Testing people with risk factors (case-finding) is recommended.[15][12] Initial treatments may include medications to lower blood pressure, blood sugar, and cholesterol.[14]Angiotensin converting enzyme inhibitors (ACEIs) orangiotensin 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.[21]Loop diuretics may be used to controledema and, if needed, to further lower blood pressure.[22][14][23]NSAIDs should be avoided.[14] Other recommended measures include staying active,[15] and "to adopt healthy and diverse diets with a higher consumption of plant-based foods compared to animal-based foods and a lower consumption of ultraprocessed foods."[15][14][24] Plant-based diets are feasible and are associated with improved intermediate outcomes and biomarkers.[25] An example of a general, healthy diet, suitable for people with CKD who do not require restrictions, is the Canada Food Guide Diet.[26] People with CKD who require dietary restrictions or who have other specific nutritional problems should be referred to a dietitian.[15] Treatments for anemia and bone disease may also be required.[27][28] Severe disease requireshemodialysis,peritoneal dialysis, or a kidney transplant for survival.[13]
Eight to 16% of the world population has chronic kidney disease.[29] Other estimates have chronic kidney disease affecting 753 million people globally in 2016 (417 million females and 336 million males).[1][30] In 2015, it caused 1.2 million deaths, up from 409,000 in 1990.[6][31] 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.[6]
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 inserum creatinine, orprotein in the urine. As the kidney function decreases, more unpleasant symptoms may emerge:[32]
Blood pressure is increased due to fluid overload and the production of vasoactive hormones created by the kidney via the renin-angiotensin system, increasing the risk of developinghypertension andheart failure. People with CKD are more likely than the general population to developatherosclerosis with consequentcardiovascular disease, an effect that may be at least partly mediated by uremic toxins.[33]
Urea accumulates, leading toazotemia and ultimatelyuremia (symptoms ranging fromlethargy topericarditis andencephalopathy). Due to its high systemic concentration, urea is excreted in eccrine sweat at high concentrations and crystallizes on the skin as the sweat evaporates ("uremic frost").
Potassium accumulates in the blood (hyperkalemia with a range of symptoms includingmalaise and potentially fatalcardiac arrhythmias). Hyperkalemia usually does not develop until theglomerular 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 (triggering the cells to release potassium into the bloodstream to neutralize the acid) and from a lack ofinsulin.[34]
Hyperphosphatemia results from poor phosphate elimination in the kidney, and contributes to increased cardiovascular risk by causing vascular calcification.[35] Circulating concentrations offibroblast 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 .[36][37]
Metabolic acidosis may result from decreased capacity to generate enoughammonia from the cells of the proximal tubule.[34] Acidemia affects the function of enzymes and increases the excitability of cardiac and neuronal membranes by the promotion of hyperkalemia.[42]
Anemia is common and is especially prevalent in those requiring hemodialysis. It is multifactorial in cause but includes increased inflammation, reduction inerythropoietin, and hyperuricemia leading to bone marrow suppression. Hypoproliferative anemia occurs due to inadequate production of erythropoietin by the kidneys.[43]
In later stages,cachexia may develop, leading to unintentional weight loss, muscle wasting, weakness, andanorexia.[44]
Cognitive decline in patients experiencing CKD is an emerging symptom revealed in research literature.[45][46][47][48] Research suggests that patients with CKD face a 35–40% higher likelihood of cognitive decline and or dementia.[45][46] 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.[48][49][46]
Sexual dysfunction is very common in both men and women with CKD. A majority of men have a reducedsex drive,difficulty obtaining an erection, and difficulty reaching orgasm, and the problems get worse with age. Most women have trouble with sexual arousal, andpainful menstruation and problems with performing and enjoying sex are common.[50]
Ankle ulcers in CKD are not simple "gravitational" venous leg ulcers; they arise from a triad of vessel-specific pathology unique torenal disease:[51][52][53]
Calcific uremic arteriolopathy (CUA) =calciphylaxisIntimal calcium deposits ➔ painful, livedo-reticularis patch ➔ black eschar ➔ full-thickness necrosis, usually on the medial malleolus, calf or inner thigh.Risk factors: serum Ca × P product > 55 mg²/dl², hyper-parathyroidism, warfarin, female sex, albumin < 3 g/dl.Histology: medial calcification + micro-thrombi; von-Kossa stain positive.Uremic small-vessel disease (USD) – "toxic vasculitis"
Endothelial injury from retained solutes (indoxyl-sulfate, guanidino-succinate) + oxidative stress ➔fragile, petechial skin, then ulceration or persistent erosion around lateralmalleolus.Biopsy: non-specific lympho-histiocytic infiltrate, but direct immunofluoresence is negative (helps rule out true vasculitis).
