Denervated Renal Graft Explants Have Extensive Damage of the Juxtaglomerular Apparatus and Neural Network
Christopher D Cendrowski, Wei Li, Michele T Rooney, Ping L Zhang. William Beaumont Hospital, Royal Oak, MI
Background: Renal innervation partially controls the juxtaglomerular apparatus and renal tubular reabsorption. Experimental denervation has been shown to cause large urinary water and sodium losses (up to 3.6 and 8.3 fold from baseline levels, respectively). In humans, a single kidney graft has a glomerular filtration rate only half that of normal and is entirely denervated (even if partial reinnervation is possible later). This study examines the renal innervation system in explanted renal grafts for other possible etiologies of renal dysfunction besides ongoing rejection and chronic changes.
Design: Ten control kidney sections (grossly normal areas taken from nephrectomy specimens for tumor) and seventeen renal transplant explants were included in the study. All sections were immunohistochemically stained with neuron specific enolase (NSE) for evaluating the juxtaglomerular apparatus, CD56 for examining the renal neural network, and calretinin (a marker for calcium influx) for evaluating viability of large renal nerves.
Results: In normal controls, staining with NSE revealed positive granular staining of the juxtaglomerular apparatus, namely the macula densa and specialized afferent arterioles. CD56 staining consistently localized nerve fibers to arterioles, peritubular spaces in the cortex and medulla, and the vasa recta in normal controls. In explants where chronic glomerular and tubular changes were extensive, both NSE staining of the juxtaglomerular apparatus and CD56 staining of the neural network were largely absent in the cortex and medulla. In both normal controls and graft explants, there was weak calretinin staining of large renal nerves, implying at least partial reinnervation of the transplant kidneys.
Conclusions: Explanted grafts appear to have at least partial reinnervation of large nerve fibers. Extensive loss of the juxtaglomerular apparatus and peritubular/perivascular innervation, however, may be additional factors compromising graft nephron regulation of glomerular filtration and tubular reabsorption, in addition to ongoing rejection and chronic injury.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 252, Monday Morning