From the Guidelines
Albuminuria is both a marker for worse outcomes and a contributor to disease progression through several pathophysiological mechanisms, as evidenced by the most recent study in 2021 1. The presence of albumin in urine not only indicates existing kidney damage but actively participates in causing further harm. When albumin leaks into the tubular system, it triggers inflammatory and fibrotic processes in the kidneys through the activation of tubular epithelial cells, which release cytokines and growth factors. This leads to interstitial inflammation, fibrosis, and progressive nephron loss. Additionally, albuminuria is associated with endothelial dysfunction and systemic inflammation that extend beyond the kidneys, contributing to cardiovascular complications. The toxic effects of filtered proteins on tubular cells create a vicious cycle of damage. This understanding explains why treatments targeting albuminuria reduction, such as ACE inhibitors and ARBs, not only improve kidney outcomes but also reduce cardiovascular risk, as supported by studies such as 1 and 1. Some key points to consider in the management of albuminuria include:
- The degree of albuminuria is associated with risk of cardiovascular disease, CKD progression, and mortality, as noted in 1.
- Treatments that lower urinary albumin excretion may slow progression of diabetic kidney disease and improve clinical outcomes, even in the absence of hypertension, as discussed in 1.
- The use of albuminuria as a surrogate marker of benefit of intervention in DKD is still a topic of debate, with some studies suggesting that changes in albuminuria may not be an adequate surrogate endpoint of long-term kidney benefit, as mentioned in 1.
- Regular screening and aggressive management of patients with conditions like diabetes and hypertension are crucial to prevent progression to more severe kidney disease and associated complications, as emphasized in 1. Overall, the dual nature of albuminuria as both marker and mechanism underscores the importance of regular screening and aggressive management in patients with conditions like diabetes and hypertension.
From the Research
Albuminuria as a Marker and Cause of Bad Outcomes
- Albuminuria is an important risk marker for adverse cardiovascular and renal outcomes, as well as mortality 2, 3, 4, 5.
- The relationship between albuminuria and risk is continuous and linear, similar to the relationship between blood pressure and cardiovascular risk 2.
- The presence of albuminuria indicates kidney damage and systemic vascular disease, including myocardial capillary disease and arterial stiffness 3.
- Albuminuria is associated with an increased risk of coronary artery disease, stroke, heart failure, arrhythmias, and microvascular disease 3.
Mechanism of Albuminuria in Causing Bad Outcomes
- Albuminuria may be a marker of both glomerular and tubular damage, whereas estimated glomerular filtration rate (eGFR) is merely a marker of glomerular damage 5.
- After leakage through the glomerular filter, albumin is not only excreted in urine but also reabsorbed by tubules, which may contribute to its role in causing bad outcomes 5.
- The use of renin-angiotensin-aldosterone system (RAAS)-blocking agents, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), can decrease albuminuria and reduce the risk of cardiovascular events 2, 6.
Treatment and Management of Albuminuria
- Cornerstones of albuminuria treatment include risk factor management, ongoing monitoring, and the use of RAAS-blocking agents in patients with hypertension, chronic kidney disease, or diabetes 2.
- ACE inhibitors and ARBs have demonstrated utility in reducing albuminuria and improving outcomes, and their use is recommended in patients with albuminuria 2, 6.
- Screening for albuminuria is important for early detection and treatment, and should be considered in patients with diabetes, hypertension, and chronic kidney disease 2, 3.