Mixed arterio-venous high-pressure ulcer
CKD plus diabetes/ageing ➔ stiff medial-calcified arteries + incompetent perforators ➔ ankle "hybrid" ulcer with both arterial pallor and venouslipodermatosclerosis.Ankle-brachial index (ABI) may be falsely high (> 1.3) because of medial calcification; toe pressure or trans-cutaneous O₂ (TcPO₂ < 30 mmHg) is more reliable.Clinical red flags
Sudden-onset, excruciating, reticular, black eschar on medial malleolus ➔ think CUA until proven otherwise.Ulcer surrounded by purplish, mottled, finely-speckled purpura, normal pulses ➔ likely USD.Plain X-ray of calf/ankle: tram-track medial calcification supports CUA; absence of calcification favours USD.
Treatment principlesPain control (opioid often required) and remove triggers: stop warfarin, correct hyper-calcaemia/phosphate, cinacalcet/parathyroidectomy if severe hyper-PTH.Sodium thiosulfate (intravenous 25 g × 3/week) – proven to chelate calcium and improve ulcer healing in CUA (retrospective cohorts > 60 % complete healing).Intensified dialysis (nocturnal or HDF) – lowers middle-molecule toxins in USD.Correct anaemia (Hb 10–11 g/dl) and albumin > 3.5 g/dl – oxygen delivery & wound matrix.Low-molecular-weight heparin for 6–12 weeks if biopsy shows micro-thrombi.Conservative debridement only; sharp surgical debridement can extend CUA necrosis.Split-thickness skin grafting + negative-pressure therapy once granulation tissue appears (often 6–8 weeks after sodium-thiosulfate).
PrognosisCUA ulcers: 1-year mortality historically 45–80 %; with modern multi-modality therapy (sodium-thiosulfate, cinacalcet, intensified dialysis) healing improves to 50–70 % and 1-year survival rises to ≈ 75 %.USD ulcers: heal in 8–16 weeks if dialysis dose and nutrition optimized; recurrence rate 20–30 %.Bottom line: an ankle ulcer in a CKD patient is a vasculopathy alarm – distinguish calciphylaxis from uremic small-vessel disease early; multidisciplinary nephrology-wound care improves limb salvage and survival.
Chronic kidney disease (CKD) is staged by its severity, manifested inglomerular filtration rate (GFR) category (G1–G5), andalbuminuria category (A1–A3). The five GFR-based stages are what people usually mean:[54][55][56]
The stages of chronic kidney disease:
Current age
Men – NO albuminuria (A1)
Men – WITH albuminuria (A2–A3)
Women – NO albuminuria (A1)
Women – WITH albuminuria (A2–A3)
30 yr
44.2
38.1
48
41.8
35 yr
39.4
33.6
43.1
37.2
40 yr
34.6
29.2
38.3
32.7
45 yr
29.9
25
33.5
28.4
50 yr
25.3
21
28.8
24.3
55 yr
20.9
17.3
24.3
20.5
60 yr
16.7
13.9
19.9
16.9
65 yr
13
10.8
15.9
13.7
70 yr
9.8
8.2
12.3
10.8
75 yr
7.2
6
9.1
8.1
80 yr
5.1
4.3
6.5
5.8
85 yr
3.6
3
4.5
Damage = persistent albuminuria, hematuria, abnormal imaging, biopsy, etc.So: G1 → G5 (often still called “stage 1–5”) with G3 split into 3a and 3b.
Chronic Kidney Disease in different people can becaused by numerous reasons, withgenetic factors playing an increasingly recognized role. The most common cases of CKD are traditionally classified into 4 categories:[57][58]
Diabetes mellitus — Diabetes, particularly type 2, is the leading cause of CKD worldwide, accounting for 30–50% of ESKD cases, with type 1 contributing about 3.9%.[59][29][34] Elevatedblood glucose damages the filtering units (glomeruli) over time, leading to diabetic kidney disease,proteinuria, and impaired urine filtration.[59][60][61] Uncontrolled diabetes accelerates the progression of CKD.[62]
High Blood Pressure (Hypertension) — The second most common cause, responsible for about 27% of ESKD cases.[59][29][34]
High blood pressure damages blood vessels in the kidneys, reducing their ability to filterurine effectively. At the same time, slower water removal (i.e. increased water retention) leads to rise in the blood pressure. This results in a vicious positive feedback, where increased blood pressure leads to further kidney damage (hypertensive nephrosclerosis), and kidney damage leads to a rise in blood pressure.[59][60][61] Examples comprise secondary glomerular diseases, such as andlupus nephritis.
