Chronic kidney disease

Short description: Abnormal kidney structure or gradual loss of kidney function

This page is about CKD in general. For the end-stage of the disease, see kidney failure.

Chronic kidney disease

Other names| Chronic renal disease, kidney failure, impaired kidney function[1]
Illustration of a kidney from a person with chronic renal failure
Specialty| Nephrology
Symptoms| Early: None[2]
Later: Leg swelling, feeling tired, vomiting, foamy urine, loss of appetite, confusion[2]
Complications| Heart disease, high blood pressure, anemia[3][4]
Duration| Long-term[5]
Causes| Diabetes, heart failure, high blood pressure, glomerulonephritis, polycystic kidney disease[5][6]
Risk factors| Smoking, genetic predisposition,
low socioeconomic status,[7] lithium treatment (disputed)[8][9][10][11]
Diagnostic method| Blood tests, urine tests[12]
Treatment| Medications to manage blood pressure, blood sugar, and lower cholesterol, renal replacement therapy, kidney transplant[13][14]
Frequency| 753 million (2016)[1]
Deaths| 1.2 million (2015)[6]

Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure.[2][5] To meet the criteria for CKD, the abnormalities must be present for at least three months.[15] Early in the course of CKD, patients are usually asymptomatic, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion.[2] Complications can relate to hormonal dysfunction of the kidneys and include high blood pressure (often related to activation of the renin–angiotensin system), insulin resistance, bone disease, and anemia.[3][4][16] Additionally CKD patients have markedly increased cardiovascular complications with increased risks of death and hospitalization.[17] CKD can lead to end-stage kidney failure requiring kidney dialysis or kidney transplantation.[13]

Chronic kidney disease can be secondary to diabetes, high blood pressure, glomerulonephritis or polycystic kidney disease.[5][6] However, in many cases people are born predisposed to CKD, which can be due genetic factors (i.e. having a family history of chronic kidney disease)[2] or due to a somatic mutation before birth.[18]

Diagnosis is by blood tests to measure the estimated glomerular filtration rate (eGFR), and a urine test to measure albumin.[12] Ultrasound or kidney biopsy may be performed to determine the underlying cause.[5] Several severity-based staging systems are in use.[19][20]

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) 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.[21] Loop diuretics may be used to control edema 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 requires hemodialysis, 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]

## Contents

* 1 Signs and symptoms
* 2 Classification
* 2.1 By stages
* 2.2 By causes
* 2.3 By anatomical location
* 2.4 Other
* 3 Diagnosis
* 3.1 Screening
* 3.2 Ultrasound
* 3.3 Additional imaging
* 3.4 Genetic testing
* 3.4.1 Inherited conditions identified through genetic testing
* 3.5 Stages
* 4 Management
* 4.1 Blood pressure
* 4.2 Other measures
* 4.3 Lifestyle interventions
* 4.3.1 Weight loss
* 4.3.2 Dietary salt intake
* 4.3.3 Omega-3 supplementation
* 4.3.4 Protein supplementation
* 4.3.5 Iron supplementation
* 4.4 Sleep
* 4.5 Referral to a nephrologist
* 4.6 Renal replacement therapy
* 5 Prognosis
* 5.1 Survival without dialysis
* 6 Epidemiology
* 6.1 CKD clusters
* 6.1.1 1\. CKD Belt
* 6.1.2 2\. Mesoamerican Nephropathy (MeN) - Central America
* 6.1.3 3\. Sri Lanka & India (chronic kidney disease of unknown aetiology)
* 6.1.3.1 4\. Persian Gulf
* 6.1.3.2 5\. Egypt & North Africa
* 6.1.3.3 6\. Southeast Asia & Pacific Islands
* 6.1.3.4 7\. Balkan Endemic Nephropathy (Historical Cluster)
* 6.2 Race
* 6.2.1 Denial of care
* 6.2.2 Race-based kidney function metric
* 7 Society and culture
* 7.1 Organisations
* 7.1.1 United States
* 7.1.2 United Kingdom
* 7.1.3 Australia
* 8 Other animals
* 8.1 Dogs
* 8.2 Cats
* 9 Research
* 10 References
* 11 External links

## 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:[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 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.[33]
* 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 the 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 (triggering the cells to release potassium into the bloodstream to neutralize the acid) and from a lack of insulin.[34]
* 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.[35] 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 .[36][37]
* Hypocalcemia results from 1,25 dihydroxyvitamin D3 deficiency (caused by high FGF-23 and reduced kidney mass)[38] and the skeletal resistance to the calcemic action of parathyroid hormone.[39] 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).[40] 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.[41]
* 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.[16] CKD–mineral and bone disorders have been associated with poor outcomes.[16][30]
* Metabolic acidosis may result from decreased capacity to generate enough ammonia 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 in erythropoietin, 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, and anorexia.[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 reduced sex drive, difficulty obtaining an erection, and difficulty 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.[50]

* Ankle ulcers in CKD are not simple "gravitational" venous leg ulcers; they arise from a triad of vessel-specific pathology unique to renal disease:[51][52][53]

Calcific uremic arteriolopathy (CUA) = calciphylaxis Intimal 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 lateral malleolus. 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 venous lipodermatosclerosis. 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 principles Pain 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).

Prognosis CUA 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.

## Classification

### By stages

Chronic kidney disease (CKD) is staged by its severity, manifested in glomerular filtration rate (GFR) category (G1–G5), and albuminuria 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.

### By causes

Chronic Kidney Disease in different people can be caused by numerous reasons, with genetic 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] Elevated blood 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 filter urine 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 and lupus 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 GN Genes: CFH, CFI, C3, CFHR gene cluster variants; often complex/structural variants in CFHRs.

* Mitochondrial and multisystem genetic disorders

Mitochondrial DNA and nuclear genes affecting mitochondrial function can present with tubulointerstitial disease, FSGS, or multisystem disease with renal involvement (inheritance maternal for mtDNA variants; nuclear genes often AR or AD).

* Chemical exposure, such as chronic Lead poisoning, chronic interstitial nephritis from drugs (e.g., NSAIDs, allopurinol)). Environmental factors, such as in Mesoamerican nephropathy, involve heat stress and agrochemical exposure.[29][63] These account for less than 4% of cases. Sjögren syndrom and sarcoidosis can be included into this category.

* Primary CKDs are usually are caused by genetic 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 utero somatic mutations before or even after the patient's birth.

Identified examples of Primary CKD comprise:

*     * Single-gene congenital diseases such as polycystic kidney disease, Alport Syndrome, Fabry Disease, Nephronophthisis, Primary Hyperoxaluria Type 1, Nephropathic Cystinosis, Primary Distal Renal Tubular Acidosis or 17q12 microdeletion syndrome.
* Membranous Nephropathy.[65]
* Genetic conditions like autosomal dominant polycystic kidney disease (ADPKD) contribute to about 3% of end-stage kidney disease (ESKD) cases, causing cyst formation and kidney enlargement.[8][3][4] Other hereditary disorders include Alport syndrome, nephronophthisis, and APOL1 gene variants, which increase risk in certain ethnic groups.[29][61][60]
* Dent disease (X‑linked proximal tubulopathy)

Genes: CLCN5 (Dent disease 1, X‑linked), OCRL (Dent disease 2; OCRL also causes Lowe syndrome). Features: low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis/nephrocalcinosis, progressive chronic kidney disease in some patients.

