Renal Biopsy


Article Author:
Michael Young


Article Editor:
Stephen Leslie


Editors In Chief:
Stephen Leslie
Karim Hamawy


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/17/2019 6:46:16 PM

Introduction

There are two general types of renal biopsies: targeted biopsies (TB) and non-targeted biopsies (NTB). Physicians perform targeted biopsies to differentiate a mass lesion better.  Non-targeted biopsies are performed to sample a relatively random area of the renal cortex to attempt to diagnose a systemic disease or pathologic response of the kidney (e.g., transplant kidney dysfunction, renal failure).

Renal biopsies can also be categorized by the method used to access the specimen. These include percutaneous, transvenous, laparoscopic, or open surgical approach.

This article will focus on percutaneous image-guided targeted and non-targeted biopsies.

Anatomy

The standard renal arterial vasculature usually starts with a single artery which then divides into anterior and posterior branches. All renal arteries are end arteries with no collaterals. The distal arterial vessels end where the anterior and posterior vasculature meets is located just posterior to the lateral renal margin and is not visible on medical imaging (Hyrtl's or Brodel's line). This is the safest place to obtain renal tissue samples for non-targeted biopsies.

The normal native kidney is situated in the retroperitoneal space. Biopsies of native kidneys should be performed in a manner that infringes only on this space to decrease complications. For the same reason, passing a needle through the central hilum of the kidney, where the larger arteries, veins, and calyces are located, should be avoided. For non-targeted biopsies, sampling the renal cortex is usually preferred, as the majority of glomeruli used for evaluation are located there.

Embryological renal variants, like horseshoe, page, pelvic and ectopic kidneys, exist and can greatly complicate renal biopsies. 

Indications

In general, a biopsy should be performed only to avoid unnecessary or incorrect treatment. Appropriate laboratory and diagnostic imaging tests should be exhausted first. Only when these steps prove to be inconclusive should a patient be subjected to the risks, discomfort, and expense of a biopsy.

Guidelines from several professional medical societies regarding when to perform renal biopsies are summarized below.

Targeted Biopsies

  • The National Comprehensive Cancer Network Guidelines state, "the recommended abdominal imaging studies provide high diagnostic accuracy. Therefore, a needle biopsy is not always necessary before surgery.  In selected individuals, needle biopsy may be considered for small lesions to establish (the) diagnosis of RCC and guide active surveillance strategies, cryosurgery, radiofrequency (sic), and ablation strategies... (or) if a central lesion or a homogeneous infiltration of renal parenchyma is observed on scans to rule out urothelial carcinoma or lymphoma, respectively."
  • The American Urological Association (AUA) Guidelines state that biopsy can be considered when it is necessary to determine whether a mass is "hematologic, metastatic, inflammatory, or infectious." (Campbell 2016).
  • The European Association of Urology (EAU) Guidelines stated in 2014 revision that "owing to the high diagnostic accuracy of current imaging, a biopsy is not necessary for the setting of localized or locally advanced disease before surgical treatment in fit patients with a long life expectancy and a highly suspicious, contrast-enhancing renal mass on CT or MRI[1]."
  • The American College of Radiology (ACR) guidelines address both targeted and non-targeted biopsies. For targeted biopsies, the guidelines state when a person has normal renal function, a biopsy is appropriate when the diagnosis is still indeterminate after all three of the following tests have been performed: CT without and with contrast, MRI without and with contrast, and the ultrasound (US) with duplex Doppler. A biopsy is more useful and appropriate than an MRI or CT without contrast. When a person has renal insufficiency (i.e., to a degree deemed too risky for intravenous (IV) contrast based on an assessment by a nephrologist), a biopsy can be considered the third most appropriate test, after (1) US with duplex Doppler and (2) MRI without contrast have been performed (and before CT without contrast). The ACR guidelines also suggest that masses with intermediate levels of enhancement from 10 HU to 20 HU (Hounsfield units) may be appropriate for biopsy as the next step versus other options (e.g., surveillance) based on work by Heilbrun[2], Vikram[3], and Jacobs[4].

Non-targeted biopsies are performed to differentiate etiologies of acute kidney injury (AKI) or chronic kidney disease (CKD) in a patient who is thought to have a chance at the recoverable renal function, as one etiology may have a different treatment than another. The ACR guidelines state that, for AKI, a biopsy is the next most appropriate radiologic test after US of both the kidneys and bladder; whereas for CKD, the US of the kidneys and bladder should be performed first, but biopsy is then of higher or equivalent appropriateness to any other radiologic test[5].

