Perhaps that most highly sought finding in urinary sediment microscopy is the presence of granular casts. In clinical grounds, granular casts are typically associated with acute tubular injury (ATI) and guide the differentiation between prerenal and overt tubular insult.
The traditional view is that the granularity of granular casts comes from tubular epithelial cell debris that fill the cylindrical structure. However, granular casts are not exclusively found during ATI. Interestingly, early studies looking at the composition of granular casts were performed in small cohorts of patients with glomerular pathologies.
Therein, it was shown that granular casts have a matrix of Tamm-Horsfall (uromodulin) mucoprotein filled with plasma proteins. Thus, the presumption is that filtered plasma proteins in proteinuric pathologies can get “stuck” in a uromodulin gel, but it can also indicate that the granularity may relate to the extravasation of plasma proteins from peritubular capillaries during loss of integrity of the tubular epithelia in ATI.
In general, presence of scattered fine granular casts (Figure 1, panel A) does not carry a strong diagnostic or prognostic value, whereas abundance of the “extreme” of coarsely granular casts, i.e., “muddy brown” granular casts (Figure 1, panel D; Figure 2 panels A-C) present in sheets are considered pathognomonic of ATI and are associated with greater likelihood of dialysis-requiring acute kidney injury. Mitochondrial pigments or lipofuscin have been considered as being responsible for the enigmatic dark brown color of muddy brown granular casts, but that aspect remains a mystery.
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