Pathological consequences of DNA damage in the kidney

The DNA damage response is essential to genomic stability. Here, the authors discuss DNA damage-induced nephrotoxicity and kidney cancer, and the essential role of DNA repair in kidney homeostasis, as well as its potential to contribute to kidney dysfunction, including the links between DNA damage, cell-cycle control and ciliopathies. DNA lesions that evade repair can lead to mutations that drive the development of cancer, and cellular responses to DNA damage can trigger senescence and cell death, which are associated with ageing. In the kidney, DNA damage has been implicated in both acute and chronic kidney injury, and in renal cell carcinoma. The susceptibility of the kidney to chemotherapeutic agents that damage DNA is well established, but an unexpected link between kidney ciliopathies and the DNA damage response has also been reported. In addition, human genetic deficiencies in DNA repair have highlighted DNA crosslinks, DNA breaks and transcription-blocking damage as lesions that are particularly toxic to the kidney. Genetic tools in mice, as well as advances in kidney organoid and single-cell RNA sequencing technologies, have provided important insights into how specific kidney cell types respond to DNA damage. The emerging view is that in the kidney, DNA damage affects the local microenvironment by triggering a damage response and cell proliferation to replenish injured cells, as well as inducing systemic responses aimed at reducing exposure to genotoxic stress. The pathological consequences of DNA damage are therefore key to the nephrotoxicity of DNA-damaging agents and the kidney phenotypes observed in human DNA repair-deficiency disorders.

Automated summary

The authors discuss the relationship between DNA damage and nephrotoxicity as well as kidney cancer. They highlight the essential role of DNA repair in kidney homeostasis and its potential implications in kidney dysfunction. The study also shows that DNA damage can lead to cell death and senescence, and it has been implicated in acute and chronic kidney injury as well as renal cell carcinoma. Understanding the pathological consequences of DNA damage is crucial for the development of effective therapeutic strategies.