Can't Improve Your Proteinuria? Discover Reasons & Solutions

In Episode 77, I discussed three medications in great detail that are known as renal-protective drugs. These medications not only help protect the kidneys, but they also reduce proteinuria (the presence of excess proteins in urine) and slow down the progression of kidney function decline. Surprisingly, after a whole year, an intelligent individual raised a very valid question in the comments: "If these medications are so important, why aren't Pakistani doctors prescribing them?" This is indeed a legitimate question, and it points to a significant issue in the healthcare practices in our region.

This episode aims to explore why such crucial medications are underprescribed in Pakistan. We'll also look at how these medications work and the reasons behind the reluctance in their use.

The Situation in Pakistan

From my experience, I’ve observed that even though many kidney patients come to clinics, only about 5% to 10% of them are already on these kidney-protective medications. This means that an alarming 90% to 95% of kidney patients in Pakistan are not receiving these vital treatments. This is in stark contrast to practices in countries like India and the Middle East, where these drugs are considered essential and are regularly prescribed to patients.

Understanding Kidney-Protective Medications

The key question here is: What do these kidney-protective medications do? And more importantly, why are Pakistani doctors hesitant to start their patients on these drugs, especially when two out of the three drugs are readily available and inexpensive in the country?

These medications can drastically reduce the burden of kidney disease in Pakistan. Yet, despite their availability and affordability, their use remains limited. In today’s discussion, I will delve into how these medications work and why they are not more widely used.

A Deeper Dive into Kidney Function and Disease Progression

To understand the role of these medications, we first need to explore the basic functioning of the kidneys and the progression of kidney disease. In a previous episode, I explained the journey of blood through the kidneys and how scientists determine the glomerular filtration rate (GFR), a crucial measure of kidney function.

If we zoom in further to examine a glomerulus—a tiny bundle of blood vessels within the kidney—it has two main arteries: the afferent arteriole, which brings blood into the glomerulus, and the efferent arteriole, which carries blood out.

In a patient with chronic kidney disease (CKD), it's estimated that more than 50% of their nephrons (the functional units of the kidney) are lost. Out of the two million nephrons that typically exist in both kidneys, only about 500,000 to 600,000 remain functional. These remaining nephrons are under immense pressure as they are tasked with doing the work that was once done by the full complement of nephrons.

The Role of Angiotensin II in Kidney Disease

Because of this pressure, the body enters a high-angiotensin II state. Angiotensin II is a hormone that the body produces to help maintain blood pressure and ensure adequate blood flow through the kidneys. However, in patients with CKD, this hormone becomes both a survival mechanism and a potential toxin.

Just like how consuming healthy food in excess can be harmful, excessive levels of angiotensin II can damage the body. While it helps maintain kidney function temporarily, in the long run, it contributes to further kidney damage by keeping the kidneys in a high-pressure state.

How Kidney-Protective Medications Work

The three groups of medications we’re focusing on, particularly the two that are widely available in Pakistan, work by reducing the high pressure within the glomeruli. This reduction in pressure leads to a temporary decrease in the GFR and a slight increase in serum creatinine levels. However, this increase is not indicative of real kidney damage; rather, it’s a sign that the medications are effectively reducing the stress on the remaining nephrons.

In medical terms, this temporary rise in creatinine is known as functional renal insufficiency. It’s important to understand that this isn’t caused by new kidney damage but by the hemodynamic changes within the glomeruli—changes that are actually beneficial in the long term.

Benefits Beyond the Kidneys

1. Reducing Proteinuria: One of the most significant effects of these medications is the reduction of proteinuria. Proteinuria is not just a marker of kidney damage; it’s also a pro-inflammatory state that accelerates kidney deterioration. High levels of protein in the urine can destroy kidney function within months and cause widespread inflammation in the body. This inflammation increases cholesterol levels and promotes atherosclerosis (the hardening of arteries), leading to a higher risk of cardiovascular diseases like heart attacks and strokes.

2. Slowing Disease Progression: These medications can slow the progression of kidney disease by 50% to 60%, as shown in several studies. By reducing the pressure within the glomeruli, they protect the remaining nephrons and extend the period of kidney function.

3. Cardiovascular Benefits: The benefits of these medications are not limited to the kidneys. They also improve heart health by counteracting the harmful effects of angiotensin II. In CKD patients, angiotensin II causes blood vessels to narrow, making it harder for the heart to pump blood effectively. This leads to hypertrophy (thickening) of the heart muscle. When these medications are used, the heart doesn’t have to work as hard, which helps reduce the thickening of the heart walls and improves its pumping ability.

4. Vascular Flexibility: Another significant benefit is the increased flexibility of blood vessels throughout the body. Angiotensin II causes blood vessels to become stiff, which can lead to high blood pressure and other cardiovascular issues. By reducing the levels of angiotensin II, these medications help keep the blood vessels more flexible and improve overall blood flow.

Conclusion

In summary, kidney-protective medications offer profound benefits for both kidney function and overall cardiovascular health. The fact that they are underprescribed in Pakistan is concerning, given their potential to reduce the burden of kidney disease significantly. By understanding how these medications work and the long-term benefits they provide, we can hope to see a shift in prescribing practices that could improve the health outcomes for many kidney patients in the region.