For non-targeted biopsies, neither the American Society of Nephrology nor the National Kidney Foundation provides guidelines in any general or specific setting, such as AKI, CKD, or post-transplant[6].

The available guidelines do not address many of the specific questions or issues encountered in everyday medical practice, such as specific imaging features or clinical parameters.

For NTB for Differentiating Causes of AKI or CKD

Fiorentino[7] created an evidence-based list of indications and conclusions and Fuiano[8] conducted a worldwide survey to obtain opinions on indications for NTB.  The specific relative indications for NTB described by Fiorentino and Fuiano (such as various types of nephrotic syndrome and glomerulonephritis) are extensive, and the reader is referred to their papers, the National Kidney Fundation guidelines[6], or numerous other available non-consensus guideline based sources with suggested indications for NTB.

Targeted Biopsy for a Mass Lesion

Enhancement to a lesser degree than the aorta of a well-defined mass is the single most important imaging finding to indicate that it is reasonable to biopsy the lesion. Pre-contrast and post-contrast CT or MRI (with or without subtraction technology) is needed to ascertain with confidence whether a lesion enhances. The differential for this type of mass in the absence of evidence of fat in the lesion is usually renal cell carcinoma (RCC) or oncocytoma. The Bosniak scale is used to estimate the likelihood that a cystic renal lesion seen on imaging is a primary renal carcinoma. A common sense approach is to only biopsy Bosniak 2F and Bosniak 3 lesions[9].

Other imaging characteristics that encourage (eventually) proceeding to renal mass biopsy are discussed in detail by Caoili[10] and listed briefly here. If these features are present, then a diagnosis of RCC is in doubt so a biopsy may avoid unnecessary treatment.

  1. Infiltrative mass that preserves a reniform shape in the absence of risk factors for urinary tract infection. This should raise suspicion for lymphoma or urothelial carcinoma over standard RCC.
  2. Multiple enhancing masses without macroscopic fat. This should raise suspicion for lymphoma or a hereditary cancer syndrome over standard RCC.

Other Clinical Scenarios where a Biopsy Might be Appropriate

  1. Mass likely to be oncocytoma or RCC in a patient with comorbidities resulting in high surgical risks. Such risks can be estimated using the American College of Surgeons calculator (riskcalculator.facs.org/RiskCalculator). A patient with high risks and life expectancy shorter than that estimated for the spread of RCC to a terminal state may wish to have a confirmed tissue diagnosis before assuming the risks of a major surgery that may not add longevity or quality of life.
  2. The unresectable renal mass. As no surgical specimen will be obtained, there is no histological diagnosis.  Oncology might decline to offer treatment without a tissue diagnosis in the medical record (although applying this strategy to all patients is not endorsed by the NCCN[11] or any other published professional society guidelines.)
  3. Multiple tumors in the kidney and/or elsewhere in the body. Renal metastases are much less common than metastases from the kidney and multiple renal primary tumors. In the setting of a renal lesion with imaging features compatible with RCC, staging of cancer should be performed by biopsying the safest lesion outside the kidney that could provide a World Health Organization stage 4 RCC diagnosis.  If that extra-renal biopsy results in a diagnosis of cancer, not of renal origin, then the renal tumor should be assessed "on its own merit."  If imaging features are compatible with RCC, then a second biopsy of the renal lesion is not needed just to prove that the lesion is truly an RCC and not a metastasis from other cancer sites[12][13].
  4. Some institutions may require patients to undergo a renal biopsy as part of a non-operative surveillance program, using histological grading of RCC to better advise patients on potential tumor advancement.  At this point, this strategy is endorsed by the EAU[1] but is not recommended by the NCCN[11] or AUA[14]. Management based on biopsy tissue grading has not yet been shown to be more clinically appropriate than management based on imaging surveillance alone, and the AUA[14] currently only endorses the latter. The NCCN[11] states that a renal mass biopsy can be considered in these situations.
  5. Renal tumor in the setting of ablation therapy. The AUA[14] recommends a tissue biopsy before ablation therapy. The NCCN[11] recommends biopsy after ablation therapy for RCC if surveillance imaging shows "new enhancement, a progressive increase in the size of an ablated neoplasm, new nodularity in or around the treated zone, failure of the treated lesion to regress over time, (or) satellite or port site lesions."

