Existing measurements don’t adequately and precisely predict
disease progression.

Albuminuria (UACR) and eGFR measurements are commonly used by doctors to diagnose kidney disease. Although these measurements are part of the standard of care for diagnosis, there are limitations in their use in disease prognosis.

REASON 1

There are issues with albuminuria.

  • Biological variability
    • The measurement of albuminuria can be imprecise due to normal biological variability. For example, studies indicate that two UACR values in the same patient – just a few weeks apart – vary significantly, such that an increase by 124% or a decrease by 55% from the prior reading can be within the normal range of variability without indicating true clinically significant changes.
  • Assay variability
    • The assays for albuminuria are not standardized nationally. Therefore, there can be differences based on the testing platform and clinical lab.
  • Regression of albuminuria over time
    • Some patients will experience spontaneous regression of albuminuria.
  • Progression without albuminuria
    • Data indicates that 20-30% of patients with DKD, who experience progression, never develop albuminuria.

Waikar SS, et al. Am J Kidney Dis. 2018. 72(4): 538-546. doi: 10.1053/j.ajkd.2018.04.023.

REASON 2

There are issues with eGFR.

  • eGFR is an “estimate.”
    • Therefore, it may be discordant with true “measured” GFR (mGFR; usually done only in research settings) by > 30% in a significant fraction of patients.
    • Data indicates that 33-50% of patients have different CKD stages based on eGFR vs. mGFR.*
  • Regression/improvement of eGFR spontaneously
    • Data from large database studies indicate that a sizable fraction of patients (roughly equal to the proportion that experience progression) with CKD experience improvement in kidney function over time. While this is contrary to the typical notion that once CKD is present it does not improve, these data points highlight the actual noise and issues with using eGFR as a part of a prediction tool for progression.

Liu P, et al. JAMA Netw Open. 2021;4(6):e2112828. doi:10.1001/jamanetworkopen.2021.12828

Waikar SS, et al. Am J Kidney Dis. 2018. 72(4): 538-546. doi: 10.1053/j.ajkd.2018.04.023.

*mGFR is a measurement of how well your kidneys are filtering certain agents not produced by your body, such as: inulin (a kind of fiber that is found in some plant foods) and iohexol (contrast agent used in imaging tests). Getting an accurate GFR level is challenging because measured GFR (mGFR) is a complicated and lengthy process. This makes it impractical for both clinicians and patients. It is for this reason that healthcare professionals use a formula to estimate GFR. Source: kidney.org/atoz/content/gfr. Accessed 03.2024.

REASON 3

And then, there’s hyperfiltration.

  • Despite significant damage to some of the kidney’s tissue, the remaining nephrons initially try to compensate via hyperfiltration, trying to preserve kidney function.
  • Hyperfiltration can cause eGFR to appear better than would be expected given underlying kidney damage, thus masking the severity of kidney disease to clinicians and patients.
  • Hyperfiltration in the remaining functional nephrons plays a critical role in chronic kidney disease in diabetes as it puts stress on the filtration barrier and post-filtration mechanisms, which ultimately results in progression.

What does all this mean?

Clinicians should continue to use current measurements to diagnose chronic kidney disease and add the kidneyintelX.dkd™ test for adult patients with type 2 diabetes and with chronic kidney disease stages 1-3b to determine who is at low, moderate, or high risk for progressive decline in kidney function.