Invited commentary by Dr. Vivekanand Jha
D’Agati and Mengel provide a fascinating account of the history of kidney pathology over last 60 years. As they note, it is impossible to imagine nephrology as it exists today without acknowledging the major, even pivotal, contributions of pathologists. Except structural abnormalities that can be detected by imaging, the nomenclature and classification of almost all kidney diseases hinges on how the kidney looks under the microscope. Immunofluorescence and electron microscopy have superbly complemented light microscopic examination. More technology intensive than the light microscopy, these modalities are not available everywhere in the world, and kidney disease epidemiology changes depending on whether these techniques were used. Probably the only other field where disease diagnosis is so heavily dependent on microscopic examination of the tissue is oncology.
It would be unfair to say that the kidney biopsy is only useful in diagnosis: it helps us assess disease severity, determine the prognosis, and make treatment decisions. Rapid evaluation of the kidney biopsy is critical in conditions like acute allograft dysfunction and rapidly progressive kidney failure. It has been said: “if you are thinking of doing a kidney biopsy, you should have already done it!”
As the authors note, nephrologists have always acknowledged the seminal contribution of pathologists to the advancement of the specialty. Also, a large number of nephrologists have trained themselves in evaluation of kidney biopsies, especially in those parts of the world where experienced kidney pathologists are scarce.
It is well known, however, that the same morphologic appearance could result from a number of diverse pathogenetic mechanisms, which was resolved by sub-classifying a diagnosis into either primary or secondary schemes. Over a period of time, these schemes were tweaked to reflect current knowledge. The best example is the evolution of the Banff classification scheme for evaluation of kidney allograft histology.
While a testimony to the pioneering pathologists who played a key role in shaping our understanding of kidney diseases, this also reflects our inability to dissect out the factors that initiate the cascade of events which culminates in a particular histologic change. The prefix “idiopathic” was applied to a majority of these descriptions. We now know that treatment decisions based on morphologic appearance alone may be inappropriate in many situations.
Valuable as they are, kidney biopsies are invasive and carry a significant risk of morbidity and even mortality. Moreover, they cannot be easily repeated. Modern biopsy guns and guidance techniques have certainly improved the safety of the procedure. Still, despite the promise of new information generated by application of modern molecular techniques, development of noninvasive tests that can substitute for a kidney biopsy would go a long way in simplifying patient management. There have been some movements in the direction. Some examples include the discovery of anti-phospholipase A2 receptor antibody in membranous nephropathy and soluble urokinase receptor in focal segmental glomerulosclerosis, improvement in our ability to evaluate complement pathway abnormalities in MPGN and thrombotic microangiopathies, and evaluation of donor specific antibodies in allograft evaluation. With any such new finding, the debate whether we could reduce our dependence on kidney biopsy starts.
While that remains the ultimate goal, it would be safe to say that for the foreseeable future, the practice of clinical nephrology will depend heavily on the kidney biopsy.
Vivekanand Jha, MD, DM
AJKD Associate Editor