Handbook of Renal Biopsy Pathology

Handbook of Renal Biopsy Pathology
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London: McGraw-Hill, 17— Lote CJ. Principles of renal physiology.

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Fourth edition. Dordrecht: Kluwer Academic, Chapter 2 General Points About Renal Biopsy Specimens Introduction to General Points A renal biopsy specimen is the best example of a specimen that a pathologist cannot interpret without clinical information.

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This practical handbook provides a short, clear and useful guide to interpretation of renal biopsy specimens. It is intended to be useful to pathologists. 1 This book is meant to be a practical guide to interpretation of renal biopsy First, the book has much less text than most on renal pathology, because only a.

From information about age and sex of the person biopsied, reason for biopsy, and other clinical features, the pathologist should have an idea of likely appearances in the specimen, before any sections are seen on a microscope. This is because there are two general rules. Common things are common. Diseases present in characteristic ways. Strictly speaking, the second rule should state that people with diseases present in characteristic ways, because diseases do not exist on their own, but in medicine, conventionally, diseases are considered to be independent entities.

For simplicity, this convention will be followed. They are more helpful in real life than the standard textbook approach, which is to describe diseases, rather than to suggest how a pathologist can give a name to something that is unknown before the specimen is examined. Lists of diseases often give each one equal prominence whether they are rare or common, which is little use in practice. The findings given here will become out of date.

New diseases will appear. There may be more than one disease in a kidney. In children there is usually only one, but in adults there is often more than one, if only because many have ischemic damage associated with age or hypertension, as well as something else. There are rare conditions, but if a specimen appears out of the ordinary, the pathologist should think of an unusual form of a common disorder, or a combination of common disorders, before something rare.

A renal biopsy specimen is a tiny proportion of a kidney, and may not be representative of it. A needle biopsy specimen weighs under mg, a kidney in an average adult weighs about g, and so a biopsy specimen is much less than one thousandth part of a kidney by weight.

A specimen may contain about twenty glomeruli, out of the several hundreds of thousands in a typical kidney. Even so, renal biopsy is helpful in most conditions, and indeed there are several in which only one glomerulus is needed to make the diagnosis. Importance of the Request Form to the Pathologist The pathologist relies on information written on the request form, which may be wrong, or incomplete, or give a misleading emphasis, especially if written by an inexperienced physician.

Ideally, the pathologist should be able to discuss clinical features of every person biopsied with a physician who understands what is going on, but this is not always possible. Indications for Renal Biopsy There are only a few indications for renal biopsy, meaning the reasons why a biopsy is taken. One indication is presence of protein in the urine, called proteinuria, which may be asymptomatic, and detected by chance or a deliberate search, or may be associated with edema and other features that are collectively called the nephrotic syndrome.

Another is presence of blood in the urine, called hematuria.

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Others are states of reduced renal excretory function, called acute renal failure or acute renal impairment, and chronic renal failure or chronic renal impairment. Most biopsies of renal allografts are to investigate acute or chronic impairment of graft excretory function. There are often combinations of these features. The terms nephritic syndrome and acute nephritis are sometimes applied to an acute illness with edema, hematuria, proteinuria, hypertension, and acute renal failure.

Because the features of the nephritic syndrome may be incomplete or atypical and one feature may dominate, and the term is sometimes used in a loose and ambiguous way, there is not a separate Indications for Renal Biopsy 7 section on it, and the disorders that can present in this way are covered in the sections on the nephrotic syndrome, acute renal failure, and hematuria.

In someone who has had a renal biopsy, the procedure may be repeated to check on the progress of the disease, or to look for effects of treatment, or to see if another condition has developed. Repeat specimens can be considered in the same ways as initial specimens, with the advantage that there is previous material for comparison. To simplify the approach to interpretation of renal biopsy specimens, the indications are considered in a way that allows for all possible combinations.

If there is the nephrotic syndrome, irrespective of other features, that is regarded as the main indication. If there is acute renal failure, irrespective of features apart from the nephrotic syndrome, acute renal failure is regarded as the main indication. If there is chronic renal failure, without the nephrotic syndrome or acute renal failure, and irrespective of proteinuria or hematuria, chronic renal failure is regarded as the main indication.

If there is hematuria with or without proteinuria, but with normal renal function, hematuria is regarded as the main indication. The last indication is asymptomatic proteinuria on its own. To summarise, the indications for biopsy are considered in this order, and the first one that applies to a specimen is regarded as the main one: first, nephrotic syndrome second, acute renal failure third, chronic renal failure fourth, hematuria fifth, asymptomatic proteinuria The scheme followed in this work is not rigid, and should allow a diagnosis to be made on specimens with misleading indications written on the request form, such as one with hematuria and proteinuria in which there is chronic renal failure, although it is not noted on the request form, or one with renal failure that is considered acute clinically but actually is chronic, or a specimen on which the pathologist is not clear which is the dominant indication.

These indications may be called medical reasons for a renal biopsy. Biopsy of a mass in or near the kidney is uncommon, and may be called a surgical or urologic reason for a renal biopsy. There are other clinical features that are not by themselves indications for a renal biopsy, although they may be present with features that are indications.

