**2. Percutaneous ultrasound-guided renal biopsy**

#### **2.1 Indications**

The indication for a kidney biopsy is determined mainly by signs and symptoms [4]. The global rate of biopsy (number of procedures per million [ppm]) in native kidneys ranges from more than 250 ppm in Australia to less than 75 ppm in the United States. This divergence in kidney biopsy rates is influenced by the prevalence of kidney disease as well as different opinions regarding the value of the procedure in terms of diagnosis, prognosis, and therapy [6].

The main objectives that lead to the indication for kidney biopsy are the need for a precise diagnosis and treatment, the need to determine the degree of activity and chronicity of the lesion in order to establish the prognosis and possible response to treatment, and the evaluation of genetic diseases [6]. The diagnostic contribution of a kidney biopsy is undeniable in cases of nephrotic syndrome, systemic disease kidney failure, unexplained AKI, and transplanted kidney dysfunction [7].

For cases of idiopathic nephrotic syndrome in adults and children older than 6 years of age, the indication for a kidney biopsy is extremely important, as the findings often influence therapeutic decision-making [8]. In a prospective study involving 276 biopsies of native kidneys, the diagnosis resulting from the biopsy influenced the management of 86% of cases of nephrotic syndrome [9]. However, there is a variety of clinical situations of nephrotic syndrome for which a kidney biopsy is not generally performed at the time of diagnosis, such as in cases of children between 1 and 6 years of age due to the high prevalence of minimal change disease [10, 11]. In such situations, corticotherapy is indicated and biopsy is only performed in cases of therapeutic failure or the appearance of another sign or symptom not associated with minimal change disease [11]. Biopsy is also not performed initially in cases of secondary nephrotic disease clearly associated with the introduction of a medication known to cause this condition, such as non-steroidal anti-inflammatory drugs, gold salts, pamidronate, penicillamine, and lithium. This group includes patients with longstanding diabetes with gradual proteinuria progression, those with morbid obesity and slowly increasing proteinuria accompanied or not by diabetes and worsening kidney function, those with systemic diseases such as primary or secondary amyloidosis in which the diagnosis can be made through less invasive methods, such as adipose tissue biopsy, and patients known to have malignant diseases involving nephrotic syndrome [6]. Patients with nephrotic syndrome generally exhibit hematuria, proteinuria, hypertension, and renal dysfunction, and the condition is also often associated with systemic diseases. Therefore, kidney biopsy contributes to the diagnosis, therapeutic decision-making, and classification of the disease (e.g., systemic lupus erythematosus). In suspected cases of post-streptococcal glomerulonephritis, biopsy is only recommended when a gradual worsening in serum levels of creatinine, prolonged hypocomplementemia, and recurring hematuria are observed [6, 7].

Cases of systemic diseases with kidney failure include non-nephrotic proteinuria, isolated glomerular hematuria, and unexplained CKD. Protein is a marker and factor related to the progression of kidney disease. Studies have demonstrated a relation between the degree of proteinuria and the progression of CKD in cases

**39**

*Post-Biopsy Complications Associated with Percutaneous Kidney Biopsy*

management in cases of the need for a kidney transplant [7].

indispensable to the follow-up of renal grafts [7].

pregnancy, and urinary tract infection [3].

**2.2 Techniques and materials**

of non-nephrotic proteinuria [7]. Thus, many nephrologists routinely perform a kidney biopsy in patients with higher non-nephrotic proteinuria (1–2 g/day) in the absence of another clinical condition that might explain the findings (e.g., diabetes mellitus or hypertension). However, in situations of low-grade proteinuria (500–1000 mg/day) in the absence of glomerular hematuria, altered kidney function, and clinical/serological evidence of a systemic disease, a biopsy is generally not performed [6]. Biopsy in cases of isolated glomerular hematuria remains controversial, as the procedure exerts little influence on therapeutic decision-making. When performed, the conditions most often encountered are Alport syndrome, thin basement membrane nephropathy, and immunoglobulin A nephropathy. In a prospective analysis, biopsy influenced the therapeutic decision-making in only one of the 36 procedures performed [9]. For patients with unexplained CKD, a kidney biopsy can provide important information, despite the greater risk of complication. In cases of exacerbated CKD, a biopsy may reveal lesions that can be treated and reversed. Moreover, a biopsy can contribute important knowledge to clinical

