This retrospective multicenter study was carried out in three tertiary University hospitals, and three central hospitals in Minia, Egypt. The hospital records were analyzed for the period between January 2011 and May 2023 to identify patients with renal vein thrombosis who were monitored for at least a year. Our hospitals have implemented clinical data repositories as a tool for researchers. The electronic health record systems are the primary source of data used in these clinical data repositories. The data elements available in these clinical data repositories include the ones that are usually recorded as discrete and coded elements in the electronic health records, such as the patient’s demographics, clinical characteristics, diagnoses, laboratory test results, medications, and diagnostic and therapeutic procedures. The study adhered to the standards of ethics of the Institutional Review Board (IRB), Faculty of Medicine, Minia University, and was assigned approval number 1207-7-2024. All study participants provided informed consent. One hundred eighty-two adult patients with renal vein thrombosis identified by computed tomography venography of renal veins or renal Doppler ultrasonography, who were above the age of 18, were eligible for enrollment in this study. Kidney transplant recipients, patients under the age of 18, and those with a disease course > 30 days were excluded. We evaluated all-cause mortality as well as renal outcomes, such as AKI and chronic kidney disease (CKD). Then, we classified the patients depending on the all-cause mortality into two groups; survivors and non-survivors.
Clinical and laboratory characteristicsWe obtained and evaluated the patients’ comprehensive medical history, taking into account the symptoms as well as findings of the physical and systemic examination. The results of laboratory investigations, including complete blood count, lipid profile, urine analysis, the spot protein to creatinine ratio or 24 h proteinuria, serum albumin, random blood sugar, C-reactive protein, kidney function tests, and liver function tests, were also examined and reviewed. The estimated glomerular filtration rate (eGFR) was determined using the formula created by the Chronic Kidney Disease Epidemiology Collaboration. Protein S, protein C, prothrombin G20210A mutation, factor V Leiden mutation, and antithrombin III were all analyzed in patients suspected of having inherited hypercoagulability. In patients with anti-phospholipid syndrome, tests for lupus anticoagulant, anti-cardiolipin antibody, and B2 anti-glycoprotein antibody were also checked and evaluated. Antinuclear antibodies, anti-double-stranded DNA antibodies, serum complement levels (C3 and C4), and anti-neutrophil cytoplasmic antibodies determined by the indirect immunofluorescence test/ELISA were further evaluated and verified in patients with systemic lupus erythematosus and vasculitis.
Imaging investigationsChest X-ray, electrocardiogram, and abdominal ultrasounds were retrieved and reviewed in all patients. All patients suspected of having pulmonary embolism underwent two- and three-dimensional transthoracic echocardiography and computed tomography pulmonary angiography. All patients underwent Doppler ultrasound or computed tomography venography to detect renal vein thrombosis.
Renal Doppler ultrasonographyPatients were placed in a supine position and the kidneys were examined initially using a convex ultrasound transducer operating at 5 MHz, using a Logic E9 ultrasound machine (GE Healthcare, Chalfont St Giles, UK). Renal vein thrombosis was shown on a greyscale examination as kidney enlargement with hypoechoic cortex due to edema in the early stages or as a shrunken kidney with increased echogenicity in the later stages. Applying color Doppler ultrasonography showed that the renal artery had significant resistance with an elevated resistive index, thrombus was visible within the lumen of the renal vein, venous flow was absent and arterial diastolic flow had reversed [21].
Computed tomography venographyUsing a multi-detector computed tomography Toshiba Aquilion CXL 128 Slice CT Scanner, computed tomography venography was performed as a conventional, non-oral, post–intravenous contrast-enhanced (2 ml/Kg) computed tomography at about 120–150 s after contrast injection, which was notably later than the portal venous phase. The size of the intravenous line, injection rate, degree of hydration, and cardiac output all had an impact on the results. Similar to other cases of renal vein thrombosis, the thrombosis was visualized as a filling defect on venous phase imaging following administration of intravenous contrast. Additional computed tomography venography findings included an enlarged kidney, delayed, reduced, or absent calyceal opacification in the affected kidney, persistent cortical enhancement without parenchymal enhancement, perinephric hemorrhage, and diffuse or focal changes in attenuation because of perfusion abnormalities. The afflicted renal vein became attenuated during the chronic phase of renal vein thrombosis due to the clot retraction. The presence of collateral kidney vessels was also recorded [22].
Renal outcomes and mortalityThe time interval from enrollment to death from any cause, regardless of whether it occurred in an outpatient or inpatient setting, was utilized to determine all-cause mortality [23]. Renal outcomes included AKI, CKD or end-stage kidney disease (ESKD). AKI was diagnosed as a reduction in urine volume less than 0.5 mL/kg/h for at least 6 h; an increase in serum creatinine of 1.5 times the baseline of the previous 7 days; or an increase in serum creatinine ≥ 0.3 mg/dL within 48 h [24]. CKD was identified as a decline in eGFR less than 60 mL/min/1.73 m2 or damage to the kidney structure lasting longer than 3 months [23]. ESKD was described as receiving chronic dialysis or having a kidney transplant.
