Chronic Kidney Disease in 2025: From Silent Epidemic to Treatable Risk State

Andrew Kowalski, MD, FASN

The Scale of the Problem

CKD has quietly emerged from the shadows of nephrology to become a defining challenge in global health. Current estimates suggest that approximately 850 million people worldwide live with CKD, with roughly 4 million receiving dialysis or living with a kidney transplant (Herrington et al., 2025). These numbers are staggering, but what makes them truly alarming is the trajectory: based on current trends, CKD is projected to become the fifth leading underlying cause of death worldwide by 2050 (Herrington et al., 2025). The perfect storm of the aging population, rising diabetes and hypertension diagnoses, and exponentially increasing obesity rates continues to push CKD up the mortality league table, ahead of many cancers, which may be a first in our current medical model and history

Yet for most of its natural history, CKD remains asymptomatic, detectable only through laboratory testing, and completely invisible to patients. This combination, high prevalence, silent progression, and potentially catastrophic outcomes makes CKD one of the most important and most underutilized levers in population health management.

Unfortunately, our primary health providers are struggeling to maintain adequate numbers to see a resonable amount of patients instead of double or tripple the ampount that is fesabel to provide adequate care. Many of these primary providers are the victims to the system of "lab flagging," where if the lab is flagged (or turns a different color on their sheet) then it draws attention, otherwise it is frequently overlooked.

With these staggering predictions, CKD cannot afford to be overlooked or treatment delaied. At this time, which maybe a first in our history, CKD has a therapeutic advantage to be tackled early on to prevent progression, which frequently happens under the radar until it's too late for any preventative approach. Our primary providers need our help to pick up on the early signs of disease "initiation" and jump on it so that a meaningful delay or a halt in progression can be achieved.

CKD Detection: Simple Tools, Massive Opportunity

One of the most striking aspects of modern CKD care is the stark contrast between diagnostic simplicity and implementation failure. The condition can be caught early, but instituting therapy is often overlooked and delayed, not due to negligence or malice, but due to the simple mistake of being overlooked among the litany of patient complaints at the time of visit or management expectation.

Lets be honest...I have written about CKD and caching it early for some time, but the pressure that has been placed on my primary care colleges is unresonable, and due to this fact I have been advocating a cultural change in nephrology management and care with the expectation to come to the aid of our primary care colleges and take the burden of interpretation and therapy implementation off their hands. NEPHROLOGY NEEDS TO BECOME MORE PROACTIVE AND INVOLVED EARLY IN PATIENT CARE. Long ago are the times of CKD Stage IIIb/IV referral as now we have a means to delay and even stop CKD formation and progression.

We need only three readily available tests to screen, diagnose, and stage CKD: serum creatinine to calculate estimated glomerular filtration rate (eGFR) using standardized equations, Cystatin C to also estimate eGFR in patients that are sarcopenic, and urine albumin measurement, typically as an albumin-to-creatinine ratio (Herrington et al., 2025). These simple laboratory values allow us to identify high-risk individuals and distinguish relatively benign CKD presentations from those requiring aggressive intervention.

Despite this diagnostic accessibility, CKD remains chronically underrecognized in primary care documentation, frequently absent from problem lists, and poorly communicated to patients. The disconnect between what we can detect and what we actually identify in clinical practice represents one of medicine's great implementation gaps, but it does not have to be and we have the means to make massive changes in identification and therapy initiation to help stop CKD formation and progression.

CKD as Cardiovascular Amplifier

For the majority of patients with CKD (especially those that have had CKD present for a number of years), kidney failure is not always the primary threat to a patients lifespan and healthspan. As Herrington and colleagues emphasize, people with CKD face elevated risks across multiple domains: progressive loss of kidney function, escalation of chronic inflammation contributing to premature cardiovascular events including myocardial infarction, stroke, heart failure, and accumulating disability long before they would ever require dialysis (Herrington et al., 2025). The sobering reality is that most patients with CKD will die from cardiovascular disease or experience major cardiovascular disability before they ever need kidney replacement therapy (Herrington et al., 2025). Unfortunately, for numerous reasons, CKD is a amplifier of cardiovascular disease due to numerous pathways involving chronic inflammation and the development of sarcopenia.

This cardiovascular predominance reflects CKD's role as springboard to worsening overall risk. The disease intertwines traditional cardiovascular risk factors (hypertension, dyslipidemia, diabetes) with CKD-specific mechanisms including uremic toxin accumulation, anemia, mineral-bone disorders, and chronic systemic inflammation. Understanding CKD primarily as a cardiovascular risk state rather than simply a kidney disease fundamentally reshapes our therapeutic priorities.

Of note, and beyond the scope of this blog post, the street does go both ways. In many circunstances cardiovascular disease may be the main driver and can also influence chronic inflammation and therefore impact renal function and contributing to CKD and the progression of CKD.

The Post-2019 Therapy Revolution

The landscape of CKD therapeutics has been transformed since 2019 by a series of landmark randomized controlled trials that have expanded our armamentarium beyond renin-angiotensin system (RAS) blockade (Herrington et al., 2025). This transformation can be conceptualized as overlapping waves of kidney-protective therapy.