*     * Bartter and Gitelman syndromes (salt‑wasting tubulopathies; some progress to chronic kidney disease)

Genes include SLC12A1, KCNJ1, CLCNKB (Bartter forms), SLC12A3 (Gitelman), etc. Mostly AR (some AD forms).

*     * Glomerular and podocyte diseases

Alport syndrome (hereditary glomerulonephritis with hematuria and progressive CKD) Genes: COL4A5 (X‑linked), COL4A3, COL4A4 (autosomal recessive or dominant forms). Features: persistent hematuria, progressive proteinuria and CKD, sensorineural hearing loss, ocular abnormalities.

*     * Monogenic steroid‑resistant nephrotic syndrome (SRNS) / congenital nephrotic syndromes (podocytopathies)

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.

*     * POL1‑associated nephropathy (risk genotype)

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.

*     * Polygenetic primary glomerular disease such as focal segmental glomerulosclerosis, IgA nephropathy,[66][67][68]

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.[69]

### 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.
* 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

* 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 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[71][72][73][74] of about 36 °C (96 °F) is suspected,[75] as are agricultural chemicals[76]

## 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.

### Screening

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 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.[80]

The GFR 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]

### 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 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 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]

* Nephrotic syndrome. Hyperechoic kidney without demarcation of cortex and medulla.[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 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.[82]

### Genetic testing

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 from Natera evaluates 397 genes, while a comprehensive panel from Mayo Clinic Laboratories covers over 300.

• Disease-specific panels: These panels focus on a smaller, curated list of genes linked to a particular type of kidney disease. Examples from providers like Invitae and Mayo Clinic Laboratories include panels for: Autosomal Dominant Polycystic Kidney Disease (ADPKD), Alport Syndrome, Atypical Hemolytic Uremic Syndrome (aHUS), Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), Nephrotic Syndrome and Focal Segmental Glomerulosclerosis (FSGS)

• 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 with Sanger 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 the PKD1 or PKD2 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 heterogeneous Representative 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 the COL4A3, COL4A4, and COL4A5 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]

• Focal Segmental Glomerulosclerosis (FSGS): A scarring of the kidney's filtering units. Some genetic causes can be identified by testing.[90]

• Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD): includes entities formerly called medullary cystic kidney disease and familial juvenile hyperuricemic nephropathy).

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 like MUC1 or UMOD.[91] Autosomal dominant tubulointerstitial kidney disease (ADTKD;

Neither IgA nephropathy nor IGF nephropathy can be diagnosed by genetics tests in 2025. Instead renal biopsy followed by microscopic examination can be used for such diagnoses.[92]

### Stages

Chronic kidney disease (CKD) staging – CKD G1-5 A1-3
glomerular filtration rate (GFR) and albumin/creatinine ratio (ACR)

ACR

GFR

| A1 | A2 | A3

|
|
|

Normal to mildly increased | Moderately increased | Severely increased
<30 | 30–300 | >300
G1  | Normal | ≥ 90 | 1 if kidney damage present | 1 | 2
G2  | Mildly decreased | 60–89 | 1 if kidney damage present | 1 | 2
G3a  | Mildly to moderately decreased | 45–59 | 1 | 2 | 3
G3b  | Moderately to severely decreased | 30–44 | 2 | 3 | 3
G4  | Severely decreased | 15–29 | 3 | 4+ | 4+
G5  | Kidney failure | < 15 | 4+ | 4+ | 4+
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 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 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 stages of CKD (stage 5), who have not yet started kidney replacement therapy, are also referred to as NDD-CKD.

## Management

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 on glomerular filtration rate (GFR) and albuminuria, 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.

### 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.[21] 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.[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]

### Other measures

* 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]
* Guidelines recommend treatment with parenteral iron prior to treatment with erythropoietin.
* Replacement of erythropoietin is often necessary in people with advanced disease.[105]
* It is unclear if androgens improve anemia.[106]
* 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.[50]
* Gadolinium based MRI contrast agents are contra-indicated in those with GFR less than 30 (stage 4 kidney disease) due to the risk of nephrogenic systemic fibrosis. However, this risk is believed to be low in people with CKD with newer contrast agents being currently used.[29]

### Lifestyle interventions

#### 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,[107] and when in advanced stages, also may hinder people's eligibility to kidney transplantation.[108] For example, the consumption of high calorie and high fructose beverages can make an individual "60% more likely to develop CKD".[109][110]

Weight management interventions in overweight and obese adults with CKD include lifestyle interventions (dietary changes, physical activity/exercise, or behavioural strategies), pharmacological (used to reduce absorption or suppress 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]

#### Dietary salt intake

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 as albuminuria.[112] Some people may experience low 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]

#### Omega-3 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. Even though Omega-3 fatty acids contribute to the production of eicosanoid molecules that reduce clotting, it does not have any impact on the prevention of vascular blockage in people with CKD.[114]

#### Protein supplementation

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, or body composition.[115]

#### Iron supplementation

Intravenous (IV) iron therapy may help more than oral iron supplements in reaching target hemoglobin levels. However, allergic reactions may also be more likely following IV-iron therapy.[116]

### Sleep

Individuals with CKD have an increased prevalence of sleep apnea compared to the general population (both obstructive sleep apnea and central 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]

### 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).[119]

In the 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]

### 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.[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]

## 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. 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 a Medicare 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 or transient ischemic attack (TIA, commonly known as a mini-stroke), heart failure or coronary 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, and nephrotic 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-cause mortality (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, the quality 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-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.[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] Medical specialty professional 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 as growth hormone.[135]

### Survival without dialysis

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 show albuminuria. An any rate, in the United 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]

## Epidemiology

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 high incidence rates (in new cases per 100,000 people per year) are Saudi Arabia with 495.8 (Makkah and Jazan have higher-than-average rates, potentially suggesting environmental and geographical factors),[141] and other Arab countries of the Persian 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.

Some regions have CKD prevalence rate significantly below the World's average: sub-Saharan Africa, South Asia and China (ca. 150 new cases per 100,000 people per year)

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]

Global burden of chronic kidney disease by age groups, 1990–2021.(A) Age-standardized prevalence rates. (B)) Age-standardized incidence rates. (C) Age-standardized death rates. (D) Age-standardized DALYs rates. DALYs, disability-adjusted life years.

### CKD clusters

Some localities are known to have significantly above average prevalence of Chronic Kidney Disease in their population. Sometimes, this can be attributed to the founder 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).

#### 1\. CKD Belt

In the USA the so-called "CDK Belt" comprises:[144]

* Appalachia (e.g., parts of Kentucky, Tennessee, West Virginia, Mississippi, Alabama).
* 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:

* Mississippi: Tunica, Sunflower, Coahoma.
* Alabama: Dallas, Wilcox, Lowndes.
* Tennessee: Haywood, Lauderdale.

