Overview

CKD is a life limiting diagnosis, and as kidney function declines, it can be the result of terminal illness. All of which to say, CKD is preventable, and the treatment regimen often targets the combination of factors that cause it, specifically HTN and T2DM. Clinical trials have shown that mineralocorticoid receptor antagonists, glucagon-like peptide 1 receptor agonists, and sodium-glucose co-transporter 2 inhibitors are beneficial in lowering adverse events in CKD, significantly increasing the options for effective treatment. These drug classes have been suggested as the four pillars of CKD, together with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. However, even in high-risk individuals, these medications are underutilized for therapy management.

Chronic Kidney Disease and its Intersection with Risk Factors

• T2DM is the primary leading cause of CKD and can serve as a predictor for kidney disease progression. Antiglycemic agents are an essential approach for lowering the risk of kidney disease irrespective of T2DM diagnosis. 

• Chronic hypertension is the second leading cause for CKD because it results in the long term increase of glomerular pressure which can damage the renal vasculature leading to the acceleration of kidney disease progression. Even mild blood pressure elevations can increase the risk of developing CKD and progressing toward ESRD. Blood pressure management in CKD patients should be considered irrespective of hypertension.
  • Per 2024 KDIGO guidelines, a standardized blood pressure of less than 120/80 mmHg is advised to lower the risk of cardiovascular disease and the onset and progression of chronic kidney disease. However, blood pressure targets should be customized based on life expectancy, frailty, and fall and fracture risk.

• AKI is becoming more widely acknowledged as a precursor to CKD. The vulnerable 7 to 90 day period following AKI when kidney function has not fully restored is known as AKD. During this timeframe, patients are at higher risk of transitioning to CKD, ESRD, cardiovascular complications, and mortality. Close monitoring is needed to ensure no further kidney damage occurs during AKD.

• T2DM, HTN, and AKI are all factors that contribute to CVD and strong indicators of CKD. As we dive into the treatment and management of CKD, it is important to recognize that optimization of these drug therapies for these indicators alone would serve as a preventative. 

Overall Prevalence in the Adult General Population

• Women are slightly more likely than men to have CKD (14.4% versus 11.8%)
• CKD affects about 20% of non-Hispanic Black adults
• CKD affects about 12% of non-Hispanic White adults
• CKD affects about 14% of non-Hispanic Asian adults
• CKD affects about 14% of Hispanic adults
• People 65 years of age or older had the highest prevalence of CKD (33.7%), followed by those 45 to 64 (12.3%), and those 18 to 44 (6.3%)

CKD: Trends in Adults with T2DM & HTN

The following charts and data below take a look at trends with respect to population and various disease states:

Source and Images: Centers for Disease Control. Available at: https://wwwn.cdc.gov/kdss/TopicHome/PrevalenceIncidence.aspx?topic=1

Without adjusting for age, sex, or other demographics (⋯ overall), the prevalence was 12.9% in 2001-2004 and 13.9% in 2017-2020. CKD was more common in women, individuals 70 years of age or older, non-Hispanic Black adults, and adults with diabetes or hypertension.

Albuminuria: Trends in Adults with T2DM & HTN

Source and Images: Centers for Disease Control. Available at: https://wwwn.cdc.gov/kdss/TopicHome/PrevalenceIncidence.aspx?topic=1

Without adjusting for age, sex, or other demographics (⋯ overall), the prevalence was 9.4% in 2001-2004 and 10.2% in 2017-2020. Albuminuria was more common in women, individuals 70 years of age or older, non-Hispanic Black adults, adults with diabetes, hypertension, and CKD Stages 4 and 5.

Note: UACR (measure of kidney damage) and eGFR (measure of renal function) are the two primary indicators of kidney disease that should be checked at least once a year in those with or at risk of CKD. The KDIGO 2024 guideline recommends repeat testing three months after the identification of an abnormal eGFR or UACR.

What are the Four Core Pillars of CKD?

RAS Inhibitors: Reduce Kidney Failure Risk

• When compared to placebo or other antihypertensive medications, ACEis or ARBs decreased the incidence of kidney failure requiring renal replacement therapy in individuals with CKD.

SGLT2 Inhibitors: Reduced CKD Progression Risk

• SGLT2 inhibitors are known to be effective in diabetes management, but studies are beginning to show that the benefits extend beyond blood glucose control. When compared to a placebo, treatment groups with SGLT2 inhibitor therapy had a 37% lower risk of kidney disease progression.

nsMRA (finerenone): Combination Therapy for UACR Reduction

• The 2024 KDIGO guidelines recommend combining finerenone with SGLT2 and RAS inhibitors. Finerenone has been demonstrated to lower composite kidney outcomes, heart failure hospitalizations, and all-cause mortality in those with CKD and T2DM. 

• The CONFIDENCE trial showed that starting empagliflozin and finerenone together resulted in significantly greater albuminuria reductions than either medication alone.
  • Combination therapy: Reduced UACR from baseline by 52%
  • Monotherapies: Finerenone or empagliflozin reduced UACR by 32% and 29%, respectively.

GLP-1 RA: Reduction in Kidney Composite Outcomes

• According to the 2024 KDIGO guidelines, individuals with T2DM and CKD who are unable to utilize metformin and a SGLT2 inhibitor or who do not achieve glycemic targets with both medications should also use a GLP-1 receptor agonist. 

• GLP-1 RAs reduce kidney composite outcomes by 21%.

The Bottom Line in CKD Management

CKD management involves a proactive and comprehensive treatment approach as incidence continues to rise. RAS inhibitors, SGLT2 inhibitors, nsMRAs, and GLP-1 RAs are the core pillars. This is a significant change in the way medical professionals manage kidney health. Blood pressure and glucose control are no longer the only ways to manage CKD; instead, these treatments are combined to delay the disease course, lower cardiovascular risk, and greatly improve long-term outcomes.

The four therapies are changing the standard of care with updated KDIGO recommendations and new evidence in support of combination therapy. In addition to refining medication regimens, pharmacists and other healthcare providers must stay up to date on these new medications in order to educate patients, detect care gaps, and promote timely screening with eGFR and UACR.

Ultimately, the best chance of influencing the course of CKD and improving quality of life for many individuals at risk is through early intervention, guideline-driven therapy, and coordinated care.

Lauren T., APPE Student

References

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