High precision isotope-ratio mass spectrometry (IRMS) is another method for measuring kinetic fractionation of isotopes for natural abundance KIE measurements. Widlanski and coworkers demonstrated  KIE at natural abundance measurements for the hydrolysis of sulfate monoesters. Their observation of a large KIE suggests S-O bond cleavage is rate controlling and likely rules out an associate reaction mechanism.
The major limitation for determining KIE's at natural abundance using IRMS is the required site selective degradation without isotopic fractionation into an analyzable small molecule, a non-trivial task.