Suffolk Reporter

Stony Brook Medicine researchers have unveiled a potential new treatment strategy for diabetic kidney disease (DKD), the leading cause of chronic kidney disease globally. Their study, published in Nature Communications, focuses on cellular signaling between kidney cells and gene induction to prevent or slow DKD progression.

Dr. Sandeep K. Mallipattu and Dr. Nehaben A. Gujarati led the research at Stony Brook University's Division of Nephrology and Hypertension. They utilized a murine model to explore this innovative therapeutic approach against DKD, which affects over 35 million adults in the United States according to the National Kidney Foundation.

The team employed a multi-omics approach to show that inducing the human KLF6 transcription factor can target cell signaling between podocyte and proximal tubule cells, crucial for kidney function. This intervention aims to reduce podocyte loss, proximal tubule dysfunction, and interstitial fibrosis associated with later stages of DKD.

Podocytes are essential for glomerular function, filtering waste from blood to form urine, while proximal tubule cells reabsorb water and maintain electrolyte balance. Both cell types are vital in preventing DKD progression.

In their DKD model, Drs. Mallipattu and Gujarati demonstrated that KLF6 triggers Apolipoprotein J (ApoJ) secretion from podocytes, priming proximal tubule cells through calcium/calmodulin-dependent protein kinase 1D (CaMK1D). This process prevents mitochondrial injury and halts DKD development.

“This cell-to-cell communication through this signaling mechanism in the kidney might serve as a protective mechanism in the early stages of DKD,” stated Dr. Mallipattu.

The study involved murine models, human cells, and tissue from patients with varying stages of DKD. Drs. Mallipattu highlighted that enhancing Apolipoprotein J-CaMK1D could be a viable therapeutic strategy for slowing or preventing DKD.

Further research will investigate pharmacological methods to activate this pathway in hopes of preventing diabetes-related DKD development. The study received funding from the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases and Dialysis Clinic Inc.