (10.7) | 25 (22.32) | 9 (33.33) | 5 (18.5) |
| Smoking | 10 (8.9) | 14 (12.5) | 7 (33.33) | 59 (23.8) |
| Alcohol intake | 10 (8.9) | 15 (13.4) | 6 (22.2) | 4 (14.8) |
| Dyslipidemia | 4 (3.6) | 6 (5.3) | 2 (7.4) | 1 (3.7) |
| Heart disease | 10 (8.9) | 22 (19.6) | 1 (3.7) | 1 (3.7) |
| Previous stroke | 5 (4.4) | 4 (3.6) | 1 (3.7) | 1 (3.7) |
| Family history | 1 (0.89) | 1 (0.89) | 1 (3.7) | 1 (3.7) |
| Factors in hospital, n (%) | ||||
| Ventilatory requirement | 15 (13.4) | 6 (5.4) | 16 (59.2) | 4 (14.8) |
| Tracheostomized | 4 (3.6) | 4 (3.6) | 10 (37.0) | 5 (18.5) |
| eGFR G2/G1 | G2:36 (32.1) | G1:15 (13.4) | G2:15 (55.5) | G1:6 (22.2) |
| GCS at presentation, median (IQR) | ||||
| GCS <8 n (%) | 6 (5.3) | 4 (3.6) | 16 (59.2) | 6 (22.2) |
| GCS 9–15, n (%) | 42 (37.5) | 70 (62.5) | 15 (55.5) | 10 (37.0) |
| Time frames, median (IQR | ||||
| Duration to death (days) | 8 (6.2–15.5) | 6 (5.2–15.5) | 12 (10.0–21.5) | 10 (7.5–20.5) |
| Hospital stay (days) | 10 (6.5–15.5) | 7 (4.5–10.5) | 12 (10.5–19.5) | 12 (10.5–19.5) |
| Duration to death (days) | 12 (7.0–17.5) | 8 (7.0–15.5) | 12 (10.0–14.5) | 10 (8.5–12.5) |
AKI=Acute kidney injury, eGFR=Estimated glomerular filtration rate, DM=Diabetes mellitus, HTN=Hypertension, BP=Blood pressure, DBP=Diastolic blood pressure, GCS=Glasgow coma Scale, GFR=Glomerular filtration rate, G1=GFR 90 mL/min/1.73 m2, G2=GFR 60–89 mL/min/1.73 m2, LDL=Low density lipoprotein, SBP=Systolic blood pressure, IQR=Interquartile range, SD=Standard deviation
Table 4.
Model for prediction of Acute kidney injury in ischemic and hemorrhage stroke
| Mortality | OR | P | 95%CI |
|---|---|---|---|
| Ischemic stroke | |||
| Age | 0.96 | 0.550 | 0.92–1.10 |
| Sex | 1.75 | 0.540 | 0.290–12.50 |
| Ventilatory requirement | 24.40 | 0.001 | 5.75–152.01 |
| Tracheostomized | 0.225 | 0.125 | 0.04–1.60 |
| NIHSS at admission | 1.40 | 0.001 | 1.24–1.72 |
| Previous HTN | 6.15 | 0.001 | 1.11–25.58 |
| eGFR | 0.96 | 0.001 | 0.82–0.98 |
| Hemorrhagic stroke | |||
| Age | 0.85 | 0.152 | 0.62–1.20 |
| Sex | 0.20 | 0.350 | 0.05–7.20 |
| Ventilatory requirement | 1.30 | 0.001 | 0.04–70.10 |
| Tracheostomized | 3.20 | 0.580 | 0.102–131.82 |
| NIHSS at admission | 1.88 | 0.155 | 0.88–4.80 |
| Previous HTN | 8.50 | 0.05 | 0.32–240.64 |
| eGFR | 0.90 | 0.121 | 0.68–1.24 |
| Smokers | 0.15 | 0.128 | 0.05–3.42 |
| Alcohol | 0.92 | 0.850 | 0.08–110.5 |
| DM | 7.80 | 0.001 | 0.05–1560.21 |
CI=Confidence interval, NIHSS=National Institute of Health Stroke Scale, eGFR=Estimated glomerular filtration rate, DM=Diabetes mellitus, HTN=Hypertension, OR=Odds ratio
Patients needed ventilatory care due to baseline stroke severity, and ventilator-associated pneumonia and sepsis may have predisposed them to AKI. AKI was highly linked with in-hospital mortality after ischemic stroke in all models, with the fully adjusted model indicating a 25.25-fold increased risk (95% CI: 4.42–225.21). The link between AKI and mortality in hemorrhagic stroke was stronger after adjusting for NIHSS score and smoking (OR 16.48, 95% CI: 0.62–340.12) [Table 5].
