The US Department of Veterans Affairs (VA) and the US Department of Defense (DoD) have issued an updated clinical practice guideline on the management of chronic kidney disease (CKD), focusing on management of early-stage disease at the primary care level. The guideline addresses major recent advances in pharmacologic management, including treatment with GLP-1 receptor agonists (RAs) and other drugs.

“CKD is associated with increased risk of cardiovascular disease, increased mortality, and poor quality of life,” first author Amy R. Schwartz, MD, of the VA Connecticut Healthcare System, in West Haven, Connecticut, told Medscape Medical News.

“Through earlier detection of CKD and the proactive use of treatments described in this guideline, primary care providers can slow the progression of CKD, improve cardiovascular outcomes, and reduce mortality.”

The guideline, recently published in the Annals of Internal Medicine, stems from a systematic evidence review conducted by the multidisciplinary VA/DoD Evidence-Based Practice Work Group in order to update the group’s 2019 clinical practice guideline for CKD management.

The review, spanning research published between 2018 and 2024, includes 23 recommendations, of which 21 are new or updated, and about half address pharmacologic management.

Pharmacologic Recommendations

In terms of recommendations involving pharmacologic decisions in CKD, some highlights listed as having the strongest supporting evidence include:

• The use of statins in patients with CKD who are not on dialysis to reduce the risk for major adverse cardiac events (MACEs) and mortality, with studies including a systematic review and meta-analysis showing reductions of MACE and all-cause mortality associated with statin use among those patients.
• The use of either an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) in patients with hypertension and albuminuria (ie, urine albumin-to-creatinine ratio [UACR] > 30 mg/g) to slow the progression of CKD.
• The addition of an SGLT2i to maximally tolerated ACEI or ARBs in patients with CKD who have type 2 diabetes (T2D), albuminuria, or heart failure to reduce the risk for MACE, heart failure, progression of CKD, and mortality. SGLT2i should be continued until the start of dialysis.
• The addition of a GLP-1 RA to an ACEI or ARB in patients with T2D and albuminuria, to reduce progression of CKD, MACE, and all-cause mortality. (Strengthened and broadened from the previous guideline).

• The work group noted, however, that “in the absence of comparative effectiveness studies between SGLT2i and GLP-1 RA, SGLT2i [are favored] as add-on therapy to ACEI or ARB before considering GLP-1 RA.”

  In general, however, “it is important to recognize that SGLT2 inhibitors and GLP-1 RAs can be used as reno- and cardio-protective medications and not just for glycemic control.”

• Patients with autosomal-dominant polycystic kidney disease (ADPKD) should be referred to a nephrology specialist to assess for the appropriateness of treatment with tolvaptan.
• “Despite tolerability and safety concerns, no other therapy currently exists for rapidly progressive ADPKD, and tolvaptan is more likely to benefit patients in earlier stages of CKD,” the work group wrote.

Another notable recommendation, albeit with weaker evidence, is that for patients with advanced CKD (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m²) who are currently on an ACEI or ARBs, this therapy should be continued.

“Despite the high prevalence of hypertension and albuminuria in patients with advanced CKD in whom ACEI or ARB use is recommended, cessation is common when the eGFR is < 30 mL/min/1.73 m²,” Schwartz explained.

However, with the strong evidence of a reno-protective benefit of ACEI and ARB, “the benefit of delaying CKD progression outweighs the potential harm from hyperkalemia and the burden of close follow-up,” she said.

“So the work group suggests continuing ACEI/ARB therapy for patients with advanced CKD, unless there is drug intolerance or other adverse event.”

To help primary care clinicians navigate the array of new or revised recommendations, the guideline includes an algorithm for the pharmacologic management of CKD among patients who are not on dialysis.

Other Strong Recommendations

In other areas of CKD management, strong recommendations include:

• For patients with CKD at an increased risk for iodinated contrast-associated acute kidney injury (AKI), preprocedural intravenous volume expansion with isotonic crystalloid should be utilized.
• The administration of N-acetylcysteine should not be used for the prevention of iodinated contrast-associated AKI, based on results from two large randomized controlled trials showing no benefit of N-acetylcysteine for the prevention of contrast-associated AKI or longer-term effects on kidney function.
• For the prediction of CKD progression, eGFR and UACR should be used, with both measures representing independent predictors of CKD progression and cardiovascular outcomes. “Importantly, both identify those who would benefit from treatments to prevent kidney failure,” the work group noted.

CKD Screening

The US Preventive Services Task Force concluded in 2012 that evidence was insufficient to assess the benefits and harms of routine screening for CKD, however, in the years since, a greater understanding of risks for cardiovascular-kidney-metabolic syndrome has emerged, while treatment options for CKD have expanded significantly.

Therefore, the guideline recommends testing individuals who are at an increased risk for CKD and who would benefit from the treatment.

“This is consistent with the American Heart Association Advisory on Cardiovascular-Kidney-Metabolic Health, which recommends annual measurement of UACR with eGFR assessment in patients with stage 2 or higher cardiovascular-kidney-metabolic syndrome,” the work group stated.

Importantly, while CKD is estimated to affect about 14% of the US population, most with kidney disease are not even aware of their diagnoses, the work group underscored.

“Through earlier detection of CKD and the interventions described in this clinical practice guideline, primary care clinicians can slow the progression of CKD, improve cardiovascular outcomes, and reduce mortality,” they wrote.

‘Exciting’ Potential to Improve Clinical Outcomes

Commenting on the guideline, James D. Oliver, III, a nephrologist practicing in Bethesda, Maryland, told Medscape Medical News, “I think the most notable changes to the guideline is the addition of recommendations for primary care providers to use newer pharmaceutical agents to slow down the progression of CKD, specifically SGLT2 inhibitors, GLP-1 RAs, and finerenone.”

“These medications are among the most significant advances in the treatment of CKD in several decades,” he said. “However, we still have older medications such as ACE inhibitors and ARBs, which are effective but being underutilized.”

Importantly, for primary care clinicians, “the guideline provides clarity for addressing the most significant risk factors in the progression of CKD, namely high blood pressure and urine albumin,” Oliver added.

Limitations of the guideline, as noted by the authors, include that “the optimal blood pressure target for CKD is still a subject of investigation, [as is] the question of whether certain combinations of medications would be preferred in particular scenarios,” he noted.

Furthermore, “we need more information on outcomes in people who have nondiabetic CKD, [with] room for improvement in the risk equations.”

Ultimately, however, “there is exciting potential to significantly improve the clinical outcomes of people with CKD, and reduce the number of people who may need dialysis or transplants,” Oliver said.

Schwartz had no disclosures to report. The disclosures of other work group authors are detailed in the published guideline. Oliver had no disclosures to report.