Diabetes

Glomerular Hyperfiltration May Not Indicate Normal Kidney Function

When people first hear the term glomerular hyperfiltration (GHF), many assume, “Isn’t a high filtration rate a sign that the kidneys are working well?” While it might sound like a good thing, GHF actually reflects a state of abnormally increased kidney workload. It can be an early sign of kidney damage and is closely associated with a higher risk of cardiovascular disease (CVD).

Recent large-scale studies have shown that GHF is not just an early feature of diabetes but an independent cardiovascular risk factor, especially in younger patients. In this post, we’ll explore what GHF is, its underlying mechanisms, its connection to diabetes and other conditions, and why it’s important to detect it early—even in people without diabetes.

🔬 What is Glomerular Hyperfiltration (GHF)?

The glomerulus is the part of the kidney that filters blood—much like a fine biological filter. The glomerular filtration rate (eGFR) measures how efficiently your kidneys perform this task. A normal eGFR usually ranges from 90 to 120 ml/min/1.73m².

But when eGFR is abnormally high—often above the 95th percentile for someone’s age and sex—it may indicate glomerular hyperfiltration.
Rather than signaling healthy kidney function, GHF suggests the kidneys are overworking, often silently, and can lead to:

Glomerular hypertension
Proteinuria
Progressive kidney damage (CKD)
Increased cardiovascular risk

⚙️ Why Is GHF Harmful? – Pathophysiology

GHF affects both the kidneys and cardiovascular system through multiple complex mechanisms:

1. Intraglomerular Hypertension

Increased blood flow into the glomerulus raises the pressure inside, damaging the delicate capillaries. Over time, this can lead to glomerulosclerosis and systemic vascular strain.

2. Suppression of Tubuloglomerular Feedback (TGF)

In diabetes, increased sodium-glucose reabsorption suppresses TGF, leading to afferent arteriole dilation → more blood flow → GHF.

3. Activation of the RAAS (Renin-Angiotensin-Aldosterone System)

This raises blood pressure and contributes to cardiac remodeling, hypertrophy, and eventual heart failure.

4. Oxidative Stress and Inflammation

GHF triggers reactive oxygen species and cytokines that damage endothelial cells, promoting atherosclerosis and CVD.

5. Increased Arterial Stiffness

GHF may affect large vessels, impairing diastolic function and leading to ventricular dysfunction.

📊 GHF and CVD – What the Research Says

A 2025 study from the Clinical Journal of the American Society of Nephrology (CJASN) followed 1.95 million patients with type 2 diabetes for up to 7 years.
Key findings:

CVD risk was 13% higher in those with GHF (HR 1.13)
Myocardial infarction risk rose by 6%, heart failure by 17%
Patients under 40 had the highest CVD risk increase (HR 1.30)

🔎 This reinforces GHF as a systemic risk marker, not just a kidney-specific phenomenon.

❓ Can GHF Occur Without Diabetes?

Absolutely. GHF can occur in people without diabetes, often due to:

• Obesity and Metabolic Syndrome

Insulin resistance suppresses TGF and increases renal blood flow.

• Early Hypertension

Increased sympathetic tone and RAAS activation lead to hyperfiltration.

• High-Protein Diets

Excessive protein intake may temporarily increase GFR—chronic overconsumption may lead to persistent GHF.

• Pregnancy

eGFR physiologically increases during the 2nd–3rd trimester. If underlying renal issues exist, GHF may become pathologic.

• Other Causes

Post-exercise (transient)
Solitary kidney (e.g., kidney donors)
Early polycystic kidney disease
Growth spurts in adolescence

🧠 The Role of eGFR Percentiles – Not Just the Number

A single eGFR value doesn’t provide the whole picture. That’s why this study used eGFR percentiles based on age and sex to define GHF.

For example:

Age	eGFR (ml/min/1.73m²)	Interpretation
25-year-old woman	110	Normal
70-year-old woman	110	Likely GHF (above age-specific 95th percentile)

This percentile approach enables more personalized, accurate risk stratification.

📋 Clinical Implications of GHF

GHF is often asymptomatic, but early identification can help prevent long-term damage.

🔹 How to Identify High-Risk Patients:

eGFR above age/sex 95th percentile
Even with “normal” values, reassess if the patient is young or non-obese
Check for trace proteinuria or signs of early cardiovascular dysfunction

🔹 What to Do if GHF is Suspected:

Lifestyle: reduce salt, avoid excess protein, manage weight
Medications: consider SGLT2 inhibitors or RAAS blockers (ACEi/ARB)
Monitor: reassess eGFR and urinary protein regularly

📌 Summary

Feature	GHF Risk Increases In…
Age	Under 40 years
Sex	Males
Obesity	Non-obese individuals
Hypertension	Those without HTN
Dyslipidemia	Those without dyslipidemia

Glomerular hyperfiltration is not a sign of kidney vitality.
It’s often an early warning signal—especially in young, lean individuals with no other obvious risk factors.
Early lifestyle changes and monitoring can significantly reduce long-term kidney and heart damage.