Table 5.
Model for predicting acute kidney injury causing in-hospital mortality
| Model | Hemorrhagic stroke (n=27) | Ischemic stroke (n=112) | ||||
|---|---|---|---|---|---|---|
|
|
|
|||||
| OR | P | 95% CI | OR | P | 95% CI | |
| Model 1 | 5.20 | 0.05 | 1.32–22.34 | 25.25 | 0.001 | 4.42–225.21 |
| Model 2 | 5.32 | 0.001 | 1.32–24.48 | 25.60 | 0.001 | 4.36–220.10 |
| Model 3 | 16.48 | 0.001 | 0.62–340.12 | 32.50 | 0.001 | 4.68–262.73 |
Model 1: AKI only, Model 2: AKI plus age plus sex, Model 3: AKI plus age plus sex plus smoker plus hypertension plus NIHSS. AKI=Acute kidney injury, CI=Confidence interval, NIHSS=National Institute of Health Stroke Scale, OR=Odds ratio
AKI occurred in 59.0% of patients (82), with a greater incidence in cerebral bleeding (77.8% vs. 54.5%, P < 0.001). Of all AKI cases, 43.9% were stage 1, and 35 (42.7%) had normalized renal function during hospitalization [Table 6]. 61 ischemic stroke patients (21 stage 1, five stage 2, and five stage 3) and 21 hemorrhagic stroke patients (15 stage 1, none stage 2, and one stage 3) suffered AKI. AKI patients’ median hospital stay was 9 days. Standard therapy included stopping nephrotoxic medicines, optimizing hydration, monitoring renal function, and dialysis when needed for all patients.
Table 6.
Overall survival according to acute kidney injury and AKIN at follow-up
| AKI stage | Mortality | |
|---|---|---|
|
| ||
| n (%) | Mean±SE | |
| No AKI | 3 (5.3) | 31.95±0.61 |
| Stage 1 | 5 (12.8) | 31.63±0.78 |
| Stage 2 | 4 (17.4) | 32.09±0.50 |
| Stage 3 | 4 (20.0) | 28.48±2.13 |
| χ2; P | 5.205; 0.157 (log rank mantel-cox) | |
| Outcome in terms of recovery, n (%) | ||
| Partial recovery | 10 (12.1) | |
| No recovery | 20 (24.3) | |
| Full recovery | 52 (63.4) | |
SE=Standard error, AKI=Acute kidney injury
DISCUSSION
AKI is considered a significant risk factor in stroke patients. We conducted our study to evaluate AKI in acute stroke patients. This research revealed that AKI was a prevalent stroke complication (58.9%), which is higher than in other studies. AKI was more common in hemorrhagic stroke (77.80%) as compared to ischemic stroke (54.4%) in study of Shrestha et al[29] 64.0% developed AKI in hemorrhagic vs 33.3% AKI in ischemic stroke. This may have several causes. Previous studies have primarily used hospital records and solely measured creatinine and urine output to assess AKI.[30] We changed all parameters to identify key causes for AKI. As a tertiary referral facility, our admission bias favors unwell patients who are more susceptible to AKI due to sepsis, medicines, and fluid/nutrition imbalance.
