El cáncer de riñón en etapas iniciales no suele causar ningún signo o síntoma debido a varias razones: estos tumores pueden aumentar de tamaño sin causar ningún síntoma; los tumores pequeños del riñón no se pueden ver o palpar durante un examen físico y no existen pruebas de detección precoz del cáncer de riñón. Los tumores de mayor tamaño pueden resultar sintomáticos produciendo: sangre en la orina (hematuria), dolor lumbar (dolor en el costado de la espalda), masa o abultamiento en el costado, cansancio, pérdida de peso inexplicable por otros motivos, fiebre de varias semanas de duración no causada por alguna infección o inflamación de los tobillos y piernas.

El diagnóstico de este tipo de tumor se puede realizar mediante ecografía urológica que es indolora y no genera radiaciones. Esta prueba ayuda a diferenciar entre una masa renal sólida o quística (benigna). Otra prueba relevante es la tomografía computarizada (TAC) o scanner que se realiza con contraste. La tomografía puede proporcionar información precisa sobre el tamaño, la forma y la posición de un tumor. Hace años se utilizaba mucho la Urografía intravenosa que consistía en una serie de radiografías del sistema urinario, tomada después de inyectar un contraste en una vena. Este contraste se eliminaba por los riñones, pasando posteriormente a los uréteres y a la vejiga. Ahora ha caído en desuso en favor del TAC. No se suelen utilizar pruebas de laboratorio para diagnosticar el cáncer de riñón.

Por último, se puede valorar en algunos casos, realizar una biopsia de la masa sospechosa. Esta prueba se realiza  si las imágenes radiológicas no son suficientemente concluyentes para justificar la extirpación de un riñón aunque por lo general, no se suelen realizar biopsias renales. Este tipo de biopsias se hace de forma percutánea utilizando una aguja a través de la piel para tomar una muestra del riñón.

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