Alternative CKD Screening Methods Cheap, Clinically Useful

When typical measures of albuminuria aren’t available in screening for chronic kidney disease (CKD), a protein-creatinine ratio might work as well, researchers suggested.

In an individual participant-based meta-analysis of over 900,000 adults, urine protein-creatinine ratio (PCR) and dipstick protein were strongly correlated with the traditional measure of urine albumin-creatinine ratio (ACR), reported Keiichi Sumida, MD, MPH, PhD, of University of Tennessee Health Science Center in Memphis, and colleagues.

For PCR values between 50 mg/g to 500 mg/g, there was a 2.99-fold increase in predicted ACR for each doubling of PCR. And for PCR values over 500 mg/g, there was a 2.16-fold increase in ACR for each doubling of PCR, the group wrote in Annals of Internal Medicine.

However, PCR values below 50 mg/g were not consistently related with ACR values.

The relationship between PCR values and ACR values were similar in a model adjusted for sex, diabetes, and hypertension. In this adjusted model, a 2.96-fold increase in predicted ACR accompanied each doubling of PCR for values between 50 mg/g to 500 mg/g, and a 2.16-fold increase in predicted ACR came with each doubling of PCR in values over 500 mg/g.

In general, a PCR value of 150 mg/g corresponded to an ACR of 33 mg/g, while a PCR value of 500 mg/g equated to an ACR of 220 mg/g.

As for staging chronic kidney disease, PCR-predicted ACR categories appeared highly accurate. For CKD screening at an ACR threshold above 30 mg/g, and subsequent classification into stages A2 and A3, the PCR conversion equations had moderate sensitivity (A1, 91%; A2, 75%; A3, 87%) and specificity (A1, 87%; A2, 89%; A3, 98%).

Sumida’s group also assessed the clinical usefulness of using urine dipstick protein for CKD screening and grading if the preferred urine ACR method was not available. For this conversion, a “trace or greater” amount of urine dipstick protein equated an ACR of 25 mg/g, while “trace to +” and “++” equated roughly to stages A2 (ACR of 67 mg/g) and stages A3 (ACR of 337 mg/g), respectively.

However, this method wasn’t quite as accurate as the PCR-predicted ACR categories, with only moderate sensitivity (A1: 62%, A2: 36%, A3: 78%), albeit high specificity (A1: 88%, A2: 88%, A3: 98%).

As for CKD prognosis, estimated 2-year 4-variable kidney failure risk equation (KFRE) using PCR-predicted ACR categories had a sensitivity and specificity of 80.5% and 99.6%, respectfully.

“The urine dipstick test has been widely used as an initial screening tool for evaluating proteinuria primarily because of its low cost, simplicity, and ability to provide rapid point-of-care information to both clinicians and patients,” the researchers pointed out. “However, commonly used reagent strip devices for total protein measurement do not adjust for urinary concentration and provide only semiquantitative results.”

Accompanying editorial authors Tyrone Harrison, MD, and Brenda Hemmelgarn, MD, PhD, both of the University of Calgary in Canada, agreed with this sentiment, noting that these alternative methods of screening for CKD are “generalizable to many settings, which is clearly a strength.”

“Further, the authors had a thoughtful methodological design and examined the utility of predicted ACR in key kidney disease domains of screening, diagnosis, and prognosis,” they praised.

Although measurement of ACR is “the gold standard for clinical use,” Harrison and Hemmelgarn further highlighted the clinical usefulness of having alternative methods of screening in settings when ACR is simply not available — largely due to cost.

“As suggested by Sumida and colleagues, as well as the KDIGO guidelines, the reagent costs to measure protein are considerably less than those for measuring albumin; therefore, it is highly likely that in some health care systems, only PCR or urine dipstick measures are available,” the editorialists noted.

In these types of settings, they added, “use of conversion equations from the inexpensive and widely available PCR or dipstick gives patients and clinicians in economically disparate locations access to such tools as the KFRE.”

Last Updated July 13, 2020