Risk Factors for Major Hemorrhage Following Percutaneous Image-Guided Renal Biopsy: What is the “core” of the Problem? A Retrospective Case–control Study

INTRODUCTION

Percutaneous renal biopsy (PRB) is an important step in the work-up of renal parenchymal disease. To improve biopsy yield and reduce complications, majority of PRBs are performed with ultrasound (US) guidance.^[1] However, despite the widespread use of US guidance, hemorrhage following PRB has been reported to occur in as many as 30% of cases, with up to 7% being life-threatening or needing additional procedures such as blood transfusion, endovascular interventions, major operations, and prolonged hospitalization.^[1-5]

Several factors have been associated with an increased risk of post-biopsy hemorrhage, including patient gender, age, serum creatinine, bleeding diathesis, hypertension, operator experience, biopsy needle size, position within the kidney, angle, depth, and number of needle passes.^[2,6-11]

To the best of our knowledge, no prior studies have analyzed the microscopic findings of the cores obtained following PRBs, with an intent to identify risk factors associated with major post-biopsy hemorrhage. Identification of pertinent findings in the biopsy cores that would predict the odds of a major hemorrhage following PRB would help to enhance the sensitivity and specificity of the risk stratification process, which would, in turn, help to decide if prolonged observation is necessary, especially in situations, where PRB is performed as an ambulatory/outpatient procedure.

MATERIAL AND METHODS

Pathologist procedure details

The slide with the most tissue present was selected, and a micrometer was used to measure the total, medullary, and cortical lengths of the biopsy cores. The AAs [Figure 1] were defined as any medium-sized arteries that are surrounded by soft tissue and not by renal parenchyma. Almost all of these were partially cut through their longitudinal walls.

Close

Figure 1:

Photomicrographs of the percutaneous renal biopsy cores (PAS-D and PAM silver stains) of six different patients (both cases and controls) demonstrating the vessels that were included or excluded as arcuate arteries in the analysis. Photomicrographs of arteries (a-c) included as arcuate arteries as they are surrounded by abundant soft tissue having thick arterial wall (indicated by black arrows). Photomicrographs of arteries (d-f) that were excluded as arcuate arteries as they have thin arterial walls without substantial surrounding soft tissue (indicated by black arrows).

Export to PPT

RESULTS

The retrospective review identified 17 of 179 patients (9.50%) with major hemorrhage within 30 days following US-guided PRB. Of the 17 patients who had major hemorrhage, 4 had angiograms looking for a vascular abnormality, but these patients did not receive any other intervention. Two patients had an angiogram with coiling of the pseudoaneurysm/ fistula [Table 3]. Sixteen patients received blood transfusions. Intergroup comparisons between cases and controls before PSM analysis [Table 4] showed that Hgb, BUN levels, and eGFR values were statistically significant for a major hemorrhage (P = 0.0348, 0.0055, and 0.0021, respectively). To avoid confounding bias and improve intergroup compatibility in terms of the histological parameters, PSM was [Table 5] done in 26 controls. Tables 1 and 2 demonstrate the summary data for histological parameters measured in renal core biopsy samples of the cases and controls. To evaluate the relationship between each histological parameter and the risk of major hemorrhage following PRB, a logistic regression was performed with risk of hemorrhage as the dependent variable. The analysis revealed that the number of AAs per specimen was a significant risk factor for a major hemorrhage (P = 0.0006). No significant association was found between medullary length (ML) (P = 0.228), M:C (P = 0.089), M:T (P = 0.108), or C:T (P = 0.112) length ratios and major hemorrhage [Table 6]. When 0, 1, or ≥2 AAs were identified, the frequency of major hemorrhage was 13%, 66%, and 75.00%, respectively. To determine the incremental risk of hemorrhage based on number of AAs, data were stratified into samples containing either one or two AAs. The odds of major hemorrhage were 6 times higher with one AA and (95% CI, 1.28–32.30) and 15 times higher with ≥2 AAs (95% CI, 1.41–169.57) [Table 7].