Metabolic, storage, and stone-forming disorders affecting kidneys
Fabry disease Gene: GLA (X‑linked).Features: angiokeratomas, neuropathic pain, proteinuria, progressive CKD/ESRD in untreated males and affected females.
Primary hyperoxaluria (oxalate overproduction leading to recurrent stones and oxalate nephropathy)Genes: AGXT (PH1; AR), GRHPR (PH2; AR), HOGA1 (PH3; AR).Features: recurrent nephrolithiasis/nephrocalcinosis, progressive CKD; systemic oxalate deposition in advanced disease.Cystinuria (stone disease)Genes: SLC3A1, SLC7A9 (AR or complex inheritance).Features: recurrent cystine stones; CKD can occur from obstructive episodes and chronic damage.
Complement‑ and TMA‑related disorders that cause kidney injury and CKD
Atypical hemolytic uremic syndrome (aHUS; complement‑mediated thrombotic microangiopathy)Genes with pathogenic variants that predispose to aHUS: CFH, CFI, MCP/CD46, CFB, C3, THBD, DGKE (DGKE-associated aHUS often recessive).Features: microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury; recurrent episodes can lead to CKD.C3 glomerulopathy and complement‑mediated GNGenes: CFH, CFI, C3, CFHR gene cluster variants; often complex/structural variants in CFHRs.
Mitochondrial DNA and nuclear genes affecting mitochondrial function can present withtubulointerstitial disease,FSGS, or multisystem disease with renal involvement (inheritance maternal for mtDNA variants; nuclear genes often AR or AD).
Primary CKDs are usually are caused bygenetic anomalies in the patient. Chronic kidney disease (CKD) affects over 800 million individuals globally and demonstrates significant genetic diversity. Advances in next-generation sequencing have identified over 600 genes associated with inherited kidney disorders, with monogenic variants accounting for 10% to 20% of adult and up to 50% of pediatric CKD cases.[64]
Sometimes such anomalies are often not inherited from a parent, but rather develop as in uterosomatic mutations before or even after the patient's birth.
Representative genes: NPHS1 (nephrin, AR, congenital NS), NPHS2 (podocin, AR), WT1 (AD or de novo; syndromic—Denys‑Drash/WAGR), LAMB2 (AR; Pierson syndrome), PLCE1, INF2 (AD), ACTN4 (AD), TRPC6 (AD).Features: massive proteinuria/nephrotic syndrome, often steroid resistant; many progress to ESRD in childhood or adulthood depending on gene.
Gene: APOL1 (two risk alleles — G1, G2 — in trans confer high risk in people of African ancestry).Features: increased risk for FSGS, collapsing glomerulopathy, progressive CKD; risk-modifying rather than classic Mendelian inheritance.
Glomerular disease (glomerulonephritis) - Inflammation of the kidney's filtering units, which can be caused by infections, autoimmune diseases, or other conditions. comprises a diverse group and is classified into:[citation needed]
Tubulointerstitial disease includes drug- and toxin-induced chronic tubulointerstitial nephritis, andreflux nephropathy
Mesoamerican nephropathy, is "a new form of kidney disease that could be called agricultural nephropathy".[70] A high and so-far unexplained number of new cases of CKD, referred to as theMesoamerican nephropathy, has been noted among male workers in Central America, mainly in sugarcane fields in the lowlands ofEl Salvador andNicaragua. Heat stress from long hours of piece-rate work at high average temperatures[71][72][73][74] of about 36 °C (96 °F) is suspected,[75] as areagricultural chemicals[76]
Diagnosis of CKD is largely based onhistory,examination, andurine dipstick combined with the measurement of the serumcreatinine level. Differentiating CKD fromacute kidney injury (AKI) is important because AKI can be reversible. One diagnostic clue that helps differentiate CKD fromAKI is a gradual rise in serum creatinine (over several months or years) as opposed to a sudden increase in 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.[citation needed]
Screening those who have neither symptoms nor risk factors for CKD is not recommended.[77][78] 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.[79]
Screening should include calculation of the estimated GFR (eGFR) from the serum creatinine level, and measurement of urinealbumin-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.[80]
TheGFR is 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. The normal GFR is >90 ml/min. The units of creatinine vary from country to country, but since the glomeruli comprise <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.[61]
Kidney ultrasonography is useful for diagnostic and prognostic purposes in chronic kidney disease. Whether the underlying pathologic change isglomerular sclerosis, tubular atrophy, interstitial fibrosis, or inflammation, the result is often increasedechogenicity of the cortex. The echogenicity of the kidney should be related to the echogenicity of the liver or the spleen. Moreover, decreased kidney size and cortical thinning are often seen, especially when the disease progresses. However, kidney size correlates to height, and short persons tend to have small kidneys; thus, kidney size as the only parameter is unreliable.[81]
Chronic renal disease caused byglomerulonephritis with increased echogenicity and reduced cortical thickness. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.[81]
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.[81]
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.[81]
Additional tests may includenuclear medicineMAG3 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 usedchelated with the radioactive elementtechnetium-99.[82]
Genetic tests for chronic kidney disease (CKD) can help identify the specific cause, predict its progression, and guide treatment. These tests range from targeted single-gene analysis to comprehensive sequencing of a person's entire genome. Genetic testing is most beneficial for patients with a family history of kidney disease, an early-onset diagnosis, or an unknown cause of their CKD.[83]
There are several types of genetic tests for CKD:[84][85]
•Targeted gene panels: These tests use next-generation sequencing (NGS) to examine hundreds of genes known to be associated with various hereditary kidney diseases. For example, the Renasight™ test fromNatera evaluates 397 genes, while a comprehensive panel fromMayo Clinic Laboratories covers over 300.