For patients with unexplained AKI, biopsy is indicated in cases of an uncertain etiology and can influence clinical management in 71% of cases [9]. Biopsy is also particularly useful for early or late-onset dysfunction of a renal graft. In cases of acute graft dysfunction, the procedure enables confirming the diagnosis of rejection and specifying the pathological mechanism (acute cellular rejection or antibody mediated rejection). Late biopsies also furnish essential information to assist in differentiating the causes of chronic nephropathy of the graft, such as chronic rejection, transplant glomerulopathy, nephrotoxicity, viral disease, lymphoproliferative diseases, and relapse of the base disease. The simplicity of the technical procedure and richness of the diagnostic and prognostic information make biopsy

Contraindications for kidney biopsy may be absolute or relative. For percutaneous kidney biopsies, absolute contraindications include uncontrolled severe hypertension, the inability of the patient to cooperate with the biopsy, having only one kidney, and uncontrollable hemorrhagic diathesis, whereas relative contraindications include severe azotemia, anatomic kidney abnormalities, anticoagulation,

Kidney biopsies can be guided by different imaging methods, the most common of which are ultrasound (US) and computed tomography (CT) due to their good performance and broad availability. In contrast, magnetic resonance is employed little due to the greater cost and need for specific material. The choice between US and CT should be individualized and based on the physician's experience, kidney volume, location of the biopsy site, patient's clinical condition, and the availability of the equipment. US is generally the imaging method of choice for guiding a kidney biopsy, since it enables obtaining samples from virtually any site and visualizing the needle in real time. It also does not expose the patient to radiation, can be performed in any environment, including at the bedside, and enables the continual monitoring of any pre-operative complications. It is also the method of choice for post-procedure follow-up, enabling the early detection of complications [4]. To be successful, US-guided kidney biopsy requires specific conditions. The patient must be placed in ventral decubitus on the examining table and the procedure must be performed in a sterile environment. The transducer should be covered with a sterile film. There are specific transducer covers on the market, but a sterile glove can be used in cases of emergency. Antisepsis should be performed on the

*DOI: http://dx.doi.org/10.5772/intechopen.89226*

#### *Post-Biopsy Complications Associated with Percutaneous Kidney Biopsy DOI: http://dx.doi.org/10.5772/intechopen.89226*

*Renal Diseases*

**2.1 Indications**

Percutaneous kidney biopsy has become part of clinical practice in nephrology, as it enables the diagnosis, prognostic assessment, and therapeutic guidance of kidney diseases [3, 4]. Since its advent in the 1950s, advances have been achieved in the technique to improve the diagnostic yield and minimize complications [5].

The indication for a kidney biopsy is determined mainly by signs and symptoms [4]. The global rate of biopsy (number of procedures per million [ppm]) in native kidneys ranges from more than 250 ppm in Australia to less than 75 ppm in the United States. This divergence in kidney biopsy rates is influenced by the prevalence of kidney disease as well as different opinions regarding the value of the procedure

The main objectives that lead to the indication for kidney biopsy are the need for a precise diagnosis and treatment, the need to determine the degree of activity and chronicity of the lesion in order to establish the prognosis and possible response to treatment, and the evaluation of genetic diseases [6]. The diagnostic contribution of a kidney biopsy is undeniable in cases of nephrotic syndrome, systemic disease kidney failure, unexplained AKI, and transplanted kidney dysfunction [7].