Contraindications

The AUA Guidelines state that biopsy usually is not indicated for a solid tumor in the setting of "1) young or healthy patients who are unwilling to accept the uncertainties associated with (biopsy) or 2) older or frail patients who will be managed conservatively independent of renal mass biopsy findings (Campbell 2016)."

Imaging characteristics that discourage proceeding to renal mass biopsy are discussed in detail by Caoili[10] and listed briefly here.

  1. Hemorrhage and protein within a complicated cyst can simulate solid tissue on either pre or post-contrast ultrasound, CT, or MRI.  That is the major reason for the need to compare precontrast and postcontrast images.
  2. Pseudoenhancement is an artifactual increase in attenuation (typically 1 HU to 25 HU) or intensity within a lesion on postcontrast imaging. It is more likely to be seen with small (less than 2 cm) hypodense or hypointense lesions adjacent to the dense renal parenchyma.
  3. Lesion enhancement equivalent to "blood pool" (in other words, to the same degree as the intensity or density of the aorta) may initially appear as a solid lesion, but may actually be a vascular anomaly, such as a pseudoaneurysm. US and/or MRI sequences optimized for detection of blood vessels should be performed as the next step in these situations.

Biopsy of isolated hemorrhage/protein or pseudo-enhancement lesions usually results in a nondiagnostic specimen, whereas biopsy of a vascular anomaly will also result in a hemorrhagic complication.

The following list of CT/MRI findings should result in favoring a benign diagnosis.

  1. Macroscopic fat is diagnostic of a benign angiomyolipoma (AML) in the absence of calcifications or aggressive behavior.
  2. Intracellular lipid-containing (minimal fat) AMLs are hypointense to normal parenchyma on T2 MRI (similar to papillary RCC) and demonstrate avid arterial enhancement (similar to clear cell RCC). The key to the diagnosis is that these two cancer mimickers of minimal fat AMLs do not share both these features.
  3. A rapidly developing, ill-defined mass in a patient with risk factors for urinary tract infection. This should suggest focal bacterial pyelonephritis or focal nephronia, and repeat imaging may be indicated if the symptoms do not resolve with treatment for the infection.  If the finding persists, then a biopsy can be used to determine whether the lesion is infectious or neoplastic.

Risks of the biopsy procedure, such as hemorrhage, may serve as relative contraindications. The Society of Interventional Radiology (SIR) Consensus Guidelines place renal biopsy, even via the transjugular approach which is usually considered safer as it lowers the risk of significant hemorrhage somewhat, in the category of highest risk for hemorrhagic complications[15]. Biopsies should be delayed until coagulation parameters are corrected so that the risks of clinically significant hemorrhage do not outweigh the benefit of a tissue diagnosis. The SIR recommends a minimum platelet count of 50,000/microliter, a maximum International Normalized Ratio (INR) of 1.5, and a maximum activated partial thromboplastin time (aPTT) of 1.5 times the control value. The SIR also recommends withholding specific medicines such as anticoagulants for precise times before the procedure. These times range from 2 hours to 10 days. Extreme hypertension also worsens hemorrhagic risks. 

Prior to the procedure, it is good practice to ask the patient if they are aware of any known allergic reaction to any of the drugs used, so any anaphylaxis risk can be addressed prophylactically. 

Equipment

Transvenous renal biopsy uses a sheathed spring-loaded needle placed after catheter-directed access to a renal vein, usually in the setting of non-targeted biopsies. A detailed discussion of the equipment and technique is beyond the scope of this article but is mentioned elsewhere[16][17].

Percutaneous targeted biopsies, and non-targeted biopsies can be performed with a variety of types of image guidance, including US alone, US with a needle guide, intermittent computed tomography (CT), fluoroscopic CT, or magnetic resonance imaging (MRI). A retrospective review concluded that US image guidance resulted in less risk of bleeding complications than a blind biopsy[18].

Usually, targeted and non-targeted biopsies are performed with an 18 or 20 gauge (g) mechanized spring-loaded needle gun placed through a 17 g or 19 g needle, respectively in a coaxial fashion. Head to head comparisons of types of needle guns have been performed and are available elsewhere. Some physicians prefer larger gauge needles, but this has not been shown in a large scale study to result in fewer passes needed. Van Sonnenberg needles can be used to aid in the setting of a potentially difficult target to reduce the chance of multiple errant punctures with a larger gauge needle. Agarwal[19] provides a more in-depth review of needles for percutaneous access and the types of equipment used to evaluate the specimens.