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 the Mesoamerican 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)

* Regions:
* Sri Lanka: North Central Province (Anuradhapura, Polonnaruwa)[147]
* India: Andhra Pradesh, Odisha, Uttar Pradesh
* Suspected Causes:
* Heavy metals (cadmium, arsenic) in groundwater and soil.
* Agrochemical overuse (glyphosate, fertilizer nitrates).
* Genetic susceptibility (e.g., APOL1 gene variants).

##### 4\. Persian Gulf

CKD in the Gulf Cooperation Council countries, especially in Kuwait, Saudi Arabia, United Arab Emirates, Qatar and Bahrain, is a public health emergency, because of its high prevalence rate of 10-15 %.[148] It is usually attributed to a diabetes 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.

##### 5\. Egypt & North Africa

* Key Drivers:
* Schistosomiasis: Parasitic infection causing kidney damage (historically endemic).
* Pharmaceutical toxins: Analgesic abuse (phenacetin) and unregulated herbals.
* Diabetes/Hypertension: Rising due to urbanization.

##### 6\. Southeast Asia & Pacific Islands

* Countries: Thailand, Indonesia, Malaysia, Fiji
* Risk Amplifiers:
* Diabetes epidemics (highest global T2DM growth).
* Traditional medicines containing aristolochic acid (kidney-toxic).
* Flood-prone regions: Contaminated water (leptospirosis, heavy metals).

##### 7\. Balkan Endemic Nephropathy (Historical Cluster)

* Regions: Bosnia, Croatia, Serbia, Bulgaria [1]
* Cause: Aristolochic acid in contaminated wheat flour (from Aristolochia weeds).
* Legacy: High rates of upper urinary tract cancers.

### Race

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

#### Race-based kidney function metric

## Society and culture

### Organisations

The International Society of Nephrology is an international body representing specialists in kidney diseases.

#### United States

* The National Kidney Foundation is a national organization representing people with chronic kidney diseases and professionals who treat kidney diseases.
* The American Kidney Fund is a national nonprofit organization providing treatment-related financial assistance to one of every five people undergoing dialysis each year.
* The Renal Support Network is a nonprofit, patient-focused, patient-run organization that provides non-medical services to those affected by CKD.
* The American Association of Kidney Patients is a nonprofit, patient-centric group focused on improving the health and well-being of CKD and people undergoing dialysis.
* The Renal Physicians Association is an association representing nephrology professionals.

#### United Kingdom

It was said to be costing the National Health Service about £1.5 billion a year in 2020.[149]

Kidney Care UK and The UK National Kidney Federation represent people with chronic kidney disease. The Renal Association represents Kidney physicians and works closely with the National Service Framework for kidney disease.

#### Australia

Kidney Health Australia serves that country.

## Other animals

### Dogs

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 the Bernese mountain dog, miniature schnauzer, and boxer. The Swedish elkhound, Siberian husky, and Finnish spitz were the breeds with the lowest rates.[150][151]

### Cats

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 in acidosis, 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]

## Research

As of 2019[update], several compounds are in development for the treatment of CKD. These include the angiotensin receptor blocker (ARB) olmesartan medoxomil; and sulodexide, a mixture of low molecular weight heparin and dermatan sulfate.[153][154]