Renin-angiotensin system inhibitors with ACE inhibitors and angiotensin receptor blockers remain foundational, reducing intraglomerular pressure, lowering albuminuria, and decreasing risks of both CKD progression and cardiovascular events in high-risk patients. This established benefit continues to anchor contemporary CKD management.

The second wave arrived with sodium-glucose cotransporter-2 (SGLT2) inhibitors, which revolutionized CKD care by extending benefits well beyond glucose control. The DAPA-CKD trial demonstrated that dapagliflozin reduced the primary composite kidney endpoint by approximately 39%, with a remarkably efficient number-needed-to-treat of about 19 over 2.4 years (Heerspink et al., 2020). Similarly, EMPA-KIDNEY showed that empagliflozin reduced the risk of CKD progression or cardiovascular death across a broad CKD population, including many patients without diabetes (The EMPA-KIDNEY Collaborative Group, 2023). These agents slow chronic eGFR decline, reduce kidney failure risk, and decrease heart failure hospitalizations and cardiovascular events—crucially, independent of glycemic effects.

The third wave encompasses non-steroidal mineralocorticoid receptor antagonists (MRAs) and GLP-1 receptor agonists. Finerenone, a selective non-steroidal MRA, demonstrated in the FIDELIO-DKD trial that it could reduce risks of both CKD progression and cardiovascular events in patients with type 2 diabetes and CKD when added to RAS inhibitor therapy, though hyperkalemia risk requires monitoring (Bakris et al., 2020). Most recently, semaglutide entered the kidney-protective arena: the FLOW trial demonstrated that this GLP-1 receptor agonist reduced the risk of major kidney outcomes and cardiovascular death in patients with type 2 diabetes and CKD, prompting regulatory recognition of these kidney benefits in drug labeling (Perkovic et al., 2024; Herrington et al., 2025).

CKD Care Requires Multi-Specialty Coordination

Because CKD functions as a systemic disease with cardiovascular, metabolic, and multi-organ manifestations, affected patients typically interface with primary care, cardiology, endocrinology, nephrology, and geriatrics or palliative care services. The Lancet review argues compellingly that every clinician encountering high-risk patients should maintain CKD awareness, implement consistent screening, and trigger standardized evidence-based interventions including blood pressure optimization, RAS inhibition, SGLT2 inhibition, statin therapy, lifestyle modification, and, where appropriate, addition of non-steroidal MRAs or GLP-1 receptor agonists (Herrington et al., 2025).

This multi-specialty reality demands that we reconceptualize CKD care less as "referral to a nephrology silo" and more as integrated cardio-renal-metabolic management, where expertise is distributed and coordination is paramount.

Implementation: Translating Evidence to Practice

The fundamental message of contemporary CKD management is that we already possess the tools to substantially reduce CKD-related complications; our challenge is deploying them earlier and more consistently across healthcare systems (Herrington et al., 2025). Successful implementation requires systematic attention to five domains.

1. We must screen appropriate populations: everyone with diabetes, hypertension, established cardiovascular disease, or age 60 years and older should receive periodic eGFR and urine albumin assessment.

2. We must properly stage and risk-stratify patients using the combined eGFR and albuminuria framework to determine follow-up intensity and therapeutic urgency.

3. We must initiate kidney- and heart-protective therapies early, with RAS inhibitors and SGLT2 inhibitors forming the foundation in appropriate patients, complemented by statins for atherosclerotic cardiovascular disease prevention and layering in finerenone or GLP-1 receptor agonists where evidence-based and tolerated (Herrington et al., 2025).

4. We must address the full spectrum of cardiovascular risk through blood pressure targets, smoking cessation, weight management, exercise prescription, and thoughtful deprescribing when appropriate.

Finally, we must recognize clear nephrology referral triggers including rapid eGFR decline, heavy albuminuria, resistant hypertension, complex electrolyte disturbances, or advanced G4-G5 CKD requiring preparation for kidney replacement therapy.

Although this final step is based on current recommendations, I challange all primary providers, specialists and patients themselves to be more proactive and pull the trigger for nephrology referral earlier so that proper, goal directed therapy, is implemented early and monitored to give the patient the best possible outcome.

Conclusion

Chronic kidney disease stands at an inflection point. We have moved from offering rudamentary therapeutic options to an evidence-rich era where multiple complementary interventions can meaningfully alter disease trajectories and reduce cardiovascular risk.

The gap between what we know and what we do remains substantial, but it is fundamentally a problem of implementation rather than knowledge. By embracing CKD as a shared responsibility across specialties, systematically applying simple screening tools, and deploying our expanding therapeutic arsenal early and comprehensively, we have an opportunity to bend the curve on what would otherwise become the fifth leading cause of death worldwide within a generation.

References

1. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219-2229.

2. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.

3. Herrington WG, Judge PK, Grams ME, Wanner C. Chronic kidney disease. Lancet. 2025; online ahead of print.

4. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109-121.

5. The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117-127.