Catching CKD sooner with kidney profile

As for urine albumin, “It’s not well standardized,” Dr. Miller says. NKDEP’s Laboratory Working Group has been working on this issue since 2010, he says, and it’s closing in on having reference materials and methods available from NIST and two other U.S. sites. “We’re relatively close to having the standardization tools available to the IVD industry. We’re at the final stages of validating the reference measurement procedures.” NIST plans to release the primary reference material later this year, he says. “So it’s coming together.”

Standardization is critical. Depending on what method is used, an at-risk patient might face a delay in being identified as having CKD. “The ability to discriminate around the nominal cutpoint, which is 30 milligrams of albumin per gram of creatinine, is affected by the bias among different procedures,” Dr. Miller says.

Dr. Vassalotti says he’s “thrilled” with the efforts of Dr. Miller and others in the Laboratory Working Group. Sooner rather than later, he hopes, urine albumin and urine creatinine will be standardized in a process analogous to what happened with serum creatinine years ago.

But even a standardized test becomes that proverbial tree in the forest if it’s not ordered. “To start with,” says Dr. Vassalotti, “some labs don’t even offer the urine albumin-to-creatinine ratio, believe it or not.” Instead, they offer total protein-to-creatinine ratio. “So of course the lab can do something there.” Other labs report only the urine concentration of albumin, not the ratio. Not only is the ratio recommended by groups such as the ADA, NKF, and KDIGO, but it also has a much narrower within-individual biological CV, he says, compared with the CV for albumin alone or creatinine alone. It adjusts for differences in hydrational level of the patient, he notes, and it correlates very well with (and is less cumbersome than) the 24-hour urine. Nor “is it subject to the overcollection and undercollection of the 24-hour urine that we see in practice.”

When these experts refer to the ratio, they do mean ratio. Reporting the urine albumin and the urine concentration as separate results, without calculating the ratio, is basically handing clinicians a suitcase, cart, and a bungee cord.

“Labs will often tell me things like, ‘Of course it’s simple to figure out—it’s just division,’” Dr. Vassalotti says. No doubt. But to busy clinicians, another step—no matter how simple—can become a barrier. “We want to report the complete result uniformly to make it easier,” Dr. Vassalotti says.

Based on his own experiences, Dr. Vassalotti offers another suggestion: that labs exercise caution about how they report eGFR results in the 60–90 range. It’s not unusual for a patient with an eGFR of, say, 72, to be classified as having CKD stage G2 based on that result alone. “Those patients don’t have kidney disease unless they have a marker of kidney damage,” such as albuminuria or an abnormal kidney biopsy.

“I’ve reviewed papers in the peer-reviewed literature that make this error,” reports Dr. Vassalotti, “and I also have been asked this question a lot and see patients” in similar situations. “They may just have a level of kidney function in that range, but may not have evidence of kidney disease.”

It’s also time to banish microalbumin, a test name that can trip up physicians trying to order urine albumin. Says Dr. Vassalotti: “I get calls from people: Where is the test? I can’t find it. They look under U for urine, they look under A for albumin. They can’t find it because it’s under microalbumin. It sounds silly, but for busy clinicians efficiency is paramount.”

The name itself is confusing. Some might think, incorrectly, that microalbumin has something to do with the size of albumin, or that it refers to a specific range (because 30–300 mg/g is sometimes called microalbuminuria). Dr. Vassalotti suggests using an alias to ensure having a legacy of the previous tests—something welcomed by many physicians.

The initial impulse for the term may have been good, Dr. Fleming says, when labs struggled to measure urine albumin. Laboratorians invented the term to account for the enhanced sensitivity needed to analyze the smaller amount of albumin found in urine versus blood. “It’s not that there’s a tiny little urine albumin molecule,” he says with a laugh. But with more sophisticated methods now in use, “We don’t need to make that designation anymore.”

The urine test is more fraught than eGFR, in part because it answers to many names. Some hospitals call it urine albumin. In some institutions physicians can simply order a urine albumin-creatinine ratio; at others, they have to order urine albumin separately from the urine creatinine. “And then there’s confusion because some people will order a urine protein instead of a urine albumin,” Dr. Vassalotti says.

As noted, there’s very little new in any of this. Much has already been published in guidelines from KDIGO and KDOQI, dating back as early as 2013.

Dr. Rocco walks back the history even further. When KDIGO refined a set of guidelines developed in 2002 by the National Kidney Foundation for the management of CKD, it built on the idea of dividing kidney disease into stages and called for assessing not only the presence of proteinuria but also its severity.

“So with today’s focus on prevention, we want to identify patients both from an eGFR standpoint as well as a urine protein standpoint, because that tells us how aggressive to be in managing these patients,” Dr. Rocco says.

It’s not that primary care providers aren’t aware of the guidelines, Dr. Rocco says. In fact, they’re probably aware of too many guidelines, from endocrinology and rheumatology to infectious disease and cardiology. “If you’re a primary care physician, you’re being bombarded.”

