Kidney biopsy guidebook 2020 in Japan

Abbreviations APTT Activated partial thromboplastin time ANCA Antineutrophil cytoplasmic antibody BP Blood pressure CKD Chronic kidney disease CT Computed tomography DKD Diabetic kidney disease ds-DNA Double-stranded DNA antibodies DM Diabetes mellitus EM Electron microscopy EGPA Eosinophilic granulomatosis with polyangiitis EB virus Epstein–Barr virus EBER Epstein–Barr virus-encoded small RNA FDP Fibrin/fibrinogen degradation products FSGS Focal segmental glomerulosclerosis GBM Glomerular basement membrane In 2020, Japanese Society of Nephrology established Committee of Practical Guide for Kidney Biopsy 2020, which published in (Jinseiken guidebook, 2020, vol. 2, page 1–180). This is the English version of that report.

Overview A kidney biopsy is performed for a treatment strategy of renal disease by pathologically diagnosing renal disease. Kidney biopsy is a reliable gold standard technique, but various complications are common when obtaining tissue from an abundant vascular kidney. During a biopsy, vasovagal reflexes, including cold sweat, discomfort, nausea, vomiting, hypotension, and bradycardia, can occur. Hemorrhagic complications after a biopsy are important; 89% of hemorrhagic complications have been reported to occur within 24 h. Therefore, a cooperation system including nurses and physicians by performing intravenous feeding and medication, while performing electrocardiogram monitoring and oxygen saturation monitoring, is necessary. Therefore, it is necessary to always take the benefits and risks of kidney biopsy into consideration and decide if there is an indication for kidney biopsy.
The conventional criteria for the indication of kidney biopsy for adults are shown in Table 1, according to previous reports [1][2][3]. However, there is an opinion that it is necessary to extend these indications [3]. The following opinions were sent by a member of the Japanese Society of Nephrology.
• There is an indication for kidney biopsy beyond the above indication. The indication must be considered in every case. It is important that it does not limit the experiencerich institutional practice. • Nephrologists, including young doctors with little experience in kidney biopsy, should recognize the safety procedures that are necessary to prevent the threshold to high-risk clinical conditions from lowering. • Cases of serious complications such as bleeding can happen, and the appropriate security guidelines for treatment should be prepared before a kidney biopsy.
The clinical treatment of renal disease is possible without performing a kidney biopsy. However, many nephrologists should note that a higher-quality clinical treatment is enabled by performing kidney biopsy.
The final decision of whether you perform kidney biopsy should be decided based on each institution's guidelines and should be judged for every individual patient carefully. With respect to the decision, it is necessary to be performed based on the concept of "shared decision making: SDM," Table 1 The conventional criteria for the indication of the kidney biopsy for adults 1. Glomerular hematuria with any degree of proteinuria 2. Isolated proteinuria > 1 g/day(or g/gCr) 3. Unexplained renal disease or intrinsic acute kidney injury 4. Renal manifestation related to systemic disease Table 2 Indication of kidney biopsy in adults 1. Isolated glomerular hematuria 2. Isolated proteinuria 3. Proteinuria and glomerular hematuria 4. Rapidly progressive glomerulonephritis 5. Intrinsic acute kidney injury 6. Systemic disease with a urinalysis abnormality 7. Systemic disease with renal dysfunction, and/or without urinalysis abnormality 8. Diabetes mellitus 9. Elderly renal disease 10. Hereditary renal disease 11. Repeated kidney biopsy after each attending physician explains the need and the risk of kidney biopsy to each patient thoroughly. We have provided explanations in the 'Kidney biopsy guidebook 2020 in Japan' along with questions and answers based on the results of a questionnaire survey for kidney biopsy that was performed in Japan from 2015 through 2017 by the Committee of Practical Guide for Kidney biopsy [4,5], while adding the outline of the first edition of 2004 [1]. For cases with gross hematuria at the time of cold, and a family history of renal disease, IgA nephropathy, or Alport syndrome is assumed, kidney biopsy is performed [6][7][8][9].