## References

1. ↑ 1.0 1.1 1.2 "Disparities in Chronic Kidney Disease Prevalence among Males and Females in 195 Countries: Analysis of the Global Burden of Disease 2016 Study". Nephron 139 (4): 313–8. 23 May 2018. doi:10.1159/000489897. PMID 29791905. https://zenodo.org/record/1283108.
2. ↑ 2.0 2.1 2.2 2.3 2.4 "What Is Chronic Kidney Disease?". June 2017. https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/what-is-chronic-kidney-disease.
3. ↑ 3.0 3.1 "Insulin resistance in patients with chronic kidney disease". Journal of Biomedicine & Biotechnology 2012. 2012. doi:10.1155/2012/691369. PMID 22919275.
4. ↑ 4.0 4.1 "Kidney Failure" (in en). https://medlineplus.gov/kidneyfailure.html.
5. ↑ 5.0 5.1 5.2 5.3 5.4 "What is renal failure" (in en). https://www.hopkinsmedicine.org/healthlibrary/conditions/kidney_and_urinary_system_disorders/end_stage_renal_disease_esrd_85,P01474.
6. ↑ 6.0 6.1 6.2 6.3 6.4 "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet 388 (10053): 1459–1544. October 2016. doi:10.1016/s0140-6736(16)31012-1. PMID 27733281.
7. ↑ 7.0 7.1 7.2 7.3 "Long-term effects of renin-angiotensin system-blocking therapy and a low blood pressure goal on progression of hypertensive chronic kidney disease in African Americans". Archives of Internal Medicine 168 (8): 832–9. April 2008. doi:10.1001/archinte.168.8.832. PMID 18443258.
8. ↑ "Long-term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study". Bipolar Disorders 23 (7): 715–723. 2021. doi:10.1111/bdi.13052. PMID 33548063.
9. ↑ "Long-term effects of lithium on renal, thyroid, and parathyroid function: A retrospective analysis of laboratory data". Lancet 386 (9992): 461–8. 2015. doi:10.1016/S0140-6736(14)61842-0. PMID 26003379.
10. ↑ "Why is lithium not the drug of choice for bipolar disorder? A controversy between science and clinical practice". International Journal of Bipolar Disorders 12 (1). 2024. doi:10.1186/s40345-023-00322-7. PMID 38228882.
11. ↑ "Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal". Nephrology 23 (10): 897–903. 2018. doi:10.1111/nep.13263. PMID 29607573. https://onlinelibrary.wiley.com/doi/10.1111/nep.13263.
12. ↑ 12.0 12.1 12.2 "Chronic Kidney Disease Tests & Diagnosis". October 2016. https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/tests-diagnosis.
13. ↑ 13.0 13.1 13.2 "Kidney Failure". https://www.niddk.nih.gov/health-information/kidney-disease/kidney-failure.
14. ↑ 14.0 14.1 14.2 14.3 14.4 "Managing Chronic Kidney Disease". October 2016. https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/managing.
15. ↑ 15.0 15.1 15.2 15.3 15.4 "KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease". Kidney International 105 (4S): S117–S314. April 2024. doi:10.1016/j.kint.2023.10.018. PMID 38490803. https://kdigo.org/wp-content/uploads/2024/03/KDIGO-2024-CKD-Guideline.pdf.
16. ↑ 16.0 16.1 16.2 KDIGO: Kidney Disease Improving Global Outcomes (August 2009). "KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)". Kidney Int 76 (Suppl 113): S1–130. doi:10.1038/ki.2009.188. PMID 19644521. http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO CKD-MBD GL KI Suppl 113.pdf.
17. ↑ "Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization". The New England Journal of Medicine 351 (13): 1296–1305. September 2004. doi:10.1056/NEJMoa041031. PMID 15385656.
18. ↑ "Somatic mutations acquired during life: state of the art and implications for the kidney". Kidney Int 107 (5): 825–834. May 2025. doi:10.1016/j.kint.2024.10.036. PMID 39988271.
19. ↑ "Summary of Recommendation Statements". Kidney International Supplements 3 (1): 5–14. January 2013. doi:10.1038/kisup.2012.77. PMID 25598998.
20. ↑ (in en) Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1. Elsevier Health Sciences. 2017. pp. 294–5. ISBN 978-0-323-52957-0. https://books.google.com/books?id=wGclDwAAQBAJ&pg=PA294.
21. ↑ 21.0 21.1 21.2 21.3 "Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials". American Journal of Kidney Diseases 67 (5): 728–41. May 2016. doi:10.1053/j.ajkd.2015.10.011. PMID 26597926.
22. ↑ "Diuretics: a review". Annals of Clinical Biochemistry 49 (Pt 5): 419–31. September 2012. doi:10.1258/acb.2011.011281. PMID 22783025.
23. ↑ "2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)". JAMA 311 (5): 507–20. February 2014. doi:10.1002/14651858.CD011339.pub2. PMID 24352797.
24. ↑ "Eating Right for Chronic Kidney Disease". https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/healthy-eating-adults-chronic-kidney-disease?dkrd=/health-information/kidney-disease/chronic-kidney-disease-ckd/eating-nutrition.
25. ↑ "Plant-based diets to manage the risks and complications of chronic kidney disease". Nature Reviews. Nephrology 16 (9): 525–542. September 2020. doi:10.1038/s41581-020-0297-2. PMID 32528189. https://pure.rug.nl/ws/files/154950434/s41581_020_0297_2.pdf.
26. ↑ Health Canada (2021-01-14). "Welcome to Canada's food guide". https://food-guide.canada.ca/en/.
27. ↑ "Anemia in Chronic Kidney Disease". July 2016. https://www.niddk.nih.gov/health-information/kidney-disease/anemia?dkrd=/health-information/kidney-disease/chronic-kidney-disease-ckd/anemia.
28. ↑ "Mineral & Bone Disorder in Chronic Kidney Disease". November 2015. https://www.niddk.nih.gov/health-information/kidney-disease/mineral-bone-disorder?dkrd=/health-information/kidney-disease/chronic-kidney-disease-ckd/mineral-bone-disorder.
29. ↑ 29.00 29.01 29.02 29.03 29.04 29.05 29.06 29.07 29.08 29.09 "Chronic Kidney Disease Diagnosis and Management: A Review". JAMA 322 (13): 1294–1304. October 2019. doi:10.1001/jama.2019.14745. PMID 31573641.
30. ↑ 30.0 30.1 "Osteoblastogenesis of adipose-derived mesenchymal stem cells in chronic kidney disease patient with regular hemodialysis". Annals of Medicine and Surgery 84. December 2022. doi:10.1016/j.amsu.2022.104796. PMID 36536732.
31. ↑ 31.0 31.1 "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet 385 (9963): 117–71. January 2015. doi:10.1016/S0140-6736(14)61682-2. PMID 25530442. Table 2, p. 137
32. ↑ "Patient-centred approaches for the management of unpleasant symptoms in kidney disease". Nat Rev Nephrol 18 (2): 001–017. Jan 3, 2022. doi:10.1038/s41581-021-00518-z. PMID 34980890.
33. ↑ "Uremic Toxins Activate Macrophages". Circulation 139 (1): 97–100. January 2019. doi:10.1161/CIRCULATIONAHA.118.037308. PMID 30592654.
34. ↑ 34.0 34.1 34.2 34.3 Chronic Kidney Disease (CKD) at eMedicine
