Primary Cilia Metaplasia in Renal Transplant Biopsies with Acute Tubular Injury

Abstract

Primary cilia are hair-like organelles singly distributed along the apical surface of proximal and distal nephron tubules as mechanosensors. The goal of this study was to use electron microscopy to systemically evaluate cilia changes in acute tubular injury (ATI) from both transplant and native renal biopsies. Three groups of cases were included: control group 1—native biopsies without major changes in renal tubules; study group 2—native biopsies with prominent ATI; and study group 3—renal transplant biopsies with prominent ATI (delayed renal function group). Extensive search for ciliary structures along renal tubules was conducted in each case, focused on proximal tubular areas with injured (diminished) apical microvilli. Singly located cilia were found in 3/19 specimens in control group 1, 4/18 in group 2 (native ATI), and 6/24 in group 3 (transplant ATI). Importantly, there were clusters of cilia in proximal tubules with markedly diminished apical microvilli in 3/24 biopsies from 2 patients in group 3, but none from groups 1 and 2. The clusters of cilia ranged from 6 to 15 individual cilia along the apical surface with diminished apical microvilli. Under high magnifications, the cilia demonstrated 9 pairs of peripheral microtubules without a central pair of microtubules, consistent with primary cilia (9 + 0) rather than motile cilia (9 + 2). In summary, the authors found clusters of cilia in proximal tubules with remarkable apical microvillar injury in 3 renal transplant biopsies with ATI, implying a reactive, or repairing, process following tubular injury, thus they name this finding “cilia metaplasia".

• Acute tubular injury
• cilia metaplasia
• primary cilia
• renal biopsy

Acknowledgement

The authors are grateful for the excellent technical assistance from Sharon K. Hicks, Joseph P. Roszka, Marie L. Kaiser, Karen L. Lewinski, Emily Stebens, and Peggy Wenk. We also appreciate the expert consultation from Chung-ho Chang for electron microscopy.