•Single-gene testing: If a family history points to a specific gene mutation, this test can confirm or rule out the diagnosis. This is often done withSanger sequencing. A well-known example is the APOL1 gene variant, which is more common in individuals of African descent and is associated with a higher risk for certain kidney diseases.
•Whole exome sequencing (WES): This technique sequences the exome, the protein-coding parts of all genes. It can identify mutations missed by gene panels, particularly when the genetic cause is less common or unknown. In adults with CKD of unknown origin, WES has provided a genetic diagnosis in up to 24% of cases.
•Whole genome sequencing (WGS): This is the most comprehensive test, sequencing the entire genome, including non-coding regions. WGS can detect genetic variations, such as copy number variants, that are missed by other methods. However, is it not used in practice because of its prohibitive cost.
•Chromosomal microarray: This test is used when large deletions, duplications, or rearrangements in chromosomes are suspected, especially in cases of congenital kidney disorders.
Inherited conditions identified through genetic testing
Genetic testing can identify many inherited kidney diseases, including:
•Autosomal Dominant Polycystic Kidney Disease (ADPKD): Caused by mutations in thePKD1 orPKD2 genes.[86]Genes: PKD1 (most severe, AD), PKD2 (AD, milder). Also associated/atypical genes: GANAB, DNAJB11 (both AD; often milder).Features: bilateral renal cysts, progressive enlargement of kidneys, hypertension; many progress to ESRD (age at ESRD depends on gene/variant).
•Autosomal recessive polycystic kidney disease (ARPKD)Gene: PKHD1 (AR).Features: perinatal/infantile or childhood presentation with enlarged echogenic kidneys, congenital hepatic fibrosis; many progress to CKD/ESRD in childhood or young adulthood.
•HNF1B-associated renal disease (variable cystic and structural anomalies; called “renal cysts and diabetes” in some contexts)Gene: HNF1B (typically AD de novo or inherited).Features: renal cysts or hypodysplasia, electrolyte tubulopathies, diabetes, variable progression to CKD.
•Congenital anomalies of the kidney and urinary tract (CAKUT) — genetically heterogeneousRepresentative genes: PAX2 (AD), EYA1 (AD), SALL1 (AD), ROBO2, RET, HNF1B; many others.Features: renal hypoplasia, dysplasia, ureteral anomalies; many CAKUT patients progress to CKD depending on severity.
•Alport Syndrome: Damages the small blood vessels in the kidneys and can also cause hearing loss. It is often caused by mutations in theCOL4A3,COL4A4, andCOL4A5 genes.[87]
•Fabry Disease: A storage disease that can lead to kidney disease.[88]
•Cystinosis: A buildup of an amino acid that can cause crystalline nephropathy.
•Nephronophthisis: A recessive disease that is a common genetic cause of kidney failure in children and young adults.[89]
Genes: UMOD (ADTKD-UMOD), MUC1 (ADTKD-MUC1), REN (ADTKD-REN). Other reported genes: HNF1B and SEC61A1 in some cases.
Features: progressive tubulointerstitial fibrosis, bland urinalysis, slowly progressive CKD often in adulthood.Caused by mutations in genes likeMUC1 orUMOD.[91] Autosomal dominant tubulointerstitial kidney disease (ADTKD;
Numbers 1–4 indicate the risk of progression as well as the 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[93]
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 as signs of damage seen in blood, urine, or imaging studies which include lab albumin/creatinine ratio (ACR) ≥ 30.[94] All people with a GFR <60 mL/min/1.73 m2 for 3 months are defined as having chronic kidney disease.[94]
Protein in the urine is regarded as an independent marker for the worsening of kidney function and cardiovascular disease. Hence, British guidelines append the letter "P" to the stage of chronic kidney disease if protein loss is significant.[95]
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.[94]
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,[94]albuminuria may be seen. Often asymptomatic; possible mild fatigue.Monitoring & tests (suggested frequency): eGFR/creatinine and urine ACR annually; more frequent if A2–A3 or uncontrolled comorbidities.