Q2: Please tell me about kidney biopsy for patients with isolated proteinuria A2
For patients with nephrotic syndrome with nephrotic-range proteinuria more than 3.5 g/day, kidney biopsy is indicated.
For patients with proteinuria of 3.5-1.0 g/day, a kidney biopsy is indicated, to the same extent as cases with nephrotic syndrome. However, if such lesions cannot be detected, and a higher frequency of sclerotic glomeruli is detected, immunosuppressive therapy is avoided or minimized.

Overview
The following renal disease was contraindicated for percutaneous native kidney biopsy under the ultrasonic guidance in the previous edition of the guidebook because the risk of hemorrhagic complications after a kidney biopsy is very high, and renal tissue sampling necessary for diagnosis is not obtained [1] (Table 3). However, as biopsy techniques, by using a newer US device and automatic biopsy needle, improved safety, there have been several reported case series that required or enabled histological diagnosis by kidney biopsy [4]. Therefore, when the benefit is judged to exceed a risk, kidney biopsy is indicated for patients with a clinical condition of high risk. A kidney biopsy should be performed in institutions that can treat hemorrhagic complications. The following diseases are not absolute contraindicated anymore but are described as a renal disease with high risk by a question and answer method. Hospitalization has become relatively long. There is the risk that the wound becomes big. CT-guided kidney biopsy is considered safe for severe obesity patients and renal mass lesions [65][66][67][68][69][70][71]. There are reports of case series that led to a diagnosis of intravascular lymphoma by kidney biopsy that was performed for the further examination of fever of unknown origin or rapidly progressive renal failure [118][119][120][121][122].

A13
Several issues must be considered in patients on chronic anticoagulation when judged that a tissue diagnosis by kidney biopsy is necessary (Table 4).
• For patients on chronic anticoagulation, kidney biopsy usually cannot be selected. • Whether kidney biopsy is essential or necessary for diagnosis, prognosis, and/or management must be discussed in the conference conducted at the institute. • If anticoagulation is temporarily stopped (e.g., mechanical heart valves), the risk of thrombosis must be judged in consideration of an individual situation, often in consultation with hematology and cardiology.
• If anticoagulation is continued, the risk for bleeding after kidney biopsy must be evaluated in consideration of an individual situation. Kidney biopsy should be performed in an institution with the facilities for emergency treatment [123][124][125] (Table 4).

Q13-1: Please tell me about kidney biopsy in patients on
antiplatelet medication

A13-1
After having considered the likelihood of a thrombotic vascular event when a drug is discontinued, a drug holiday (period when the patient stops taking medication): (1) criteria following minor operation and (2) criteria following major operation [e.g., Aspirin: (1) 3-5 days, (2) 7-10 days] [125]. Many institutes in Japan agree to criteria following a major operation. It is desirable to cope according to each institution's guidelines, in every case.
Many institutes agree to an option "since the time when hemostasis was confirmed" as the restarting time of the antiplatelet drug after kidney biopsy.

A13-2
When it is judged that a tissue diagnosis by kidney biopsy is necessary, the drug holiday before kidney biopsy is as follows; warfarin (3-5

A15
For such patients, a kidney biopsy is not indicated.
However, for pediatrics, the agreement of parents is given priority over the agreement of the patient.

Overview
Kidney biopsy is a gold standard for renal disease diagnosis and is the testing that we cannot miss in renal disease practice. However, it is invasive testing, and adequate informed consent is necessary. With respect to the nephrologist, it is necessary to explain the possible complications by the testing procedures, including hemorrhagic complications, in addition to the benefits of kidney biopsy to the patients. With respect to the patients, it is important to consent to kidney biopsy based on their own intention after having understood the benefits (merits) and disadvantages (demerits) of kidney biopsy explained by a physician [126]. In Japan, informed consent is obtained before kidney biopsy, and kidney biopsy is performed after, as a general rule, having acquired an agreement by letter. In this issue, the informed consent is commented by a question and answer method. Explanation document to the patients Q1: What kind of testing is kidney biopsy?

A1
There are various causes for renal disease to induce proteinuria, hematuria, and a decrease in renal function.
There are many cases that it is difficult to diagnose the cause only by blood, urinalysis, and imaging study.
We take some kidney tissue by using the needle with the core size of the ball-point pen, observe it with a microscope, and clarify a cause of renal disease occurring in kidney. If a cause of the illness is understood, we can suggest an optimal therapy. A procedure or an operation to take out kidney tissue is named kidney biopsy.

