What happens to the body when kidney function begins to deteriorate

When the kidneys start to fail, their effects are felt on the internal system of the body. With the gradual decline in renal-homeostatic function, hormonal, structural changes ensue that compromise health and all functions of the body. This goes without saying, the toxin buildup in the body is another thing that happens when the kidney function starts to deteriorate.

One of the major consequences of reduced renal function is the accumulation of uremic toxins such as indoxyl sulfate and p‑cresyl sulfate. These are poorly excreted when kidneys are damaged and have also been shown in research studies to contribute to endothelial dysfunction and inflammation. Indeed, a systematic review titled "Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease" identified indoxyl sulfate, p-cresyl sulfate, phosphate, and other compounds as main culprits. These toxins activate oxidative stress and inflammatory pathways like NF-κB, damaging the inner lining of blood vessels.

Further, a study in JBMR Plus (“Uremic toxin indoxyl sulfate decreases osteocyte RANKL/OPG …”) found that indoxyl sulfate directly affects bone cells, called osteocytes, changing their signaling in ways that impair bone health.

The kidneys maintain electrolyte balance. Once their function suffers, the levels of potassium, phosphate, and other ions become unstable. High potassium, or hyperkalemia, can be especially dangerous in disrupting heart rhythm. Meanwhile, impaired acid excretion leads to metabolic acidosis, a condition where the blood becomes more acidic, contributing to muscle breakdown, bone demineralization, and chronic inflammation. Clinical reviews illustrate how these imbalances worsen with the progression of kidney disease.
The combination of uremic toxins, mineral imbalance, inflammation, and vascular calcification leads to a significantly higher risk of CVD in people with CKD. A major review entitled “The Non‑Traditional Cardiovascular Culprits in Chronic Kidney Disease” detailed how these non-classical risk factors-toxins and mineral disturbance-drive endothelial dysfunction, oxidative stress, vascular calcification, and ultimately cardiovascular events.

Reduced kidney function causes an impairment of mineral metabolism, especially regarding phosphate and calcium. The classic review “Cardiovascular risk in chronic kidney disease: the CKD–mineral bone disorder (CKD-MBD)” describes how high levels of phosphate can stimulate vascular smooth muscle cells to transform into cells that promote vascular calcification.

Another key paper entitled “Role of Uremic Toxins in Early Vascular Ageing and Calcification” explained that uremic toxins, including indoxyl sulfate, drive vascular calcification through osteogenic changes in the vessel wall.

A related mechanistic review in PubMed describes how elevated phosphate and calcium directly drive vascular calcification through VSMCs' undergoing apoptosis, releasing calcifying vesicles, and taking on bone-like properties.

These mineral imbalances are central to the CKD–mineral bone disorder (CKD‑MBD) and contribute to bone disease (renal osteodystrophy) and arterial stiffness. In people with end-stage kidney disease, a BMC Nephrology study demonstrated that there was an association between abnormal bone turnover-as determined by bone biopsy-and arterial calcification.

Healthy kidneys produce EPO, a hormone that induces the production of red blood cells. As kidneys fail, EPO levels fall, and anemia commonly ensues. Concurrently, chronic inflammation secondary to toxin accumulation disrupts iron metabolism, diminishing the body's ability to produce red blood cells.
Furthermore, indoxyl sulfate acts through the aryl hydrocarbon receptor to impair bone cell function in a manner that can aggravate the features of mineral and bone disorder in CKD.