Why does Chronic Kidney Disease (CKD) cause albuminuria?

From the Guidelines

Chronic kidney disease (CKD) causes albuminuria due to damage to the kidney's filtration barrier, which is exacerbated by hypertension, inflammation, and diabetes, leading to increased pressure, podocyte injury, and altered glomerular basement membrane structure and permeability 1.

Mechanisms of Albuminuria in CKD

The kidney's filtration barrier, composed of the glomerular basement membrane and podocytes, prevents large proteins like albumin from passing into the urine in healthy kidneys. However, in CKD, this barrier is damaged through several mechanisms, including:

• Hypertension, which increases pressure within the glomeruli, forcing albumin through the damaged filter
• Inflammation, which leads to podocyte injury and the formation of gaps in the barrier, allowing albumin to leak through
• Diabetes, which causes glycation of proteins in the glomerular basement membrane, altering its structure and permeability
• Tubular dysfunction, which reduces the kidney's ability to reabsorb albumin that passes through the filter

Clinical Implications

As CKD progresses, these mechanisms worsen, leading to increasing levels of albumin in the urine. Albuminuria is both a marker of kidney damage and a factor that contributes to further kidney injury through inflammatory and fibrotic processes. The degree of albuminuria is associated with risk of cardiovascular disease, CKD progression, and mortality, and should be quantified to guide treatment decisions 1.

Key Considerations

• The Kidney Disease: Improving Global Outcomes (KDIGO) recommends a comprehensive CKD staging system that incorporates albuminuria at all stages of eGFR, which is more closely associated with risk but also more complex 1
• Both eGFR and albuminuria must be quantified to guide treatment decisions, including modifications of medication dosages or restrictions of use, and choice of antihypertensive or glucose-lowering medications 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

CKD and Albuminuria

• Chronic Kidney Disease (CKD) is often associated with albuminuria, which is the presence of albumin in the urine 2.
• Albuminuria is a major risk factor for CKD progression, and its presence is associated with an increased risk of progressive renal function loss over time [(2,3)].
• The mechanism by which CKD causes albuminuria is not fully understood, but it is thought to involve damage to the glomerular filter, allowing albumin to leak into the urine 4.

Pathophysiology of Albuminuria

• Albuminuria may be a marker of both glomerular and tubular damage, whereas estimated glomerular filtration rate (eGFR) is merely a marker of glomerular damage 4.
• Emerging data report that elevated albuminuria causes tubulointerstitial damage through activation of proinflammatory mediators, which ultimately leads to a progressive decline in renal function 2.

Clinical Significance of Albuminuria

• The presence of albuminuria is a strong predictor of CKD progression, and its measurement is essential for risk stratification and management of patients with CKD [(2,3,5)].
• The level of albuminuria is inversely associated with CKD regression, and lower levels of albuminuria are associated with a higher probability of CKD regression 6.
• Measurement of urinary albumin-to-creatinine ratio (UACR) is recommended as the preferred method for assessment of albuminuria in both diabetic and non-diabetic patients 5.