The high incidence of AKI may be due to its high sensitivity definition. Due to the absence of preadmission creatinine, the baseline renal function level is unclear. However, only 20.1% of patients developed persistent AKI upon discharge. Covi et al.[30] found a slightly lower incidence of AKI (14.5% out of 932 individuals).[31] A meta-analysis found a pooled prevalence rate of 11.6% (95% CI: 10.6–12.7) for AKI after all stroke types.[21] Ischemic stroke patients with AKI had 30 times the risk of in-hospital death compared to those without. Similar to our analysis, Khatri et al. found that AKI increased hospital mortality for ischemic stroke (OR: 3.08) but not ICH (OR: 0.82, 95% CI: 0.50–1.35).[8] Recent studies indicate that AKI independently predicts short-term mortality after acute stroke. In another study, SCr independently predicted stroke survivors’ mortality, even after controlling for covariates.[32,33] The average hospital stay for ICH patients with AKI was 13 days, compared to 8 days for those without AKI.[4]
In our study, dialysis was needed for 2.9% of stroke patients and 6.7% of those with AKI. Acute kidney injury requiring dialysis (AKI-D) was more common in hemorrhagic stroke (8.3%) compared to ischemic stroke (0.69%) (P = 0.001). Nadkarni et al. found that hospitalized patients with ischemic stroke had a 0.15% incidence of AKI-D and 0.35% in ICH, with a greater risk of mortality and poor outcomes upon release.[32] Out of 89 individuals with AKI, 30 died, with 33.7% in the AKI group and 3.4% in the non-AKI group. Khatri et al. found a 33% mortality rate in ischemic stroke patients and a 40% mortality rate in hemorrhagic stroke patients with AKI.[8] Previous hypertension and ventilatory need were predictors of AKI in our study.
Acute Kidney Injury requiring dialysis (AKI-D) was 8.3% more common in hemorrhagic stroke than in ischemic stroke (0.69%) (P = 0.001). Nadkarni et al. found that hospitalized patients with ischemic stroke had a 0.15% incidence of AKI-D and 0.35% in ICH, with a greater risk of mortality and poor outcomes upon release.[32] Out of 89 individuals with AKI, 30 died, with 33.7% in the AKI group and 3.4% in the non-AKI group. Khatri et al. found a 33% mortality rate in ischemic stroke patients and a 40% mortality rate in hemorrhagic stroke patients with AKI.[8] Previous hypertension and ventilatory need were predictors of AKI in our study.
The greater occurrence of AKI in ICH patients compared to AIS may be attributable to underlying arterial hypertension. The usage of mannitol, nephrotoxic medications, and antibiotics differs for hemorrhagic versus ischemic stroke management. Mannitol and frusemide were the most commonly used diuretics. The logistic regression analysis of another study showed that age, renal function, estimated GFR, comorbidities, and stroke type at the time of admission as independent predictors of AKI. AKI was found to predict mortality in both forms of stroke, with ischemic stroke having a higher risk of death than hemorrhagic stroke with AKI.[11] Nephrotoxic antibiotics, antiepileptic medications, fluid balance, and sepsis (measured by fever and TLC) were significant predictors of AKI in this cohort.[4,14] Adjusted multivariate analysis identified TLC as the only critical predictor.
Our investigation focused on changes in kidney function after hospital admission, where mortality was higher than in ischemic stroke patients. In the case of ICH, we believe the severity of the stroke nullified any smaller effect of AKI. This may negate the impact of AKI on hemorrhagic stroke mortality. However, subgroup analysis showed a substantial link between AKI and ischemic stroke mortality. A potential issue is the absence of biomarkers for defining AKI. Interventions could prevent or treat AKI. The study cohort had a large proportion of AKI patients with ICH, which is associated with much higher rates of mortality.
