BDNF: mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function

Abstract

Podocyte loss and changes to the complex morphology are major causes of chronic kidney disease (CKD). As the incidence is continuously increasing over the last decades without sufficient treatment, it is important to find predicting biomarkers. Therefore, we measured urinary mRNA levels of podocyte genes NPHS1, NPHS2, PODXL and BDNF, KIM‐1, CTSL by qRT‐PCR of 120 CKD patients. We showed a strong correlation between BDNF and the kidney injury marker KIM‐1, which were also correlated with NPHS1, suggesting podocytes as a contributing source. In human biopsies, BDNF was localized in the cell body and major processes of podocytes. In glomeruli of diabetic nephropathy patients, we found a strong BDNF signal in the remaining podocytes. An inhibition of the BDNF receptor TrkB resulted in enhanced podocyte dedifferentiation. The knockdown of the orthologue resulted in pericardial oedema formation and lowered viability of zebrafish larvae. We found an enlarged Bowman's space, dilated glomerular capillaries, podocyte loss and an impaired glomerular filtration. We demonstrated that BDNF is essential for glomerular development, morphology and function and the expression of BDNF and KIM‐1 is highly correlated in urine cells of CKD patients. Therefore, BDNF mRNA in urine cells could serve as a potential CKD biomarker.

The Neglectable Impact of Delayed Graft Function on Long-term Graft Survival in Kidneys Donated After Circulatory Death Associates With Superior Organ Resilience

“…Strong associations exist between BDNF and the kidney injury molecule (KIM-1), and BDNF has been recently proposed as a biomarker for glomerular injury. 37 As such, the relative downregulation of BDNF in DCD grafts might indicate that the glomerular injury is less in DCD than in DBD grafts.…”

Angiotensin II disrupts the cytoskeletal architecture of human urine-derived podocytes and results in activation of the renin-angiotensin system

“…Unique genes from our data that are associated with the filtration barrier or cytoskeleton of podocytes include the genes CX3CL1 [37], DNM3 [38], DPP4 [39] and NRX1 [40]. Unique genes from our data that are associated with podocyte function or survival include BDNF [41], CXCL16 , [42] GRIA3 [43], PDGF-C [44], RAB3A [45] and VEGF-C [46]. Members of Semaphorin gene family SEMA3A and SEMA3C were also significantly upregulated.…”

Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis

“…Moreover, a recent study demonstrated that BDNF is required for glomerular development, morphology, and function, and the expression of BDNF and KIM-1 is highly correlated in urine cells of CKD patients. Therefore, BDNF mRNA in urine cells could serve as a potential prognostic biomarker for CKD [ 203 ]. Some studies demonstrated that H 2 S reversed the decrease in TrKB receptors against chronic unpredictable mild stress (CUMS)-induced hippocampal oxidative stress, demonstrating the critical role of neurotrophic signaling in the antidepressant effects mediated by H 2 S [ 204 ].…”