The Role of the Kidneys

What are the organs in the body?
When asked, many might answer the heart or liver. Generally, organs refer to the structures within the thoracic and abdominal cavities, known as the five organs in traditional medicine: the heart, liver, lungs, spleen, and the kidneys, which are the focus of this paper.

The primary function of the kidneys is to produce urine. The human body generates various waste products and toxins due to environmental factors and diet. The kidneys filter these unnecessary components from the blood and excrete them from the body as urine along with water, fulfilling a crucial detoxification role.

The filtered urine (primary urine) contains not only waste products and toxins but also essential nutrients like amino acids, glucose, and various minerals (electrolytes) necessary for bodily functions. The kidneys reabsorb these vital components back into the bloodstream, maintaining the body’s internal environment.

Additionally, the kidneys have various other functions, such as producing erythropoietin (a hormone that stimulates red blood cell production), regulating blood pressure, and activating vitamin D to promote calcium absorption. In this sense, the kidneys are essential organs that support overall health, working behind the scenes as true unsung heroes.

The Unsung Hero: The Role of the Kidneys

Among organs, particularly the liver and kidneys, are known as silent organs because they often show no symptoms even when something is wrong, making it possible for diseases to progress unnoticed.

When kidney function declines, the body cannot excrete waste products, toxins, and excess water, leading to various symptoms such as swelling, abnormal urine, and fatigue. A condition where kidney function falls below 30% of normal is called renal failure, which can be acute (acute kidney injury, AKI) or chronic (chronic kidney disease, CKD).

The theme of this paper is acute kidney injury (AKI). AKI can cause reduced urine output (oliguria or anuria) and elevated blood nitrogen levels. While recovery is possible with appropriate treatment, severe cases may require dialysis.

One cause of AKI is medication, known as drug-induced AKI. Between 14-26% of AKI patients have this condition due to medications such as antibiotics, anticancer drugs, antirheumatic drugs, gout medications, and contrast agents. It is also known that the frequency of AKI increases with age as kidney weight and volume decrease.

How Does NMN Affect Kidney Function?

Experiment Details

In the experiment, we divided mice into two groups: ① 3-month-old young mice and ② 20-month-old aged mice. On the first day of the experiment, we injected both groups with cisplatin, an anticancer drug known to damage the kidneys, to induce AKI.

The AKI-induced mice were then further divided as follows, and their kidney function, cell morphology, and mitochondrial count were evaluated on the fourth day of the experiment.

■ Evaluation of Kidney Function
Blood urea nitrogen (BUN) and creatinine are waste products that increase in the blood when kidney function declines, serving as indicators of kidney function. In both young and aged AKI mice administered NMN, the levels of BUN and serum creatinine were suppressed.

■ Evaluation of Kidney Cells
Kidney cell damage and apoptosis (programmed cell death) were evaluated using the following three methods:
1. Hematoxylin and Eosin Staining

Drug-induced kidney damage often shows injury in the kidney tubules. Hematoxylin and eosin staining (HE staining) was performed on AKI mice to confirm tubular damage. Injured areas stain blue. In aged mice, fewer blue spots (less damage) were observed in NMN-administered mice.

2. Measurement of Caspase-3 Levels
Recent studies have shown that proteinuria (presence of serum proteins in urine) is a sign of declining kidney function. Caspases are proteases that lead to cell death through apoptosis. Caspase-3, in particular, plays a central role in apoptosis. Increased caspase-3 activity indicates loss of anti-apoptotic function within tissues and cells.

In caspase-3 immunostaining, a method for detecting apoptosis histochemically, darker coloration indicates higher levels of activated caspase-3, suggesting tubular cell damage. NMN-administered AKI mice showed suppressed increases in caspase-3 levels in both young and aged mice.

3. Detection of Apoptotic Cells by TUNEL Staining
TUNEL staining was performed to detect fragmented DNA, an indicator of apoptosis. NMN-administered AKI mice had fewer TUNEL-positive cells, indicating suppressed apoptosis.

■ Evaluation of Mitochondrial Quantity
During the progression of AKI, mitochondrial damage is prone to occur in proximal tubular cells, which contain many mitochondria. The number of mitochondria in the kidney tissue of aged AKI mice with and without NMN administration was measured using an electron microscope. The results showed that NMN-administered mice had a smaller decrease in mitochondrial quantity compared to non-administered mice, suggesting that NMN promotes mitochondrial function improvement.

※Graphs and photos are from the original paper

NMN Potentially Suppresses Kidney Damage and Drug Side Effects

This experiment revealed that NMN suppresses kidney cell apoptosis and may be particularly useful in treating AKI in the elderly.

Although this experiment used cisplatin’s nephrotoxicity to induce AKI, cisplatin is a historic anticancer drug still widely used as a first-line treatment in many medical settings. Further research on NMN may one day recognize it as an aid in preventing and treating various kidney diseases, including drug-induced AKI.

Known as the “silent organ,” the kidneys often show no symptoms even when afflicted with disease, and once function is lost, recovery is difficult. This is why kidney care in daily life is crucial. Summer is a season when dehydration is common, placing a burden on the kidneys. Integrate NMN into your lifestyle to support the hardworking kidneys.

【References】
Reference paper: Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1-Dependent