Q2: Please tell me the purpose of kidney biopsy A2
The purpose of a kidney biopsy is three.
1. We find renal cause and severity of illness.
2. We can predict a prospect of illness.
3. We can suggest an optimal therapy. Q3: When is kidney biopsy required?

A3
Kidney biopsy is required in the following case.

A4
The patients with the following disease require scrupulous attention for the complication.
1. There is only one kidney. Only one kidney functions. → Renal function worsens on renal hemorrhage after kidney biopsy.
2. The renal form is different from that of the normal kidney; for example, it is atrophic kidney, horseshoe kidney, hydronephrosis. → Kidney biopsy is difficult to perform.
3. The kidney has many cysts (bag-formed structure). → Kidney biopsy is difficult to perform.
4. Blood pressure is very high. → It is easy to bleed 5. Platelet counts are less than 100,000/μL; coagulation ability decreases, and patients take medicines that help prevent blood clots. → It is easy to bleed. 6. Pregnant → Kidney biopsy is difficult to perform.
7. High percentage of fat → Kidney biopsy is difficult to perform.

Q6: Please tell me, in specifics, how kidney biopsy is performed A6
Kidney biopsy is usually carried out using an automatic biopsy needle under the ultrasonic guidance (Fig 1). 1. We put an indwelling needle for intravenous feeding in the blood vessel of the arm before testing. An antimicrobial agent and/or hemostatic are usually given before testing. When BP falls or you came to feel sick during testing, a drug is given through an indwelling needle. 2. We cancel your diet before the testing. This is because you come to feel sick, and you may vomit by the pressure from a back hemostasis. 3. There is the kidney at the position near a back. You lie on your face and the stomach. A renal place is confirmed by US. From the skin of the back surface to the renal surface, a local anesthetic is injected in place to prick with a needle. We cut about a 2-3 mm opening in the skin surface. This section may remain as a minimal wound subsequently. 4. The thickness of the needle taking the renal tissue is a core size of the ball-point pen, and the length is around 2 cm. When a needle is inserted, there is no pain, but there is the sense that the back is pushed. When the needle reaches the kidney, we signal you. Please hold your breath for 5-10 s. We take the renal tissue at that moment. You hear a clicking sound at the moment that we take the renal tissue. Because there is no pain, do not worry. We conduct this operation 2-4 times. 5. When kidney biopsy is completed, we exert pressure from the back for 10-15 min to stop bleeding. 6. The testing is completed in approximately 30 min. After testing, you turn over on your back. Rest is required in a bed for 6-24 h. Eating and drinking after the testing is performed lying down. Urination and the defecation are carried out on the bed, too. When urination is difficult, we may use a tube called a urethral catheter. After testing, fever may occur. The cause is considered absorption fever occurring when the hematoma that occurred after a biopsy is absorbed. 7. For 4 weeks from the next morning, walking is possible, but please avoid running up the stairs, and please avoid intense, laborious work to avoid exerting stress on the area that was affected by the procedure. ney biopsy is considerably safer than when performed blindly, and it may be said that it is an established testing method. However, when it may be hard to obtain renal tissue, we may cancel testing on the way without overdoing it. When we cannot obtain renal tissue, or when glomeruli necessary for a diagnosis are not included, we may make a testing plan again. There is a "laparoscopic kidney biopsy," which takes the renal tissue while confirming the kidney using laparoscopy as other methods directly (Fig. 1).
When there is the high-risk clinical condition and hemorrhagic complications by percutaneous kidney biopsy, when renal tissue is not gained by percutaneous kidney biopsy, "opening kidney biopsy" or "laparoscopic kidney biopsy" is chosen.
Q8: How is the tissue which we obtained by kidney biopsy examined?

