While CKD primarily causes damage to kidneys, it is also a major risk factor for accelerated cardiovascular disease and premature death. Progressive fibrosis, which is the scarring of the kidneys – is a common feature in all CKD, but the mechanism underlying this connection is not fully understood. Our team has identified a subset of epithelial cells, which make up the tubules of the kidney, produce Indian Hedgehog (IHH) and are only present within aged or injured mouse kidneys. We also found that these cells produced IHH in response to being activated by the protein TNF alpha – a well-recognised driver of inflammation. Using in vivo models of kidney scarring, our team found that scar production in the kidney was reduced and kidney function was also better preserved. Increased levels of scarring in the heart also returned to normal levels. Importantly, our team showed that circulating IHH levels were significantly raised in patients with CKD. Patients with cardiovascular disease also had higher levels of IHH than those without cardiac problems. Our findings offer hope that blocking the TNF/IHH signalling pathway could improve both kidney and heart fibrosis problems – the leading cause of morbidity and mortality in patients with CKD. The study was funded by Kidney Research UK, the Wellcome Trust and the Medical Research Council UK.