Chronic Kidney Disease: Treatment Should Start Sooner

❗ Why Early Treatment Matters

Chronic kidney disease (CKD) affects approximately 10% of the global population. The more concerning fact is that the leading cause of death in CKD patients is not kidney failure but cardiovascular disease (CVD). Even stage 3 CKD patients are six times more likely to die from heart disease or stroke than to progress to kidney failure.

To delay CKD progression and prevent cardiovascular complications, modern medicine recommends four key drug classes:

RAS inhibitors (ACEi, ARB)
SGLT2 inhibitors
Non-steroidal mineralocorticoid receptor antagonists (nsMRA)
GLP-1 receptor agonists (GLP-1RA)

Each therapy has proven benefits, but the critical question remains: when and how should these be started in real-world clinical practice?

📉 The Reality of Residual Risk

According to a 2025 CJASN studyresidual_risk_of_advers…, even patients receiving at least one of these recommended treatments still faced significant residual risk:

Kidney disease progression: up to 75.9 events/1000 patient-years
Kidney failure: up to 68 events/1000 patient-years
Cardiovascular death or heart failure hospitalization: up to 56 events/1000 patient-years

This highlights a critical reality: current standard treatments are not enough.

📊 Real-World Treatment Adoption is Low

In practice, it’s rare for CKD patients to receive all four recommended therapies at once. Several factors contribute to the low uptake of parallel or rapid therapy combinations.

▶ SGLT2 and GLP-1RA usage rates

Among U.S. Medicare beneficiaries with CKD and type 2 diabetes, the initiation rates for SGLT2 inhibitors were low, particularly among Black patients and older adults. Similar trends were seen with GLP-1RAs, influenced by race, socioeconomic status, and insurance coverage.

▶ SGLT2 monotherapy adherence

One study found that more than half of CKD patients who started SGLT2 inhibitors continued therapy after one year. However, this only reflects single-drug use — there is limited real-world data on combined use of all four drug classes.

❓ Why Is Combined Therapy Rare?

1. Sequential Clinical Guidelines

Current guidelines recommend starting medications one at a time, discouraging simultaneous use.

2. Safety Concerns

Combination therapy raises concerns about side effects such as hypotension, hyperkalemia, or acute kidney injury, requiring intensive monitoring.

3. Economic and Insurance Barriers

GLP-1RAs are expensive injectable drugs, often not fully covered by insurance, making them less accessible.

4. Conservative Clinical Practice

Doctors unfamiliar with newer therapies may be reluctant to initiate multiple medications at once.

🚀 The Solution – Parallel and Rapid Initiation Strategies

✅ 1. Parallel Initiation

Start two or more therapies at the same time to reduce risk earlier.
Example: Begin RASi and SGLT2i at diagnosis, then add nsMRA and GLP-1RA.

✅ 2. Rapid Sequential Initiation

Add one medication every 1–2 weeks.
Inspired by the STRONG-HF model in heart failure care.

👩‍⚕️ Practical Tips: 4-Week Outpatient Protocol

Week	Action Plan
Week 1	Start RASi + SGLT2i, test blood pressure, eGFR, potassium
Week 2	Review labs, add either nsMRA or GLP-1RA
Weeks 3–4	Add remaining drug, monitor for side effects
Week 5+	Maintain or adjust dosage, reinforce lifestyle changes

📌 Case Example – 65-Year-Old Man with Stage 3b CKD, Diabetes, and Hypertension

Initial findings:

eGFR: 39
UACR: 580
BP: 148/86
HbA1c: 7.9%

Treatment Timeline:

Day 1: Start RASi + SGLT2i
Week 2: Add nsMRA
Week 4: Add GLP-1RA
At 3 months: Proteinuria reduced, blood pressure stable, no side effects

💬 Conclusion – A Shift in Paradigm is Needed

We must move from the passive “wait-and-see” approach to an active “treat aggressively and early” mindset. All four therapies have independently demonstrated benefit. Starting them faster, or together, can save lives.

In chronic kidney disease, timing is everything.

Reference
Khan MS, Rashid AM, Shafi T, et al. Residual Risk of Adverse Kidney and Cardiovascular Outcomes in Patients with CKD. Clin J Am Soc Nephrol. 2025;20:451–454. https://doi.org/10.2215/CJN.0000000588

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