A8
We observe the specimen, which we obtained by three methods; light microscopy, fluorescent microscopy, and electron microscopy.
By light microscopy, we can observe the whole, including glomeruli, renal tubules, and the blood vessels, and can obtain basic information.
By fluorescent microscopy, we observe the presence or absence of deposition and a deposition place of immunoglobulin, including IgG, IgA, and IgM, and complements, such as C3 and C1q.
By electron microscopy, we confirm the cellular internal structure, including glomerular and tubular structure, and a deposit causing nephritis, which spreads approximately 15,000 times.
After performing three tests, a diagnosis of renal disease is made. According to questionnaire survey by the Japanese Society of Nephrology for kidney biopsy that was performed in Japan from 2015 through 2017, out of 15,657 adult patients who underwent kidney biopsy by a nephrologist, transfusion was required in 121 cases (0.8%), hemostasis treatment by renal artery embolization in 31 cases (0.2%), gross hematuria with no treatment in 431 cases (2.8%), vesicoclysis in 56 cases (0.4%), death in one (0.006%). Close evaluation of the death cases clarified that bleeding after kidney biopsy is not a direct cause, but the overall status of these cases was poor before kidney biopsy and worsened after kidney biopsy.

Blood test ① Complete blood cell count
Erythrocyte transfusion is considered for severe anemia before kidney biopsy. The cutoff value of Hb is 7-8 g/dL. Platelet transfusion is considered for severe thrombocytopenia with platelet count less than 50,000/ μL. ② Coagulation study Tests for prothrombin time (PT), APTT, fibrinogen, and fibrin/fibrinogen degradation products (FDP) (or D-dimer) are recommended for pre-operative screening. When a coagulation abnormality is found, close examination and adequate treatment are required before kidney biopsy. When a thrombotic tendency is pointed out, especially in high-risk patients with nephrotic syndrome, screening tests for deep vein thrombosis and pulmonary embolism are also considered. ③ Biochemistry Serum tests include total protein, albumin, urea nitrogen, creatinine, uric acid, AST, ALT, LDH, and electrolytes (Na, K, Cl, Ca, P, and Mg). Estimated GFR by using serum creatinine or cysteine C values are important to evaluate renal function. Arterial blood gas analysis (including anion gap) is also helpful for the differential diagnosis of kidney diseases with acid-base abnormality. ④ Blood sugar (glucose) test As well as fasting plasma glucose (sugar), HbA1C and glycoalbumin are useful for evaluation of hyperglycemic conditions. ⑤ Immunology Immunological tests include immunoglobulin (IgG, IgA, IgM, IgG4), complement (CH50, C3, C4), autoantibody (antinuclear antibody, ds-DNA, SM, RNP, ANCA, GBM, anticardiolipin, lupus anticoagulant), serum monoclonal protein.
Urinary protein is measured by using spot urine or 24-h collected urine. NAG, β2MG, and α1MG are useful markers for tubular dysfunction. Selectivity index (SI) is also helpful in the differential diagnosis of nephrotic proteinuria.

