The Kidneys - Why Keeping Them Healthy Matters

Why the Kidneys Matter

The kidneys are two bean-shaped organs located at the back of the upper part of the abdomen whose main function is to filter blood and remove waste. While that sounds simple enough, I would argue that their physiology is some of the most complex in the body. Calculating the filtration of various substances, the effect of hormones, and the impact of conditions like acid-base disturbances in the body becomes remarkably complex, so I will not spend much time detailing that. There are whole textbooks on that topic if you are interested. Instead, I will specifically address chronic kidney disease (CKD), a rapidly growing condition worldwide. By the end of this article, you should have a better understanding of how CKD changes normal kidney function, what normal kidney function looks like, what causes CKD, and the treatments/therapies that address CKD. 

CKD = chronic kidney disease

Normal Kidney Function:

To understand why CKD has a high morbidity and mortality (i.e. it decreases health and ultimately leads to death), you need to understand some basics of renal function. The kidneys are each composed of approximately one million individual filters called nephrons. As blood passes through a capillary bed at one end of the filter, pressure draws out fluid and filterable substances like glucose, amino acids, and electrolytes from the blood. What is filtered out of the blood moves into a tubule (i.e. a small tube that makes up the bulk of the nephron). The fluid that leaves the blood is called filtrate. As the filtrate moves down the tubule, most of the fluid and electrolytes are reabsorbed. Under normal conditions, all of the glucose and amino acids are reabsorbed. Additionally, some substances are secreted into the remaining fluid. Understanding that the kidneys filter the blood becomes very important when dealing with medications because most are handled by the kidneys in some way. Once the filtrate reaches the end of the tubule, it enters a collecting chamber, along with the filtrate from all the other nephrons, and makes its way to the bladder. The kidneys produce urine. If you did not already know this, now you do.

Description of the image above:

This image shows the structure of a nephron. There are about one million of these filters in each healthy kidney. Blood moves through a capillary bed called the glomerulus and pressure draws out the filtrate. As the filtrate moves through the various sections of the nephron, the proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct, most of the water and many important substances are reabsorbed. Some additional waste products are secreted (i.e., added to the filtrate), and urine is left at the end of the collecting duct. This will make its way to the bladder.

Kidney function is measured by a number called the glomerular filtration rate (GFR). This refers to how much fluid is being filtered by the kidneys in a given amount of time. In a clinical setting, measuring the concentration of creatinine in the plasma is the standard way to estimate GFR. Creatinine is a substance that is made by the muscles at a constant rate and is only filtered by the kidneys. It is not reabsorbed or secreted. This makes it a great way to estimate kidney function. Since a poorly functioning kidney will filter less creatinine, a higher concentration of creatinine will be retained in the blood plasma. Measuring creatinine concentrations in the plasma and urine over a 24-hour span allows one to estimate the glomerular filtration rate.

Lab Values:

Normal creatinine = 0.74-1.35 mg/dL for men and 0.59 to 1.04 mg/dL for women

Normal GFR = about 125 mL/minute

Chronic Kidney Disease:

CKD is a progressive loss of the kidney's ability to filter blood. Generally, this means that the number of functioning nephrons decreases. As kidney function declines, the body has a harder time regulating blood pressure, eliminating waste and excess fluids, maintaining electrolyte balance, and performing its other roles. CKD is generally considered irreversible, and it only worsens once it begins. Progression through its stages is measured by declining GFR as shown below. 

Stage 1) GFR of 90 ml/min and above

Stage 2) GFR of 60 to 89 ml/min 

Stage 3a) GFR of 45 to 59 ml/min 

Stage 3b) GFR of 30 to 44 ml/min 

Stage 4) GFR of 15 to 29 ml/min

Stage 5) GFR of less than 15 ml/min or treatment by dialysis

Typically, symptoms do not begin to manifest until stage four. 

Once CKD reaches stage five, the patient will need dialysis, an artificial system that filters the blood, until they can either get a kidney transplant or until death. 

What leads to CKD?

Diabetes: diabetic nephropathy is the leading cause for of CKD, according to the Centers for Disease Control. The hyperglycemia associated with diabetes mellitus leads to the formation of reactive oxygen species, which cause inflammation. This attracts macrophages (a type of immune cell that eats debris or damaged tissue) which eventually leads to the formation of fibrous, non-functional tissue which replaces normal nephrons. Additionally, inflammation from diabetes damages the filtration membrane in the nephron and can cause albumin (i.e. a type of protein that should stay in the blood plasma) to show up in the urine. In fact, protein in the urine can be an early warning sign of the often silent early stages of CKD [2]. 