35. ↑ "Hyperphosphatemia of chronic kidney disease". Kidney International 74 (2): 148–57. July 2008. doi:10.1038/ki.2008.130. PMID 18449174.
36. ↑ "FGF23 induces left ventricular hypertrophy". The Journal of Clinical Investigation 121 (11): 4393–408. November 2011. doi:10.1172/JCI46122. PMID 21985788.
37. ↑ "Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis". The New England Journal of Medicine 359 (6): 584–92. August 2008. doi:10.1056/NEJMoa0706130. PMID 18687639.
38. ↑ "Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes". Journal of Bone and Mineral Research 28 (1): 46–55. January 2013. doi:10.1002/jbmr.1740. PMID 22886720.
39. ↑ "The calcemic response to PTH in the rat: effect of elevated PTH levels and uremia". Kidney International 46 (2): 310–7. August 1994. doi:10.1038/ki.1994.276. PMID 7967341.
40. ↑ Harrison's Principles of Internal Medicine (18th ed.). New York: McGraw-Hill. 2012. p. 3109. ISBN 978-0-07-174890-2.
41. ↑ "Calciphylaxis: a still unmet challenge". Journal of Nephrology 24 (2): 142–8. 2011. doi:10.5301/jn.2011.6366. PMID 21337312.
42. ↑ "Changes in plasma potassium concentration during acute acid-base disturbances". The American Journal of Medicine 71 (3): 456–67. September 1981. doi:10.1016/0002-9343(81)90182-0. PMID 7025622.
43. ↑ "Anemia Of Chronic Renal Disease". StatPearls [Internet]. StatPearls Publishing. January 2021. NBK539871. https://www.ncbi.nlm.nih.gov/books/NBK539871/.
44. ↑ "Wasting in chronic kidney disease". Journal of Cachexia, Sarcopenia and Muscle 2 (1): 9–25. March 2011. doi:10.1007/s13539-011-0019-5. PMID 21475675.
45. ↑ 45.0 45.1 "Vitamin K Status and Cognitive Function in Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort". Current Developments in Nutrition 6 (8). August 2022. doi:10.1093/cdn/nzac111. PMID 35957738.
46. ↑ 46.0 46.1 46.2 "Association between kidney function and incidence of dementia: 10-year follow-up of the Whitehall II cohort study". Age and Ageing 51 (1). January 2022. doi:10.1093/ageing/afab259. PMID 35061870.
47. ↑ "Cognition in People With End-Stage Kidney Disease Treated With Hemodialysis: A Systematic Review and Meta-analysis" (in English). American Journal of Kidney Diseases 67 (6): 925–935. June 2016. doi:10.1053/j.ajkd.2015.12.028. PMID 26919914.
48. ↑ 48.0 48.1 "Cognitive disorders and dementia in CKD: the neglected kidney-brain axis" (in en-US). Journal of the American Society of Nephrology 24 (3): 353–363. February 2013. doi:10.1681/ASN.2012050536. PMID 23291474.
49. ↑ "Cognitive impairment in chronic kidney disease". Journal of the American Geriatrics Society 52 (11): 1863–9. November 2004. doi:10.1111/j.1532-5415.2004.52508.x. PMID 15507063.
50. ↑ 50.0 50.1 "Interventions for treating sexual dysfunction in patients with chronic kidney disease". The Cochrane Database of Systematic Reviews (12). December 2010. doi:10.1002/14651858.CD007747.pub2. PMID 21154382.
51. ↑ Nigwekar S.U. et al. 2018. Calciphylaxis. NEJM 378: 1704-14. DOI: 10.1056/NEJMra1705293.
52. ↑ Brandenburg V. et al. 2022. Sodium-thiosulfate for calcific uremic arteriolopathy: systematic review. Clin J Am Soc Nephrol 17: 124-136. DOI: 10.2215/CJN.05760421.
53. ↑ USRDS 2023 Atlas, Chapter 11: CKD non-healing wounds. DOI: 10.47672/ursa.ie0w-tf75.
54. ↑ "Chapter 1: Definition and classification of CKD" (in en). Kidney International Supplements 3 (1): 19–62. January 2013. doi:10.1038/kisup.2012.64. PMID 25018975. PMC 4089693. https://linkinghub.elsevier.com/retrieve/pii/S2157171615311011.
55. ↑ "Stevens P.E., Levin A. 2013. Evaluation and management of chronic kidney disease: synopsis of the KDIGO 2012 Clinical Practice Guideline". Annals of Internal Medicine 158 (12): 825-830. doi:10.7326/0003-4819-158-12-201306180-00007.
56. ↑ Johnson, Richard J.; Feehally, John; Floege, Jürgen, eds (2018). "Definition and classification of CKD". Comprehensive Clinical Nephrology. table 2-1 (6th ed.). Philadelphia: Elsevier. p. 16. ISBN 978-0-323-35942-6.
57. ↑ "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet 388 (10053): 1545–1602. October 2016. doi:10.1016/S0140-6736(16)31678-6. PMID 27733282.
58. ↑ "Kidney Disease: Fact Sheet" (in en). https://www.kidney.org/about/kidney-disease-fact-sheet.
59. ↑ 59.0 59.1 59.2 59.3 "Chronic Kidney Disease". Cleveland Clinic. May 2023. https://my.clevelandclinic.org/health/diseases/15096-chronic-kidney-disease.
60. ↑ 60.0 60.1 60.2 "Chronic Kidney Disease (CKD)". https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd.
61. ↑ 61.0 61.1 61.2 61.3 "Chronic Kidney Disease". StatPearls [Internet]. July 2024. NBK535404. PMID 30571025. https://www.ncbi.nlm.nih.gov/books/NBK535404/.
62. ↑ "A narrative review of Chronic Kidney Disease in Clinical Practice: Current challenges and future perspectives". Adv Ther 39 (1): 33–43. January 2022. doi:10.1007/s12325-021-01927-z. PMID 34739697.
63. ↑ "Chronic kidney disease of unknown aetiology: A comprehensive review of a global public health problem". Trop Med Int Health 28 (8): 588–600. August 2023. doi:10.1111/tmi.13913. PMID 37403003.
64. ↑ Kil SY, Yang WS, Kim YN, Shin HS, Jung Y, Rim H. Genes, kidneys, and the future: transforming chronic kidney disease management through genomic insights. Child Kidney Dis. 2025;29(2):39-45 doi: 10.3339/ckd.25.016
65. ↑ "GWAS-Based Discoveries in IgA Nephropathy, Membranous Nephropathy, and Steroid-Sensitive Nephrotic Syndrome". Clin J Am Soc Nephrol 16 (3): 458–466. March 2021. doi:10.2215/CJN.14031119. PMID 32680915.
66. ↑ "An Update on the Genetics of IgA Nephropathy". J Clin Med 13 (1): 123. December 2023. doi:10.3390/jcm13010123. PMID 38202130.
67. ↑ "Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy". Nat Genet 55 (7): 1091–1105. July 2023. doi:10.1038/s41588-023-01422-x. PMID 37337107.
68. ↑ "Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens". Nat Genet 46 (11): 1187–96. November 2014. doi:10.1038/ng.3118. PMID 25305756.
69. ↑ "United States Renal Data System (USRDS)". http://www.usrds.org/.
70. ↑ "Epidemiology of chronic kidney disease in adults of Salvadoran agricultural communities". MEDICC Review 16 (2): 23–30. April 2014. doi:10.37757/MR2014.V16.N2.5. PMID 24878646. http://www.medicc.org/mediccreview/index.php?issue=28&id=351&a=va.
71. ↑ Tangri N (29 July 2013). "MesoAmerican Nephropathy: A New Entity". eAJKD. National Kidney Foundation. http://ajkdblog.org/2013/07/29/mesoamerican-nephropathy-a-new-entity/.