Imaging test
Diagnostic imaging includes US, CT, and MRI. Radioisotope examinations are also useful for understanding renal pathophysiology. 99mTc-MAG3, an isotope secreting from proximal tubules, is utilized for evaluating effective renal plasma flow (ERPF) of right and left kidneys. 99mTc-DTPA, an isotope filtrating from glomeruli, is used for the measurement of glomerular filtration rate (GFR) of right and left kidneys. Automatic biopsy needles (biopsy gun) came to be used widely in Japan from the 1990s.
Because confirmation method of the renal place was blind at first and was performed on palpitation, there was an increased risk for puncturing big arteries and other organs.
Then the method of taking renal tissue while visualizing kidney using US was started in the 1980s.
Currently, kidney biopsy under the ultrasonic guidance using the automatic biopsy needle is widely performed in a prone position [136][137][138][139]. laparoscopic biopsy in 5% [4][5]. • Setting the patient in lateral jack-knife position, through 3 cm of horizontal incision from 12 rib tip the muscles are divided in each layer to reach the inferior pole of the kidney covered by adipose tissue. Confirming not to damage the peritoneum, the circumrenal fat and Gerota fascia are cut to reach the surface of kidney. The biopsy gun for needle biopsy on the kidney or the wedge incision for block type specimen is used to take a piece of the kidney. After biopsy, hemostasis is securely performed by pressure with the forefinger for 10-15 min. The muscles and skin are closed in layers to finish the procedure. [144,145]. After inserting a forefinger, and having abraded, we insert a PDB balloon (an orbicular type or kidney type) and extend retroperitoneum. We insert a 12 mm trocar and start pneumoperitoneum at 8-12 mmHg for the first port (camera port).
We place a 5-mm trocar on the dorsolumbar group of muscles circumference of the 20 mm head side than the first port at the speculum and assume it the second port (operator left hand).
We put a 5 mm or 12 mm trocar on the middle point between the anterior armpit line and the rectus abdominis muscle circumference of 20 mm head side than the first port, and we assume it the third port (the operator right hand).
We confirm the inferior pole of the kidney covered We insert a biopsy needle from the second port (the operator right hand) and the third port (operator left hand) and obtain renal tissue at an angle of 60°-90° on the nephric surface.
The operation using the biopsy needle is simpler and easier as a procedure for laparoscopic approach.
The hemostasis is carried out using bipolar and soft coagulation, and we perform certain • Because hemostasis pressure can be provided surely as compared with a native kidney biopsy, it is not necessary to discontinue the anticoagulant therapy. However, it is desirable to conduct an examination for coagulation system in advance. • Under local anesthesia the biopsy needle is put into the kidney to take a piece of the kidney. This may be performed 2-3 times to obtain an adequate specimen. • Just after the procedure, the physician presses the puncture area for 10-15 min for hemostasis. After that A 1 kg sandbag is put on the puncture area to maintain pressure for an hour. A small pillow is fixed with elastic tape on the area. Thereafter the patient must lie in bed for 6 h or until seen by the doctor. The patient must pay attention for blood in their urine after the biopsy. • The fixing elastic tape will be removed on next morning. Before discharge a blood count, biochemistry test, and urinalysis are examined. The discharge is permitted after having confirmed that there is no hematoma and hydronephrosis around the renal graft by US [147][148][149].

Chapter 6: After care of the biopsy and post procedure observation
Aftercare of the biopsy and postprocedure observation are essential to prevent hemorrhagic complications. After biopsy, bed rest for 6-8 h in an extraneous dressing room is mandated in Europe and America. In Japan, kidney biopsy is performed during hospitalization. Just after the biopsy is performed, pressure is exerted on the back by using both hands and a sandbag for hemostasis. Subsequently, bed rest in the dorsal (supine) position is common [98,[150][151][152][153][154][155][156][157][158][159][160]. Drawing blood the next morning is normative [164].

Q5: Please tell me about US after kidney biopsy A5
US just after kidney biopsy is normative. If hematoma is detected, an observation that is more elaborate is necessary [167,168]. Resumption at 1-2 days after biopsy is normative, or resumption at the time when hemostasis was confirmed is normative. It is determined in consideration of the underlying disease, drug type, dose, and amount bleeding after the biopsy. There is a report of discontinuation of anticoagulant for 7 days in cases that are not of high thrombotic risk [4,5].

Q7: Please tell me about the days of physical limitation
after kidney biopsy A7: It is reported that bleeding after kidney biopsy occurs for 5-7 days after the procedure. As for physical limitation after kidney biopsy, normal exercise and light work are permitted after 1-2 weeks, and strong exercise including loading is permitted after four weeks [4,5].
Q8: Please tell me about the period of hospital stay for kidney biopsy

A8
In Japan, kidney biopsy and recovery are undergone in a hospital. Four days and three nights to 6 days and five nights of hospital stay are normative [4,5]. In Europe and America, there are two types of options including overnight hospitalization and the outpatient department. Complete bed rest of 4-h is required after kidney biopsy, and subsequently for 12-24 h, bed rest is also required.
Moreover, in these cases, recovering near the hospital, including at a hotel, is required.

