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Primary Care and Nephrology CKD
Enhancing CKD Outcomes: Primary Care and Nephrology Collaboration

Released: November 16, 2023

Expiration: November 16, 2024

Nayan Arora
Nayan Arora, MD
Jay H. Shubrook
Jay H. Shubrook, DO, FACOFP, FAAFP
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Key Takeaways
  • When referring an individual to nephrology for chronic kidney disease, it is important to evaluate both serum and urine markers before referral.
  • SGLT2 inhibitors provide a significant cardiorenal metabolic benefit to individuals with chronic kidney disease.
  • When starting an SGLT2 inhibitor, it is important to consider patient-specific factors such as A1C, blood pressure, and concomitant medications.

When evaluating chronic kidney disease (CKD) in the primary care setting, what are some things to consider prior to referring to a nephrologist?

Dr Shubrook: From the primary care perspective, the first thing to understand is that patients typically do not present with symptoms. Usually some laboratory tests have already been completed which have led to identifying CKD. This speaks to the importance of evidence-based screening, particularly for high-risk patients who have hypertension or diabetes. That being said, when you identify an abnormal lab value, it is worthwhile to determine whether these labs reflect a stable or acute condition. It's also important to recognize that when we evaluate the kidneys, we must evaluate both serum and urine markers, including estimated glomerular filtration rate (eGFR), potassium, blood, proteinuria, sediment, and casts. These provide important information and may help determine the urgency for a nephrology referral.

Dr Arora: I agree, as a nephrologist I think you first want to make sure that acute kidney injury is ruled out, whether that's volume-related, medication-related, whatever it may be, and evaluate the longitudinal data. After that, I think a lot of times we focus on the serum markers of kidney disease and ignore the urine markers. Both are equally important. The definition of CKD is an eGFR less than 60 mL/min/m2 for at least 3 months, so there is a timeline associated with a new diagnosis.

Once a diagnosis is made, how can we accelerate a first-time nephrology consultation? At minimum, a basic metabolic panel, eGFR, and a urine screen for protein, blood, and other abnormalities should be ordered prior to a nephrology referral. I think urine albumin-creatinine ratio can be very helpful. Oftentimes I like to get a spot urine protein-creatinine ratio and a urine albumin-creatinine ratio to differentiate between the 2 types of protein that you can see in the urine. Lastly, if a patient has a reduced eGFR, having a kidney ultrasound prior to seeing nephrology to rule out anatomic abnormalities can also be helpful: do they have hydronephrosis, is there obstructive uropathy, etc, especially when we do not have significant historical data.

What considerations are there when picking between sodium-glucose cotransporter-2 (SGLT2) inhibitors in CKD?

Dr Arora: Several years ago, when SGLT2 inhibitors were relatively new, the narrative we would see was “why should I start this patient on an SGLT2 inhibitor?” I think with the data we have now, it has flipped to “why shouldn't I start this patient on an SGLT2 inhibitor?” I can't emphasize enough that SGLT2 inhibitors are the best cardiorenal, cardiometabolic medications that we have available. They should be used in both proteinuric and nonproteinuric kidney disease based on trial data. Patients with proteinuric kidney disease are generally going to progress much faster, so the urgency is greater to start those patients on one of these agents.

In terms of practical considerations, what is the right timing? If a patient with diabetic kidney disease doesn’t have appropriate glycemic control and their A1C is greater than 12%, that’s not the right time to start an SGLT2 inhibitor, since these patients were not included in CKD clinical trials. The worse a patient’s glycemic control at the time of initiation, the more glycosuria they will experience, resulting in polyurea, nocturia, orthostasis, and volume depletion. In addition, I'm still somewhat cautious in the sense that if they have severe active lower extremity ischemia or open wounds, that may not be the right time to initiate. It’s also important to look at their other medications. If a patient with heart failure is on a significant number of diuretics, I look at their volume status. If they're hypervolemic, it's probably okay to start the SGLT2 inhibitor. If they’re euvolemic, I’m generally decreasing their diuretics by 50% when I’m starting. We really don’t want them to get volume depleted, because that’s the number one risk factor for people discontinuing these medications.

