Screen, Stage, Sequence: CKD Care Pharmacists Can Lead

In an interview with Pharmacy Times, Elizabeth K. Van Dril, PharmD, BCPS, BCACP, CDCES, clinical associate professor and clinical pharmacist at the University of Illinois Chicago (UIC) Retzky College of Pharmacy, and Lauren Cunningham, PharmD, BCACP, CDCES, clinical assistant professor at UIC Retzky College of Pharmacy, discussed the pharmacist's role across the chronic kidney disease (CKD) care continuum in diabetes. They explained why both estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) screening are often missed and urged full Kidney Disease: Improving Global Outcomes (KDIGO) staging.

Cunningham described sequencing a layered regimen—an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a glucagon-like peptide-1 (GLP-1) receptor agonist, and finerenone (Kerendia; Bayer)—while anticipating dips in eGFR. Van Dril outlined barriers, including cost and misread labs, and both stressed integrating lifestyle steps such as nonsteroidal anti-inflammatory drug (NSAID) avoidance and sodium reduction. Their central message: CKD in diabetes is no longer inevitable when pharmacists identify risk early.

Pharmacy Times: What screening and staging steps for CKD are still being missed in practice, and how can pharmacists help standardize them?

Elizabeth K. Van Dril, PharmD, BCPS, BCACP, CDCES: Despite clear recommendations for screening in both the diabetes and kidney disease guidelines, early identification of CKD remains one of the biggest opportunities for improvement. Many people with diabetes still don't receive the recommended components of CKD screening: an eGFR to assess kidney function and a UACR to assess kidney damage. That matters because CKD is often asymptomatic early on, much like a lot of our other chronic disease states. Someone can feel completely well while kidney damage is progressing, and many people don't learn that they have kidney disease until it's more advanced. The screening recommendations for people with diabetes are pretty straightforward. For people with type 1 diabetes (T1D), annual CKD screening should begin 5 years after diagnosis. For people with type 2 diabetes (T2D), screening should begin at diagnosis and continue annually. Both eGFR and UACR should be checked, because either one alone can be abnormal and indicate CKD.

Another step that's frequently missed is complete staging when patients are diagnosed. A lot of the time in our patients' notes, we see CKD classified on the basis of eGFR alone, and that albuminuria component is missing. Both eGFR and albuminuria provide important prognostic information, and together they help determine a patient's risk for both kidney disease progression and cardiovascular events, too—and we know cardiovascular disease is the most common cause of death in people with CKD. Pharmacists should really encourage the use of the full CKD classification system from the KDIGO guidelines. That includes staging based on GFR—stages G1 through G5—and the albuminuria category, A1 through A3. A person can have completely preserved eGFR but significant albuminuria and still be at risk for kidney disease progression and cardiovascular complications.

Pharmacists are really well-positioned to standardize these processes across care. We can build reminders into diabetes management programs for screening, review laboratory data to identify patients who are meeting CKD criteria, and make sure we get those albuminuria results appropriately confirmed when they're abnormal. We can also do a better job documenting CKD staging consistently and facilitating timely nephrology referral when appropriate. Most importantly, we can help close the gap between identifying CKD and acting on it. A CKD diagnosis should lead to evidence-based treatment and not simply become another item on a patient's problem list.

Pharmacy Times: Among the current kidney-protective agents, how should pharmacists think about sequencing or combining them?

Lauren Cunningham, PharmD, BCACP, CDCES: The approach to diabetes-related kidney disease has shifted from a single-drug strategy to a layered approach. Rather than asking which therapy to choose, the more useful question becomes whether all appropriate foundational therapies are in place. Current evidence supports a framework that includes renin-angiotensin system (RAS) blockade with an ACE inhibitor or ARB, an SGLT2 inhibitor, and, when appropriate, a GLP-1 receptor agonist and/or a nonsteroidal mineralocorticoid receptor antagonist (MRA). These agents target different pathways involved in CKD progression, and the benefit of using them together can be greater than the benefit of any one therapy alone.

In general, treatment starts with optimizing blood pressure and initiating or titrating an ACE inhibitor or ARB when indicated, particularly when albuminuria is present, or eGFR is indicative of CKD. While ACE inhibitors and ARBs are important for hypertension management in this population, albuminuria itself is also a key reason to consider them, even in people without hypertension, because of their kidney-protective and albuminuria-lowering effect. It's also important to remember that the kidney outcome trials demonstrating benefit with ACE inhibitors and ARBs used maximally tolerated doses, not just the lowest doses. Pharmacists can advocate for thoughtful titration toward evidence-based targets while monitoring serum creatinine and potassium.