Chapter 7: Complications
According to the questionnaire survey results that were performed for the publication of this book, among 21,648 kidney biopsy cases that were performed in Japan, gross hematuria after kidney biopsy was found in 511 patients (2.4%), bladder wash was in 79 cases (0.36%), red blood cell transfusion was in 161 cases (0.74%), renal arterial embolization was in 44 cases (0.22%), and death occurred in one case (0.005%). The underlying cause of death in this case was not due to bleeding after kidney biopsy, but the overall status of this case was confirmed poor before kidney biopsy and worsened after kidney biopsy (Table 5) [1,4,5,66,74,156,[169][170][171][172][173][174].

A6
Pain lasting more than 12 h is observed and is considered due to ureteral obstruction from a blood clot in patients with gross hematuria, or due to stretching of the renal capsule by a subcapsular hematoma. Arteriovenous fistulas formation due to damage to the walls of an adjacent artery and vein is important but resolves spontaneously over 1-2 years. The "page kidney" related to a large subcapsular hematoma can lead to chronic hypertension due to persistent activation of renin angiotensin. Puncture of the liver, pancreas, spleen, or intestine may occur. Urinoma formation from puncture of the urinary tract occurs rarely.

Q7: Please tell me about the treatment for subcapsular
bleeding, perinephric bleeding, and intrarenal bleeding after kidney biopsy A7: These types of bleeding subside within a few days or within 1 month, but there are serious cases requiring renal transarterial embolization (TAE). According to the questionnaire survey that was performed for the publication of this book, renal TAE for these serious bleedings was performed in 32 cases (0.17%) [4,5,[194][195][196]. It is suggested that we avoid extreme hypertension during kidney biopsy, but absolute restriction on BP is not described. Many institutions in Japan aim for systolic BP that is lower than 160 mmHg, and diastolic BP that is lower than 100 mmHg. For patients receiving antihypertensive medications, these drugs are administered on the morning before biopsy and are adjusted while examining the status of the BP, after kidney biopsy enforcement [184].

Q8: Please tell me about the treatment for gross hematuria due to bleeding into a urinary tract A8
This bleeding also subsides spontaneously within a few days or within 1 month, but when gross hematuria due to massive bleeding into the urinary tract persists, hematoma occludes exit parts of the bladder, resulting in bladder tamponade. A urethral catheter is inserted, and the hematoma is removed while performing a bladder wash.
However, for serious cases, renal TAE is required.
According to the questionnaire survey that was performed for the publication of this book, renal TAE for this type of serious bleeding was performed in five cases (0.02%) [4,5,167,197 ]. .

Chapter 8: Histological evaluation of kidney biopsy specimen
Kidney biopsy remains the gold standard to diagnose renal disease and evaluate acute and chronic renal damages. Specimens are processed for the diagnostic approach of light microscopy (LM), immunostaining by immunofluorescence (IF) or immunohistochemistry, and electron microscopy (EM). To minimize the bleeding risk, less passes to obtain tissue is desirable; on the other hand, sufficient quantity of tissue is required for definite diagnosis. When small sample size of renal tissues was obtained, dividing samples appropriately into LM, IF, and EM studies should be carefully considered (Fig. 2).  2). Regarding LM examination, it is estimated that glomerular number of 20-25 is necessary to evaluate glomerular lesion appropriately [198][199][200][201]. may be also added for a diagnosis of IgA-containing immune type glomerulonephritis [202].

Chapter 9: Kidney biopsy in children
Kidney biopsy in the pediatric population was reported for the first time in 1958 and has a history of more than 60 years [204]. The procedure has become relatively safe in children as well as in adults owing to technical advances and improvement of medical devices. However, the indication for kidney biopsy must be carefully determined based on benefits and potential risks for serious bleeding complications.

A4
Kidney biopsy is indicated according to adult criteria [4,5]. Kidney biopsy is not essential in the current medical care that genetic screening developed but is useful for diagnosis or differential diagnosis [210][211][212][213].

Kidney biopsy for clinical condition with high risk
Kidney biopsy is indicated according to adult criteria [214].

Pre-biopsy evaluation
We may need sedation or general anesthesia in children. Therefore, it is necessary to evaluate the airway and the overall status (underlying disease) beforehand. The final decision whether you perform kidney biopsy or not should be judged based on each institutional forum [220][221][222].  Just after the puncture, we suppress the puncture department with both hands while using our weight in prone position for 10-15 min. This follows from adult cases [195].