72. ↑ 72.0 72.1 "The epidemic of chronic kidney disease of unknown etiology in Mesoamerica: a call for interdisciplinary research and action". American Journal of Public Health 103 (11): 1927–30. November 2013. doi:10.2105/AJPH.2013.301594. PMID 24028232.

73. ↑ "Chronic kidney disease: Mesoamerican nephropathy—new clues to the cause". Nature Reviews. Nephrology 9 (10): 560–1. October 2013. doi:10.1038/nrneph.2013.174. PMID 23999393.
74. ↑ "Fructokinase activity mediates dehydration-induced renal injury". Kidney International 86 (2): 294–302. August 2014. doi:10.1038/ki.2013.492. PMID 24336030.
75. ↑ "Global heating 'may lead to epidemic of kidney disease'" (in en). 2021-10-21. https://www.theguardian.com/global-development/2021/oct/21/global-heating-may-lead-to-epidemic-of-kidney-disease.
76. ↑ "Thousands of sugar cane workers die as wealthy nations stall on solutions". International Consortium of Investigative Journalists. 12 December 2011. http://www.icij.org/project/island-widows/thousands-sugar-cane-workers-die-wealthy-nations-stall-solutions.
77. ↑ "Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians". Annals of Internal Medicine 159 (12): 835–47. December 2013. doi:10.7326/0003-4819-159-12-201312170-00726. PMID 24145991.
78. ↑ "Diagnosis and management of non-dialysis chronic kidney disease in ambulatory care: a systematic review of clinical practice guidelines". BMC Nephrology 19 (1). October 2018. doi:10.1186/s12882-018-1048-5. PMID 30305035.
79. ↑ Farrell, Douglas R.; Vassalotti, Joseph A. (2024-01-25). "Screening, identifying, and treating chronic kidney disease: why, who, when, how, and what?". BMC Nephrology 25 (1): 34. doi:10.1186/s12882-024-03466-5. ISSN 1471-2369. PMID 38273240.
80. ↑ "4. CKD Screening and Management: Overview". Handbook of Chronic Kidney Disease Management. Lippincott Williams and Wilkins. 2011. pp. 32–43. ISBN 978-1-58255-893-6. http://hdcn.com/CKDhandbook/toc.htm.
81. ↑ 81.0 81.1 81.2 81.3 81.4 Content initially copied from: "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics 6 (1): 2. December 2015. doi:10.3390/diagnostics6010002. PMID 26838799. (CC-BY 4.0)
82. ↑ "Kidney scans". https://www.singhealth.com.sg/patient-care/conditions-treatments/kidney-scans/overview.
83. ↑ "Genetic testing and counseling for kidney disease". American Kidney Fund. October 2024. https://www.kidneyfund.org/all-about-kidneys/tests/genetic-testing-and-counseling.
84. ↑ "Clinical Genetic Testing in Nephrology: Core Curriculum 2024". Am J Kidney Dis 84 (5): 632–645. November 2024. doi:10.1053/j.ajkd.2024.05.011. PMID 39340488.
85. ↑ "Emerging Role of Clinical Genetics in CKD". Kidney Med 4 (4). April 2022. doi:10.1016/j.xkme.2022.100435. PMID 35372818.
86. ↑ "Polycystic Kidney Disease, Autosomal Dominant". GeneReviews® [Internet]. University of Washington, Seattle. 2022. NBK1246.
87. ↑ "Alport Syndrome". GeneReviews® [Internet]. University of Washington, Seattle. August 2025. NBK1207.
88. ↑ "Fabry Disease". GeneReviews® [Internet]. University of Washington, Seattle. April 2024. NBK1292.
89. ↑ "Nephronophthisis-Related Ciliopathies". GeneReviews® [Internet]. University of Washington, Seattle. March 2023. NBK368475.
90. ↑ "PAX2-Related Disorder". GeneReviews® [Internet]. University of Washington, Seattle. August 2025. NBK1451. "PAX2 pathogenic variants have been identified in multiple sporadic and familial cases of nonsyndromic renal disease including renal hypodysplasia and focal segmental glomerulosclerosis."
91. ↑ "Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1". GeneReviews® [Internet]. University of Washington, Seattle. October 2021. NBK153723.
92. ↑ "Building Toward Clinical Translation: New Study Refines Genetic Architecture of IgA Nephropathy". Am J Kidney Dis 83 (1): 108–111. January 2024. doi:10.1053/j.ajkd.2023.09.001. PMID 37716417.
"Genetic studies of IgA nephropathy: past, present, and future". Pediatr Nephrol 25 (11): 2257–68. November 2010. doi:10.1007/s00467-010-1500-7. PMID 20386929. "Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently demonstrated. Recent data indicates that these IgA1 glycosylation defects are inherited and constitute a heritable risk factor for IgAN.".
93. ↑ CKD Evaluation and Management 2012\. Kidney Disease Improving Global Outcomes (KDIGO). Retrieved 2019-07-06.
94. ↑ 94.0 94.1 94.2 94.3 94.4 94.5 94.6 National Kidney Foundation (2002). "K/DOQI clinical practice guidelines for chronic kidney disease". http://www.kidney.org/professionals/KDOQI/guidelines_ckd.
95. ↑ 95.0 95.1 National Institute for Health and Clinical Excellence. Clinical guideline 73: Chronic kidney disease. London, 2008.
96. ↑ "Chronic kidney disease". Lancet 398 (10302): 786–802. August 2021. doi:10.1016/S0140-6736(21)00519-5. PMID 34175022. https://researchonline.lshtm.ac.uk/id/eprint/4663580/1/Kalantar-Zadeh_etal_2021-Preserving-Kidney-Function-in-People.pdf.
97. ↑ "Association Between More Intensive vs Less Intensive Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease Stages 3 to 5: A Systematic Review and Meta-analysis". JAMA Internal Medicine 177 (10): 1498–1505. October 2017. doi:10.1001/jamainternmed.2017.4377. PMID 28873137.
98. ↑ "Dyslipidemia in chronic kidney disease: managing a high-risk combination". Postgraduate Medicine 121 (6): 54–61. November 2009. doi:10.3810/pgm.2009.11.2077. PMID 19940417.
99. ↑ "Nutritional Management of Chronic Kidney Disease". The New England Journal of Medicine 377 (18): 1765–76. November 2017. doi:10.1056/NEJMra1700312. PMID 29091561. https://escholarship.org/uc/item/02m5c6qr.
100. ↑ "Reducing the Dietary Acid Load: How a More Alkaline Diet Benefits Patients With Chronic Kidney Disease". J Ren Nutr 27 (3): 151–160. May 2017. doi:10.1053/j.jrn.2016.11.006. PMID 28117137.
101. ↑ "Altered dietary salt intake for people with chronic kidney disease". The Cochrane Database of Systematic Reviews 2021 (6). June 2021. doi:10.1002/14651858.cd010070.pub3. PMID 34164803.
102. ↑ "Target haemoglobin to aim for with erythropoiesis-stimulating agents: a position statement by ERBP following publication of the Trial to reduce cardiovascular events with Aranesp therapy (TREAT) study". Nephrology, Dialysis, Transplantation 25 (9): 2846–50. September 2010. doi:10.1093/ndt/gfq336. PMID 20591813.
103. ↑ "The impact of selecting a high hemoglobin target level on health-related quality of life for patients with chronic kidney disease: a systematic review and meta-analysis". Archives of Internal Medicine 169 (12): 1104–12. June 2009. doi:10.1001/archinternmed.2009.112. PMID 19546410.
104. ↑ 104.0 104.1 "Guidelines for the management of chronic kidney disease". CMAJ 179 (11): 1154–62. November 2008. doi:10.1503/cmaj.080351. PMID 19015566.
105. ↑ "Anaemia management in people with chronic kidney disease (CG114)". NICE Clinical Guideline. UK National Institute for Health and Care Excellence. February 2011. http://guidance.nice.org.uk/CG114.
106. ↑ "Androgens for the anaemia of chronic kidney disease in adults". The Cochrane Database of Systematic Reviews 2014 (10). October 2014. doi:10.1002/14651858.CD006881.pub2. PMID 25300168.
107. ↑ "The dose-response relationship between body mass index and the risk of incident stage ≥3 chronic kidney disease in a general japanese population: the Ibaraki prefectural health study (IPHS)". Journal of Epidemiology 24 (6): 444–451. 2014. doi:10.2188/jea.JE20140028. PMID 24998954.
108. ↑ "Obesity and the risk of cardiovascular and all-cause mortality in chronic kidney disease: a systematic review and meta-analysis". Nephrology, Dialysis, Transplantation 32 (3): 439–449. March 2017. doi:10.1093/ndt/gfw075. PMID 27190330.
109. ↑ "High-fructose corn syrup-sweetened soft drink consumption increases vascular resistance in the kidneys at rest and during sympathetic activation". American Journal of Physiology. Renal Physiology 318 (4): F1053–65. April 2020. doi:10.1152/ajprenal.00374.2019. PMID 32174139.
110. ↑ "Associations of sugar-sweetened and artificially sweetened soda with chronic kidney disease: a systematic review and meta-analysis". Nephrology 19 (12): 791–7. December 2014. doi:10.1111/nep.12343. PMID 25251417.
111. ↑ 111.0 111.1 "Interventions for weight loss in people with chronic kidney disease who are overweight or obese". The Cochrane Database of Systematic Reviews 2021 (3). March 2021. doi:10.1002/14651858.CD013119.pub2. PMID 33782940.
112. ↑ 112.0 112.1 "Altered dietary salt intake for people with chronic kidney disease". The Cochrane Database of Systematic Reviews 2021 (6). June 2021. doi:10.1002/14651858.CD010070.pub3. PMID 34164803.
