Outcomes of acute ischemic stroke in kidney transplant recipients: An analysis of US Nationwide inpatient sample

2.1 Data source

This population-based, retrospective observational study extracted all data from the US Nationwide Inpatient Sample (NIS) database, which is the largest all-payer, continuous inpatient care database in the United States, including about eight million hospital stays each year [16]. The database is administered by the Healthcare Cost and Utilization Project (HCUP) of the US National Institutes of Health (NIH). Patient data include primary and secondary diagnoses, primary and secondary procedures, admission and discharge status, patient demographics, expected payment source, duration of hospital stay, and hospital characteristics (i.e., bed size/location/teaching status/hospital region). All admitted patients are initially considered for inclusion. The continuous, annually updated NIS database derives patient data from about 1,050 hospitals from 44 States in the US, representing a 20% stratified sample of US community hospitals as defined by the American Hospital Association.

1. Ethics statement: All data were obtained through request to the Online HCUP Central Distributor (available at: https://www.distributor.hcup-us.ahrq.gov/), which administers the database (certificate # HCUP-1K60EVP88). This study conforms to the NIS data-use agreement with HCUP. Because this study analyzed secondary data from the NIS database, patients and the public were not involved directly. Since all data in the NIS database are de-identified, the requirement for informed consent was also waived.

2.2 Study population

Data of hospitalized adults aged 18–85 years or older who had a principal diagnosis of ischemic stroke between 2005 and 2018 were identified in the NIS database through the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification (ICD-9-CM and ICD-10-CM) codes: 433, 434, 436, and I63. Exclusion criteria were: kidney graft failure requiring dialysis (ICD-9-CM: V42.0 or 996.81 combined with ICD-9-PCS 39.95 or 54.98; ICD-10-CM: Z94.0 or T8610 combined with 5A1D70Z, 5A1D80Z, 5A1D90Z, or 3E1M39Z); CKD G1–G4 and unspecified stage CKD (585.1–585.4, 585.9, N18.1–18.4, or N18.9); patients admitted to the hospital electively (non-emergently), and no information of study outcome variables (i.e., mortality, LOS, and transfer to nursing home/long-term facilities). The patient cohort was further classified into three groups for further comparisons: CKD G5D, i.e., patients with codes of CKD G5 treated by dialysis (ICD-9-CM: 585.5, 585.6 or ICD-9-PCS: 39.95, or 54.98 excluding the codes of acute kidney injury, and ICD-10-CM: N18.5, N18.6, or ICD-10-PCS: 5A1D70Z, 5A1D80Z, 5A1D90Z, or 3E1M39Z excluding the codes of acute kidney injury); KTRs (V42.0 and Z94.0); and CKD-free, i.e., none of the abovementioned codes.

2.3 Study outcomes

Study outcomes were: (1) in-hospital mortality; (2) transfer to nursing homes or long-term care facilities; (3) the occurrence of major medical complications; and (4) LOS.

Major medical complications with applicable ICD-9 and ICD-10 codes included: intracranial hemorrhage, acute myocardial infarction (AMI), respiratory complication, pneumonia, sepsis, infection, deep vein thrombosis (DVT)/pulmonary embolism (PE), received mechanical ventilation and parenteral nutrition.

2.4 Covariates

Patients’ characteristics included age, gender, race, household income level, and insurance status (primary payer). Reperfusion treatment including thrombolysis, endovascular thrombectomy, or none, comorbidities and Charlson’s Comorbidity Index (CCI) were identified using ICD-9 and ICD-10 diagnostic codes. Hospital-related characteristics (year of hospitalization, bed size, location/teaching status, hospital region, and annual caseload) were also extracted from the database as part of the comprehensive data available for all participants.

2.5 Statistical analysis

Comparisons of the continuous data were performed using the Analysis of Variance (ANOVA) and presented as mean value ± standard deviation (SD). Comparisons of the categorical data were performed using the chi-square test and presented as n (%). Univariable and multivariable logistic regressions and linear regressions were utilized to determine the associations between study variables and in-hospital mortality, transfer to nursing homes and long-term care facilities, medical complications, and length of stay. A two-sided P-value of <0.05 was regarded as statistically significant. Data management and statistical analyses were conducted by using SAS version 9.4 software (SAS Institute, Inc.).

