Peter S. Topham, Yipu Chen Percutaneous renal biopsy was first described in the early 1950s by Iversen and Brun1 and Alwall.2 These early biopsies were performed with the patient in the sitting position by use of a suction needle and intravenous urography for guidance. An adequate tissue diagnosis was achieved in less than 40% of these early cases. In 1954, Kark and Muehrcke3 described a modified technique using the Franklin-modified Vim-Silverman needle, with the patient in a prone position and an exploring needle used to localize the kidney before insertion of the biopsy needle. These modifications yielded a tissue diagnosis in 96% of cases, and no major complications were reported. Since then, the basic renal biopsy procedure has remained largely unchanged, although the use of real-time ultrasound and refinement of biopsy needle design have offered significant improvements. Renal biopsy is now able to provide a tissue diagnosis in more than 95% of patients, with a life-threatening complication rate of less than 0.1%. Ideally, analysis of a renal biopsy sample should identify a specific diagnosis, reflect the level of disease activity, and provide information to allow informed decisions about planned treatment. Although not always able to fulfill these criteria, the renal biopsy remains a valuable clinical tool and is of particular benefit in the clinical situations discussed next (Box 6-1). Routine clinical and serologic examination of patients with nephrotic syndrome usually allows the clinician to determine whether a systemic disorder is present. In adults and in adolescents beyond puberty without systemic disease, there is no reliable way to predict the glomerular pathologic process with confidence by noninvasive criteria alone; therefore a renal biopsy should be performed. In children age 1 year up to puberty, a presumptive diagnosis of minimal change disease (MCD) can be made. Renal biopsy is reserved for nephrotic children with atypical features, including microscopic hematuria, reduced serum complement levels, renal impairment, and failure to respond to corticosteroids. In most patients with acute kidney injury or AKI on a background of chronic kidney disease (CKD), the cause can be determined without a renal biopsy. Obstruction, reduced renal perfusion, and acute tubular necrosis (ATN) can usually be identified from other lines of investigation. In a minority of patients, however, a confident diagnosis cannot be made, and a renal biopsy should be performed on an urgent basis so that appropriate treatment can be started before irreversible renal injury develops. This is particularly true in patients with AKI accompanied by active urine sediment or with suspected drug-induced or infection-induced acute interstitial nephritis. Patients with diabetes mellitus and renal dysfunction do not usually require biopsy if the clinical setting is associated with diabetic nephropathy, as in isolated proteinuria, diabetes of long duration, or evidence of other microvascular complications. Renal biopsy should be performed, however, if the presentation is atypical, such as proteinuria associated with glomerular hematuria (acanthocytes), absence of retinopathy or neuropathy (in patients with type 1 diabetes), onset of proteinuria less than 5 years from documented onset of diabetes, uncharacteristic change in renal function or renal disease of acute onset, and presence of immunologic abnormalities. Serologic testing for antineutrophil cytoplasmic antibody (ANCA) and for anti–glomerular basement membrane antibodies has allowed a confident diagnosis of renal small-vessel vasculitis or Goodpasture disease without invasive measures in most patients. Nonetheless, a renal biopsy should still be performed to confirm the diagnosis and to clarify the extent of active inflammation versus chronic fibrosis and thus the potential for recovery. This information may be important in helping to decide whether to initiate or continue immunosuppressive therapy, particularly in patients who may tolerate immunosuppression poorly. Lupus nephritis can usually be diagnosed by noninvasive criteria such as autoantibodies, urine protein excretion, renal function, and urine sediment abnormalities. Some experts argue that this information can be used to gauge the severity of renal involvement and to inform decisions about initial immunosuppressive treatment. However, a renal biopsy will clarify the underlying pathologic lesion, level of acute activity, and extent of chronic fibrosis, thereby providing robust guidance for evidence-based therapy. The diagnosis of viral infection–related nephropathy (e.g., hepatitis B virus–associated membranous nephropathy) is suggested by the presence of the expected glomerular lesion in association with evidence of active viral infection. However, the identification of virus-specific protein or DNA or RNA in the renal biopsy tissue by immunopathologic and molecular pathologic techniques (e.g., in situ hybridization) can ensure the diagnosis. Other systemic diseases, such as amyloidosis, sarcoidosis, and myeloma, can be diagnosed with renal biopsy. However, because these diagnoses can often be made by other investigative approaches, a renal biopsy is indicated only if the diagnosis remains uncertain or if knowledge of renal involvement would change management. Renal allograft dysfunction in the absence of ureteral obstruction, urinary sepsis, renal artery stenosis, or toxic levels of calcineurin inhibitors requires a renal biopsy to determine the cause. In the early post-transplantation period, this is most useful in differentiating acute rejection from ATN and the increasingly prevalent BK virus nephropathy. Later, renal biopsy can differentiate late acute rejection from chronic allograft nephropathy, recurrent or de novo glomerulonephritis (GN), and calcineurin inhibitor toxicity. The accessible location of the renal transplant in the iliac fossa facilitates biopsy of the allograft and allows repeated biopsies when indicated. This has encouraged many units to adopt a policy of protocol (surveillance) biopsies to detect subclinical acute rejection and renal scarring and to guide the choice of immunosuppressive therapy (see Chapter 104). The value of renal biopsy in patients with non-nephrotic proteinuria is debatable. All conditions that result in nephrotic syndrome can cause non-nephrotic proteinuria, except for MCD. However, the benefit of specific treatment with corticosteroids and other immunosuppressive agents in these patients probably