chronic kidney disease chronic kidney disease chronic kidney disease (ckd) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. complications can relate to hormonal dysfunction of the kidneys and include (in chronological order) high blood pressure (often related to activation of the renin–angiotensin system system), bone disease, and anemia. additionally ckd patients have markedly increased cardiovascular complications with increased risks of death and hospitalization. chronic kidney diseaseother nameschronic renal disease, kidney failure, impaired kidney functionillustration of a kidney from a person with chronic renal failurespecialtynephrologysymptomsearly: nonelater: leg swelling, feeling tired, vomiting, loss of appetite, confusioncomplicationsheart disease, high blood pressure, anemiadurationlong-termcausesdiabetes, high blood pressure, glomerulonephritis, polycystic kidney diseasediagnostic methodblood tests, urine teststreatmentmedications to manage blood pressure, blood sugar, and lower cholesterol, renal replacement therapy, kidney transplantfrequency753 million (2016)deaths1.2 million (2015) causes of chronic kidney disease include diabetes, high blood pressure, glomerulonephritis, and polycystic kidney disease. risk factors include a family history of chronic kidney disease. diagnosis is by blood tests to measure the estimated glomerular filtration rate (egfr), and a urine test to measure albumin. ultrasound or kidney biopsy may be performed to determine the underlying cause. several severity-based staging systems are in use. screening at-risk people is recommended. initial treatments may include medications to lower blood pressure, blood sugar, and cholesterol. angiotensin converting enzyme inhibitors (aceis) or angiotensin ii receptor antagonists (arbs) are generally first-line agents for blood pressure control, as they slow progression of the kidney disease and the risk of heart disease. loop diuretics may be used to control edema and, if needed, to further lower blood pressure. nsaids should be avoided. other recommended measures include staying active, and certain dietary changes such as a low-salt diet and the right amount of protein. treatments for anemia and bone disease may also be required. severe disease requires hemodialysis, peritoneal dialysis, or a kidney transplant for survival. chronic kidney disease affected 753 million people globally in 2016 - 417 million females and 336 million males. in 2015, it caused 1.2 million deaths, up from 409,000 in 1990. the causes that contribute to the greatest number of deaths are high blood pressure at 550,000, followed by diabetes at 418,000, and glomerulonephritis at 238,000. signs and symptoms uremic frost on the head in someone with chronic kidney disease ckd 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 kidney function decreases, more unpleasant symptoms may emerge: blood pressure is increased due to fluid overload and production of vasoactive hormones created by the kidney via the renin–angiotensin system, increasing the risk of developing hypertension and heart failure. people with ckd 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 ckd and cardiovascular disease have significantly worse prognoses than those with only cardiovascular disease. 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, when the kidneys have decreased ability to excrete potassium. hyperkalemia in ckd 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 kidney, and contributes to increased cardiovascular risk by causing vascular calcification. circulating concentrations of fibroblast growth factor-23 (fgf-23) increase progressively as the kidney capacity for phosphate excretion declines, which may contribute to left ventricular hypertrophy and increased mortality in people with ckd . hypocalcemia results from 1,25 dihydroxyvitamin d3 deficiency (caused by high fgf-23 and reduced kidney 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, kidney 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 (kidney osteodystrophy); and 3) vascular or other soft-tissue calcification. ckd-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 kidneys. in later stages, cachexia may develop, leading to unintentional weight loss, muscle wasting, weakness, and anorexia. cognitive decline in patients experiencing ckd is an emerging symptom revealed in research literature. current research suggests that patients with ckd face a 35-40% higher likelihood of cognitive decline and or dementia. this relation is dependent on the severity of ckd in each patient; although emerging literature indicates that patients at all stages of ckd will have a higher risk of developing these cognitive issues. sexual dysfunction is very common in both men and women with ckd. a majority of men have a reduced sex drive, difficulty obtaining an erection, and reaching orgasm, and the problems get worse with age. most women have trouble with sexual arousal, and painful menstruation and problems with performing and enjoying sex are common. causes the three most common causes of ckd in order of frequency as of 2015 are diabetes mellitus, hypertension, and glomerulonephritis. about one of five adults with hypertension and one of three adults with diabetes have ckd. if the cause is unknown, it is called idiopathic. by anatomical location vascular disease includes large-vessel disease such as bilateral kidney artery stenosis and small-vessel disease such as ischemic nephropathy, hemolytic-uremic syndrome, and vasculitis. glomerular disease comprises a diverse group and is classified into: primary glomerular disease such as focal segmental glomerulosclerosis and iga nephropathy (or nephritis) secondary glomerular disease such as diabetic nephropathy and lupus nephritis tubulointerstitial disease includes drug- and toxin-induced chronic tubulointerstitial nephritis, and reflux nephropathy obstructive nephropathy, as