Allison Inserro

Most patients with chronic kidney disease (CKD), in the early stages at least, typically start out under the care of a primary care provider, who may have limited time and may not be up to date on the latest guidelines, particularly on newer FDA-approved therapies.

An abstract and a session at Kidney Week discussed the idea of using the population health framework as being laser-focused on a certain set of patients with chronic disease, in this case, CKD.

Khaled Abdel-Kader MD, MS, a nephrologist and assistant professor of medicine at Vanderbilt University, reviewed 

, an ongoing study funded by the National Institutes of Health that seeks to use an electronic health record (EHR)–based population health management (PHM) approach to improve CKD care.

He and Manisha Jhamb, MD, MPH, at the University of Pittsburgh, are leading the study, along with pharmacists, a nurse, and a chief medical informatics specialist.

The hypothesis of the pragmatic, randomized controlled trial is to see if an EHR-based PHM will improve hypertension control, use of renin-angiotensin-aldosterone system (RAAS) 

, and avoidance of renally contraindicated medications and delay CKD progression

The 42-month study is cluster randomized at the practice level and stratified by the number of high-risk CKD patients per practice; it ultimately seeks to enroll 1650 patients.

Thus far, there are 365 PCPs enrolled, about 65 of those are advanced practice providers.

Eligible patients are those aged 18 to 85 years who are not being followed by a nephrologist, with at least 2 visits to their PCP in the past 24 months and an estimated glomerular filtration rate (eGFR) ratio below 60 ml/min/1.73

The patients are considered “high-risk CKD” if 1 of 3 criteria are met:

5-year risk of end-stage renal disease defined by a validated kidney failure risk equation of 4% or greater

Flagged using an internally validated machine learning model that takes into account healthcare utilization, longitudinal change in serum creatine, and medication use.

Patients in the intervention arm receive a nephrologist-led electronic consult and pharmacist-led telephonic medication therapy management (MTM). The consult is done via the EHR for the PCP to review and order at the upcoming office visit. Medication recommendations included use of RAAS inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and statins.

In the first set of data from the study, collected from July 1, 2019, to January 31, 2020, 125 patients received an e-consult and 121 patients received MTM.

A total of 83 recommendations were provided to PCPs in the EHR, but their uptake varied.

For initiation or dose escalation of RAAS inhibitors, 41% (19 of 46) were ordered. 

Two of 8 recommendations regarding GLP-1 receptor agonists were implemented (25%) and 2 of 24 recommendations for SGLT2 inhibitor initiation were implemented (8%).

Although 5 recommendations were made for statins, none were implemented, but baseline statin use was already higher than 75%.

Additional strategies are needed to improve the use of evidence-based recommendations, the study says.

Weltman MR, Chen H, Yabes J, et al Uptake of evidence-based recommendations to improve care for CKD patients in the kidney coordinated health management partnership (Kidney CHAMP) study. Presented at American Society of Nephrology Kidney Week. Abstract PO0579.

Articles

Can a population health framework focused on a certain set of patients with chronic disease (ie, chronic kidney disease [CKD]) improve care in the primary care setting?

Can EHR Tools Induce Improved Care of Patients With CKD?

Could dialysis centers become sites for patients with kidney disease to become clinical trial participants?

During the American Society of Nephrology’s (ASN) 

, a panel discussed that and other ideas about how the nephrology community is coping during the ongoing coronavirus disease 2019 (COVID-19) pandemic and how they are sharing knowledge to help patients.

“Hopefully everyone is aware that COVID-19 has had an enormous impact on the kidney community, on patients and their families, as well as providers,” said moderator Raymond Harris, MD, FASN, co-chair of the Kidney Health Initiative (KHI) and a professor of medicine at Vanderbilt University.

Founded in 2012, KHI is a public-private partnership between the ASN, FDA, and over 100 companies, developers, and organizations in renal disease. Most of the panel speakers were also KHI members:

Paul Conway, chair of policy and global affairs and immediate past president of the American Association of Kidney Patients

T. Alp Ikizler, MD, FASN, chief of nephrology at Vanderbilt University

Patrick Nachman, MD, FASN, chief of neurology at the University of Minnesota

Uptal Patel, MD, a research scientist at Gilead Sciences

Amy Young, vice president at DaVita Clinical Research

Harris started out by noting that acute kidney injury (AKI) occurs in up to 5% of all hospitalized patients with COVID-19; many of whom will need dialysis. The incidence soars to between 50% and 90% for patients in intensive care units. Those with kidney diseases show anywhere between a 2- to 16-fold increased risk for developing severe symptoms if they developed COVID-19, studies indicate.

