Uremia is defined as "the illness accompanying kidney failure that cannot be explained by derangements in extracellular volume, inorganic ion concentrations, or lack of known renal synthetic products."[1]
It is a clinical syndrome; the glomerular filtration rate (GFR), blood urea nitrogen, and creatinine do not always correlate to the severity of disease. [2] No single toxin causes it, but those implicated include as parathyroid hormone (PTH), beta2-microglobulin, polyamines, and advanced glycosylation end products.[3]
Nevertheless, the GFR is a guideline. Signs such as well-being, fatigue, and reduced stamina may occur when it falls below 50 to 60 ml per minute per 1.73 m2. Subtle cognitive dysfunction may occur when it is less than 30 to 60 ml per minute per 1.73 m2.[1]
Spontaneous subdural hematomas are more frequent in patients with uremia, particularly if the BUN level is greater than 150-200 mg/dL. Brain CT should be considered if the mental state alters, especially after trauma, even mild trauma.
Fatigue is also associated with anemia of chronic disease, which may be due to the kidneys failing to produce inadequate erythropoietin (EPO), a hormone that triggers erythropoiesis in the bone marrow. In non-diabetic patients, this may be seen when GFR) is < 50 mL/min or when the serum creatinine is greater than 2 mg/dL. Diabetic patients may experience anemia with a GFR of less than 60 mL/min. Anemia associated with chronic kidney disease is characteristically normocytic, normochromic, and hypoproliferative.[3]
In renal disease, anemia may be due to factors other than inadequate EPO, including iron deficiency, , folic acid or vitamin B-12 deficiency, hyperparathyroidism, hypothyroidism, and decreased red blood cell survival. Iron deficiency can be due to occult bleeding, but also from overly aggressive blood drawing for diagnostic tests, and must be excluded. While EPO can be administered to correct deficiency, it is not a benign drug and is extremely expensive.
Parathyroid hormone is believed to cause calcification of the bone marrow, and can be treated with surgical parathyroidectomy.[3]
Insulin resistance may occur when the GFR falls below 50 ml per minute per 1.73 m2.[1]
Diabetes is the most common cause of renal failure in the United States, and it must be understood and treated. Reductions in renal function can lead to reduced insulin clearance, causing increased insulin secretion and episodes of hypoglycemia and normalization of hyperglycemia in diabetic patients. In patients with existing diabetes, apparent improvement in blood glucose control may actually be a grave sign of renal dysfunction, requiring reduction of insulin or oral hypoglycemic drug doses.[3]
Treatment options include hemodialysis, peritoneal dialysis, or renal transplant. Hemodialysis is usually done three times a week and each session removes about two-thirds of the total-body urea content.[1]
The five year survival for patients starting both hemodialysis and peritoneal dialysis is about 35%.[1]