CONCLUSION
AKI is a common issue during stroke hospitalizations and is linked to in-hospital mortality from both ischemic and hemorrhagic strokes. The majority of AKI patients were stage 1, emphasizing the significance of even moderate creatinine increase during hospitalization for early diagnosis and management. Impairment of kidney function in acute stroke patients is linked to higher all-cause mortality, regardless of age, sex, or comorbidities. We found that hemorrhagic stroke, greater age, high baseline creatinine, and diabetes mellitus are independent predictors of outcome in stroke patients at risk of developing AKI. More research is needed to evaluate whether therapies aimed at preventing or aggressively treating early AKI symptoms can reduce stroke mortality.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
REFERENCES
- 1.Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of stroke during 1990-2010: Findings from the Global Burden of Disease Study 2010. Lancet. 2014;383:245–54. doi: 10.1016/s0140-6736(13)61953-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Arnold J, Ng KP, Sims D, Gill P, Cockwell P, Ferro C. Incidence and impact on outcomes of acute kidney injury after a stroke: A systematic review and meta-analysis. BMC Nephrol. 2018;19:283. doi: 10.1186/s12882-018-1085-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Katan M, Luft A. Global burden of stroke. Semin Neurol. 2018;38:208–11. doi: 10.1055/s-0038-1649503. [DOI] [PubMed] [Google Scholar]
- 4.Writing Group Members. , Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Heart disease and stroke statistics-2016 update: A report from the American Heart Association. Circulation. 2016;133:e38–360. doi: 10.1161/CIR.0000000000000350. [DOI] [PubMed] [Google Scholar]
- 5.Kamalakannan S, Gudlavalleti AS, Gudlavalleti VS, Goenka S, Kuper H. Incidence and prevalence of stroke in India: A systematic review. Indian J Med Res. 2017;146:175–85. doi: 10.4103/ijmr.IJMR_516_15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Koza Y. Acute kidney injury: Current concepts and new insights. J Inj Violence Res. 2016;8:58–62. doi: 10.5249/jivr.v8i1.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Wang D, Guo Y, Zhang Y, Li Z, Li A, Luo Y. Epidemiology of acute kidney injury in patients with stroke: A retrospective analysis from the neurology ICU. Intern Emerg Med. 2018;13:17–25. doi: 10.1007/s11739-017-1703-z. [DOI] [PubMed] [Google Scholar]
- 8.Khatri M, Himmelfarb J, Adams D, Becker K, Longstreth WT, Tirschwell DL. Acute kidney injury is associated with increased hospital mortality after stroke. J Stroke Cerebrovasc Dis. 2014;23:25–30. doi: 10.1016/j.jstrokecerebrovasdis.2012.06.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Snarska K, Kapica-Topczewska K, Bachórzewska-Gajewska H, Małyszko J. Renal function predicts outcomes in patients with ischaemic stroke and haemorrhagic stroke. Kidney Blood Press Res. 2016;41:424–33. doi: 10.1159/000443444. [DOI] [PubMed] [Google Scholar]
- 10.Qureshi AI, Aslam H, Zafar W, Huang W, Lobanova I, Naqvi SH, et al. Acute kidney injury in acute ischemic stroke patients in clinical trials. Crit Care Med. 2020;48:1334–9. doi: 10.1097/CCM.0000000000004464. [DOI] [PubMed] [Google Scholar]
- 11.Yaqub S, Aziz A. Acute kidney injury in acute stroke. J Pak Med Assoc. 2022;72:1889. doi: 10.47391/JPMA.5549. [DOI] [PubMed] [Google Scholar]
- 12.Ramírez-Guerrero G, Baghetti-Hernández R, Ronco C. Acute kidney injury at the neurocritical care unit. Neurocrit Care. 2022;36:640–9. doi: 10.1007/s12028-021-01345-7. [DOI] [PubMed] [Google Scholar]
- 13.Lee M, Saver JL, Chang KH, Liao HW, Chang SC, Ovbiagele B. Low glomerular filtration rate and risk of stroke: Meta-analysis. BMJ. 2010;341:c4249. doi: 10.1136/bmj.c4249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Kumai Y, Kamouchi M, Hata J, Ago T, Kitayama J, Nakane H, et al. Proteinuria and clinical outcomes after ischemic stroke. Neurology. 2012;78:1909–15. doi: 10.1212/WNL.0b013e318259e110. [DOI] [PubMed] [Google Scholar]