Both KHI and the ASN COVID-19 Response Task Force worked as the pandemic started to emerge to release information and guidelines about the impact on those with kidney diseases, based on what was first seen in Italy and Spain. The first person to die in the United States was someone in a long-term care facility on dialysis, noted Ikizler.

Then, in a similar manner, as nephrologists in Minnestota saw what was happening in New York and New Jersey in March, the practices started banding together to make plans for a surge in the Midwest, including sharing equipment as well as providers, said Nachman.

“It was a grassroots phenomenon that was very unique,” he said.

The urgency of the pandemic and the need to care for people still needing dialysis treatments 3 times a week created collaborations that did not exist before, noted Young. In addition, she said “clinical trials are having their moment in the sun, and hopefully in kidney care that will sort of continue to happen. I think it's highlighted a gap in the kidney community, in terms of really understanding how to think about clinical trials in ways that are outside of the typical way that we engage with patient populations and with physicians.”

As examples, Young said DaVita conducted an awareness campaign for nephrologists to tell them that renal disease was not an exclusion for some vaccine clinical trials, sent physician letters, and reached out to patients through letters, social media, and other channels.

Roy asked Patel, "What do you think may be some opportunities for more innovative trial design that we may be able to see in the future so that nephrologists can really participate in a seamless way, as Amy was talking about?”

Historically, over 80% of cancer trials and over 50% of cardiovascular trials exclude patients with kidney diseases, Patel noted. The most common reason for that is concern about possible nephrotoxicity or adverse events, or because the patients with these underlying diseases have had a greater number of adverse events. Sometimes patients with mild or moderate kidney diseases are excluded from trials without a pharmacologic basis.

As a result, this patient population is not used to being asked to participate, he said.

On the other hand, Conway, who was on dialysis for years himself before receiving a transplant, also reminded the panel that patient participation in trials has a long, at times unsavory, history, starting with the infamous Tuskegee syphilis trials of Black men in the 1930s.

Another barrier, he said, is one of “nomenclature, which is, what is it exactly that's being asked of me? And what exactly is the risk to me and to my family, in talking in plain language?”

Peer-to-peer communication works best, and physician-patient conversation has to flow both ways, he said.

With the impact of coronavirus disease 2019 (COVID-19) evident in patients with renal disease, a discussion at Kidney Week focused on ways to engage them in clinical trials.



Exploring What’s Possible With COVID-19 Trials and Kidney Disease

In August, the American Society of Nephrology (ASN) and the National Kidney Foundation (NKF) created a joint 

 to reevaluate the long-standing use of including race in a calculation to diagnose kidney disease. The inclusion of race can affect care decisions, according to proponents of making a change.

One of those advocates, Nwamaka D. Eneanya, MD, MPH, a nephrologist and assistant professor of medicine at the Hospital of the University of Pennsylvania, walked attendees at an ASN Kidney Week session this weekend through the history, hazards, and pitfalls of using estimated glomerular filtration rate (eGFR) equations, which use a multiplier to assign higher values to Black patients.

As higher values indicate better kidney function, there has been increasing recognition that this may lead to inequitable and delayed care.

Eneanya, one of the members of the task force, also discussed how she uses alternative diagnostic approaches with her patients, ones that meet the standards of transparency and shared decision making.

Her talk, part of a wider session on race and ethnicity in chronic kidney disease (CKD), comes as more institutions have moved to stop relying on the eGFR, such as the 

, Beth Israel Deaconess Medical Center, and Mass General Brigham.

GFR is the total volume of filtrate passing through the glomeruli each minute, but that is challenging to assess in real-time in a physician’s office. Using serum creatine, factoring in age, height, weight, and gender, gives an estimate.

 that proposed the eGFR and included a coefficient for Black patients did so on the basis of 3 flawed, small, poor quality studies, Eneanya said, and these faulty assumptions were carried forward through later iterations. The study said that “previous studies have shown that on average, black persons have greater muscle mass than white persons” but that assertion relied on 3 small studies published in between the 1970s and 1990s.

One looked at the body composition of roughly 240 Black and White children and said that Black children had lower body fat and different body densities; the second looked at about 40 adults and said Blacks had higher total body potassium and calcium compared with Whites; and the third, looking at 60 healthy hospital workers, said that Blacks had higher on average serum creatinine kinase levels.

However, muscle mass on a living human cannot be measured, only on a cadaver, Eneanya noted; moreover, based on human genome studies, we know that there are no biological differences between races.

Sociodemographic differences in clinical trial participation, rather than race, are a more likely factor in variation, and those factors could affect creatine levels, she said. Possible explanations for differences in serum creatinine include muscle mass, excretion, ancestral, enzymatic, and transport processes, as well as diet, especially ones that include meat. Medications can also be a factor.