For cases of idiopathic nephrotic syndrome in adults and children older than 6 years of age, the indication for a kidney biopsy is extremely important, as the findings often influence therapeutic decision-making [8]. In a prospective study involving 276 biopsies of native kidneys, the diagnosis resulting from the biopsy influenced the management of 86% of cases of nephrotic syndrome [9]. However, there is a variety of clinical situations of nephrotic syndrome for which a kidney biopsy is not generally performed at the time of diagnosis, such as in cases of children between 1 and 6 years of age due to the high prevalence of minimal change disease [10, 11]. In such situations, corticotherapy is indicated and biopsy is only performed in cases of therapeutic failure or the appearance of another sign or symptom not associated with minimal change disease [11]. Biopsy is also not performed initially in cases of secondary nephrotic disease clearly associated with the introduction of a medication known to cause this condition, such as non-steroidal anti-inflammatory drugs, gold salts, pamidronate, penicillamine, and lithium. This group includes patients with longstanding diabetes with gradual proteinuria progression, those with morbid obesity and slowly increasing proteinuria accompanied or not by diabetes and worsening kidney function, those with systemic diseases such as primary or secondary amyloidosis in which the diagnosis can be made through less invasive methods, such as adipose tissue biopsy, and patients known to have malignant diseases involving nephrotic syndrome [6]. Patients with nephrotic syndrome generally exhibit hematuria, proteinuria, hypertension, and renal dysfunction, and the condition is also often associated with systemic diseases. Therefore, kidney biopsy contributes to the diagnosis, therapeutic decision-making, and classification of the disease (e.g., systemic lupus erythematosus). In suspected cases of post-streptococcal glomerulonephritis, biopsy is only recommended when a gradual worsening in serum levels of creatinine, prolonged hypocomplement-

Cases of systemic diseases with kidney failure include non-nephrotic proteinuria, isolated glomerular hematuria, and unexplained CKD. Protein is a marker and factor related to the progression of kidney disease. Studies have demonstrated a relation between the degree of proteinuria and the progression of CKD in cases

**2. Percutaneous ultrasound-guided renal biopsy**

in terms of diagnosis, prognosis, and therapy [6].

emia, and recurring hematuria are observed [6, 7].

**38**

of non-nephrotic proteinuria [7]. Thus, many nephrologists routinely perform a kidney biopsy in patients with higher non-nephrotic proteinuria (1–2 g/day) in the absence of another clinical condition that might explain the findings (e.g., diabetes mellitus or hypertension). However, in situations of low-grade proteinuria (500–1000 mg/day) in the absence of glomerular hematuria, altered kidney function, and clinical/serological evidence of a systemic disease, a biopsy is generally not performed [6]. Biopsy in cases of isolated glomerular hematuria remains controversial, as the procedure exerts little influence on therapeutic decision-making. When performed, the conditions most often encountered are Alport syndrome, thin basement membrane nephropathy, and immunoglobulin A nephropathy. In a prospective analysis, biopsy influenced the therapeutic decision-making in only one of the 36 procedures performed [9]. For patients with unexplained CKD, a kidney biopsy can provide important information, despite the greater risk of complication. In cases of exacerbated CKD, a biopsy may reveal lesions that can be treated and reversed. Moreover, a biopsy can contribute important knowledge to clinical management in cases of the need for a kidney transplant [7].

For patients with unexplained AKI, biopsy is indicated in cases of an uncertain etiology and can influence clinical management in 71% of cases [9]. Biopsy is also particularly useful for early or late-onset dysfunction of a renal graft. In cases of acute graft dysfunction, the procedure enables confirming the diagnosis of rejection and specifying the pathological mechanism (acute cellular rejection or antibody mediated rejection). Late biopsies also furnish essential information to assist in differentiating the causes of chronic nephropathy of the graft, such as chronic rejection, transplant glomerulopathy, nephrotoxicity, viral disease, lymphoproliferative diseases, and relapse of the base disease. The simplicity of the technical procedure and richness of the diagnostic and prognostic information make biopsy indispensable to the follow-up of renal grafts [7].

Contraindications for kidney biopsy may be absolute or relative. For percutaneous kidney biopsies, absolute contraindications include uncontrolled severe hypertension, the inability of the patient to cooperate with the biopsy, having only one kidney, and uncontrollable hemorrhagic diathesis, whereas relative contraindications include severe azotemia, anatomic kidney abnormalities, anticoagulation, pregnancy, and urinary tract infection [3].