A modest reduction in eGFR following initiation or dose escalation of an ACE inhibitor or ARB is expected and does not necessarily indicate acute kidney injury. Historically, continuation of therapy was considered acceptable if serum creatinine increased by no more than 30% from baseline, and current guidelines similarly support continuation when the decline in eGFR does not exceed 30% from baseline, recognizing that this initial change is a predictable hemodynamic effect rather than evidence of actual kidney injury.

When adding an SGLT2 inhibitor, it's also important to anticipate this initial decline in eGFR. This occurs because the medications reduce intraglomerular pressure through restoration of tubuloglomerular feedback. Since both ACE inhibitors/ARBs and SGLT2 inhibitors can cause this expected hemodynamic decline in eGFR shortly after initiation, many clinicians prefer to stagger their initiation or dose increases. One practical approach may be to initiate or optimize the ACE inhibitor or ARB first, repeat lab monitoring in 2 to 4 weeks, and then add the SGLT2 inhibitor once we know kidney function and potassium are stable.

The same principle applies to ACE inhibitor and ARB dose escalations, initiation of an SGLT2 inhibitor, and addition of something like finerenone. They don't all need to happen on the same day. Spacing these agents out makes it easier to interpret the lab changes, assess tolerability, and identify the cause of any adverse effects if one occurs. Some clinicians might separate the initiation of a RAS inhibitor and an SGLT2 inhibitor by 1 to 2 weeks, or maybe a little longer.

It's also important to balance kidney protection with immediate glycemic needs. SGLT2 inhibitors provide substantial kidney and cardiovascular benefit even at lower eGFRs, but their glucose-lowering effects decline as eGFR falls and become quite limited when eGFR is 30 or below. When someone has CKD but a very high [hemoglobin] A_1C [HbA_1C], it helps to consider the main clinical priority at that visit. For example, if someone has obesity and an [HbA_1C] above goal, a GLP-1 receptor agonist may provide more immediate [HbA_1C] reduction and weight loss, along with long-term kidney and cardiovascular benefits. That doesn't lessen the value of an SGLT2 inhibitor; it simply reflects thoughtful sequencing. We might start with a GLP-1 receptor agonist to address the immediate glycemic concern, then make a plan to add an SGLT2 inhibitor shortly after for the kidney and cardiovascular protection. The goal isn't to choose one over the other, but to determine which intervention provides the most immediate benefit.

Nonsteroidal MRAs like finerenone are generally best viewed as another layer of protection for people with type 2 diabetes, persistent albuminuria, and acceptable potassium levels. Current KDIGO recommendations position nonsteroidal MRAs after foundational therapy, including RAS blockade and an SGLT2 inhibitor, if there's still some residual kidney risk remaining. Before starting this therapy, pharmacists can make sure that potassium and kidney function are stable and implement repeat monitoring approximately 4 weeks after any initiation or dose adjustment to confirm no hyperkalemia has developed. The manufacturer’s prescribing information for finerenone has very clear guidance on how to manage potassium and eGFR levels with initiation and dose titrations, while targeting the maximum dose of 20 mg per day for CKD. And most recently, we have evidence from the [phase 2] CONFIDENCE trial [NCT05254002] suggesting that simultaneous initiation of finerenone with an SGLT2 inhibitor produces greater reductions in albuminuria than either therapy alone, which reinforces the value of combination therapy when appropriate.

Pharmacy Times: What are the biggest barriers to initiating kidney-protective therapy, and how can pharmacists overcome them?

Van Dril: One of the biggest barriers we see in practice is that these therapies aren't always recognized as kidney- and cardiovascular-protective therapies first and glucose-lowering therapies second. Historically, medications such as the SGLT2 inhibitors were often viewed mainly through the lens of diabetes management, but their kidney and cardiovascular benefits extend well beyond glucose lowering. That shift in thinking doesn't always make its way into practice, which can delay the initiation of therapies that may substantially slow kidney decline.

Another common barrier is concern about laboratory changes after therapy begins. Lauren mentioned this previously, but modest declines in eGFR after starting an ACE inhibitor, ARB, SGLT2 inhibitor, and even finerenone are expected physiologic effects. This often reflects the reduced intraglomerular pressure when these agents are started, which helps prevent long-term damage to the glomeruli and does not indicate kidney damage or injury. If clinicians aren't familiar with that expected response, they may stop a beneficial medication inappropriately or early. Pharmacists can help by educating care teams and the patients they care for about what to expect, establishing appropriate monitoring plans, and distinguishing expected changes in the hemodynamic function of the kidney from clinically meaningful adverse effects.