Treatment protocolA multidisciplinary team of nephrologists, cardiologists, vascular surgeons, and hematologists decided treatment for each patient based on their general condition and comorbidities [1]. Therapeutic anticoagulation was given to all patients. Parenteral heparin was used to achieve initial anticoagulation regardless of whether renal vein thrombosis was unilateral, bilateral, acute, or chronic. Patients were then switched to a vitamin K antagonist as warfarin, within three to ten days. Depending on the persistence of risk factors or on recurrence of renal vein thrombosis, anticoagulant medication was administered for a minimum of one year to lifetime. Specific therapy for underlying diseases was implemented [14]. The markers of coagulation and kidney function were strictly monitored. After an average of 5 days of anticoagulation treatment, kidney function and thrombus clearance were re-evaluated by the same imaging modalities that were used for the initial diagnosis.
Endovascular treatment, including catheter-directed thrombolysis and mechanical thrombectomy, was considered in cases of treatment failure on adequate anticoagulation, bilateral renal vein thrombosis, acute decline in kidney function or extension to the inferior vena cava. Endovascular treatment was carried out under local anesthesia and renal computed tomography venography was performed using a right internal jugular vein approach. The treatment approach was based on the thrombus location. The AngioJet System (Boston Scientific, Marlborough, MA) was utilized for patients with impaired coagulation who were not suitable candidates for long-term thrombolytic therapy for percutaneous mechanical thrombectomy. Renal artery angiography was carried out using a common femoral artery access when the thrombus was found surrounding the branches of the renal veins. The combination modality (percutaneous mechanical thrombectomy followed by catheter-directed thrombolysis through the renal vein and indirect catheter thrombolysis through the renal artery) was performed when the thrombus was in the main trunk and branches of the renal veins (mixed type). The contrast agent utilized was iodixanol (32 g/50 mL), with a mean dosage of 15 g per procedure. After the thrombolytic catheter was positioned, the patients received daily urokinase infusions (4400 IU/kg). Patients’ coagulation indicators were assessed three or four times a day while receiving thrombolytic therapy. The whole blood euglobulin lysis time was the first choice, but if not available, fibrinogen concentration, prothrombin time (PT) or partial thromboplastin time (PTT), were monitored. A prolonged PTT, PT or a lower fibrinogen concentration confirmed the establishment of systemic lysis [25].
Renal vein Doppler ultrasonography or computed tomography venography was performed before discharge (after about 10 days of treatment) (Supplemental Fig. 1). Patients who had either partial or complete resolution of the thrombus were discharged from the hospital with anticoagulant treatment (warfarin) to keep their international normalized ratio (INR) between 2.0 and 3.0 [1].
Statistical analysisThe results were analyzed using SPSS version 25. Numbers and percentages were employed with categorical data, while medians with interquartile ranges (IQR) or means with standard deviations (SD) were utilized for continuous data. Non-parametric continuous variables for two-group comparisons were assessed using the Mann–Whitney test. Categorical data were analyzed utilizing the chi-square test. All-cause mortality and declining kidney function were the dependent outcome variables, and were adjusted for independent variables including age, body mass index (BMI), diabetes mellitus, hypertension, nephrotic syndrome, sepsis, malignancy, chronic renal vein thrombosis, bilateral renal vein thrombosis, serum albumin, and hemoglobin (Hb) level. Univariate logistic regression analyses were performed to obtain the odds ratio (OR) and 95% confidence interval (CI) for worsening kidney function adjusted for the potential risk factors including age, BMI, diabetes mellitus, hypertension, nephrotic syndrome, malignancy, sepsis, bilateral renal vein thrombosis, chronic renal vein thrombosis, and serum albumin. Similarly, the hazard ratio (HR) and 95% CI for all-cause mortality, adjusted for potential risk factors such as age, BMI, diabetes mellitus, hypertension, nephrotic syndrome, malignancy, sepsis, bilateral renal vein thrombosis, chronic renal vein thrombosis, serum albumin, Hb level, and worsening kidney function, were also calculated using Cox regression analyses. Variables that showed an association with worsening kidney function or all-cause mortality with p < 0.05 in univariate analysis were included in the multivariate regression. Kaplan–Meier analysis was employed to assess patient survival by treatment modality and baseline disease. Paired sample t-test was utilized to compare serum creatinine levels before and after treatment in both treatment groups.
We tried to avoid selection, information, and confounding biases. Confounding was minimized by restriction (strict exclusion criteria), age and gender matching. We reviewed electronic health records to identify the patients on regular follow up.
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