<unk>  is initially without symptoms, and is usually detected on routine screening blood work by either an increase in serum creatinine, or protein in the urine. As the<unk>  function decreases, more unpleasant symptoms may emerge: * Blood pressure is increased due to fluid overload and production of vasoactive hormones created by the<unk>  via the renin–angiotensin system, increasing the risk of developing hypertension and heart failure. * Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Due to its high systemic concentration, urea is excreted in eccrine sweat at high concentrations and crystallizes on skin as the sweat evaporates ("uremic frost"). * Potassium accumulates in the blood (hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias). Hyperkalemia usually does not develop until the glomerular filtration rate falls to less than 20–25 ml/min/1.73 m2, at which point the<unk> s have decreased ability to excrete potassium. Hyperkalemia in<unk>  can be exacerbated by acidemia (which leads to extracellular shift of potassium) and from lack of insulin. * Fluid overload symptoms may range from mild edema to life-threatening pulmonary edema. * Hyperphosphatemia results from poor phosphate elimination in the<unk> . Hyperphosphatemia contributes to increased cardiovascular risk by causing vascular calcification. Circulating concentrations of fibroblast growth factor-23 (FGF-23) increase progressively as the<unk>  capacity for phosphate excretion declines which may contribute to left ventricular hypertrophy and increased mortality in people with<unk>  . * Hypocalcemia results from 1,25 dihydroxyvitamin D3 deficiency (caused by high FGF-23 and reduced<unk>  mass) and resistance to the action of parathyroid hormone. Osteocytes are responsible for the increased production of FGF-23, which is a potent inhibitor of the enzyme 1-alpha-hydroxylase (responsible for the conversion of 25-hydroxycholecalciferol into 1,25 dihydroxyvitamin D3). Later, this progresses to secondary hyperparathyroidism,<unk>  osteodystrophy, and vascular calcification that further impairs cardiac function. An extreme consequence is the occurrence of the rare condition named calciphylaxis. * Changes in mineral and bone metabolism that may cause 1) abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or vitamin D metabolism; 2) abnormalities in bone turnover, mineralization, volume, linear growth, or strength<unk>  osteodystrophy); and 3) vascular or other soft-tissue calcification.<unk> -mineral and bone disorders have been associated with poor outcomes. * Metabolic acidosis may result from decreased capacity to generate enough ammonia from the cells of the proximal tubule. Acidemia affects the function of enzymes and increases excitability of cardiac and neuronal membranes by the promotion of hyperkalemia. * Anemia is common and is especially prevalent in those requiring haemodialysis. It is multifactorial in cause, but includes increased inflammation, reduction in erythropoietin, and hyperuricemia leading to bone marrow suppression. Hypoproliferative anemia occurs due to inadequate production of erythropoietin by the<unk> s. * In later stages, cachexia may develop, leading to unintentional weight loss, muscle wasting, weakness and anorexia. * Sexual dysfunction is very common in both men and women with<unk> . A majority of men have a reduced sex drive, difficulty obtaining an erection, and reaching orgasm, and the problems get worse with age. A majority of women have trouble with sexual arousal, and painful menstruation and problems with performing and enjoying sex are common. * People with<unk>  are more likely than the general population to develop atherosclerosis with consequent cardiovascular disease, an effect that may be at least partly mediated by uremic toxins. People with both<unk>  and cardiovascular disease have significantly worse prognoses than those with only cardiovascular disease.
Chronic kidney disease
Chronic liver disease
End stage pulmonary disease
Hypertensive kidney disease
Diabetes
Proteinopathy
Cirrhosis
Chronic critical illness