Type 2a sodium-phosphate co-transporter serves as a histological predictor of renal dysfunction and tubular apical damage in the kidneys of septic mice

Abstract

Acute renal failure (ARF) occurs in septic patients and is histologically characterized by tubular apical damages, including brush border breakdown. Nevertheless, little information is available to identify the apical injury at a molecular level. Type 2a Na-phosphate (Pi) co-transporter (NaPiT2a) is constitutively expressed by brush borders of proximal tubules under a healthy condition. Therefore, we investigated if NaPiT2a could be used as a negative marker to predict the renal dysfunction, using an animal model of septic ARF. After the treatment of lipopolysaccharide (LPS), mice manifested the tubular apical injury and renal dysfunction, as evidenced by the increase in blood urea nitrogen (BUN) levels. Immunohistochemical examination revealed that the expression of NaPiT2a by renal proximal tubules became faint, being reciprocal to the development of tubular hypoxia during sepsis. Inversely, the loss in apical NaPiT2a was restored in a regenerating stage, associated with the recovery from renal hypoxia. Overall, there was a negative correlation between the NaPiT2a expression and BUN levels or tubular injury scores in septic mice. Our data indicate that the loss of NaPiT2a is a reliable marker for predicting the progression of septic ARF, while local hypoxia might be involved in the decrease of NaPiT2a expression.

Targeting Endogenous Repair Pathways after AKI

“…The apical expression of NaPiT2a by the proximal tubule was decreased in kidneys from septic mice, and restored in a regenerating stage associated with the recovery from renal hypoxia. 16 Thus, the recovery of the urinary NaPiT2a levels, if detectable, would reflect the restoration of tubular brush border. Recently, proteomic analysis of urinary exosomes, which contain proteins from cellular membranes, as well as cytoplasmic and nuclear compartments provides biomarker candidates for the diagnosis of AKI.…”

Multi‐organ injuries caused by lipopolysaccharide‐induced periodontal inflammation in rats: role of melatonin

“…After treatment with LPS, mice manifested tubular apical injury and renal dysfunction, as evidenced by the increase in blood urea nitrogen (BUN) levels. However, there is still insufficient evidence to claim a causal association between oral infection and other systemic diseases .…”

Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth

“…The decreased expression of these genes may also play a role in the development of acute kidney injury (AKI). In a murine model of sepsis, down-regulation of sodium phosphate type 2a transporter in the proximal tubule correlated with evidence of AKI 77 . Severe preterm birth is commonly associated with AKI in preterm neonates 8 , and most preterm neonates are exposed to proximal tubule-specific nephrotoxins such as gentamicin 52 .…”