Other barriers include hyperkalemia concerns with RAS inhibitors and nonsteroidal MRAs, medication costs, polypharmacy, and hesitancy about adding another agent or multiple agents. Pharmacists can address these issues by developing monitoring protocols, deprescribing diabetes and hypertension medications that don't have cardiovascular or kidney benefit, helping with affordability programs when they're available, and explaining the long-term impact of CKD progression. Framing these therapies as an investment in preserving kidney function and reducing cardiovascular risk really helps improve acceptance and adherence.

Pharmacy Times: How can pharmacists reinforce the lifestyle and pharmacotherapy pieces together in an individualized CKD plan?

Cunningham: The most effective CKD plans integrate lifestyle and pharmacologic interventions instead of presenting them as separate strategies. For many people, medications can feel disconnected from daily choices about food, physical activity, and weight management. Pharmacists can bridge that gap by explaining that each intervention addresses a different contributor to kidney disease progression, and meaningful risk reduction occurs when they work together. For example, an ACE inhibitor or ARB lowers blood pressure and reduces albuminuria. An SGLT2 inhibitor can lower intraglomerular pressure and slow kidney decline and may lower blood glucose if kidney function is adequate. A GLP-1 receptor agonist improves glycemic management, supports weight loss, and may have direct anti-inflammatory effects. Nonsteroidal MRAs target the inflammatory and fibrotic pathways that contribute to progressive kidney damage. These strategies complement lifestyle interventions that improve blood pressure, glucose levels, and cardiovascular health. When people understand how each therapy fits into their broader kidney-protective plan, engagement and adherence often improve, and that's what we see in practice.

Mediterranean-style or plant-forward eating patterns, sodium reduction, weight management, regular aerobic and resistance exercise, smoking cessation, and avoiding nephrotoxic medications like NSAIDs all play a role in slowing CKD progression and reducing cardiovascular risk. If you notice a person picking up several medications that are CKD pillars of care, along with OTC or prescription NSAIDs, consider having a conversation about the potential damage they may be doing to their kidneys through regular NSAID use, and discuss safer alternatives—especially for people in early stages of CKD. Their primary care and other providers might not know they're using OTC NSAIDs, and this can be a major strategy in reducing their risk.

Lastly, current evidence doesn't support aggressive protein restriction for most people with nondialysis CKD, and excessive restriction may lead to a risk of malnutrition. Current guidance is to target somewhere between 0.8 and 1.0 g/kg/day of protein for patients with CKD not on dialysis. At the same time, very high protein intake—over 1.3 g/kg/day—may worsen albuminuria and accelerate kidney disease progression. So individualized nutrition counseling should focus on overall dietary quality rather than a highly restrictive meal plan. Pharmacists can help turn these broad recommendations into practical actions by identifying small, sustainable changes that fit a person's preferences, routines, and treatment goals. For instance, instead of simply telling someone to reduce their sodium intake, we might help them identify lower-sodium substitutions for commonly eaten foods or teach them how to read labels for sodium levels. This makes lifestyle counseling feel connected to the person rather than separate from them and collaborative with the medications.

Pharmacy Times: Do either of you have anything else you'd like to add?

Van Dril: Lauren and I would probably agree that the most important message is that diabetes-related kidney disease should no longer be viewed as an inevitable consequence of diabetes. Over the past several years, the treatment landscape has changed dramatically, and we now have multiple therapies that can slow CKD progression, reduce cardiovascular events, and lower the risk of kidney failure. The challenge is no longer a lack of therapies but making sure people are identified early enough in their disease course to benefit from them.

Pharmacists are ideally positioned to lead that effort. We can support annual screening, identify candidates for treatment, optimize therapy sequencing, monitor for safety and efficacy, reinforce lifestyle strategies, and provide ongoing education. Pharmacists can be involved in and influence nearly every step in the CKD care continuum. Successful CKD management requires a proactive rather than reactive approach—by identifying risk early and implementing comprehensive, evidence-based interventions before substantial nephron loss occurs, pharmacists can help preserve kidney function, reduce cardiovascular risk, and support quality of life for years to come. And since cardiovascular disease remains the leading cause of death among people with CKD, every discussion about kidney protection should also be viewed as a discussion about cardiovascular risk reduction.