Chronic kidney disease (CKD) often causes persistent itching, medically known as uremic pruritus or CKD-associated pruritus (CKD-aP). This itch can significantly reduce quality of life, affecting sleep, mood, and overall well-being. It is common, impacting many individuals with advanced kidney disease and those undergoing dialysis.
Waste Product Accumulation
Healthy kidneys filter waste products from the blood, maintaining a balanced internal environment. Each kidney contains millions of nephrons, which remove waste products like urea and creatinine from the blood. When kidney function declines, these waste products, called “uremic toxins,” accumulate in the bloodstream. This buildup creates a toxic environment within the body, directly irritating nerve endings in the skin.
The accumulated toxins can also trigger an inflammatory response, further contributing to the sensation of itching. Other specific protein-bound uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, are difficult for impaired kidneys to remove and are linked to pruritus. These substances can directly act on skin receptors or contribute to systemic irritation, leading to the persistent and often severe itching experienced by kidney disease patients. The severity of itching can sometimes fluctuate with dialysis, as toxins are temporarily removed.
Mineral and Hormone Imbalances
Kidney disease disrupts the balance of essential minerals and hormones, leading to imbalances that can contribute to itching. Healthy kidneys regulate levels of calcium, phosphorus, and parathyroid hormone (PTH). In kidney disease, the kidneys struggle to excrete excess phosphorus, leading to elevated levels in the blood.
High phosphorus can cause calcium to be pulled from the bones, leading to an altered calcium-phosphorus ratio. This imbalance, along with reduced active vitamin D production, stimulates the parathyroid glands to release more PTH, a condition known as secondary hyperparathyroidism. Elevated PTH levels are associated with skin irritation and itching, possibly due to direct effects on skin cells or nerve sensitivity.
Systemic Inflammation
Chronic kidney disease often creates ongoing, low-grade inflammation, which contributes to itching. Impaired kidney function can lead to an immune system imbalance, causing the body to react as if constantly under attack. This sustained inflammatory state results in the release of various inflammatory mediators, such as cytokines and histamines.
These chemical signals can directly stimulate nerve fibers in the skin, initiating or intensifying the sensation of itch. Elevated levels of inflammatory markers, such as C-reactive protein and certain interleukins, are observed in individuals with kidney disease-associated pruritus. This inflammatory response is considered a distinct mechanism contributing to itching, separate from the direct toxic effects of waste products.
Nerve Dysfunction
Alterations within the nervous system can also contribute to persistent itching in individuals with kidney disease. Kidney disease can affect the health and function of nerves, leading to conditions like peripheral neuropathy. Nerves that transmit sensations from the skin to the brain may become damaged or hypersensitive.
This nerve damage can result in abnormal signaling pathways, causing the brain to interpret these signals as an itch, even without a clear external irritant. Some theories suggest an imbalance in the body’s opioid receptors, where an overactivity of certain receptors and a blockage of others contribute to the itch sensation. These neurological changes highlight how kidney disease impacts the complex communication network responsible for sensation.