During protein metabolism, nitrogenous wastes such as urea, uric acid, ammonia, and creatinine are produced.
[7] However, due to conditions such as renal insufficiency, the under-functioning kidney is unable to excrete these metabolic wastes, causing them to accumulate in the body and lead to toxicity.
The most relevant disorders on the urea cycle are genetic, leading to defective enzymes or transporters inhibiting the reabsorption of urate with the subsequent increase in ammonia levels, which is toxic.
Certain transporters located in the nephron in the apical and basolateral surfaces regulate uric acid serum levels.
The well-known Nurse's Health Study found a correlation between the loss of kidney function and an increased dietary intake of animal protein by people who had already been diagnosed with renal disease.
For this reason, dietary protein restriction is a common treatment for people with renal disease in which proteinuria is present.
[17] Diets that regularly exceed the recommendations for protein intake have been found to lead to an increased glomerular filtration rate in the kidneys and also have an effect on the hormone systems in the body.
[15] Currently, evidence suggests that changes in renal function that occur in response to an increased dietary protein intake are part of the normal adaptive system employed by the body to sustain homeostasis.
Protein toxicity and other metabolic disorders associated with chronic kidney failure have been shown to be related to more systemic complications such as atherosclerosis, anemia, malnutrition, and hyperparathyroidism.
People with kidney disease who are not on dialysis are advised to avoid consumption of protein if possible, as consuming too much accelerates the condition and can lead to death.
[21] Under normal conditions in the body, ammonia, urea, uric acid, and creatinine are produced by protein metabolism and excreted through the kidney as urine.
[23] Increased creatinine levels in the blood can also be a sign of kidney damage and inability to excrete protein waste by-products properly.
[25] Lifestyle modifications like a diet low in protein, decreased sodium intake, and exercise can also be in incorporated as part of a treatment plan.
[25] Accumulation of protein metabolic waste products in the body can cause diseases and serious complications such as gout, uremia, acute renal failure, seizure, encephalopathy, and death.
Long-standing hyperuricemia can cause deposition of monosodium urate crystals in or around joints, resulting in an arthritic condition called gout.
Symptoms of uremia include nausea, vomiting, fatigue, anorexia, weight loss, and change in mental status.
[36] Protein toxicity, specifically ammonia buildup, can affect preterm newborns that have serious defects in the urea cycle enzymes with almost no physical manifestations at birth.
Clinical symptoms can manifest within a few days of birth, causing extreme illness and intellectual disability or death, if left untreated.
[3] Hyperammonemia in newborns can be diagnosed with visual cues like sepsis-like presentation, hyperventilation, fluctuating body temperature, and respiratory distress; blood panels can also be used to form differential diagnoses between hyperammonemia caused by urea cycle disorders and other disorders.
[38] Cellular deficits and genetic mutations caused by these neurodegenerative diseases can pathologically alter gene transcription, negatively affecting protein metabolism.