letter "p" to the stage of chronic kidney disease if protein loss is significant. stage 1: slightly diminished function; kidney damage with normal or relatively high gfr (≥90 ml/min/1.73 m2) and persistent albuminuria. kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. stage 2: mild reduction in gfr (60–89 ml/min/1.73 m2) with kidney damage. kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. stage 3: moderate reduction in gfr (30–59 ml/min/1.73 m2):. british guidelines distinguish between stage 3a (gfr 45–59) and stage 3b (gfr 30–44) for purposes of screening and referral. stage 4: severe reduction in gfr (15–29 ml/min/1.73 m2) preparation for kidney replacement therapy. stage 5: established kidney failure (gfr <15 ml/min/1.73 m2), permanent kidney replacement therapy, or end-stage kidney disease. the term "non-dialysis-dependent chronic kidney disease" (ndd-ckd) is a designation used to encompass the status of those persons with an established ckd who do not yet require the life-supporting treatments for kidney failure known as kidney replacement therapy (rrt, including maintenance dialysis or kidney transplantation). the condition of individuals with ckd, who require either of the two types of kidney replacement therapy (dialysis or transplant), is referred to as the end-stage kidney disease (eskd). hence, the start of the eskd is practically the irreversible conclusion of the ndd-ckd. even though the ndd-ckd status refers to the status of persons with earlier stages of ckd (stages 1 to 4), people with advanced stage of ckd (stage 5), who have not yet started kidney replacement therapy, are also referred to as ndd-ckd. management apart from controlling other risk factors, the goal of therapy is to slow down or halt the progression of ckd. control of blood pressure and treatment of the original disease are the broad principles of management. blood pressure angiotensin converting enzyme inhibitors (aceis) or angiotensin ii receptor antagonists (arbs) are recommended as first-line agents since they have been found to slow the decline of kidney function, relative to a more rapid decline in those not on one of these agents. they have also been found to reduce the risk of major cardiovascular events such as myocardial infarction, stroke, heart failure, and death from cardiovascular disease when compared to placebo in individuals with ckd. aceis may be superior to arbs for protection against progression to kidney failure and death from any cause in those with ckd. aggressive blood pressure lowering decreases people's risk of death. other measures aggressive treatment of high blood lipids is recommended. a low-protein, low-salt diet may result in slower progression of ckd and reduction in proteinuria as well as controlling symptoms of advanced ckd to delay dialysis start. a tailored low-protein diet, designed for low acidity, may help prevent damage to kidneys for people with ckd. additionally, controlling salt ingestion helps to decrease the incidence of coronary heart disease, lowering blood pressure and reducing albuminuria. anemia – a target hemoglobin level of 9–12 g/dl is recommended; raising hemoglobin levels to the normal range has not been found to be of benefit. guidelines recommend treatment with parenteral iron prior to treatment with erythropoietin. replacement of erythropoietin is often necessary in people with advanced disease. it is unclear if androgens improve anemia. calcitriol is recommended for vitamin d deficiency and control of metabolic bone disease. phosphate binders are used to control the serum phosphate levels, which are usually elevated in advanced chronic kidney disease. phosphodiesterase-5 inhibitors and zinc may improve sexual dysfunction in men. weight loss obesity may have a negative impact in ckd, increasing the risk of disease progression to eskd or kidney failure compared to controls with healthy weight, and when in advanced stages also may hinder people's eligibility to kidney transplantation. for example, the consumption of high calorie and high fructose beverages can make an individual "60% more likely to develop ckd". weight management interventions in overweight and obese adults with ckd (of various stages) have been studied to assess its safety and efficacy. a recent systematic review collected evidence from 17 studies which evaluated lifestyle (including dietary, physical activity/exercise, or behavioural strategies used in isolation or in combination), pharmacological (used to reduce absorption or suppress appetite) and surgical interventions. the review concluded that lifestyle interventions may provide some health benefits, namely improving body weight, low density lipoprotein (ldl) cholesterol and diastolic blood pressure (dbp), when compared to usual care or controls. whether these benefits extend to help reducing cardiovascular events, kidney function and risk of death is uncertain. these conclusions were based on very low quality of evidence, so future robust studies are needed. thus, it is recommended that weight management interventions should be individualised, according to a thorough patients' assessment regarding clinical condition, motivations and preferences. dietary salt intake high dietary sodium intake may increase the risk of hypertension and cardiovascular disease. the effect of dietary restriction of salt in foods has been investigated in people with chronic kidney disease. a 2021 cochrane review of controlled trials in people with ckd at any stage, including those on dialysis, found high-certainty evidence that reduced salt intake may help to lower both systolic and diastolic blood pressure, as well as albuminuria. however there was also moderate certainty evidence that some people may experience hypotensive symptoms, such as dizziness, following sudden sodium restriction. it is unclear whether this affects the dosage required for anti-hypertensive medications. the effect of salt restriction on extracellular fluid, oedema, and total body weight reduction was also uncertain. omega-3 fatty acid supplementation in people with ckd who require hemodialysis, there is a risk that vascular blockage due to clotting, may prevent dialysis therapy from being possible. omega-3 fatty acids contribute to the production of eicosanoid molecules that reduce clotting. however, a cochrane review in 2018 did not find clear evidence that omega-3 supplementation has any impact on the prevention of vascular blockage in people with ckd. there was also moderate certainty that supplementation did not prevent hospitalisation or death within a 12-month period. protein supplementation there is moderate-certainty evidence that regular consumption of oral protein-based nutritional supplements may increase serum albumin