Personnel

In addition to the physician performing the biopsy, several other healthcare practitioners perform critical functions during the procedure. These include:

  1. A nurse and/or anesthesiologist to administer conscious sedation and monitor vital signs.
  2. A technologist to assist with the equipment.
  3. A cytotechnologist or pathologist to assess the adequacy of specimens and to ensure that specimens are deposited in the most appropriate preservatives for the laboratory tests that best address the clinical scenario.

Preparation

The AUA[14] states that "patients should be counseled regarding rationale, positive and negative predictive values, potential risks and non-diagnostic rates of TB." The referring urologist, nephrologist, or another clinician who has determined that the biopsy should be performed, should address these issues before sending the patient to another specialist such as an interventional radiologist for the actual performance of the biopsy. It should be clear to all involved who will be responsible for management of any immediate complications of the procedure. Ideally, the referring clinician should either (1) be available at the time of the consent with the performing physician to address the rationale, benefits, and alternatives or (2) accept that the patient may wish to delay the procedure until the referring clinician addresses such information. The patient should be informed about positioning (usually prone oblique or prone but with exceptions[20], sedation and analgesia to be used.

The depth of the target and route of the needle should be pre-planned before the procedure. Depth measurements are helpful in optimizing special supplies as an obese patient may require an extra long needle.

Patients with difficult to reach targets are served best by coordinating the biopsy such that both US and CT can be used as necessary to afford the advantages of both modalities (i.e., the speed of ultrasound, tissue contrast and resolution of CT). CT guided biopsies of upper pole lesions protected by ribs may benefit from CT gantry angling and/or basic level trigonometric analysis.

The angle at which to direct the needle concerning the level of the table can be calculated by first dividing the depth of the lesion by the distance of the lesion from the skin entry point and then by calculating the inverse tangent of that number.

Technique

The 2014 EAU Guidelines and the AUA Guidelines state that the coaxial technique is the preferred approach for percutaneous biopsy and has not been associated with tract seeding. The alternative to the coaxial technique is to remove and then reinsert a needle for each pass. A small retrospective study of renal biopsies found no difference in complications or outcomes between the two techniques[21], but a randomized controlled trial comparison has not been done.

Core biopsy specimens result in greater sensitivity and specificity than fine needle aspiration (FNA) specimens for both TB[22] and NTB. For this reason, the AUA 2017 Guidelines state that "multiple core biopsies are preferred over fine needle aspiration" for TB, and many laboratories evaluating NTB specimens will not even accept FNA samples. The EAU Guidelines agree.

There is no standard minimum amount of tissue requirement for a targeted biopsy, as some pathologists can make a diagnosis with the yield from a single FNA pass. The physician performing the biopsy should consult with the pathologist providing the diagnostic interpretation for an estimate of the amount of tissue needed for the performance of tests for genetic markers, flow cytometry, culture, and sensitivity because the necessary sample size can be highly variable from one institution to another.

For non-targeted biopsies, a minimum of about five to ten intact glomeruli is required to make a diagnosis[23], Pirani C. Evaluation of kidney biopsy specimens. In: Tisher BBC, ed. Renal Pathology with Clinical and Functional Correlations. Philadelphia: Lippincott; 1989:11–42].

Yoshinari[24] demonstrated that each 1 cm length of an 18 g specimen of renal cortex averaged over 11 glomeruli. A minimum of two to three specimens is needed to enable evaluation under light microscopy, electron microscopy, and immunofluorescence[25].

Some physicians plug the needle track with thrombin, FFP, or gelatin sponge, but randomized controlled trials comparing any of these products with no intervention or placebo for percutaneous renal biopsies in people, have not been performed.

Complications

The SIR 2013 practice guidelines[15], citing primary sources[26], state that bleeding complications resulting in the need for transfusion when using an 18 g or smaller needle are expected to be less than 3%, and that a 5% rate should result in a change in practice habits. The guidelines also state that using a larger needle is expected to result in a slightly higher complication rate but do not address other complications.

Patel[27] states the following risk percentages: clinically significant renal hematoma (4.9%), clinically significant pain (1.2%), pneumothorax (0.6%) and hemorrhage requiring transfusion (0.4%).