### **2.2 Techniques and materials**

Kidney biopsies can be guided by different imaging methods, the most common of which are ultrasound (US) and computed tomography (CT) due to their good performance and broad availability. In contrast, magnetic resonance is employed little due to the greater cost and need for specific material. The choice between US and CT should be individualized and based on the physician's experience, kidney volume, location of the biopsy site, patient's clinical condition, and the availability of the equipment. US is generally the imaging method of choice for guiding a kidney biopsy, since it enables obtaining samples from virtually any site and visualizing the needle in real time. It also does not expose the patient to radiation, can be performed in any environment, including at the bedside, and enables the continual monitoring of any pre-operative complications. It is also the method of choice for post-procedure follow-up, enabling the early detection of complications [4].

To be successful, US-guided kidney biopsy requires specific conditions. The patient must be placed in ventral decubitus on the examining table and the procedure must be performed in a sterile environment. The transducer should be covered with a sterile film. There are specific transducer covers on the market, but a sterile glove can be used in cases of emergency. Antisepsis should be performed on the

entire side of the back corresponding to the kidney to be biopsied. The selection of the puncture site is determined by US considering the best path (least distance between the skin and renal capsule and the absence of vascular structures and/or interposed intestinal loops). This region in the center of the US image ensures the safest path for the biopsy and provides better control and resolution of the image.

Once the region to be punctured has been defined, the skin at the puncture site is anesthetized and the area of anesthesia is then extended to the deep layers, preferably reaching the perirenal layers, including adjacencies external to Gerota's fascia and the renal capsule. An alternative is the use of a long 18G peripheral intravenous catheter with the administration of 20 ml of anesthetic solution (10 ml of 2% xylocaine with no vasoconstrictor +10 ml of 0.9% saline solution or bi-distilled water). The entire anesthetic procedure as well as the subsequent steps should be guided by US. Some authors prefer performing a biopsy with their hands free. The two techniques (with or without US) have the same rates of minor and major complications and obtain adequate material for analysis, but the hands-free method requires greater experience and has a somewhat slower learning curve [1, 12]. Next, the biopsy needle is aligned with the transducer (when US is used) and introduced at a 45° angle to the skin. To ensure the safety of the procedure and control of complications, both the needle and its path should be kept within the US viewing field. The path to follow with the needle in the renal parenchyma should only involve the renal cortex (glomerular region), without transfixing the renal medulla, which contributes little to the study and has large-caliber vessels that could be associated with vascular complications; this also avoids the occurrence of injury to the renal calyces and pelvis [4, 13]. The number of fragments to collect depends on the number and types of exams requested as well as the presence of the pathologist during the exam, who may express opinions regarding the quality of the specimen collected. In procedures without the presence of a pathologist, two fragments are normally collected for each exam solicited.

Different needle calibers, lengths, and tip shapes are available on the market for the collection of material for microscopic analysis. Thin-needle punctures are performed with calibers ranging from 20 to 25, whereas thick-needle biopsies are performed with 14- to 19-gauge needles. Authors state that thin needles provide smaller fragments for analysis, but the fragments have similar quality and anatomopathological interpretation to those obtained with thick needles. Nonetheless, larger fragments enable a more complete study of renal pathologies. Moreover, although a smaller caliber is related to a lower rate of complications stemming from the procedure, it does not assist in the renal evaluation [14]. Along with a core biopsy needle (thick needle), coaxial needles can be used, which have a larger diameter with sufficient inner diameter to enable the navigation of the core biopsy needle in its interior. The use of coaxial needle kits avoids multiple punctures of the capsule, as this mechanism enables acquiring several tissue samples with a single perforation, which reduces the procedure time. However, portions of the organ cannot be sampled with this method and the use of such needles increases the cost of the procedure. The use of coaxial needles enables the operator to easily embolize the needle path with an absorbable gelatin sponge when removing the outer needle at the end of the procedure. This embolization promoted by the coaxial method is believed to reduce the risks of post-biopsy bleeding, but this characteristic is reported to not be an advantage of the method. Thus, both the coaxial and non-coaxial techniques do not appear to influence the bleeding complication rate [15]. The use of springloaded tools is currently recommended. These needles are classified based on the form of discharge into the tissue: automatic or semi-automatic (disposable). Such tools are reported to be more effective and safer than classic percutaneous renal biopsies that use the Tru-Cut or Vim-Silverman needle. Automatic tools are more