Hypertension: High blood pressure causes sclerosis, or damage, to the glomerular capillary bed in the nephron [3]. Since this is the location where blood is filtered, damage decreases the kidney's ability to filter the blood. As kidney function, as measured by GFR, declines, underlying hypertension tends to worsen because the kidneys play a central role in regulating blood pressure. This causes a vicious downward spiral to worsening blood pressure and kidney function.

Age: with each decade after age 40, the average person loses about 10% of their functioning nephrons. This significantly increases the chance of developing CKD, especially if there are other contributing factors to a lowering GFR. According to the CDC, 38.4% of those over age 70 had some stage of CKD [1]. 

Ethnicity: individuals from certain races are at an increased risk of developing CKD. These include being black, Asian, or Native American, and genetic factors account for the increased risk. For instance, variants of the ApoL1 gene found in those of African descent can account for a nearly threefold increase in the chance of developing CKD in one's lifetime [6].

Other factors that can increase the chance of developing CKD include smoking, obesity, abnormal kidney development, and other congenital diseases that lower kidney function like polycystic kidney disease.

Kidney Health and Slowing the Progression of CKD:

Manage diabetes and high blood pressure: These are two of the most important factors in slowing the progression of CKD. If you have any of these risk factors, then you should work with your doctor to address their cause. 

Don’t smoke: This comes up as a modifiable risk factor for almost every chronic disease. It damages the endothelium of blood vessels, causing inflammation that damages so many aspects of health. Please don’t smoke. If it is something that you do, it is your choice but I strongly encourage you to do everything in your power to completely stop. 

Limit salt intake: The FDA reports that most Americans consume about 3,400 mg of sodium daily while the recommended amount is around 2,300 mg [4]. Most of the sodium in people's diets comes from packaged and processed foods, not necessarily table salt. Fresh fruits and vegetables contain extremely low amounts of salt. Conversely, fresh produce contains very high levels of potassium and other vitamins and minerals. From an evolutionary perspective, human diets were plentiful in potassium and low in sodium. For this reason, we tend to retain sodium but have an easier time ridding ourselves of excess potassium. In the modern world where sodium is overly abundant, long-term overconsumption correlates with hypertension, which can lead to cardiovascular disease and CKD [5]. 

General healthy living: I will lump these together since they are all linked to blood pressure and indirectly affect kidney health. 

• Getting 7-8 hours of sleep per night
• Maintaining a healthy weight
• Avoiding excess sugar intake
• Managing and reducing unhealthy stress
• Limiting/eliminating alcohol from the diet

It is important to mention that having risk factors does not necessarily mean that one will develop CKD. It just indicates an increased risk. If you have any of these risk factors, it is probably worth discussing your kidney function with your doctor. CKD develops gradually, and its earlier stages are usually non-symptomatic. Unfortunately, it is generally not possible to regain kidney function with CKD. Once the damage is done, it is permanent. However, medications and lifestyle interventions are available to significantly slow the disease progression. 

Lastly, if you are someone who deals with CKD, you should unquestionably work with your doctor on managing symptoms and slowing the disease progression. There are far more causes of kidney disease than I have listed here, and each person’s treatment will therefore be unique. What I have listed here are general guidelines for informational purposes only. 

Sources:

1. Centers for Disease Control and Prevention. (n.d.). Kidney Disease Surveillance System. Centers for Disease Control and Prevention. https://nccd.cdc.gov/CKD/ 
2. Kumar, M., Dev, S., Khalid, M. U., Siddenthi, S. M., Noman, M., John, C., Akubuiro, C., Haider, A., Rani, R., Kashif, M., Varrassi, G., Khatri, M., Kumar, S., & Mohamad, T. (2023). The Bidirectional Link Between Diabetes and Kidney Disease: Mechanisms and Management. Cureus, 15(9), e45615. https://doi.org/10.7759/cureus.45615
3. Vaidya SR, Aeddula NR. Chronic Kidney Disease. [Updated 2022 Oct 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535404/
4. https://www.fda.gov/food/nutrition-education-resources-materials/sodium-your-diet
5. Grillo, A., Salvi, L., Coruzzi, P., Salvi, P., & Parati, G. (2019). Sodium Intake and Hypertension. Nutrients, 11(9), 1970. https://doi.org/10.3390/nu11091970
6. Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329(5993):841-845. doi:10.1126/science.1193032