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Microvascular Decline as a Key Driver of CKD Progression:

In general, each blood vessel entering an organ branches six to eight times before becoming arterioles (10–15 µm (micrometer)), which in turn branch two to five times into smaller vessels, reaching diameters of 9 µm or lower where they supply blood to the capillaries. The microcirculation is constituted by those vessels between 0 and 200 µm that are embedded within organs and are responsible for the distribution of blood within tissues. An intact microcirculation is vital for the function of every organ and system in the human body for transportation of oxygen and nutrients as well as for the removal of toxins. The blood flow is generally regulated according to the specific needs of the tissues as long as the arterial pressure is sufficient to sustain adequate tissue perfusion (bringing oxygenated blood to the tissue). It is generally accepted in the physiology field that “form follows function.” In the microvasculature, the “form” of the microvascular (MV) network in general and the single vessel in particular will follow the “function” that is imposed by the environment.

The abnormalities in the microcirculation play an important role in the progression of and are possibly the starting point of several diseases.

Depending on the severity and the duration of the stimulus causing long-term changes in tissue blood flow, alterations in the MV layers may consequently take place, leading to permanent and sometimes progressive modifications in the vessel, a process also known as vascular remodeling

The combination of functional and structural MV changes can eventuate in the loss of the contribution of these vessels to organ function, a process that is known as vascular rarefaction.

A defective renal microcirculation, also known as MV disease is a prominent pathological feature in chronic kidney disease (CKD), irrespective of the cause, and progresses as CKD evolves.

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Changes in MV tone—endothelial dysfunction

 

Endothelial dysfunction has been implicated in the disease mechanism of hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, diabetes, and chronic renal disease.

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The endothelium is a thin layer of cells lining all blood vessels.
It controls:

  • What moves between the blood and tissues

  • How tight or relaxed blood vessels are

  • How easily fluid leaks out

  • Whether vessels grow or repair themselves
     

A healthy endothelium keeps blood flow normal and tissues well-supplied.

Endothelial dysfunction happens when it stops working properly.

  • Vessels don’t relax well (poor vasodilation)

  • There is an imbalance of chemicals that control vessel tightening and relaxing
    (like nitric oxide [NO], prostacyclin, endothelin-1, angiotensin II from RAAS system)

  • More inflammation and clotting occur

  • Vessel walls become “stickier,” allowing immune cells to attach and enter tissues​
     

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Nitric Oxide (NO) Loss Is a Big Part of the Problem

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NO is a gas made by endothelial cells that:

  • Relaxes blood vessels

  • Fights inflammation

  • Prevents blood clots

In endothelial dysfunction:

  • The body makes less NO

  • Or free radicals (ROS) destroy the NO that is made

  • Other helpful relaxing factors are also reduced

This creates a vicious cycle:

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Less NO → More vessel tightening → More inflammation → More NO destruction → Even worse dysfunction.

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Because vessels can’t relax and NO is low, you get:

  • Long-lasting vasoconstriction (tight blood vessels)

  • Lower blood flow to tissues

  • Less oxygen and nutrients delivered

  • Leakier vessels, letting harmful substances escape into tissues

  • More tissue damage over time
     

The kidneys rely on many small blood vessels to filter blood. When endothelial function is bad:

  • Kidney vessels stay too tight

  • Blood flow inside the kidneys drops

  • Kidney cells don’t get enough oxygen or nutrients
     

This can lead to:

  • Functional microvascular rarefaction (vessels stop working even if they’re still physically there)

  • Eventually structural rarefaction (tiny blood vessels disappear or are destroyed)

This contributes to worsening kidney disease.

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Conclusion:

 

The kidneys rely on many small blood vessels to filter blood.
When endothelial function is bad:

·        Kidney vessels stay too tight

·        Blood flow inside the kidneys drops

·        Kidney cells don’t get enough oxygen or nutrients

This can lead to:

·        Functional microvascular rarefaction (vessels stop working even if they’re still physically there)

·        Eventually structural rarefaction (tiny blood vessels disappear or are destroyed)

This contributes to worsening kidney disease.

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