There is no certain answer to this question, but wise choices can be made, depending on what is known about the clinical situation, and taking into consideration, the probabilities of various diagnostic possibilities, and the relative risks to the particular patient produced by the biopsy procedure. 

      A biopsy consisting of a minute piece of kidney, containing perhaps 5 to 50 glomeruli from an total of about 2,000,000 found in the kidney of an average person, often produces meaningful information when properly examined for two reasons:

         a)  the functional units of the kidney, the 2 million nephrons, are very uniformly distributed in the renal cortices, and

         b)  most of the “medical” diseases of the kidney affect the nephrons uniformly.

        For example, if a patient has nephrotic syndrome, serum proteins are leaking across the glomerular basement membranes in every glomerulus.   If the patient has minimal change disease, every glomerulus will exhibit foot process effacement by EM, if the patient has membranous glomerulopathy, every glomerulus will exhibit immune deposits in small “humps” on the epithelial side of the basement membrane, and if the patient has amyloidosis, amyloid fibrils will probably be visible in the mesangium and/or along the glomerular basement membranes of most glomeruli.

        Therefore, in such cases, a small number of glomeruli, occasionally even one, or less, is enough to make a diagnosis, in a well-defined clinical context.

        Renal lesions which do not typically affect all or almost all nephrons still tend to be distributed evenly in the kidney.   As a consequence, therefore, in the circumstance where, for example, fifty percent of the glomeruli contain a particular lesion, let us say, a focal necrotizing glomerulonephritis, a biopsy containing 10 glomeruli is very likely to exhibit a typical lesion.    On the other hand in such a case in which only 10 percent of the glomeruli exhibit the focal lesions, a biopsy containing only 10 glomeruli is likely to be inadequate to demonstrate the lesions.

         In many common clinical situations, lesions may be widespread, well defined, and dramatic, yet in small biopsies, containing only a few nephrons and associated structures, the lesions may be sparse in the biopsy, or, in fact, not obtained, if the biopsy is too small.   Biopsies from patients with “cast nephropathy”, atheromatous embolism, necrotizing arteritis, focal-segmental glomerulosclerosis, and early necrotizing pauci-immune GN are often found in only one or two foci in biopsy which ordinarily be "adequate", i.e. containing 10 to 20 glomeruli. Therefore it follows clearly that the appropriate amount of tissue to be obtained at biopsy should be judged based on a consideration of the clinical situation, the "differential diagnosis", and the comparative likelihood and importance of suspected lesions.

         Certain other generalization can be made about whether a small biopsy is likely to be adequate, or whether attempts should be made to obtain a larger sample.

          A small sample is more likely to be adequate when:

   a)      the patient is younger,

   b)      has no indication of chronic renal disease,

   c)      the disease process is of short duration,

   d)      and renal function is unimpaired.

     Conversely, larger biopsies are likely to needed

   a)      in older patients, with greater likelihood of confounding or multiple processes,

   b)      and when there is chronically impaired renal function.

   An obverse observation may be made, utilizing the logic above regarding the sample size required to demonstrate sparsely occurring lesions.   It is this.  If even a single well characterized lesion is seen is a kidney biopsy, of whatever size, given the randomness of the biopsy sample, it is quite likely that this lesion, seen in one glomerulus, or in one of 10, or in one of 100, is not an insignificant finding, but, on the other hand, it is quite likely that many similar lesions are present among the other 2 million glomeruli not included in the biopsy sample.

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   It is my deeply held conviction, that a kidney biopsy is not truly adequately examined, unless tissue is examined thoroughly by an experienced pathologist, using the techniques of light microscopy, immunofluorescence microscopy and electron microscopy.

The clinical syndromes of medical renal disease are many and complex, and for each one of them, multiple underlying etiologies are possible.  Many patients have more than one pathologic process in the kidney.   Many disorders can ONLY be diagnosed by electron microscopy and/or immunofluorescence.

It is pertinent to know that a lesion is present, and conversely, that it is not present.

You will not know, if you do not look, and look carefully.

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