113. ↑ "eHealth interventions for people with chronic kidney disease". The Cochrane Database of Systematic Reviews 2019 (8). August 2019. doi:10.1002/14651858.cd012379.pub2. PMID 31425608.
114. ↑ "Omega-3 fatty acids for dialysis vascular access outcomes in patients with chronic kidney disease". The Cochrane Database of Systematic Reviews 2018 (11). November 2018. doi:10.1002/14651858.CD011353.pub2. PMID 30480758.
115. ↑ 115.0 115.1 115.2 "Oral protein-based supplements versus placebo or no treatment for people with chronic kidney disease requiring dialysis". The Cochrane Database of Systematic Reviews 5 (5). May 2020. doi:10.1002/14651858.CD012616.pub2. PMID 32390133.
116. ↑ "Parenteral versus oral iron therapy for adults and children with chronic kidney disease". The Cochrane Database of Systematic Reviews 2019 (2). February 2019. doi:10.1002/14651858.CD007857.pub3. PMID 30790278.
117. ↑ Lin CH; Lurie RC; Lyons OD (March 2020). "Sleep Apnea and Chronic Kidney Disease: A State-of-the-Art Review". Chest 157 (3): 673–685. doi:10.1016/j.chest.2019.09.004. PMID 31542452.
118. ↑ "Interventions for improving sleep quality in people with chronic kidney disease". The Cochrane Database of Systematic Reviews 5 (5). May 2019. doi:10.1002/14651858.cd012625.pub2. PMID 31129916.
119. ↑ "CKD Stage 4". https://www.davita.com/education/kidney-disease/stages/stage-4-of-chronic-kidney-disease.
120. ↑ https://pmc.ncbi.nlm.nih.gov/articles/PMC7015670/#:~:text=Those at high risk of,promptly referred to a nephrologist.
121. ↑ "Review on uremic toxins: classification, concentration, and interindividual variability". Kidney International 63 (5): 1934–43. May 2003. doi:10.1046/j.1523-1755.2003.00924.x. PMID 12675874.
122. ↑ "Removal of uremic toxins by renal replacement therapies: a review of current progress and future perspectives". Renal Replacement Therapy 2 (1). 14 September 2016. doi:10.1186/s41100-016-0056-9.
123. ↑ "Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis". European Heart Journal 35 (7): 455–69. February 2014. doi:10.1093/eurheartj/eht386. PMID 24164864.
124. ↑ 124.0 124.1 "Increased mortality in chronic kidney disease: a call to action". The American Journal of the Medical Sciences 331 (3): 150–3. March 2006. doi:10.1097/00000441-200603000-00007. PMID 16538076.
125. ↑ "Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention". Circulation 108 (17): 2154–69. October 2003. doi:10.1161/01.CIR.0000095676.90936.80. PMID 14581387.
126. ↑ "Chronic kidney disease and mortality risk: a systematic review". Journal of the American Society of Nephrology 17 (7): 2034–47. July 2006. doi:10.1681/ASN.2005101085. PMID 16738019. http://jasn.asnjournals.org/cgi/content/full/17/7/2034.
127. ↑ "Quality of life". Daily and Nocturnal Hemodialysis. Contributions to Nephrology. 145. 2004. pp. 99–105. doi:10.1159/000081673. ISBN 978-3-8055-7808-0.
128. ↑ "Challenges and future of renal replacement therapy". Hemodialysis International 10 (Suppl 1): S19–23. January 2006. doi:10.1111/j.1542-4758.2006.01185.x. PMID 16441862.
129. ↑ "Long-term outcomes of children with end-stage renal disease". Pediatric Nephrology 20 (7): 849–53. July 2005. doi:10.1007/s00467-005-1878-9. PMID 15834618.
130. ↑ "Choice of renal replacement therapy in patients with diabetic end stage renal disease". EDTNA/ERCA Journal 30 (3): 138–42. 2004. doi:10.1111/j.1755-6686.2004.tb00353.x. PMID 15715116.
131. ↑ "Quotidian dialysis—update 2005". Current Opinion in Nephrology and Hypertension 14 (2): 119–24. March 2005. doi:10.1097/00041552-200503000-00006. PMID 15687837. https://zenodo.org/record/896982.
132. ↑ 132.0 132.1 "Cancer in patients on dialysis for end-stage renal disease: an international collaborative study". Lancet 354 (9173): 93–9. July 1999. doi:10.1016/S0140-6736(99)06154-1. PMID 10408483.
133. ↑ American Society of Nephrology. "Five Things Physicians and Patients Should Question". Choosing Wisely: An Initiative of the ABIM Foundation. http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Neph.pdf. Retrieved August 17, 2012.
134. ↑ "Cost-effectiveness of cancer screening in end-stage renal disease". Archives of Internal Medicine 156 (12): 1345–50. June 1996. doi:10.1001/archinte.1996.00440110117016. PMID 8651845.
135. ↑ "Growth Failure in Children with Chronic Kidney Disease". https://www.niddk.nih.gov/health-information/kidney-disease/children/caring-child-kidney-disease/growth-failure-chronic-kidney-disease.
136. ↑ Rood, I. M.; Deegens, J. K. J.; Wetzels, J. F. M. (2012-03-01). "Genetic causes of focal segmental glomerulosclerosis: implications for clinical practice" (in en). Nephrology Dialysis Transplantation 27 (3): 882–890. doi:10.1093/ndt/gfr771. ISSN 0931-0509. https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfr771.
137. ↑ United States Renal Data System. 2023 Atlas of CKD & ESRD, Life-expectancy tables; Table 1.5. DOI: 10.47672/ursa.ie0w-tf75.
138. ↑ "Does conservative kidney management offer a quantity or quality of life benefit compared to dialysis? A systematic review". BMC Nephrology 22 (1). September 2021. doi:10.1186/s12882-021-02516-6. PMID 34507554.
139. ↑ "Long-term Outcomes Among Patients With Advanced Kidney Disease Who Forgo Maintenance Dialysis: A Systematic Review". JAMA Network Open 5 (3): e222255. March 2022. doi:10.1001/jamanetworkopen.2022.2255. PMID 35285915.
140. ↑ "Conservative Care for Kidney Failure—The Other Side of the Coin". JAMA Netw Open 5 (3): e222252. March 2022. doi:10.1001/jamanetworkopen.2022.2252. PMID 35285925.
141. ↑ Alshehri, Mohammed A.; Alkhlady, Husain Y.; Awan, Zuhier A.; Algethami, Mohammed Ridha; Al Mahdi, Hadiah B.; Daghistani, Hussam; Orayj, Khalid (2025-01-24). "Prevalence of chronic kidney disease in Saudi Arabia: an epidemiological population-based study" (in en). BMC Nephrology 26 (1). doi:10.1186/s12882-025-03954-2. ISSN 1471-2369. PMID 39849386.
142. ↑ "Trends in Prevalence of CKD among U.S. Adults". Centers for Disease Control Prevention (CDC). https://nccd.cdc.gov/CKD/detail.aspx?Qnum=Q9#refreshPosition.
143. ↑ Morgan T (21 January 2009). "Chronic Kidney Disease (stages 3–5) prevalence estimates using data from the Neoerica study (2007)". Association of Public Health Observatories. http://www.apho.org.uk/resource/item.aspx?RID=63798.
144. ↑ Alves, T. Palmer; Lewis, J. (2011-01-12). "Racial differences in chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States: a social and economic dilemma". Clinical Nephrology. doi:10.5414/cnp74s072. ISSN 0301-0430. https://doi.org/10.5414/cnp74s072.
145. ↑ CDC (2025-08-13). "Chronic Kidney Disease in the United States, 2023" (in en-us). https://www.cdc.gov/kidney-disease/php/data-research/index.html.
146. ↑ 146.0 146.1 "The mystery epidemic striking Nicaragua's sugar cane workers – a photo essay". The Guardian. 27 November 2020. https://www.theguardian.com/global-development/2020/nov/27/the-mystery-epidemic-striking-nicaraguas-sugar-cane-workers-a-photo-essay.
147. ↑ "CKD of Unknown Etiology (CKDu) in Sri Lanka: A Multilevel Clinical Case Definition for Surveillance and Epidemiological Studies". Kidney International Reports 4 (6): 781–5. June 2019. doi:10.1016/j.ekir.2019.03.020. PMID 31194108.
148. ↑ Hassanien, Amal A.; Al-Shaikh, Fahdah; Vamos, Eszter P.; Yadegarfar, Ghasem; Majeed, Azeem (2012-06-01). "Epidemiology of end-stage renal disease in the countries of the Gulf Cooperation Council: a systematic review" (in EN). JRSM Short Reports 3 (6): 38. doi:10.1258/shorts.2012.011150. ISSN 2042-5333. PMID 22768372. PMC 3386663. https://doi.org/10.1258/shorts.2012.011150.
149. ↑ "Tackling the £1.5bn a year cost of chronic kidney disease". Health Service Journal (Southfields, Essex, UK: Wilmington Healthcare Limited). 20 March 2020. https://www.hsj.co.uk/the-hsj-awards/tackling-the-15-billion-a-year-cost-of-chronic-kidney-disease/7027154.article.
150. ↑ (in en) Chronic kidney disease in the dog. 2018. ISBN 978-91-7760-208-8. https://pub.epsilon.slu.se/15458/. Retrieved 8 June 2018.
151. ↑ "Incidence of and mortality from kidney disease in over 600,000 insured Swedish dogs". The Veterinary Record 176 (25): 656. June 2015. doi:10.1136/vr.103059. PMID 25940343. http://researchonline.rvc.ac.uk/id/eprint/9424/.
152. ↑ "Chronic Kidney Disease" (in en). 2017-10-16. https://www.vet.cornell.edu/departments-centers-and-institutes/cornell-feline-health-center/health-information/feline-health-topics/chronic-kidney-disease.
153. ↑ Clinical trial number NCT00151827 for "Olmesartan Medoxomil in Hypertension and Renal Impairment" at ClinicalTrials.gov
154. ↑ "Angiotensin II Receptor Blockers (ARBs)". MedicineNet. 20 December 2019. https://www.medicinenet.com/angiotensin_ii_receptor_blockers/article.htm#what_are_the_side_effects_of_arbs.