Stage 3: Moderate reduction in GFR (30–59 mL/min/1.73 m2):.[94] Modern guidelines distinguish between stage 3A (GFR 45–59) and stage 3B (GFR 30–44) for purposes of screening and referral.[95] Monitoring & tests (suggested frequency): eGFR/creatinine and urine ACR every 6–12 months; electrolytes and CBC every 6–12 months. Monitoring & tests (suggested frequency): eGFR and basic metabolic panel every 1–3 months; CBC, Ca/PO4, PTH every 3–6 months; iron studies as needed. Routine nephrology follow-up recommended; discuss renal replacement therapy (RRT) planning as eGFR approaches <15 or for refractory complications.
Stage 4: Severe reduction in GFR (15–29 mL/min/1.73 m2)[94] Typical symptoms: Marked uremic symptoms — severe fatigue, nausea/vomiting, anorexia, pruritus, cognitive impairment, dyspnea from fluid overload, bleeding tendency. Key labs / common complications: Marked azotemia (↑BUN/Cr), persistent hyperkalemia, metabolic acidosis, severe anemia, pronounced bone–mineral disorder.Preparation for kidney replacement therapy.
Stage 5: Established kidney failure (GFR <15 mL/min/1.73 m2), permanent kidney replacement therapy,[94] 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 forkidney failure known askidney replacement therapy (RRT, including maintenancedialysis orkidney transplantation). The condition of individuals with CKD, who require either of the two types of kidney replacement therapy (dialysis ortransplant), is referred to as end-stage kidney disease (ESKD). Hence, the start of the ESKD is practically theirreversible 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 stages of CKD (stage 5), who have not yet started kidney replacement therapy, are also referred to as NDD-CKD.
Chronic kidney disease (CKD) is a serious condition often linked to diabetes and high blood pressure. There is no cure (for most forms), but a combination of lifestyle changes and medications can help slow its progression. This might include a plant-dominant diet with less protein and salt, medications to control blood pressure and sugar, and potentially newer anti-inflammatory drugs. Doctors may also focus on managing heart disease risk, preventing infections, and avoiding further kidney damage. While dialysis may eventually be needed, a gradual transition can help preserve remaining kidney function. More research is ongoing to improve CKD management and patient outcomes.[96]
Chronic Kidney Disease (CKD) management focuses on slowing progression, managing complications, and improving quality of life. Treatment is staged based onglomerular filtration rate (GFR) andalbuminuria, following guidelines like those from KDIGO (Kidney Disease: Improving Global Outcomes). Early stages (1–3) emphasize risk factor modification, while advanced stages (4–5) may require renal replacement therapy. Multidisciplinary care involving nephrologists, dietitians, and pharmacists is key. Goals include controlling blood pressure (<130/80 mmHg), glycemic control (HbA1c <7%), and reducing cardiovascular risk. Below is an overview of main options.
Angiotensin converting enzyme inhibitors (ACEIs) orangiotensin 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.[21] They have also been found to reduce the risk of major cardiovascular events such asmyocardial infarction,stroke,heart failure, and death from cardiovascular disease when compared to placebo in individuals with CKD.[21] ACEIs may be superior to ARBs for protection against progression to kidney failure and death from any cause in those with CKD.[21] Aggressive blood pressure lowering decreases people's risk of death.[97]
Aggressive treatment of high blood lipids is recommended.[98]Statins are recommended for those with CKD older than 50 years old, and those younger if certain other indications exist.[29]
Certain medications that are cleared from the body by the kidneys may need dose adjustments or discontinuation in those with chronic kidney disease to prevent accumulation of the medications in the body.[29]
Sodium/glucose cotransporter 2 medications have shown kidney protective effects and protective effects in death from cardiovascular disease in those with chronic kidney disease and diabetes.