does not justify the risk of significant drug-related side effects. In patients with proteinuria of more than 1 g/day, generic treatment with strict blood pressure control and angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) alone or in combination reduces proteinuria and reduces the risk for development of progressive renal dysfunction (see Chapter 80). Nonetheless, although the renal biopsy may not lead to an immediate change in management, it can be justified in these circumstances because it will provide prognostic information, may identify a disease for which a different therapeutic approach is indicated, and may provide clinically important information about the future risk of disease recurrence after renal transplantation. Patients with microhematuria should initially be evaluated to identify structural lesions such as renal stones or renal and urothelial malignant neoplasms if they are older than 40 years. The absence of a structural lesion suggests that the hematuria may have a glomerular source. Biopsy studies have identified glomerular lesions in up to 75% of biopsies.4 In all series, IgA nephropathy has been the most common lesion, followed by thin basement membrane nephropathy. In the absence of nephrotic proteinuria, renal impairment, or hypertension, the prognosis for patients with these conditions is excellent, and because specific therapies are not available, renal biopsy is not necessary and patients require only follow-up. Biopsy should be performed only if the result would provide reassurance to the patient, avoid repeated urologic investigations, or provide specific information, as in the evaluation of potential living kidney donors, in familial hematuria, or for life insurance and employment purposes. Renal biopsy can be informative in the patient with unexplained chronic renal impairment and normal-sized kidneys, because in contrast to AKI, it is often difficult to determine the underlying cause with clinical criteria alone. Studies have shown that in these patients with CKD, the biopsy will demonstrate disease that was not predicted in almost half.5 However, if both kidneys are small (<9 cm on ultrasound), the risks of biopsy are increased, and the diagnostic information may be limited by extensive glomerulosclerosis and tubulointerstitial fibrosis. In this setting, however, immunofluorescence studies may still be informative. For example, glomerular IgA deposition may be identified despite advanced structural damage. A renal biopsy can be helpful in the investigation of patients with a family history of renal disease. A biopsy performed in one affected family member may secure the diagnosis for the whole family and avoid the need for repeat investigation. Conversely, a renal biopsy may unexpectedly identify disease that has an inherited basis, thereby stimulating evaluation of other family members. In some patients, a repeat biopsy may be indicated. For example, the pathologic changes in lupus nephritis may evolve, necessitating treatment adjustment. Also, corticosteroid-resistant/dependent MCD or frequently relapsing MCD may actually represent a missed diagnosis of focal segmental glomerulosclerosis (FSGS), which may be detected on repeat biopsy. Some nephrologists believe that repeat biopsy in patients who have had aggressive immunosuppressive therapy of crescentic GN can help determine the most appropriate next line of therapy. In the assessment of a renal biopsy, the number of glomeruli in the sample is the major determinant of whether the biopsy will be diagnostically informative. For a focal disease such as FSGS, the diagnosis could be made on a biopsy specimen containing a single glomerulus that contains a typical sclerosing lesion. However, the probability that FSGS is not present in a patient with nephrotic syndrome and minimal changes on the biopsy specimen depends on the actual proportion of abnormal glomeruli in the kidney and the number of glomeruli obtained in the biopsy specimen. For example, if 20% of glomeruli in the kidney have sclerosing lesions and five glomeruli are sampled, there is a 35% chance that all the glomeruli in the biopsy specimen will be normal and that the biopsy will miss the diagnosis. By contrast, in the same kidney, if 10 or 20 glomeruli are sampled, the chance of obtaining all normal glomeruli is reduced to 10% and less than 1%, respectively, and the biopsy is more discriminating. This argument assumes that any segmental lesions present in the biopsy specimen are actually identified; this requires the biopsy specimen to be sectioned at multiple levels. Unless all glomeruli are affected equally, the probability that the observed involvement in the biopsy specimen accurately reflects true involvement in the kidney depends not only on the number of glomeruli sampled but also on the proportion of affected glomeruli. For example, in a biopsy specimen containing 10 glomeruli, of which three are abnormal (30%), there is a 95% probability that the actual glomerular involvement is between 7% and 65%. In the same kidney, if the biopsy specimen contained 30 glomeruli with 30% being abnormal, the 95% confidence intervals are narrowed to 15% and 50%. Therefore the interpretation of the biopsy needs to take into account the number of glomeruli obtained. A typical biopsy sample will contain 10 to 15 glomeruli and will be diagnostically useful. Nonetheless, it must be appreciated that because of the sampling issue, a biopsy sample of this size will occasionally be unable to diagnose focal diseases and at best will provide imprecise guidance on the extent of glomerular involvement. An adequate biopsy should also provide samples for immunohistology and electron microscopy (EM). Immunohistology is provided by either immunofluorescence on frozen material or immunoperoxidase on fixed tissue, according to local protocols and expertise. It is helpful for the biopsy cores to be viewed under an operating microscope immediately after being taken to ensure that they contain cortex and that when the cores are divided, the immunohistology and EM samples both contain glomeruli.
Renal Biopsy
Definition
Indications for Renal Biopsy
Nephrotic Syndrome
Acute Kidney Injury
Systemic Disease Associated with Renal Dysfunction
Renal Transplant Dysfunction
Non-nephrotic Proteinuria
Isolated Microhematuria
Unexplained Chronic Kidney Disease
Familial Renal Disease
Role of Repeat Renal Biopsy
Value of Renal Biopsy
Biopsy Adequacy
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Renal Biopsy
Chapter 6