**41**

**Table 1.**

*Post-Biopsy Complications Associated with Percutaneous Kidney Biopsy*

economical, since only part of the kit is disposable. However, the disadvantage is the lower control over the progression of the needle during discharge and capture of the fragment as well as the longer procedure time due to the increase in the number of preparation steps of the needle/spring-loaded tool with the risk of contamination. Semi-automatic tools are more costly due to the fact that the entire system is disposable. The advantages are the security in maintaining all material sterile throughout all steps of the procedure, greater control over the advancing of the needle for the extraction of the fragment, the possibility of checking the intralesional position prior to discharge, and the reduction in procedure time, since no preparation of the

Prior to presenting the biopsy technique to the patient or legal guardian, it is advisable to consult with the physician in charge of the procedure. This moment orientates the patient and family regarding the risks, benefits, and preparation for the procedure. It is also possible to identify possible techniques linked to the peculiarities of each patient, such as having a physical disability that precludes the standard position, deforming kyphoscoliosis, scars, skin diseases, and anxiety disorders. To ensure a successful examination, it is of extreme importance to evaluate recent laboratory exams (within the previous 30 days) and determine the patient's health condition. Patients should meet basic criteria before being submitted to the procedure (**Table 1**). If a patient does not meet the minimum requirements, the procedure should be rescheduled until after the base disorder has been corrected. For patients with an urgent need for the procedure, immediate corrective measures should be assessed. For instance, plasma and platelet transfusion may be options in cases of a high international normalized ratio (INR) and low platelet count, respectively. An imaging study should be performed prior to the kidney biopsy to gain knowledge on renal anatomy and determine the presence of ectopias, congenital

A kidney biopsy is an important diagnostic tool and considered the "gold standard" for the best definition of the majority of nephropathies. It is capable of changing the clinical diagnosis approximately 50% of the time and changing the therapy to be administered approximately 40% of the time [16]. For this to happen,

A 19-gauge needle generally furnishes very small, narrow specimens that are often inadequate for the assessment of vessels. Thus, smaller needles, such as 18 or

*DOI: http://dx.doi.org/10.5772/intechopen.89226*

needle and spring-loaded tool is needed.

dysplasia, or polycystic kidneys.

**Criteria that impede a kidney biopsy**

Platelet count <60,000/mm3

*Conditions that impede a kidney biopsy.*

Use of anticoagulant Systolic BP > 140 mm Hg Urinary infection Acute persistent cough Skin lesions at puncture site Altered mental state

INR > 1.3

**2.3 Quality of material/pathologist present**

however, an adequate sample must be obtained.

Clotting disorders characterized by prothrombin activity <60%

### *Post-Biopsy Complications Associated with Percutaneous Kidney Biopsy DOI: http://dx.doi.org/10.5772/intechopen.89226*

*Renal Diseases*

collected for each exam solicited.

entire side of the back corresponding to the kidney to be biopsied. The selection of the puncture site is determined by US considering the best path (least distance between the skin and renal capsule and the absence of vascular structures and/or interposed intestinal loops). This region in the center of the US image ensures the safest path for the biopsy and provides better control and resolution of the image. Once the region to be punctured has been defined, the skin at the puncture site is anesthetized and the area of anesthesia is then extended to the deep layers, preferably reaching the perirenal layers, including adjacencies external to Gerota's fascia and the renal capsule. An alternative is the use of a long 18G peripheral intravenous catheter with the administration of 20 ml of anesthetic solution (10 ml of 2% xylocaine with no vasoconstrictor +10 ml of 0.9% saline solution or bi-distilled water). The entire anesthetic procedure as well as the subsequent steps should be guided by US. Some authors prefer performing a biopsy with their hands free. The two techniques (with or without US) have the same rates of minor and major complications and obtain adequate material for analysis, but the hands-free method requires greater experience and has a somewhat slower learning curve [1, 12]. Next, the biopsy needle is aligned with the transducer (when US is used) and introduced at a 45° angle to the skin. To ensure the safety of the procedure and control of complications, both the needle and its path should be kept within the US viewing field. The path to follow with the needle in the renal parenchyma should only involve the renal cortex (glomerular region), without transfixing the renal medulla, which contributes little to the study and has large-caliber vessels that could be associated with vascular complications; this also avoids the occurrence of injury to the renal calyces and pelvis [4, 13]. The number of fragments to collect depends on the number and types of exams requested as well as the presence of the pathologist during the exam, who may express opinions regarding the quality of the specimen collected. In procedures without the presence of a pathologist, two fragments are normally

