Major Changes Highlighted in New CKD Management Guidelines

Updates on chronic kidney disease (CKD) diagnosis, use of sodium–glucose cotransporter-2 (SGLT-2) inhibitors as first-line therapy, and personalized treatment approaches for kidney and cardiovascular risk reduction are among the new CKD management recommendations from the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“The last CKD guideline was published in 2012, and there have been so many exciting contributions to nephrology in the past years that the guideline required an update,” Magdalena Madero, MD, of the National Heart Institute in Mexico City, Mexico, told Medscape Medical News. “SGLT-2 inhibitors, glucagon-like peptide-1 (GLP-1) agonists, and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs) are some of the new fascinating drugs that [have] modified the course of CKD.”

Madero is lead author of a recent synopsis of the KDIGO guideline, published online this week in the Annals of Internal Medicine, that focuses on the recommendations with the most evidence. 

According to Madero, the most important takeaways for clinicians are:

• Broad implementation of albuminuria and cystatin C for CKD diagnosis and risk stratification
• The use of SGLT2 inhibitors as first-line therapy for CKD
• Stopping angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) for hyperkalemia management, and, in addition, only using nsMRAs as a last resort, “after diet/potassium binders/loop diuretics have been used.”

“Constant Innovation”

To develop the guidelines, a team from Johns Hopkins University conducted an evidence synthesis and meta-analysis of relevant studies published through July 2023. A working group that included nephrologists, primary care physicians, internal medicine physicians, people living with CKD, and other experts helped inform the clinical practice points and assist in guideline development. 

The full guideline included 28 recommendations and 141 practice points. Among the key recommendations are the following:

• Greater emphasis on cystatin C for assessment of estimated glomerular filtration rate (eGFR) when evaluating CKD
• Point-of-care testing for creatinine and urine albumin in remote areas
• Shift to an individualized, risk-based approach to predict kidney failure, using validated prediction equations, such as the Kidney Failure Risk Equation
• SGLT-1 inhibitor use for patients with CKD with and without diabetes;
• Statin use for adults with CKD aged 50 and older.

In addition, the guideline recommends considering reducing the dose of (or discontinuing) ACE inhibitors or ARBs in the setting of either symptomatic hypotension or, as Madera suggested, uncontrolled hyperkalemia despite medical treatment, or to reduce uremic symptoms while treating kidney failure.

Furthermore, the guideline recommends a 2-year kidney failure risk threshold of >40% can be used to determine the timing of preparation for kidney replacement therapy, including vascular access planning or referral for transplantation, in addition to eGFR-based criteria and other clinical considerations.

“Clinicians should be aware that new studies have been released since the guideline was published, such as the FLOW study of semaglutide on CKD patients with type 2 diabetes,” Madero noted. “KDIGO Guidelines will be updated regularly but we live in a fascinating era where constant innovation is moving the field forward very quickly.”

Patient Care Will Benefit

Nephrologist F. Perry Wilson, MD, associate professor of medicine and public Health and director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, New Haven, Connecticut, commented on the synopsis paper and full guidelines for Medscape Medical News. 

“The paper does a nice job highlighting the major changes in CKD care the new KDIGO guidelines will lead to,” he said. Of note, “the recommendation to increase the use of cystatin C (in addition to creatinine) as a marker for kidney disease is a great step toward better measurement of kidney function. But this test is not widely available and, when it is, it may not be reported as quickly as creatinine. 

“These guidelines may lead that to change as health systems try to ramp up this line of testing to better stratify the risk of patients with CKD,” he said.

The recommendation to use risk prediction to guide care brings the guidelines into the “digital age of the electronic health record, where such equations can be ‘built in,’ ” said Wilson. “I don’t expect docs to go to some website to enter factors and click ‘calculate’ for their CKD patients, but I do believe the electronic health record systems will start to incorporate these models, which will likely benefit patient care.”

Referral for transplant evaluation is a complicated issue, usually initiated by nephrologists, he said. “Typically, patients are considered eligible for referral at a given eGFR (less than 20 is the standard). I am eager to see if these guidelines will allow earlier referral among high-risk patients.”

Wilson also pointed out that while there is no discussion in the paper of the role of GLP-1 receptor agonists, the full guidelines recommend them for patients with CKD who also have diabetes. However, he added, “the guidelines make no recommendation about the use of the drugs for patients with CKD without diabetes but with overweight or obesity. I suspect, however, that data will bear out that GLP-1s are beneficial in that population as well.” 

The guideline is supported by KDIGO, and no funding is accepted for the development of specific guidelines. 

Madero reports receiving consultancy fees from AstraZeneca, Bayer, and Boehringer Ingelheim; research support paid to her institution from AstraZeneca, Bayer, Boehringer Ingelheim, Renal Research Institute, and Tricida; speaker honoraria and travel from AstraZeneca; and funding for expert testimony for AstraZeneca, Bayer, and Boehringer Ingelheim. Wilson is a regular contributor to Medscape. He declares no other relevant financial relationships.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.