And then finally, from a cardiorenal protective standpoint, you just need the lower doses of these meds. Empagliflozin 25 mg is often used by primary care and endocrinology for glycemic management, but you only need the 10 mg dose for cardiorenal protection and will wind up with fewer side effects. In terms of which agent I use, I'm using whichever agent I can get my hands on. I do believe the CKD benefit is predominantly a class effect.

Dr Shubrook: I also think that it's important to remember in the primary care space that these agents are sometimes considered diabetes agents, sometimes they're considered kidney agents, and sometimes they're considered cardiology agents. It's important to know that a patient may return after seeing a nephrologist or a cardiologist and be on an SGLT2 inhibitor. So please don't stop them without talking to the team.

Dr Arora: It’s also very important to emphasize that you will see a rise in creatinine or a drop in eGFR when you start these medications. That is a sign that these medications are working, and it's not a reason to stop. That initial drop is not a reason to stop and would in fact be the wrong thing to do, and would generally be the wrong thing to do in the vast majority of cases. So, we generally say 30% is an acceptable decline. It's not clear that greater declines are necessarily a reason to stop. If you see more than that, individuals should be evaluated for other reasons they may have had a more robust eGFR decline, such as volume depletion, but the reflex shouldn’t be, hey, we need to stop it.

What practical insights do you have for primary care clinicians when considering SGLT2 inhibitor therapy in CKD?

Dr Shubrook: I think these are relatively easy agents to use if you have a couple of things in mind. First, because there's permissive glucosuria, you do want to make sure that they don't already have problems within the urinary tract or repeated problems with mycotic genital infections. I also don't typically use these in patients with an A1C above 10% because although it is a relatively mild glucose-lowering agent, it has both glucosuresis and natriuresis, so it does change volume. If I have an older adult who's already got low blood pressure, I've got to have a plan to make room for the SGLT2 inhibitor to have that effect. I also would not want my patients to be dealing with the constant need to urinate while they are very hyperglycemic.

Now, if you have a patient who has a history of diabetic ketoacidosis (DKA), then you need to have a strategy for how to talk to the patient about the risk of DKA with these medicines when they have known diabetes. I would say that's not a hard stop for me, but if you're not comfortable with DKA, maybe you need to work with someone who is because these agents have been associated with DKA. The other thing is, because they have both glucose and natriuretic effects, you're going to be able to reduce other things such as diuretics or other blood pressure agents. And this is really a good chance to use a team approach with the other specialists to say, “how do we optimize this menu of meds for this patient, so we get the maximum benefit with the least number of meds?”

Dr Arora: Yeah, all great points. Whenever I start any SGLT2 inhibitor on a patient, my counseling to them is that the greatest risk initially is volume depletion. And so that's where you're looking at their other meds, you're talking to them about what they might expect if they have orthostatic symptoms, and if they do have symptoms, I ask them to call me. In addition, about 6% of patients may develop a mycotic infection based on trial data. That's probably your highest longer term risk. I tell patients we can typically treat through them if they occur and rarely need to discontinue therapy. I let them know what the symptoms are and then usually treat them with a topical antifungal, or even a one-time oral antifungal if needed. Hygiene is something that we emphasize when we're starting these because that can really mitigate that risk. 

I think the biggest thing I tell folks is that the risk of euglycemic DKA is almost exclusively in patients with diabetes. In these individuals, if they are going to be NPO because they are having a procedure, I ask that they just hold their agent for 5 days before. Some say 3, some say 5, some say 7. Being off these meds for 5 days is not going to cause any damage. I also tell them that if they are ill or can't eat or drink normally, they should hold it. I'd rather they hold and avoid any problems and have them wind up in DKA. We always have the intention of restarting it later. If they do develop euglycemic DKA, I generally restart if there was a provoking factor or stressor, which is almost always the case. That being said, it can be difficult to convince individuals to restart. So just be conservative. In my mind, stopping an SGLT2 inhibitor for 5 days before someone is NPO to avoid an adverse outcome is worth it.

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