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.[99] A tailored low-protein diet, designed for low acidity, may help prevent damage to kidneys for people with CKD.[100] Additionally, controlling salt ingestion helps to decrease the incidence of coronary heart disease, lowering blood pressure and reducing albuminuria.[101]
Anemia – A target hemoglobin level of 100–120 g/L is recommended;[102][103] raising hemoglobin levels to the normal range has not been found to be of benefit.[104]
Gadolinium basedMRI contrast agents are contra-indicated in those with GFR less than 30 (stage 4 kidney disease) due to the risk ofnephrogenic systemic fibrosis. However, this risk is believed to be low in people with CKD with newer contrast agents being currently used.[29]
Obesity may have a negative impact in CKD, increasing the risk of disease progression to ESKD orkidney failure compared to controls with healthy weight,[107] and when in advanced stages, also may hinder people's eligibility tokidney transplantation.[108] For example, the consumption of high calorie andhigh fructose beverages can make an individual "60% more likely to develop CKD".[109][110]
Weight management interventions inoverweight andobese adults with CKD include lifestyle interventions (dietary changes,physical activity/exercise, or behavioural strategies), pharmacological (used to reduce absorption orsuppress appetite) and surgical interventions. Any of these can help people with CKD lose weight; however, it is not known if they can also prevent death or cardiovascular events like heart complications or stroke.[111] It is recommended that weight management interventions should be individualised, according to a thorough patient assessment regarding clinical condition, motivations, and preferences.[111]
High dietary sodium intake may increase the risk of hypertension and cardiovascular disease. The effect of dietary salt restriction in foods has been investigated in people with chronic kidney disease. For people with CKD, including those on dialysis, reduced salt intake may help to lower both systolic and diastolic blood pressure, as well asalbuminuria.[112] Some people may experiencelow blood pressure and associated symptoms, such as dizziness, with lower salt intake. The effect of salt restriction on extracellular fluid, oedema, and total body weight reduction is unknown.[112]
EHealth interventions may improve dietary sodium intake and fluid management for people with CKD.[113]
In people with CKD who require hemodialysis, there is a risk thatvascular blockage due toclotting, may prevent dialysis therapy from being possible. Even thoughOmega-3 fatty acids contribute to the production ofeicosanoid molecules that reduce clotting, it does not have any impact on the prevention of vascular blockage in people with CKD.[114]
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.[115]Prealbumin level and mid-arm muscle circumference may also be increased following supplementation.[115] Despite possible improvement in these indicators of nutritional status, it is not certain that protein supplements affect the quality of life, life expectancy, inflammation, orbody composition.[115]
Individuals with CKD have an increased prevalence ofsleep apnea compared to the general population (bothobstructive sleep apnea andcentral sleep apnea). The presence of sleep apnea in CKD has been associated with an increased risk of cardiovascular events and mortality.[117]
People with CKD also experience sleep disorders, thus unable to get quality sleep. There are several strategies that could help, such as relaxation techniques, exercise, and medication. Exercise may be helpful with sleep regulation and may decrease fatigue and depression in people with CKD. However, none of these options have been proven to be effective in the treatment of sleep disorders. This means that it is unknown what the best guidance is to improve sleep quality in this population.[118]
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).[119]
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 a 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.[citation needed]
Inthe USA, a person with Chronic Kidney Disease (CKD) is usually referred to a nephrologist when their estimated GFR is less than 30 mL/min/1.73 m² (CKD Stage 4 or 5), but a referral may also be recommended with a GFR between 30-59 mL/min/1.73 m² (CKD Stage 3) if there are other risk factors like albuminuria or a rapid decline in kidney function.[120]
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.[121] 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.[122]
CKD increases the risk of cardiovascular disease, and people with CKD often have other risk factors for heart disease, such ashigh blood lipids. People with both CKD and cardiovascular disease have significantly worse prognoses than those with only cardiovascular disease.[123] Those with CKD have a higher prevalence of cardiovascular disease (65% compared to 32% in aMedicare population of people older than 66. Those with CKD in the population also had worse 2-year survival after a heart attack,atrial fibrillation,stroke ortransient ischemic attack (TIA, commonly known as a mini-stroke), heart failure orcoronary heart disease.[29]
Rapidly progressive CKD (rapid declines in the GFR or increasing albuminuria), uncontrolled hypertension, severe electrolyte abnormalities, structural abnormalities of the kidneys, hereditary kidney disease, blood in the urine, recurrent severe kidney stones, andnephrotic syndrome (high levels of protein in the urine) are all associated with a poor prognosis and more rapid progression to ESKD.[29]
Chronic kidney disease results in worse all-causemortality (the overall death rate) which increases as kidney function decreases.[124] The leading cause of death in chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.[124][125][126]
While kidney replacement therapies can maintain people indefinitely and prolong life, thequality of life is negatively affected.[127][128] Kidney transplantation increases the survival of people with stage 5 CKD when compared to other options;[129][130] however, it is associated with an increased short-term mortality due to complications of the surgery. Transplantation aside, high-intensityhome hemodialysis appears to be associated with improved survival and a greater quality of life, when compared to the conventional three-times-a-week hemodialysis andperitoneal dialysis.[131]
People with ESKD are at increased overall risk for cancer.[132] This risk is particularly high in younger people and gradually diminishes with age.[132] Medicalspecialtyprofessional organizations recommend that physicians do not perform routine cancer screening in people with limited life expectancies due to ESKD because the evidence does not show that such tests lead to improved outcomes.[133][134]
In children, growth failure is a common complication of 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 asgrowth hormone.[135]
Life expectancy of patients, who are diagnosed with Stage 2 CKD decreases with their age, as shown in the table below. For all ages, the life expectancy is higher for women than for men and for those, who do not showalbuminuria. An any rate, in theUnited States someone who is diagnosed at the of 55 can be expected to live till the age of 72.[136][137]
Life expectancy for a patient diagnosed with Stage 2 Chronic Kidney Disease vs the patient's age?
