ORCHARD PARK, N.Y. — Through the first quarter and more on Sunday night, San Francisco 49ers running back Christian McCaffrey appeared poised for the breakthrough he has sought since returning from an Achilles tendon injury.

That momentum ended with 11:23 left in the second quarter against the Buffalo Bills when McCaffrey made a pitch to right and, as he planted his feet to turn up, instead chose to slide down without contact.

After the 5-yard loss, McCaffrey jumped up and quickly hobbled straight to the blue injury tent. After a few minutes, McCaffrey went to the locker room for further examination.

McCaffrey’s return was initially considered questionable due to a right knee injury, but he was forced out at halftime. The 49ers lost 35-10 as the Bills won the AFC East.

McCaffrey will undergo an MRI of his knee on Monday, ESPN’s Adam Schefter reported.

McCaffrey’s final injury apparently occurred about 95 seconds before the play on which he retired. With 12:58 left in the second quarter, McCaffrey stormed down the middle for an 18-yard gain.

But as McCaffrey tried to evade Buffalo’s last line of defense, Bills safety Taylor Rapp tripped on his right ankle, forcing McCaffrey to fall hard on his right knee.

McCaffrey checked out shortly after the play, but went back in a few plays later for a run to right that would ultimately end his night.

At the time of McCaffrey’s injury, he had seven carries for 53 yards and two receptions for 14 yards. This included season-best runs of 19 and 18 yards.

Sunday night was just McCaffrey’s fourth game since returning from bilateral Achilles tendonitis that kept him out for most of training camp and the first eight games in San Francisco.

McCaffrey had been slowly working his way back into form over the last three weeks and said this week that he felt a breakout game was near.

“I feel like I’m doing a lot better,” McCaffrey said Wednesday. “You often have to keep your expectations in mind, but for me at the moment, statistically speaking, it’s not about anything. I’m thrilled.

Niners defensive tackle Kevin Givens was also sidelined with a pectoral injury.