Urine Periostin as a Biomarker of Renal Injury in Chronic Allograft Nephropathy

Background

Chronic allograft nephropathy (CAN) represents the main cause of renal allograft failure after transplantation. Noninvasive CAN testing is required. Periostin promotes the expression of a mesenchymal phenotype in renal tubules and is a promising urine biomarker for progressive renal injury. Information regarding periostin expression in the setting of CAN remains scarce.

Methods

Subjects were recruited from our outpatient transplantation clinic. Random urine samples were collected from CAN patients (n = 24) and renal transplant patients with normal renal function (transplant controls, n = 18). Control samples were collected from healthy volunteers (n = 18) who had normal renal function. Urine periostin was measured by enzyme-linked immunosorbent assay.

Results

The median urine periostin in CAN patients was significantly higher than in transplant and healthy controls (1.74 vs 0.00 vs 0.14 ng/mg creatinine, respectively; P < .001). Urine periostin enzyme-linked immunosorbent assay at a cutoff value of 0.152 ng/mg creatinine demonstrated the sensitivity, specificity, and accuracy for distinguishing CAN patients from transplant patients with normal renal function (91.7%, 77.8%, and 85.7%, respectively). In addition, urine periostin levels correlated directly with urine protein creatinine ratio (R = 0.566, P < .001) and serum creatinine (R = 0.522; P < .001), whereas inverse significant correlations were evidenced with estimated glomerular filtration rate (R = −0.431; P < .001).

Conclusion

The appearance of urine periostin in CAN patients but not in healthy and transplant controls underscores its value as a potential biomarker for chronic progressive renal injury in transplant recipients.     

A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell’s Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury

Acute kidney injury (AKI) following Eastern Russell’s viper (Daboia siamensis) envenoming is a significant symptom in systemically envenomed victims. A number of venom components have been identified as causing the nephrotoxicity which leads to AKI. However, the precise mechanism of nephrotoxicity caused by these toxins is still unclear. In the present study, we purified two proteins from D. siamensis venom, namely RvPLA₂ and RvMP. Protein identification using LCMS/MS confirmed the identity of RvPLA₂ to be snake venom phospholipase A₂ (SVPLA₂) from Thai D. siamensis venom, whereas RvMP exhibited the presence of a factor X activator with two subunits. In vitro and in vivo pharmacological studies demonstrated myotoxicity and histopathological changes of kidney, heart, and spleen. RvPLA₂ (3–10 µg/mL) caused inhibition of direct twitches of the chick biventer cervicis muscle preparation. After administration of RvPLA₂ or RvMP (300 µg/kg, i.p.) for 24 h, diffuse glomerular congestion and tubular injury with minor loss of brush border were detected in envenomed mice. RvPLA₂ and RvMP (300 µg/kg; i.p.) also induced congestion and tissue inflammation of heart muscle as well as diffuse congestion of mouse spleen. This study showed the significant roles of PLA₂ and SVMP in snake bite envenoming caused by Thai D. siamensis and their similarities with observed clinical manifestations in envenomed victims. This study also indicated that there is a need to reevaluate the current treatment strategies for Thai D. siamensis envenoming, given the potential for irreversible nephrotoxicity.