Survival rates of CKD are generally longer with dialysis than without (having only conservative kidney management). However, from the age of 80 and in elderly patients with comorbidities, there is no difference in survival between the two groups. Quality of life might be better for people without dialysis.[138]
People, who had decided against dialysis treatment, when reaching end-stage chronic kidney disease, could survive several years and experience improvements in their mental well-being in addition to sustained physical well-being and overall quality of life until late in their illness course. However, use of acute care services in these cases is common, and the intensity of end-of-life care is highly variable among people opting out of dialysis.[139][140]
Chronic kidney disease is fairly common, particularly in people over 60 years old. Worldwide, about one in ten people has chronic kidney disease. Countries with particular highincidence rates (in new cases per 100,000 people per year) areSaudi Arabia with 495.8 (Makkah andJazan have higher-than-average rates, potentially suggesting environmental and geographical factors),[141] and other Arab countries of thePersian Gulf with ca. 500 cases per 100,000 people. Iran, Israel and North African countries also have high incidence rates. Another high-prevalence region is Central America.
In Canada, 1.9 to 2.3 million people were estimated to have CKD in 2008.[104] CKD affected an estimated 13.9% of U.S. adults aged 18 years and older in the period from 2017 to 2020.[142] In 2007 8.8% of the population of Great Britain and Northern Ireland had symptomatic CKD.[143]
Chronic kidney disease was the cause of 956,000 deaths globally in 2013, up from 409,000 deaths in 1990.[31]
Some localities are known to have significantly above average prevalence of Chronic Kidney Disease in their population. Sometimes, this can be attributed to thefounder effect or other genetic vulnerabilities (e.g.,APOL1 variants in African ancestry). Sometimes, to environmental toxins (heavy metals, agrochemicals, contaminated water), or occupational hazards (heat stress, dehydration, toxin exposure), or to infections (Schistosomiasis,Leptospirosis).
Southeastern U.S., especially rural areas with high diabetes/hypertension rates.
Counties in the Mississippi Delta show some of the nation’s highest CKD incidence.
Although the town-level CKD prevalence rate in the USA are not available due to privacy concerns, country-level statistics is maintained.[145] Some of the highest rates are reported in the following counties:
Outside the USA, there are other CDK clusters, many of which are not caused by the "founder effect", but rather by occupation or environmental exposures. The cause of chronic kidney disease is sometimes unknown; it is referred to as chronic kidney disease of unknown aetiology (CKDu).
2. Mesoamerican Nephropathy (MeN) - Central America
As of 2020[update], a rapidly progressive chronic kidney disease, unexplained by diabetes and hypertension, had increased dramatically in prevalence over a few decades in several regions in Central America and Mexico, a CKDu referred to as theMesoamerican nephropathy (MeN). It was estimated in 2013 that at least 20,000 men had died prematurely, some in their 20s and 30s; a figure of 40,000 per year was estimated in 2020. In some affected areas, CKD mortality was five times the national rate. MeN primarily affects men working as sugarcane labourers.[72] The cause is unknown, but in 2020 the science found a clearer connection between heavy labour in high temperatures and incidence of CKDu; improvements such as regular access to water, rest and shade, can significantly decrease the potential CKDu incidence.[146]
Countries: Nicaragua, El Salvador, Costa Rica, Guatemala
Affected Groups: Male agricultural workers (sugarcane, cotton, corn)
Suspected Causes:
Heat stress/dehydration from repeated work in extreme temperatures.
Toxic exposures (pesticides, heavy metals like arsenic in groundwater).
Infections (leptospirosis, hantavirus).