DISCUSSION

Kidney biopsy is an essential procedure for nephrologists to make a diagnosis, assess prognosis, and formulate a treatment plan and for the research of various kidney diseases.^[12-14] It is the gold standard for diagnosis of native and transplant kidney diseases. Majority of the PRBs in the United States and around the world are being performed by fellowship trained interventional radiologists (IRs) comfortable with US-guided procedures.^[15,16] Despite this, additional intervention in the form of blood transfusions or endovascular procedures is required after 0.3–9.0% of PRBs.^[6,17-22] IRs perform coil embolization/stent placement for bleeding complications in several vascular territories, which makes them ideal to treat bleeding complications from PRBs that may need additional endovascular interventions.^[23-26] Post-renal biopsy hemorrhage is likely the result of multiple factors including the intrinsic renal vascularity, the non-compressible location of the kidneys, the need for multiple needle passes to ensure an adequate tissue sample, and medical comorbidities such as obesity, liver dysfunction, and diabetes.^[27-29] Post-biopsy bleeding can be further categorized into major and minor hemorrhage, with major hemorrhage requiring additional interventions, such as blood transfusion, endovascular intervention, or nephrectomy.^[30,31]

Imaging-related risk factors such as cortical tangential angle, biopsy location, needle path distance from the capsule, and needle passes through the collecting system have been previously described to be associated with major hemorrhage following PRB.^{[10,11,17,32-34]} Based on our search of the literature, we could not find a study which looked into the microscopic evaluation of the cores following PRB with the intent to identify risk factors that would be associated with major post-biopsy hemorrhage. To minimize the confounding influence of the other risk factors, the cases and controls were matched using the PSM method.^[35,36]

The overall frequency of major hemorrhage in our study was 9.5%. After most previously described risk factors for biopsy-related hemorrhage were matched through PSM, microscopic analysis of the cores obtained in patients with and without major hemorrhage identified the number of AAs as a statistically significant risk factor associated with major post-biopsy hemorrhage. There was no significant association found between ML, M:C, M:T, or C:T length ratios and major bleeding.

Mejia-Vilet et al. formulated a risk score for major bleeding after PRB, which had a good discrimination capacity.^[37] Each of the parameters used by Mejia-Vilet et al. has been previously described to be associated with renal hemorrhage.^{[2,3,7,37,38]} The addition of the histologic features associated with a significant risk for major post-biopsy hemorrhage in our study (not previously described), could greatly enhance the sensitivity and specificity of such a risk score. In many centers, PRB is mainly performed as an outpatient procedure with shortening of in-hospital post- procedure surveillance.^[39-41] Even though up to 85% of major hemorrhages present in the first 8 h post-procedure, there is still a risk of major hemorrhage after 24 h of the procedure^.[4,18,19] In our study, about 6/17(35%) of the major bleeds were identified after 24 h of the biopsy. This makes it even more important to devise a risk score for accurate risk assessment, risk counseling, and risk reduction. An accurate risk score could also facilitate the use of preventive interventions such as desmopressin (DDAVP) in the high-risk population. Given the focus on cost-containing strategies, and classification of PRB as an “ambulatory” procedure, there is a need for a reliable and easy tool for risk stratification that can determine individual risk for major hemorrhage after PRB and thus plan accordingly.^{[4,13,18,39-41]}

Based on previous studies that have alluded to the fact that deeper needle penetration into the renal sinus increases the chances of major hemorrhage, we thought that the ML and the M:C ratio would be major determinants of hemorrhage risk.^[10] Of the two, M:C ratio was “nearly” significant (P = 0.089) but was not strongly significant as we expected.

There was an incrementally higher risk of major hemorrhage associated with the presence of AAs in the core sample. The presence of one AA versus none resulted in a 6.5 increase in the odds of a bleed while two AAs versus none, a 15.5-fold increase [Table 7]. About 75% of cases with major hemorrhage had 1 or 2 AAs in the core specimen. Similarly, 75% of the cases without major hemorrhage had no AAs in the sample. These results suggest that incorporation of the AA score into the risk stratification tool, devised by Mejia-Vilet et al., could make the score more specific and accurate.

Limitations of the present study include its retrospective nature, small sample size, and single-center experience with fixed practices. The availability of a board-certified pathologist to assess the adequacy of a sample and provide information regarding the number of AAs may limit its application for smaller hospitals that may not have the luxury of onsite pathology services. Another potential factor that could have contributed to major hemorrhage was biopsies performed by the radiology residents (under the supervision of the IRs) versus the IRs themselves, which we did not account for due to non-availably of relevant documentation.

CONCLUSION

After matching previously described risk factors for renal hemorrhage, we found a strong and incremental association between major renal hemorrhage following PRB and the number of AAs per core specimen. Identification of AAs by the pathologist, while assessing sample adequacy, in the US suite can help predict major hemorrhage in patients undergoing PRBs. The number of AAs could be used along with other risk factors to devise a simple score which can be used to assess the risk stratification following PRB.