From the Guidelines
Glomerular hyperfiltration is characterized by an abnormally high glomerular filtration rate (GFR), typically exceeding 140 mL/min/1.73m², and is often associated with microalbuminuria, mild proteinuria, and elevated creatinine clearance, as evident in patients with Type 1 Diabetes Mellitus (T1DM) 1. The clinical features of glomerular hyperfiltration can be subtle, with patients initially being asymptomatic, and the condition detected only through laboratory testing. However, over time, persistent hyperfiltration can lead to glomerular hypertension, glomerular enlargement, and eventually glomerulosclerosis. Some key features of glomerular hyperfiltration include:
- Microalbuminuria (small amounts of albumin in the urine)
- Mild proteinuria
- Elevated creatinine clearance
- Glomerular hypertension
- Glomerular enlargement
- Eventual glomerulosclerosis As noted in a study published in Circulation, renal disease in youth with diabetes mellitus differs significantly between patients with T1DM and T2DM, with glomerular hyperfiltration being a common feature in T1DM 1. The pathophysiology of glomerular hyperfiltration involves increased intraglomerular pressure and blood flow, often due to afferent arteriolar dilation and/or efferent arteriolar constriction, which can damage the glomerular filtration barrier, leading to protein leakage and eventual nephron loss 1. If left untreated, glomerular hyperfiltration can progress to chronic kidney disease with declining GFR, worsening proteinuria, and eventual development of edema, hypertension, and other manifestations of kidney dysfunction.
From the Research
Clinical Features of Glomerular Hyperfiltration
The clinical features of glomerular hyperfiltration can be understood by examining the various studies that have investigated this phenomenon.
- Glomerular hyperfiltration is a phenomenon that can occur in various clinical conditions, including kidney disease, diabetes, and obesity 2, 3, 4, 5.
- It is characterized by an increase in glomerular filtration rate (GFR) above normal values, which can lead to glomerular hypertension and renal injury 2, 4.
- The pathophysiological mechanisms of glomerular hyperfiltration are not well explored, but it is thought to be caused by afferent arteriolar vasodilation and/or efferent arteriolar vasoconstriction 2.
- Glomerular hyperfiltration can be associated with glomerular and tubular hypertrophy, increased glomerular capillary pressure, and mechanical stress on the podocyte foot processes and body surface 4.
- This can lead to podocyte injury, detachment of viable podocytes, and segmental sclerosis, ultimately contributing to the progression of chronic kidney disease (CKD) 4, 5.
Associated Conditions
Glomerular hyperfiltration has been associated with various conditions, including:
- Diabetes mellitus 2, 3, 5
- Obesity 2, 3, 4
- Polycystic kidney disease 2
- Sickle cell anemia 2
- High altitude renal syndrome 2
- Secondary focal segmental glomerulosclerosis caused by a reduction in renal mass 2
Diagnostic Threshold
The diagnostic threshold for glomerular hyperfiltration is not well established, but a consensus pediatric threshold has been proposed as 135 mL/min/1.73 m2 for children aged >2 years 6.
- Measured and estimated GFR can be used to diagnose glomerular hyperfiltration, but estimating GFR from serum creatinine (SCr) may not be reliable in subjects with reduced muscle mass 6.