Anecdotally, vascular injuries not requiring treatment are much more common than are reported in such studies. Whereas an arteriovenous fistula (AVF) is not mentioned in either of the two sources above, an AVF requiring clinical attention occurred after about 1% of biopsies done by an experienced physician[28]. In the author's experience, AVFs can be seen at a higher percentage than that if a physician searches explicitly for them on the post-biopsy ultrasound. 

Every patient develops at least some degree of perirenal hematoma which is detected more easily on CT or MRI than ultrasound. One in several thousand patients will lose their kidney secondary to a complication, and deaths have occurred following complications of renal biopsies.

Clinical Significance

The vast majority of studies report that core targeted biopsies have high sensitivity, specificity, and positive predictive value, with comparatively low (but still more than 50%) negative predictive value[29][30],[31]. Patel[27] performed a meta-analysis of 2979 patients and 3113 biopsies and found a mean sensitivity more than 95% (95%, confidence interval (CI) 78 to 100), mean specificity more than 95% (95% CI 75 to 100), and mean positive-predictive value more than 99% (95% CI 97 to 100). RCC subtyping (e.g., clear cell, papillary, or chromophobic) is about 95% accurate [27][32], but this does not change management as of yet based on AUA or NCCN Guidelines.

Richard[32] concluded that, in patients with questionable RCC versus oncocytoma, treatment could have been avoided in at least 26% of cases because the lesion was benign.  However, the converse point is that about 75% of patients underwent "unnecessary" biopsies and could have proceeded straight to surgical resection. TB should be performed if it has a low to zero chance of changing treatment.

Limitations of TB include:

  1. The non-diagnostic rate of first TB is approximately greater than or equal to 10%[32][27].
  2. A small (probably around less than 5%) subset of patients with benign oncocytoma have concurrent RCC that could be missed with TB[33].
  3. TB has a low negative predictive value (NPV) for malignant tumors, with a percentage likely no higher than in the low 60s[27] (meaning that false negatives are probably somewhere above 30%).
  4. Fuhrman histologic grading based on core biopsy is only somewhere between 50% to 75% accurate[27]. The AUA Guidelines[14] describe this as indicating that the accuracy of histologic grading is "variable."

NTB was shown in a prospective study of 80 patients to change the pre-biopsy clinical diagnosis in 44% of cases and to change therapy in 31% of cases[34], meaning that NTB was unnecessary in about 70% of cases. A larger or more recent prospective study was not identified in the literature.

Thus, non-targeted and targeted biopsies provide a role in confirming or changing management decisions, but there are still many patients who will not derive any benefit.

Enhancing Healthcare Team Outcomes

Healthcare Team

A renal biopsy is usually done by a nephrologist or radiologist.  Usually a nurse is present to monitor the patient and administer medicines including drugs for conscious sedation.  An anesthesiologist may be needed in some cases instead.  A pathologist and a cytotechnologist present at the time of the biopsy can reduce nondiagnostic and other types of false negative biopsies.  Equipment technologists are usually present and can sometimes be critical to biopsy success.  Any physician who refers a patient for a renal biopsy should be aware of the potential adverse outcomes and alternatives so as to be able to assist the patient with making informed decisions in the process (informed consent).

Outcomes

Research on renal biopsies, as discussed above (primarily Level II and III evidence), shows that renal biopsies are usually successful at achieving a diagnosis and are usually without complications, but they change patient outcome in a minority of cases if patients are not selected carefully.


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Renal Biopsy - Questions

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How long should one avoid intense activity after a renal biopsy?



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A patient has a 1.5 cm enhancing renal cortical mass with a cystic component. For purposes of informed consent, according to American Urological Association guidelines, which of the following statements is incorrect regarding the limitations of renal mass biopsy?



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If you are performing a non-targeted renal biopsy, which of the following steps would be advantageous in limiting the number of passes you need to take?



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A patient with a glomerular filtration rate of 40 ml/min has an incidental 2 cm cortically based solid renal lesion that is hyperdense and T2 hypointense to normal renal cortex on noncontrast CT and MRI, respectively. The radiologist reading both reports is unable to provide a diagnosis. Which of the following is the most appropriate next step?



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Which of the following is true regarding the yield of renal biopsy?



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Renal Biopsy - References

References

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