Chronic kidney disease (CKD) progresses slowly, but irreversibly, and current treatment options are limited when it comes to further slow down the disease. A need to target parenchymal cell loss, chronic inflammation, renal fibrosis, and reduced regenerative capacity in the kidneys is necessary to advance the treatment—and prevention of—CKD. New preclinical studies, however, have shown various promising approaches to reduce, and even stop, CKD progression.*

What is renal fibrosis?

Once the kidneys have sustained an injury, they have a limited ability to regenerate, which causes renal fibrosis. This is when kidney tissue can no longer heal itself. As renal fibrosis progresses, it ultimately leads to end-stage renal disease (ESRD).

Previous treatments, such as canagliflozin and atrasentan, have beneficial antifibrotic effects in various CKD models, but they are unable to completely stop or reverse the disease—hence the need to develop or discover new medication options.

New approaches for renal fibrosis

Several new methods that reduce renal fibrosis have shown promising results. They target cytokines, transcription factors, microRNAs, and other substances that alter the communication both inside and between kidney cells.

Cytokines 

Cytokines are small proteins or peptides that modulate the immune system and act similar to hormones. One example is a high level of pro-inflammatory cytokine IL-17A induces fibrosis, and IL-17A blockers have protective effects in experimental kidney injury models. 

Transcription factors 

Transcription factors (TFs) are proteins that regulate gene activity, including genes that control fibrosis development. TFs bind to DNA and switch on gene activity, which causes a specific type of protein formation.

Recent findings point to a specific TF, SOX9, to aid in kidney tissue regeneration through protein stimulation. Regenerated cells may replace damaged tissue. Increasing SOX9 production promotes tubular regeneration and decreases fibrosis in the kidneys. 

MicroRNAs 

MicroRNAs (miRNA) are small RNA molecules that also regulate gene activity—but later on in the process than TFs. One specific miRNA, miR-21, stimulates fibrosis, and researchers have seen it halt the progression of fibrotic processes in the kidneys. 

Anti-inflammatory substances

Anti-inflammatory substances possess a beneficial effect that can be used as CKD treatment. They prevent injury to kidney cells and reduce the number of active myofibroblasts, which are cells that produce an inflammatory response to injury. In kidney disease, myofibroblasts produce collagen, which is a protein that accumulates in renal fibrosis scarring.   

Results and conclusions

Due to the preclinical studies on these new potential treatments, a number of these options are now being tested in clinical trials. Researchers stated that the preclinical studies have further highlighted “the need for alternative approaches to CKD therapy, as strategies that target a single pathogenic process may result in unexpected negative effects on simultaneously occurring processes.”

Further reading can be done in the Clinical Medicine (London) journal article, “Drug Therapies to Delay the Progression of Chronic Kidney Disease.”

*Ruiz-Ortega, M.; Rayego-Mateos, S.; Lamas, S.; et al. (2020, Feb. 14). “Targeting the progression of chronic kidney disease.” Nature Reviews Nephrology.