Most physicians know to order creatinine in patients with diabetes or hypertension, Dr. Rocco says, given that it’s part of a routinely ordered metabolic profile. “You would think it would be common sense,” he says.

Part of the problem, he adds, is that non-nephrologists aren’t always aware of when to screen or refer. Numerous studies show that patients who are referred late to a nephrologist progress faster to end-stage renal disease and tend to have worse outcome once they begin dialysis, Dr. Rocco says. There is also a fair percentage of patients who are so-called gatecrashers, who see a nephrologist only when they are at end stage.

Change, like voting habits, waxes and wanes and often requires fresh steps to revitalize—think registering voters at the DMV. Even leaders like Dr. Vassalotti struggle. At large academic systems, “we’ve had less success” trying to implement the kidney profile.

The first step might be to line up the leadership in each area, says Dr. Vassalotti—laboratory, administrative, nephrology, and primary care leadership. All need to see that kidney disease is a problem, and helping them see that could help bring about change.

It’s partly an institutional issue, Dr. Rocco agrees, citing a need for clinical pathologists to talk to hospital administrators about the need to add the kidney profile to testing menus. Beyond that, clinical pathologists and nephrologists need to educate primary care providers—physicians, physician assistants, and nurse practitioners—about the value of the profile versus a creatinine level.

Dr. Fleming says it’s the laboratory’s responsibility to educate physician colleagues about the CKD-CVD-diabetes triad. “I have no qualms about making that statement,” he says. “It is pathologists and the laboratory who must herald that trumpet.” Currently, he says, many primary care practitioners think CKD is the province of nephrologists, “that when your patient has almost no filtration left they’re referred, when in fact they should be referred much earlier. You need to drive home the message that while kidney disease may not be preventable, you can certainly slow its progress.”

The typical primary care provider is inundated with patients, Dr. Miller says, but if they know what tests to order, they’ll order them. Providing that education about the kidney profile “is where we as laboratorians, as well as our physician colleagues, need to put more energy.” He also suggests that the CAP could provide materials to help pathologists engage with colleagues on the topic—“How to go forth and do good,” as he puts it. “I’d appreciate concrete guidance,” he adds, conceding that while he talks regularly with nephrologists at Virginia Commonwealth about testing, he has fewer conversations with GPs and others.

“You don’t need to convince nephrologists,” Dr. Miller continues. But “Laboratory directors need to reach out to their primary care physician colleagues and recommend that we introduce the kidney profile,” he says. The basic message is not that complicated: “If a patient is suspected of having diabetes, or has been diagnosed with diabetes, order a kidney profile. If a patient has hypertension, order a kidney profile. If a patient has a family history of kidney disease, order a kidney profile.”

Dr. Vassalotti would like to see labs consider linking results to educational materials from groups such as the NKF, either on the clinical or patient awareness side.

The CDC reports that chronic kidney disease affects 15 percent of American adults. But, Dr. Vassalotti rues, that has not been a call to action in and of itself. “One of the most important things I’ve learned in the last two decades is that population health for kidney disease works best if the intervention is integrated into an existing but related chronic disease program. If you start talking kidney, people fall asleep. Their eyes glaze over. You have to talk about population health for diabetes and how kidney disease fits into that. Or population health for hypertension, and how kidney disease fits into that, or cardiovascular disease, or obesity.”

Dr. Rocco reports good news on one front: The FDA has acknowledged (Levey AS, et al. Am J Kidney Dis, article in press) that change in urinary excretion of albumin could be used as a marker of risk for progression of kidney disease in clinical trials. “For the FDA to say urine albumin is important, that’s really a big deal.”

LabCorp has been offering a combination of eGFR and uACR for well over a decade, Dr. Fleming says. “And for every creatinine result in any panel, we automatically attach calculation for the eGFR. It’s very easy to do.”

LabCorp has also dropped the term “microalbumin” and replaced it with “urinary albumin,” having taken the initial steps to notify clients more than a year ago. “We thought that was going to raise some eyebrows, that we’d get pushback from clients who’ve been so used to the term over many, many years. But I don’t think we’ve received one call.”

Dr. Miller suspects that one stumbling block may be the current lack of a CPT code for the kidney profile.

“But that shouldn’t be a barrier,” he continues. “We can offer order sets that include reimbursable tests. We just have to bill for each individual test. So I don’t personally see this as that big of a hurdle.”

Dr. Fleming agrees. The eGFR, a calculation, is not currently reimbursed. And while LabCorp is trying to address that, through its corporate coding group, “We do get paid for the tests that are performed.”

Few observers seem confident that CPT reimbursement will be forthcoming anytime soon, if at all. Perhaps it doesn’t matter. “The calculation does not have a lot of cost associated with it, but it has tremendous value in terms of patient care,” says Dr. Fleming. “We will always provide a test that has medical benefit to the patient. I think any laboratory would do that—we always attempt to improve the clinical outcome for the patient. These calculations are necessary for appropriate patient care.”

Karen Titus is CAP TODAY contributing editor and co-managing editor.