Treatment-Induced Changes in Albuminuria and Cardiovascular Outcomes: A Systematic Review and Trial-Level Meta-Regression of Renin–Angiotensin–Aldosterone System Inhibition

Heart and kidney diseases often occur together and are among the leading causes of illness and death worldwide. Millions of people are affected by chronic kidney disease (long-term damage to the kidneys that reduces their ability to filter waste) and cardiovascular disease (conditions affecting the heart and blood vessels, such as heart attack and stroke (loss of blood flow to part of the brain)). An early warning sign of kidney damage is albuminuria, which means having higher-than-normal levels of a protein called albumin in the urine. People with higher levels of albumin in their urine are at greater risk of cardiovascular events such as heart attack, stroke, heart failure (when the heart cannot pump blood effectively), and death from heart disease.

Several widely used medicines lower blood pressure and protect the heart and kidneys by blocking a hormone system in the body called the renin–angiotensin–aldosterone system (RAAS). These include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists. These treatments are known to reduce albuminuria and improve health outcomes. However, it is still unclear whether the reduction in albuminuria itself directly reflects a lower risk of future cardiovascular events.

In this research, we will carry out a systematic review (a structured and comprehensive summary of all relevant studies) and a meta-regression (a statistical method that examines patterns across studies). We will identify randomized controlled trials (RCTs) that tested medicines known to lower albuminuria. We will collect information on how much albuminuria was reduced and how many participants experienced major heart-related events.

We will then analyze whether trials showing larger reductions in albuminuria also showed larger reductions in cardiovascular events. We will examine whether the size of the change in albuminuria is linked to the size of the change in cardiovascular risk.

This research is important because if albuminuria can reliably predict cardiovascular benefit, it could serve as a surrogate marker (an early measurement that predicts long-term outcomes). This would help researchers design more efficient clinical trials and allow doctors and regulators to interpret results more confidently. Ultimately, we hope this work will improve how treatments are evaluated and support better care for people living with heart and kidney disease.