Different needle calibers, lengths, and tip shapes are available on the market for the collection of material for microscopic analysis. Thin-needle punctures are performed with calibers ranging from 20 to 25, whereas thick-needle biopsies are performed with 14- to 19-gauge needles. Authors state that thin needles provide smaller fragments for analysis, but the fragments have similar quality and anatomopathological interpretation to those obtained with thick needles. Nonetheless, larger fragments enable a more complete study of renal pathologies. Moreover, although a smaller caliber is related to a lower rate of complications stemming from the procedure, it does not assist in the renal evaluation [14]. Along with a core biopsy needle (thick needle), coaxial needles can be used, which have a larger diameter with sufficient inner diameter to enable the navigation of the core biopsy needle in its interior. The use of coaxial needle kits avoids multiple punctures of the capsule, as this mechanism enables acquiring several tissue samples with a single perforation, which reduces the procedure time. However, portions of the organ cannot be sampled with this method and the use of such needles increases the cost of the procedure. The use of coaxial needles enables the operator to easily embolize the needle path with an absorbable gelatin sponge when removing the outer needle at the end of the procedure. This embolization promoted by the coaxial method is believed to reduce the risks of post-biopsy bleeding, but this characteristic is reported to not be an advantage of the method. Thus, both the coaxial and non-coaxial techniques do not appear to influence the bleeding complication rate [15]. The use of springloaded tools is currently recommended. These needles are classified based on the form of discharge into the tissue: automatic or semi-automatic (disposable). Such tools are reported to be more effective and safer than classic percutaneous renal biopsies that use the Tru-Cut or Vim-Silverman needle. Automatic tools are more

**40**

economical, since only part of the kit is disposable. However, the disadvantage is the lower control over the progression of the needle during discharge and capture of the fragment as well as the longer procedure time due to the increase in the number of preparation steps of the needle/spring-loaded tool with the risk of contamination. Semi-automatic tools are more costly due to the fact that the entire system is disposable. The advantages are the security in maintaining all material sterile throughout all steps of the procedure, greater control over the advancing of the needle for the extraction of the fragment, the possibility of checking the intralesional position prior to discharge, and the reduction in procedure time, since no preparation of the needle and spring-loaded tool is needed.

Prior to presenting the biopsy technique to the patient or legal guardian, it is advisable to consult with the physician in charge of the procedure. This moment orientates the patient and family regarding the risks, benefits, and preparation for the procedure. It is also possible to identify possible techniques linked to the peculiarities of each patient, such as having a physical disability that precludes the standard position, deforming kyphoscoliosis, scars, skin diseases, and anxiety disorders. To ensure a successful examination, it is of extreme importance to evaluate recent laboratory exams (within the previous 30 days) and determine the patient's health condition. Patients should meet basic criteria before being submitted to the procedure (**Table 1**). If a patient does not meet the minimum requirements, the procedure should be rescheduled until after the base disorder has been corrected. For patients with an urgent need for the procedure, immediate corrective measures should be assessed. For instance, plasma and platelet transfusion may be options in cases of a high international normalized ratio (INR) and low platelet count, respectively. An imaging study should be performed prior to the kidney biopsy to gain knowledge on renal anatomy and determine the presence of ectopias, congenital dysplasia, or polycystic kidneys.
