The succinate receptor GPR91 is a known regulator of a number of adaptive processes in response to a (locally) altered metabolic state. These include regulation of profibrotic factors, neovascularization, cell survival and cellular function. GPR91 is expressed in several tissues, including kidney, heart, liver, retina and blood cells. In kidney, it likely acts as an important direct and indirect regulator of the renin-angiotensin system, blood pressure, renal sodium transport and fibrosis. We set out to determine succinate release in response to oxidative stress in vivo and in vitro, and the effects of SUCNR1 on renal sodium handling and blood pressure. To gain insight in the effects of succinate on the kidney, succinate was administred to mice via injection of minipumps. Blood pressure was measured, and urine and blood collected for measurement of succinate levels, somolality and electrolytes. In addition, expression levels of major renal sodium transporters were determined. Since oxidative stress is known to trigger succinate release, we tested wheter plasma and succinate levels were increased in mice subjected to renal ischemia/reperfusion. Succinate adminstration for three days did not affect blood pressure. Interestingly, urinary and plasma levels decreased when high concentrations of succinate were given, suggesting that succinate is rapidly cleared from the circulation. Succinate administration affected major apical sodium transporters in the distal nephron, including the sodium-chloride cotransporter NCC and the epithelial sodium channel ENaC. Moreover, we found that renal ischemia caused increased plasma and urine succinate levels. Succinate represents a novel mediator in the body's sodium and water balance in renal ischemia/reperfusion.