Although there are several criteria for recommending when a patient should be referred to nephrology specialty care, “most clinicians take the path of least resistance and they will use what is available to them and the easiest thing is an eGFR, even though the KDIGO [

Kidney Disease: Improving Global Outcomes] 

But if the multiplication factor assigns black patients as having higher kidney function, then there will be delays in referral to nephrology specialty care, as well as kidney transplantation evaluation. The dosing of drug treatments can also be affected.

Given that implicit and explicit bias factors into provider communications and decisions, this could come into play as more Americans identify as mixed race and lead to less transparency in those recommendations, she cautioned.

There is no guidance for mixed race in the eGFR and there was a roughly 30% increase of individuals identifying as mixed race in the US Census between 2000 and 2010, and that number will keep increasing, Eneanya noted. 

She cited a recent study that found that removing race as a factor in recommending care resulted one-third of Black patients reclassified to a more severe stage of CKD; this has implications for CKD management, referrals for kidney transplant specialty care, and dialysis access planning.

“And that speaks to, or supports the literature, that Black patients on average progress more quickly due to social and genetic reasons to kidney failure compared to other racial groups,” she said.

She did note the counterargument that removing the race qualifier could lead to an overdiagnosis of CKD, or to a patient receiving unnecessary dialysis or transplantation or lower doses of drug therapy.

But using race in eGFR equations fails 4 criteria she and others developed about when to justify using race in clinical care:

The use of race provides a substantial benefit

The benefit cannot be achieved through other feasible methods

That patients who reject race categorization can be accommodated fairly

Physicians should look more at these “non-GFR” determinants of serum creatinine (generation, tubular handling, extrarenal elimination, muscle mass), she said.

She also called for alternative eGFR equations or other measures of kidney function without including race, such as cystatin C and cystatin C-Cr.

“False biological beliefs will absolutely affect clinical care,” she said later.

The use of estimated glomerular filtration rate (eGFR) equations in assessing chronic kidney disease (CKD) for Black patients may lead to underdiagnosis and undertreatment, according to a nephrologist speaking at Kidney Week.


Flawed Racial Assumptions in eGFR Have Care Implications in CKD

A recent global study found that pregnancy can delay the onset of multiple sclerosis (MS) by more than 3 years.

The study looked at 2557 women who were patients in Australia and the Czech Republic with clinically isolated syndrome, a subset of MS.

MS is most often diagnosed in women of childbearing years. Pregnancy could reduce the abnormal over-activity of the immune system that causes MS, potentially long term, said the authors, writing in 

Researchers collected data on gravida, defined as any pregnancy, whether live or spontaneous miscarriage or termination, and parity, defined as childbirth after gestational age of more than 10 weeks, including livebirth and stillbirth.

Of these women, 1188 (46%) had at least 1 pregnancy and 1100 (43%) had at least 1 childbirth. Investigators found that later-onset CIS was more common in women with previous pregnancies and childbirths compared to those who had never been pregnant (HR, 0.68; 95% CI, 0.62–0.75; 

<.001), with a median delay of 3.3 years (95% CI, 2.5–4.1).

A similar delay in MS onset was also observed in women who had delivered at term, with onset delayed, on average, by 3.4 years.

Of the 2557 women, 71 (3%) had their first MS symptom during pregnancy.

Having 1 (HR, 0.70; 95% CI 0.61–0.79), 2 (HR, 0.67; 95% CI, 0.60–0.76), or 3 or more pregnancies (HR, 0.66; 95% CI, 0.58–0.75) delayed the onset of CIS compared with no pregnancies 

A higher number of pregnancies and childbirths was not associated with later CIS onset.

The researchers noted that although it is known that pregnancy is linked to reduced MS activity, 

the effect of pregnancy before MS diagnosis is unclear.

Investigators noted that further studies are needed to help explain the mechanisms behind the associations between pregnancy and onset of MS.

Nguyen A, Vodehnalova K, Klinicik T, et al. Association of pregnancy with the onset of clinically isolated syndrome. J

Published online September 14, 2020. doi: 10.1001/jamaneurol.2020.3324.

The researchers noted that although it is known that pregnancy is linked to reduced MS activity, the effect of pregnancy before MS diagnosis is unclear.


Author | Allison Inserro

Articles

Can EHR Tools Induce Improved Care of Patients With CKD?

Exploring What’s Possible With COVID-19 Trials and Kidney Disease

Flawed Racial Assumptions in eGFR Have Care Implications in CKD

Pregnancy Can Delay MS Onset by 3 Years, Study Says