Quality in urine microscopy: The eyes of the beholder

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The urine is the window to the kidney.This oft-repeated adage impresses upon medical students and residents the importance of urine microscopy in the evaluation of patients with renal disorders.

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While this phrase is likely an adaptation of the idea in ancient times that the urine reflected on humors or the quality of the soul, the understanding of the relevance of urine findings to the state of the kidneys likely rests with the pioneers of urine microscopy. As reviewed by Fogazzi and Cameron, 1,2 the origins of direct inspection of urine under a microscope lie in the 17th century, with industrious physicians who used rudimentary microscopes to identify basic structures in the urine and correlated them to clinical presentations. 1 At first, only larger structures could be seen, mostly crystals in patients with nephrolithiasis. As microscopes advanced, smaller structures such as “corpuscles” and “cylinders” could be seen that described cells and casts. 1

In correlating these findings to patient presentations, a rudimentary understanding of renal pathology evolved long before the advent of the kidney biopsy. Lipid droplets were seen 1 in patients swollen from dropsy, and later known to have nephrotic syndromes. In 1872, Harley first described the altered morphology of dysmorphic red blood cells in patients with Bright disease or glomerulonephritis. 1,3 In 1979, Birch and Fairley recognized that the presence of acanthocytes differentiated glomerular from nonglomerular hematuria. 4


An acanthocyte seen in a patient with glomerulonephritis.

Figure 1. An acanthocyte seen in a patient with glomerulonephritis. The arrow notes a typical bleb (× 40).

The term dysmorphic refers to any misshapen red blood cell found in the urine. Dysmorphic cells have a variety of causes. The term acanthocyte is reserved for red blood cells that show evidence of damage thought to be induced by passage through the glomerular basement membrane, characterized by vesicle-shaped protrusions or blebs ( Figure 1 ). These cells are considered quite specific for glomerular hematuria. Köhler et al found that in patients with biopsy-proven glomerular disease, 12.4% of excreted cells were acanthocytes, whereas they were rarely found in people with nonglomerular hematuria. 5 As these cells then pass through the renal tubules, they can become encased in Tamm-Horsfall proteins, forming red blood cell casts ( Figure 2 ), another hallmark of glomerular disease.
A red blood cell cast in a patient with glomerulonephritis.

Figure 2. A red blood cell cast in a patient with glomerulonephritis. Casts form when red blood cells that have passed through a damaged glomerular basement membrane are encased in urinary proteins before being excreted into the urine (× 40).

The kidney biopsy from a patient with immunoglobulin A nephropathy presented by Daza et al in this issue 6 reminds us of the amazing pathophysiology of glomerular disease. A red blood cell can somehow contort enough to squeeze through the pores of an inflamed glomerular basement membrane roughly one-tenth its size, with only blebbing to show for it. The image Daza et al present captures this rarely seen event and should give us pause. In an age when the electronic medical record too often replaces the patient history, when ultrasonography and echocardiography are replacing the stethoscope, and when reports by machines and technicians with no understanding of the patient’s condition replace direct examination of bodily fluids, there is merit in seeing what is going on for ourselves. This image allows us to understand the value of urine microscopy in the workup of patients with renal disease.


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