These include hypertension, loin pain or other abdominal pain, and anemia. Suspected or definite urinary tract infection is usually considered a contraindication to biopsy. A pathologist may see renal biopsy specimens taken for unusual or accidental reasons. Kidney may be seen in attempted biopsy of other structures, particularly of liver and masses in the region of the kidney. The specimen should be examined as if it were an intentional biopsy of the kidney, because abnormalities may be found Fig.

Occasionally, there are none of the common indications, but a biopsy is taken to investigate the possibility of subclinical disease in the kidney, such as vasculitis, or there is a familial renal problem, or a kidney is assessed as a possible 8 2 General Points About Renal Biopsy Specimens Fig. This is a specimen not of liver, but of renal cortex. There is chronic damage, particularly seen as tubular atrophy.

One potential explanation is effects of a calcineurin inhibitor, used as an immunosuppressant. IgA nephropathy is another common finding when attempted liver biopsy specimens include kidney.

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Renal comes from the Latin for kidney, nephro- comes from Greek for kidney, and the word kidney is of obscure origin. Biopsy comes from Greek words meaning life and vision. In Latin, cortex meant bark of a tree. Tubule is derived from the Latin for a little pipe or tube graft, or there is a known or suspected metabolic or tubular disorder, especially in children. During surgical exploration of a graft for a vascular or ureteric problem, a biopsy may be done simply because the surgeon is there.

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Different nephrologists and renal transplant surgeons have different indications for biopsy. Some may not biopsy people with hematuria alone, or asymptomatic proteinuria, or chronic renal failure. Not all children with the nephrotic syndrome have a renal biopsy, and in some places this is also true of adults. In some transplant units, allografts are biopsied at set times irrespective of function. Different renal biopsy practices will give different frequencies of findings, but the findings given in this work are likely to be comparable with those in many centres. Findings in some parts of the world, such as in developing or low income countries, may be markedly different.

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Summary: General Points About Renal Biopsy Specimens 9 When allografts are excluded, the frequencies of indications for biopsy are different at different ages, and in different parts of the world. In some countries in adults, chronic renal failure, acute renal failure, and nephrotic syndrome each account for nearly a third of specimens, in descending order of commonness, with fewer taken for hematuria, and even fewer for asymptomatic proteinuria.

In some countries in children, nearly half are taken for hematuria, and the order of indications for the rest is nephrotic syndrome, acute renal failure, asymptomatic proteinuria, and chronic renal failure. In some parts of the world, almost the only indication for renal biopsy is the nephrotic syndrome. A satisfactory specimen for a pathologist is one with definite features, on which a clear cut diagnosis can be made. The next are hematuria and chronic renal failure. Either form of hemorrhage may require blood transfusion, or less commonly radiologic embolisation of material into renal arteries to block them, or even less commonly nephrectomy if there is otherwise uncontrollable bleeding.

A puzzling observation is that the pathologist is hardly ever able to predict when there will be clinically significant bleeding after a renal biopsy. Large blood vessels may be seen in specimens without clinically obvious bleeding afterwards, while there may be no large vessels in specimens complicated by hemorrhage. Other complications include development of arteriovenous fistulas and consequences of puncture of intra-abdominal organs. Summary: General Points About Renal Biopsy Specimens The two general rules are that common things are common, and diseases present in characteristic ways.

The main indications for a renal biopsy are the nephrotic syndrome, acute renal failure, chronic renal failure, hematuria, and asymptomatic proteinuria. Combinations of these occur.

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Biopsy of a renal allograft is usually to investigate acute or chronic graft failure. Renal biopsy may also be done to investigate a mass in the kidney. One is a needle biopsy specimen, usually taken through the skin, and called a percutaneous specimen. Transjugular specimens are similar specimens, but are taken by an internal approach to the kidney, through a cannula passed from the jugular vein into the renal vein.

The other type of specimen is taken directly from a kidney by incision at operation, and often called a wedge biopsy specimen. Fixation and Processing of Specimens Different laboratories have different methods of fixation. Formal saline has several advantages over other fixation methods. All routine histologic staining methods work well after this fixation. Many immunohistologic methods also work well. If necessary before further processing, a part of the specimen can be transferred to another fixative for electron microscopy, with little effect on the quality of the electron microscopic images.

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This may mean that there is no need for technical staff to attend each time a biopsy is done. In some centres, immediately after removal, the renal biopsy specimen is examined with a low magnification binocular microscope or other magnifying lens to allow identification of glomeruli, which can be seen as red dots Fig. A small piece, about 1 mm long, containing glomeruli is cut off and put into a solution of glutaraldehyde in buffer suitable for electron microscopy.

Another piece is frozen for immunohistologic studies on unfixed sections. The rest of the specimen is then put in a fixative for orthodox light microscopic studies. The term orthodox light A. Glomeruli are the dark round structures. Small pieces containing a couple of glomeruli can be cut off, and either frozen for immunofluorescence study or put in fixative suitable for electron microscopy. In Latin, glomerulus meant a little ball of thread, and the name was first used in microscopy as a description of what is now called the glomerular tuft.

Glomerulus is used now instead of Malpighian corpuscle.