A5
In Japan, kidney biopsy is undergone at the hospital. More than 5 days and five nights of hospital stay is normative [4,5,127,247].

A1
Bleeding complications after kidney biopsy are important, but the occurrence of serious cases is rare. According to the questionnaire results that obtained for the publication of this book, among 1685 pediatric kidney biopsy cases that were performed in Japan, gross hematuria after kidney biopsy was found in 105 patients (6.2 %) and bladder wash in 9 cases (0.5%). Renal arterial embolization occurred in one case (0.03%) ( Table 5) [4,77,176,222,248].

Chapter 10: Biopsy of transplanted kidney
For the long-term engraftment after the renal transplant, early detection and early treatment for rejection or early detection of the side effect with the immunosuppressive drug are important. Because treatment totally varies according to clinical condition, the pathological evaluation of the renal graft tissue is important in treatment strategy decision. These clinical conditions occur asymptomatically and may progress.

Q1: Please tell me about transplant kidney biopsy A1
Kidney biopsy that is performed at renal dysfunction such as rejection is named episode biopsy, and premeditated kidney biopsy that is also performed just after renal transplant and at constant time even for the time when renal function is stable is named protocol biopsy.
1. Episode biopsy: Transplant kidney biopsy is generally performed when an acute renal allograft rejection is suspected within a year after operation. The main clinical indicator is an increase in serum creatinine levels of 20% above a baseline value. Furthermore, a year after operation, for patients with renal dysfunction or proteinuria, the following diseases are clarified by kidney biopsy; chronic allograft nephropathy (CAN), chronic rejection (antibody-mediated rejection and T cell-mediated rejection), recurrence of underlying disease and calcineurin inhibitors nephrotoxicity [76,149,249]. 2. Protocol biopsy: kidney biopsy is performed at the renal transplant surgery for 0 h (just after perfusion of the isolated kidney), an hour (after renal graft blood flow resumption), at post transplantation 2-3 months, and at a year after. Whether immunosuppressive therapy is appropriate, asymptomatic acute rejection occurs, or underlying disease recurs can be determined.

A3
In Japan, almost of kidney biopsy are undergone as inpatient. Two days and one night (47%) or 3 days and two nights (29%) of hospital stay are more frequent. The rate of occurrence of hospital stay for more than 4 days and three nights is 24% [4].

A1
The following situation is included; (1) when there is an Surgeons directly look at the surface of the kidneys and determine the area from which the tissue samples should be taken. There are two type of methods including a needle biopsy and wedge biopsy. The incidence of severe bleeding of renal surface is very low, and mortality is rare, but the risk of hemorrhage into the urinary tract exists. Attention is necessary for the development of renal arteriovenous fistula (arteriovenous fistula: AVF) causing bleeding to the urinary tract. Other relatively minor postoperative complications including fever, atelectasis, and ileus can occur. In addition, an open biopsy under general anesthesia is associated with a longer hospital stay and a larger surgical scar. On wedge biopsy, the specimens may increase the proportion of shallow layer of the cortex resulting in less information of the cortex deep part and medulla [4].

Q2: Please tell me about complication of open (surgical)
kidney biopsy

A2
According to the questionnaire survey that was performed for the publication of this book, among 1,156 kidney biopsy cases that were performed in Japan, gross hematuria after kidney biopsy was found in 9 patients (0.78%), renal TAE for this serious bleeding was performed in 2 cases (0.17%) ( Table 5).

Japan A3
Laparoscopic kidney biopsy is advocated by some surgeons as an alternative method to open kidney biopsy for patients unable or unwilling to undergo percutaneous kidney biopsy.
• As for the complications peculiar to laparoscopic kidney biopsy, nephric subcapsular hematoma, subcutaneous emphysema, peritoneal injury, and injury of the circumference organ are reported. • An advantage of laparoscopic kidney biopsy in comparison with the percutaneous kidney biopsy includes certain sampling of renal tissue as well as confirmation and hemostasis of a bleeding point.
• An advantage of laparoscopic kidney biopsy in comparison to open kidney biopsy includes shortening of the hospital stay, pain reduction, and compatibility of the incised wound [4].