3.1 Baseline characteristics of patients hospitalized for AIS

Table 1 summarizes the characteristics of all patients hospitalized for AIS, grouped by CKD and KT status: CKD-free: n = 986,945, CKD G5D: n = 26,767, and KTR: n = 1,833. Of the study cohort, the mean age was 66.56 and 50.74% were males. Patients in the KTR group were the youngest (CKD-free: 66.61 ± 12.75 y/o, CKD G5D: 64.95 ± 12.72 y/o, KTR: 61.70 ± 10.95 y/o, respectively; p-value <0.001). Patients in the CKD G5D group had the greatest proportion of female (CKD-free: 49.17%; CKD G5D: 53.17%; KTR: 42.23%; p-value < 0.001), black race (CKD-free: 16.86%; CKD G5D: 36.30%; KTR: 21.76%; p-value < 0.001), lowest household income (CKD-free: 30.55%; CKD G5D: 38.25%; KTR: 26.69%; p-value < 0.001), insurance covered by Medicare/Medicaid (CKD-free: 67.65%; CKD G5D: 86.15%; KTR: 76.19%; p-value <0.001), and no reperfusion treatment (CKD-free: 91.55%; CKD G5D: 94.86%; KTR: 93.67%; p-value <0.001).

Clinical outcomes of AIS hospitalizations are shown in Table 2. Among the patient groups, the CKD G5D group had the greatest percentage of in-hospital mortality (CKD-free: 3.37%; CKD G5D: 7.36%; KTR: 3.98%; p-value < 0.001), transfer to nursing homes and long-term care facilities (CKD-free: 35.45%; CKD G5D: 41.36%; KTR: 32.79%; p-value < 0.001), and occurrence of any medical complication (CKD-free: 17.55%; CKD G5D: 28.98%; KTR: 19.01%; p-value < 0.001). In addition, the CKD G5D group also had the longest LOS (CKD-free: 4.80 ± 5.98 days ; CKD G5D: 7.57 ± 9.5 days5; KTR: 5.08 ± 10.32 days; p-value < 0.001).

3.2 Associations between clinical outcomes and KTR, CKD G5D vs CKD-free

The results of logistic regression and linear regression are presented in Table 3. After adjusting for relevant confounders, CKD G5D was significantly and independently associated with an increased risk for in-hospital mortality (adjusted odds ratio (aOR) = 2.04, 95% CI = 1.93–2.14), any medical complication (aOR = 1.49, 95% CI = 1.45–1.54), and transfer to nursing homes or long-term care facilities (aOR = 1.10, 95% CI = 1.07–1.13) as compared with CKD-free. CKD G5D was also associated with a longer LOS (β = 0.07, 95% CI = 0.06–0.08) as compared with CKD-free. On the other hand, after adjustment, KTR was significantly associated with an increased risk of any medical complication (aOR = 1.20, 95% CI = 1.05–1.36) as compared with CKD-free.

3.3 Associations between medical complications and KTR, CKD G5D vs CKD-free

Figure 2 demonstrates the associations between each medical complication, KTR and CKD G5D (versus CKD-free) during AIS admission. CKD G5D was associated with increased risk for AMI, respiratory complication, pneumonia, sepsis, DVT/PE, and mechanical ventilation than CKD-free. There were no significant differences in the risk for AMI, respiratory complication, pneumonia, sepsis, and mechanical ventilation between KTR and CKD-free. However, KTR had a greater odds ratio for infection than that of CKD G5D.

Figure 2

Impact of KTR and CKD G5D on medical complications of stroke hospitalizations. All models are adjusted by age, gender, race, household income, primary payer, reperfusion, comorbidities, year of hospitalization, hospital bed size, location/teaching status, hospital region, and hospital annual caseload of ischemic stroke.