J WANG1, Q CAO1, Y WANG1, N ROGERS1, B NANKIVELL2, N LALEE2, V JAMES1, T CHEN1, D HARRIS1, G ROBERTSON3, V LEE1
1Westmead Institute of Medical Research, Sydney, Australia, 2Westmead Hospital, Sydney, Australia, 3Lyramid Ltd., Sydney, Australia
Aim: To examine Midkine (MK) expression in association with renal injury and inflammatory features in human kidney disease biopsies.
Background: MK is a growth factor which has been implicated as a pathological factor in experimental kidney disease by mediating renal inflammation, however its expression, localisation and relevance in human kidney disease remains unclear.
Methods: MK protein expression was quantified by immunohistochemistry from kidney biopsies of 3 healthy donors, and 30 patients with various acute or chronic kidney diseases. MK expression was then correlated with histopathological features and leukocyte infiltration.
Results: MK expression was pronounced in the renal tubules of biopsies from healthy donors and patients with diagnosed kidney disease. In comparison to health donors, there were no significant differences in MK expression in the glomeruli of biopsies from patients with IgA nephropathy, lupus nephritis (LN), diabetic nephropathy (DN), focal segmental glomerulosclerosis (FSGS), interstitial nephritis (IN), deceased donor implantation, and acute tubular necrosis (all p > 0.999). MK expression was significantly increased in the tubulointerstitium of patients with DN (p = 0.013), but also quantitatively increased in that of biopsies from patients with LN (p = 0.257), FSGS (p = 0.303) and IN (p = 0.076) as compared to healthy donors. Higher MK expression in the tubulointerstitium was associated with greater tubular atrophy (p = 0.009) and interstitial fibrosis (p = 0.014), and also correlated positively with the number of infiltrating macrophages and T cells (p < 0.001) from biopsies of healthy donors and patients with diagnosed kidney disease.
Conclusions: These findings suggest that MK expression in the tubulointerstitium may be important to pro-inflammatory responses that mediate progressive kidney injury in human kidney disease.
I completed my Bachelor of Science degree with honours majoring in Biochemistry and Molecular and Cellular Biology at the University of Sydney, and the University of New South Wales. I am currently completing my PhD research degree in medicine, focusing on chronic kidney disease, with the University of Sydney. My primary background is biochemistry, molecular biology and immunology. To date I have publications in the field of nutrition, immunology, and clinical epidemiology.