Journal Article

Kidney tubule iron loading in experimental focal segmental glomerulosclerosis

Smeets, Bart, Wiegerinck, Erwin T. G., van der Vlag, Johan, Dijkman, Henry, Roelofs, Rian, Wetzels, Jack F. M., Beurskens, Sanne, Thévenod, Frank, Swinkels, Dorine W., van Swelm, Rachel P. L.

2022

Overview

Kidney iron deposition may play a role in the progression of tubulointerstitial injury during chronic kidney disease. Here, we studied the molecular mechanisms of kidney iron loading in experimental focal segmental glomerulosclerosis (FSGS) and investigated the effect of iron-reducing interventions on disease progression. Thy-1.1 mice were injected with anti-Thy-1.1 monoclonal antibody (mAb) to induce proteinuria. Urine, blood and tissue were collected at day (D)1, D5, D8, D15 and D22 after mAb injection. Thy-1.1 mice were subjected to captopril (CA), iron-deficient (ID) diet or iron chelation (deferoxamine; DFO). MAb injection resulted in significant albuminuria at all time points (p < 0.01). Kidney iron loading, predominantly in distal tubules, increased in time, along with urinary kidney injury molecule-1 and 24p3 concentration, as well as kidney mRNA expression of Interleukin-6 ( Il-6) and Heme oxygenase-1 ( Ho-1) . Treatment with CA, ID diet or DFO significantly reduced kidney iron deposition at D8 and D22 (p < 0.001) and fibrosis at D22 (p < 0.05), but not kidney Il-6 . ID treatment increased kidney Ho-1 (p < 0.001). In conclusion, kidney iron accumulation coincides with progression of tubulointerstitial injury in this model of FSGS. Reduction of iron loading halts disease progression. However, targeted approaches to prevent excessive kidney iron loading are warranted to maintain the delicate systemic and cellular iron balance.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 692/4022 / 692/4022/1585 / 692/699/1585/104 / Angiotensin-Converting Enzyme Inhibitors - therapeutic use / Animals / Blood pressure / Captopril - therapeutic use / Chelation / Chelation therapy / Cytokines / Deferoxamine / Deferoxamine - therapeutic use / Diabetes / Diet / Disease Models, Animal / Distal tubules / Female / Fibrosis / Gene expression / Glomerulosclerosis, Focal Segmental - diet therapy / Glomerulosclerosis, Focal Segmental - drug therapy / Glomerulosclerosis, Focal Segmental - metabolism / Heme / Heme oxygenase (decyclizing) / Humanities and Social Sciences / Injection / Interleukin 6 / Iron / Iron - metabolism / Iron deficiency / Kidney diseases / Kidney Tubules, Distal - metabolism / Kidneys / Laboratories / Life sciences / Male / Mice / Molecular modelling / Monoclonal antibodies / multidisciplinary / Nephrology / Nutrient deficiency / Oxidative stress / Oxygenase / Proteins / Proteinuria / Receptors, Cell Surface - metabolism / Science / Science (multidisciplinary) / Siderophores - therapeutic use / Urine