3. Sri Lanka & India (chronic kidney disease of unknown aetiology)
CKD in theGulf Cooperation Council countries, especially inKuwait,Saudi Arabia,United Arab Emirates,Qatar andBahrain, is a public health emergency, because of its highprevalence rate of 10-15 %.[148] It is usually attributed to adiabetes epidemics and genetic susceptibility. While healthcare systems in the region are advanced (e.g., high dialysis access), prevention remains inadequate. National strategies now prioritize screening, but climate change and lifestyle trends may worsen the crisis.
African,Hispanic, and South Asian (particularly those from Pakistan, Sri Lanka, Bangladesh, and India) populations are at high risk of developing CKD. Africans are at greater risk due to the number of people affected by hypertension among them. As an example, 37% of ESKD cases in African Americans can be attributed to high blood pressure, compared with 19% among Caucasians.[7] Treatment efficacy also differs between racial groups. Administration of antihypertensive drugs generally halts disease progression in white populations but has little effect in slowing kidney disease among black people, and additional treatment such as bicarbonate therapy is often required.[7] While lower socioeconomic status contributes to the number of people affected by CKD, differences in the number of people affected by CKD are still evident between Africans and Whites when controlling for environmental factors.[7]
Although CKD of unknown etiology was first documented among sugar cane workers in Costa Rica in the 1970s, it may well have affected plantation laborers since the introduction of sugar cane farming to the Caribbean in the 1600s. In colonial times, the death records of slaves on sugar plantations were much higher than for slaves forced into other labor.[146]
Denial of care in chronic kidney disease treatment and management is a significant issue for minority populations. This can be due to healthcare provider prejudice, structural barriers, and health insurance coverage disparities. Healthcare provider biases can lead to under-treatment, misdiagnosis, or delayed diagnosis. Structural barriers, such as a lack of insurance and limited healthcare facilities, hinder access to timely care. Furthermore, health insurance coverage disparities, with minority populations lacking adequate coverage, contribute to these disparities. Denial of care worsens health outcomes and perpetuates existing health inequities.[citation needed]
Race-based kidney function metrics, particularly normalizing creatinine, pose ethical challenges in diagnosing and managing chronic kidney disease (CKD). While certain racial and ethnic groups are at higher risk, using race as a reference range may reinforce stereotypes and perpetuate health disparities. This approach fails to account for the complex interplay of genetic, environmental, and social factors influencing kidney function. Depending solely on race-based metrics may lead to misdiagnosis or underdiagnosis in minority populations. Alternative approaches that consider socioeconomic status, environmental exposures, and genetic vulnerability are needed to accurately assess kidney function and address CKD care disparities.[citation needed]
TheNational Kidney Foundation is a national organization representing people with chronic kidney diseases and professionals who treat kidney diseases.
TheAmerican Kidney Fund is a national nonprofit organization providing treatment-related financial assistance to one of every five people undergoing dialysis each year.
TheRenal Support Network is a nonprofit, patient-focused, patient-run organization that provides non-medical services to those affected by CKD.
The incidence rate of CKD in dogs was 15.8 cases per 10,000 dog years at risk. The mortality rate of CKD was 9.7 deaths per 10,000 dog years at risk. (Rates developed from a population of 600,000 insured Swedish dogs; one dog year at risk is one dog at risk for one year). The breeds with the highest rates were theBernese mountain dog,miniature schnauzer, andboxer. TheSwedish elkhound,Siberian husky, andFinnish spitz were the breeds with the lowest rates.[150][151]
Cats with chronic kidney disease may have a buildup of waste products usually removed by the kidneys. They may appear lethargic, unkempt, and lose weight, and may have hypertension. The disease can prevent the appropriate concentration of urine, causing cats to urinate in greater volumes and drink more water to compensate. Loss of important proteins and vitamins through urine may cause abnormal metabolism and loss of appetite. The buildup of acids within the blood can result inacidosis, which can lead to anemia (which can sometimes be indicated by pink or whitish gums, but by no means does the presence of normal colored gums guarantee that anemia is not present or developing), and lethargy.[152]
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![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.[81]](/mt/?noimg=&dark=on&url=http%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aUltrasonography_of_chronic_renal_disease_caused_by_glomerulonephritis.jpg)
![Nephrotic syndrome. Hyperechoic kidney without demarcation of cortex and medulla.[81]](/mt/?noimg=&dark=on&url=http%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aUltrasonography_of_kidney_with_nephrotic_syndrome.jpg)
![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.[81]](/mt/?noimg=&dark=on&url=http%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aUltrasonography_of_chronic_pyelonephritis_with_reduced_kidney_size_and_focal_cortical_thinning.jpg)
![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.[81]](/mt/?noimg=&dark=on&url=http%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aUltrasonography_of_end-stage_chronic_kidney_disease.jpg)
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