Can painkillers affect the kidneys? It depends on the type of painkillers. Doctor-prescribed painkillers are safe but if you take over-the-counter medications, it can affect the kidneys. Symptoms of kidney problems caused by painkillers • Inflammation of the feet • Weight gain • Stomach problems • Loss of appetite Watch Dr. R. Kishor Kumar of Kauvery Hospital, one of the best Nephrologists in Salem talk about whether painkillers help relieve pain or harm your kidneys.