levels slightly in people with ckd, especially among those requiring hemodialysis or who are malnourished. pre-albumin levels and mid-arm circumference measurements may also be increased following supplementation, though the certainty of evidence is low. despite possible improvement in these indicators of nutritional status, it is not certain that protein supplements affect quality of life, life expectancy, inflammation or body composition. iron supplementation a cochrane review of controlled trials comparing intravenous (iv) iron therapy with oral iron supplements, found low-certainty evidence that people receiving iv-iron treatment were 1.71 times as likely to reach their target hemoglobin levels. overall, hemoglobin was 0.71g/dl higher than those treated with oral iron supplements. iron stores in the liver, estimated by serum ferritin, were also 224.84 µg/l higher in those receiving iv-iron. however there was also low-certainty evidence that allergic reactions were more likely following iv-iron therapy. it was unclear whether type of iron therapy administration affects the risk of death from any cause, including cardiovascular, nor whether it may alter the number of people who may require a blood transfusion or dialysis. sleep people with ckd experience sleep disorders, thus not being able to get quality sleep. there are several strategies that could help, such as relaxation techniques, exercise, acupressure and medication: exercise: weak evidence demonstrates that exercise may be helpful with sleep regulation. nevertheless, exercise possibly decreases fatigue and depression in people with ckd. acupressure: evidence suggests that this technique may have slight effects on latency and sleep duration, as well as on fatigue reduction, although these results are not reliable due to the diversity of conclusions in several articles. despite all the available options studied so far, evidence shows that none of them is effective in the treatment of sleep disorders. this means that we are not able to conclude which is the best guidance to improve sleep quality in this type of population. ehealth interventions there is currently limited evidence suggesting that ehealth interventions may improve dietary sodium intake and fluid management for people with chronic kidney disease (ckd). the findings are based on low certainty evidence of 43 studies. so, more large and higher quality research studies are needed to understand the impact of ehealth on the health of people with ckd. referral to a nephrologist guidelines for referral to a nephrologist vary between countries. most agree that nephrology referral is required by stage 4 ckd (when egfr/1.73m2 is less than 30 ml/min; or decreasing by more than 3 ml/min/year). it may also be useful at an earlier stage (e.g. ckd3) when urine albumin-to-creatinine ratio is more than 30 mg/mmol, when blood pressure is difficult to control, or when hematuria or other findings suggest either a primarily glomerular disorder or secondary disease amenable to specific treatment. other benefits of early nephrology referral include proper education regarding options for kidney replacement therapy as well as pre-emptive transplantation, and timely workup and placement of an arteriovenous fistula in those people with chronic kidney disease opting for future hemodialysis. renal replacement therapy at stage 5 ckd, kidney replacement therapy is usually required, in the form of either dialysis or a kidney transplant. in ckd numerous uremic toxins accumulate in the blood. even when eskd (largely synonymous with ckd5) is treated with dialysis, the toxin levels do not go back to normal as dialysis is not that efficient. similarly, after a kidney transplant, the levels may not go back to normal as the transplanted kidney may not work 100%. if it does, the creatinine level is often normal. the toxins show various cytotoxic activities in the serum and have different molecular weights, and some of them are bound to other proteins, primarily to albumin. uremic toxins are classified into three groups as small water-soluble solutes, middle molecular-weight solutes, and protein-bound solutes. hemodialysis with high-flux dialysis membrane, long or frequent treatment, and increased blood/dialysate flow has improved removal of water-soluble small molecular weight uremic toxins. middle molecular weight molecules are removed more effectively with hemodialysis using a high-flux membrane, hemodiafiltration and hemofiltration. however, conventional dialysis treatment is limited in its ability to remove protein-bound uremic toxins. prognosis ckd increases the risk of cardiovascular disease, and people with ckd often have other risk factors for heart disease, such as high blood lipids. the most common cause of death in people with ckd is cardiovascular disease rather than kidney failure. chronic kidney disease results in worse all-cause mortality (the overall death rate) which increases as kidney function decreases. the leading cause of death in chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5. while kidney replacement therapies can maintain people indefinitely and prolong life, the quality of life is negatively affected. kidney transplantation increases the survival of people with stage 5 ckd when compared to other options; however, it is associated with an increased short-term mortality due to complications of the surgery. transplantation aside, high-intensity home hemodialysis appears to be associated with improved survival and a greater quality of life, when compared to the conventional three-times-a-week hemodialysis and peritoneal dialysis. people with eskd are at increased overall risk for cancer. this risk is particularly high in younger people and gradually diminishes with age. medical specialty professional organizations recommend that physicians do not perform routine cancer screening in people with limited life expectancies due to eskd because evidence does not show that such tests lead to improved outcomes. in children, growth failure is a common complication from ckd. children with ckd will be shorter than 97% of children the same age and sex. this can be treated with additional nutritional support, or medication such as growth hormone epidemiology about one in ten people have chronic kidney disease. in canada 1.9 to 2.3 million people were estimated to have ckd in 2008. ckd affected an estimated 16.8% of u.s. adults aged 20 years and older in the period from 1999 to 2004. in 2007 8.8% of the population of great britain and northern ireland had symptomatic ckd. chronic kidney disease was the cause of 956,000 deaths globally in 2013, up from 409,000 deaths in 1990. chronic kidney disease of unknown aetiology the cause of chronic kidney disease