exemplified by bilateral kidney stones and benign prostatic hyperplasia of the prostate gland; rarely, pinworms infecting the kidney can cause obstructive nephropathy. other genetic congenital disease such as polycystic kidney disease or 17q12 microdeletion syndrome. mesoamerican nephropathy, is "a new form of kidney disease that could be called agricultural nephropathy". a high and so-far unexplained number of new cases of ckd, referred to as the mesoamerican nephropathy, has been noted among male workers in central america, mainly in sugarcane fields in the lowlands of el salvador and nicaragua. heat stress from long hours of piece-rate work at high average temperatures of about 36 °c (96 °f) is suspected, as are agricultural chemicals diagnosis a 12-lead ecg of a person with ckd and a severe electrolyte imbalance: hyperkalemia (7.4 mmol/l) with hypocalcemia (1.6 mmol/l). the t-waves are peaked and the qt interval is prolonged. diagnosis of ckd is largely based on history, examination, and urine dipstick combined with the measurement of the serum creatinine level (see above). differentiating ckd from acute kidney injury (aki) is important because aki can be reversible. one diagnostic clue that helps differentiate ckd from aki is a gradual rise in serum creatinine (over several months or years) as opposed to a sudden increase in the serum creatinine (several days to weeks). in many people with ckd, previous kidney disease or other underlying diseases are already known. a significant number present with ckd of unknown cause. screening screening those who have neither symptoms nor risk factors for ckd is not recommended. those who should be screened include: those with hypertension or history of cardiovascular disease, those with diabetes or marked obesity, those aged > 60 years, subjects with african american ancestry, those with a history of kidney disease in the past, and subjects who have relatives who had kidney disease requiring dialysis. screening should include calculation of the estimated gfr (egfr) from the serum creatinine level, and measurement of urine albumin-to-creatinine ratio (acr) in a first-morning urine specimen (this reflects the amount of a protein called albumin in the urine), as well as a urine dipstick screen for hematuria. the gfris derived from the serum creatinine and is proportional to 1/creatinine, i.e. it is a reciprocal relationship; the higher the creatinine, the lower the gfr. it reflects one aspect of kidney function, how efficiently the glomeruli - the filtering units - work. normal gfr is 90-120 ml/min. the units of creatinine vary from country to country, but since the glomeruli make up <5% of the mass of the kidney, the gfr does not indicate all aspects of kidney health and function. this can be done by combining the gfr level with the clinical assessment of the person, including fluid status, and measuring the levels of hemoglobin, potassium, phosphate, and parathyroid hormone. ultrasound kidney ultrasonography is useful for diagnostic and prognostic purposes in chronic kidney disease. whether the underlying pathologic change is glomerular sclerosis, tubular atrophy, interstitial fibrosis, or inflammation, the result is often increased echogenicity of the cortex. the echogenicity of the kidney should be related to the echogenicity of either the liver or the spleen (figure 22 and figure 23). moreover, decreased kidney size and cortical thinning are also often seen and especially when disease progresses (figure 24 and figure 25). however, kidney size correlates to height, and short persons tend to have small kidneys; thus, kidney size as the only parameter is not reliable. chronic renal disease caused by glomerulonephritis with increased echogenicity and reduced cortical thickness. measurement of kidney length on the us image is illustrated by '+' and a dashed line. nephrotic syndrome. hyperechoic kidney without demarcation of cortex and medulla. chronic pyelonephritis with reduced kidney size and focal cortical thinning. measurement of kidney length on the us image is illustrated by '+' and a dashed line. end-stage chronic kidney disease with increased echogenicity, homogenous architecture without visible differentiation between parenchyma and renal sinus and reduced kidney size. measurement of kidney length on the us image is illustrated by '+' and a dashed line. additional imaging additional tests may include nuclear medicine mag3 scan to confirm blood flow and establish the differential function between the two kidneys. dimercaptosuccinic acid (dmsa) scans are also used in kidney imaging; with both mag3 and dmsa being used chelated with the radioactive element technetium-99. stages chronic kidney disease (ckd) staging - ckd g1-5 a1-3 glomerular filtration rate (gfr) and albumin/creatinine ratio (acr) acr a1a2a3 normal to mildly increasedmoderately increasedseverely increased <3030–300>300 g f r g1normal≥ 901 if kidney damage present12 g2mildly decreased60–891 if kidney damage present12 g3amildly to moderately decreased45–59123 g3bmoderately to severely decreased30–44233 g4severely decreased15–2934+4+ g5kidney failure<154+4+4+ numbers 1 – 4 indicates risk of progression as well as frequency of monitoring (number of times a year). kidney disease improving global outcomes - kdigo 2012 clinical practice guideline for the evaluation and management of chronic kidney disease a glomerular filtration rate (gfr) ≥ 60 ml/min/1.73 m2 is considered normal without chronic kidney disease if there is no kidney damage present. kidney damage is defined signs of damage seen in blood, urine, or imaging studies which includes lab albumin/creatinine ratio (acr) ≥ 30. all people with a gfr <60 ml/min/1.73 m2 for 3 months are defined as having chronic kidney disease. protein in the urine is regarded as an independent marker for worsening of kidney function and cardiovascular disease. hence, british guidelines append the