## External links

* Dialysis Complications of Chronic Renal Failure at eMedicine
* Chronic Renal Failure Information from Great Ormond Street Hospital
* Note also the External resources links in the table below.

Classification|

* ICD-11: GB61
* ICD-10: N18
* ICD-9-CM: 585.9 585.1-585.5 403
* MeSH: D007676
* DiseasesDB: 11288

|

External resources|

* MedlinePlus: 000471
* eMedicine: article/238798

* v
* t
* e

Diseases of the urinary system (N00–N39, 580–599)

Kidney disease|

| Glomerules|

| Primarily
nephrotic|

| Non-proliferative|

* Minimal change
* Focal segmental
* Membranous

|

Proliferative|

* Mesangial proliferative
* Endocapillary proliferative
* Membranoproliferative/mesangiocapillary

By condition|

* Diabetic
* Amyloidosis

Primarily
nephritic,
RPG|

| Type I RPG/Type II hypersensitivity|

* Goodpasture's syndrome

|

Type II RPG/Type III hypersensitivity|

* Post-streptococcal
* Lupus
* DPGN
* IgA/Berger's

Type III RPG/Pauci-immune|

* Granulomatosis with polyangiitis
* Microscopic polyangiitis
* Eosinophilic granulomatosis with polyangiitis

General|

* glomerulonephritis
* glomerulonephrosis

Tubules|

* Renal tubular acidosis
* proximal
* distal
* Acute tubular necrosis
* Genetic
* Fanconi syndrome
* Bartter syndrome
* Gitelman syndrome
* Liddle's syndrome

Interstitium|

* Interstitial nephritis
* Pyelonephritis
* Balkan endemic nephropathy

General|

| General syndromes|

* Nephritis
* Nephrosis
* Renal failure
* Acute renal failure
* Chronic kidney disease
* Uremic pericarditis
* Uremia
* Diabetes insipidus
* Nephrogenic
* Renal papilla
* Renal papillary necrosis
* Major calyx/pelvis
* Hydronephrosis
* Pyonephrosis
* Reflux nephropathy

|

Vascular|

* Renal artery stenosis
* Renal ischemia
* Hypertensive nephropathy
* Renovascular hypertension
* Renal cortical necrosis

Other|

* Analgesic nephropathy
* Renal osteodystrophy
* Nephroptosis
* Abderhalden–Kaufmann–Lignac syndrome

Urinary tract|

| Ureter|

* Ureteritis
* Ureterocele
* Megaureter

|

Bladder|

* Cystitis
* Interstitial cystitis
* Hunner's ulcer
* Trigonitis
* Hemorrhagic cystitis
* Neurogenic bladder dysfunction
* Bladder sphincter dyssynergia
* Vesicointestinal fistula
* Vesicoureteral reflux

Urethra|

* Urethritis
* Non-gonococcal urethritis
* Urethral syndrome
* Urethral stricture/Meatal stenosis
* Urethral caruncle

Any/all|

* Obstructive uropathy
* Urinary tract infection
* Retroperitoneal fibrosis
* Urolithiasis
* Bladder stone
* Kidney stone
* Renal colic
* Malakoplakia
* Urinary incontinence
* Stress
* Urge
* Overflow

* v
* t
* e

Organ failure

General|

* Heart failure
* Respiratory failure
* Liver failure
* Acute
* Chronic
* Renal failure
* Acute
* Chronic
* Encephalopathy

Multiple|

* Multiple organ dysfunction syndrome

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Original source: https://en.wikipedia.org/wiki/Chronic kidney disease. Read more

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