Polarized Ends of Human Macula Densa Cells: Ultrastructural Investigation and Morphofunctional Correlations

ABSTRACT The morphology of the kidney macula densa (MD) has extensively been investigated in animals, whereas human studies are scanty. We studied the fine structure of human MD cells focusing on their apical and basal ends and correlating structure and function. The MD region was examined by transmission electron microscopy in six renal biopsies from patients with kidney disease. Ultrastructural analysis of MD cells was performed on serial sections. MD cells show two polarized ends. The apical portion is characterized by a single, immotile cilium associated with microvilli; apically, cells are joined by adhering junctions. In the basal portion, the cytoplasm contains small, dense granules and numerous, irregular cytoplasmic projections extending to the adjacent extraglomerular esangium. The projections often contain small, dense granules. A reticulated basement membrane around MD cells separates them from the extraglomerular mesangium. Although the fact that tissue specimens came from patients with kidney disease mandates extreme caution, ultrastructural examination confirmed that MD cells have sensory features due to the presence of the primary cilium, that they are connected by apical adhering junctions forming a barrier that separates the tubular flow from the interstitium, and that they present numerous basal interdigitations surrounded by a reticulated basement membrane. Conceivably, the latter two features are related to the functional activity of the MD. The small, dense granules in the basal cytoplasm and in cytoplasmic projections are likely related to the paracrine function of MD cells.