- 15.McCullough PA, Ahmad A. Cardiorenal syndromes. World J Cardiol. 2011;3:1–9. doi: 10.4330/wjc.v3.i1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Nongnuch A, Panorchan K, Davenport A. Brain-kidney crosstalk. Crit Care. 2014;18:225. doi: 10.1186/cc13907. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.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]
- 18.Barnum SR. Complement in central nervous system inflammation. Immunol Res. 2002;26:7–13. doi: 10.1385/IR:26:1-3:007. [DOI] [PubMed] [Google Scholar]
- 19.Woiciechowsky C, Asadullah K, Nestler D, Eberhardt B, Platzer C, Schöning B, et al. Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med. 1998;4:808–13.3. doi: 10.1038/nm0798-808. [DOI] [PubMed] [Google Scholar]
- 20.Ott L, McClain CJ, Gillespie M, Young B. Cytokines and metabolic dysfunction after severe head injury. J Neurotrauma. 1994;11:447–72. doi: 10.1089/neu.1994.11.447. [DOI] [PubMed] [Google Scholar]
- 21.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]
- 22.Saeed F, Adil MM, Khursheed F, Daimee UA, Branch LA, Jr, Vidal GA, et al. Acute renal failure is associated with higher death and disability in patients with acute ischemic stroke: Analysis of nationwide inpatient sample. Stroke. 2014;45:1478–80. doi: 10.1161/STROKEAHA.114.004672. [DOI] [PubMed] [Google Scholar]
- 23.Hao Z, Wu B, Lin S, Kong FY, Tao WD, Wang DR, et al. Association between renal function and clinical outcome in patients with acute stroke. Eur Neurol. 2010;63:237–42. doi: 10.1159/000285165. [DOI] [PubMed] [Google Scholar]
- 24.Praught ML, Shlipak MG. Are small changes in serum creatinine an important risk factor? Curr Opin Nephrol Hypertens. 2005;14:265–70. doi: 10.1097/01.mnh.0000165894.90748.72. [DOI] [PubMed] [Google Scholar]
- 25.Huang Y, Wan C, Wu G. Acute kidney injury after a stroke: A PRISMA-compliant meta-analysis. Brain Behav. 2020;10:e01722. doi: 10.1002/brb3.1722. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Tsagalis G, Akrivos T, Alevizaki M, Manios E, Theodorakis M, Laggouranis A, et al. Long-term prognosis of acute kidney injury after first acute stroke. Clin J Am Soc Nephrol. 2009;4:616–22. doi: 10.2215/CJN.04110808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Spratt N, Wang Y, Levi C, Ng K, Evans M, Fisher J. A prospective study of predictors of prolonged hospital stay and disability after stroke. J Clin Neurosci. 2003;10:665–9. doi: 10.1016/j.jocn.2002.12.001. [DOI] [PubMed] [Google Scholar]
- 28.Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31. doi: 10.1186/cc5713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Shrestha P, Thapa S, Shrestha S, Lohani S, Bk S, MacCormac O, et al. Renal impairment in stroke patients: A comparison between the haemorrhagic and ischemic variants. F1000Res. 2017;6:1531. doi: 10.12688/f1000research.12117.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Covic A, Schiller A, Mardare NG, Petrica L, Petrica M, Mihaescu A, et al. The impact of acute kidney injury on short-term survival in an Eastern European population with stroke. Nephrol Dial Transplant. 2008;23:2228–34. doi: 10.1093/ndt/gfm591. [DOI] [PubMed] [Google Scholar]
- 31.MacWalter RS, Wong SY, Wong KY, Stewart G, Fraser CG, Fraser HW, et al. Does renal dysfunction predict mortality after acute stroke? A 7-year follow-up study. Stroke. 2002;33:1630–5. doi: 10.1161/01.str.0000016344.49819.f7. [DOI] [PubMed] [Google Scholar]
- 32.Nadkarni GN, Patel AA, Konstantinidis I, Mahajan A, Agarwal SK, Kamat S, et al. Dialysis requiring acute kidney injury in acute cerebrovascular accident hospitalizations. Stroke. 2015;46:3226–31. doi: 10.1161/STROKEAHA.115.010985. [DOI] [PubMed] [Google Scholar]
- 33.Arora S, Agrawal A, Vishnu VY, Singh MB, Goyal V, Srivastava PM. Navigating the nexus: Acute kidney injury in acute stroke – A prospective cohort study. Ann Indian Acad Neurol. 2024;27:384–92. doi: 10.4103/aian.aian_177_24. [DOI] [PMC free article] [PubMed] [Google Scholar]