Chronic kidney disease

• Chronic kidney disease (CKD) is a sustained abnormality of kidney structure or function, present for more than 3 months, that usually develops gradually and is often silent until advanced. ^[1]
• It is staged by two measures together: the estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (ACR), because each independently predicts risk.
• Diabetes and long-standing hypertension are the commonest causes worldwide; many other diseases can produce it.
• The important complications are anaemia, chronic kidney disease-mineral and bone disorder, metabolic acidosis, and hyperkalaemia.
• Slowing progression rests on controlling blood pressure, blocking the renin-angiotensin-aldosterone system, and adding an SGLT2 inhibitor; advanced disease needs nephrology referral.

By the end of this page you should be able to:

1. Define CKD and explain why the diagnosis requires a reduction in function or evidence of damage for more than 3 months.
2. Stage CKD in adults using GFR and ACR categories, and read the risk table that combines them.
3. List the principal causes of CKD and the risk factors for faster progression.
4. Explain why anaemia, bone disease, acidosis, and hyperkalaemia arise in CKD.
5. Choose and monitor drug treatment to slow progression, including ACE inhibitors or ARBs and SGLT2 inhibitors.
6. Recognise when to refer a person with CKD.

Two separate ideas are often confused, and the distinction matters. A single abnormal blood test does not diagnose CKD, because kidney function fluctuates with hydration, drugs, and illness. Reduced eGFR must be confirmed on repeat testing, usually within 2 weeks if it is a new finding, and must persist beyond 3 months. Equally, a normal eGFR does not exclude CKD: a person with a structurally damaged kidney, for example diabetic nephropathy with proteinuria, has CKD even if the eGFR is above 90 ml/min/1.73 m2. ^[1]

CKD is common and largely hidden. A systematic review and meta-analysis of observational studies pooled data on 6.9 million people and estimated a global prevalence of 13.4% (95% CI 11.7 to 15.1%) when all five stages are counted, and 10.6% (95% CI 9.2 to 12.2%) when stages 3 to 5 alone are counted. ^[3] The largest single stage is stage 3, the majority of which is stage 3a, and prevalence rises steeply with age. ^[3] Diabetes, hypertension, obesity, and an ageing population are the main drivers of this burden. ^[3]

In stages 3b to 5 the age-standardised prevalence varies by region, but CKD produces most of its morbidity and all end-stage kidney disease. Because early disease causes no symptoms, a large fraction of affected adults are undiagnosed until an incidental blood or urine test is performed.

CKD is a final common pathway. Different diseases damage the kidney in different ways, but all eventually reduce the number of functioning nephrons and, with it, the filtration surface.

The leading causes in most of the world are:

• Diabetes mellitus. Both type 1 and type 2 diabetes damage glomeruli through metabolic and haemodynamic mechanisms; diabetic kidney disease is the single commonest cause of kidney failure requiring replacement therapy in many countries.
• Hypertension. Long-standing, poorly controlled high blood pressure injures renal small vessels and produces nephrosclerosis; the relationship runs in both directions, since CKD also raises blood pressure.
• Glomerulonephritis. Immune-mediated inflammation of the glomeruli, including IgA nephropathy, lupus nephritis, and vasculitic disease, can be subclinical for years.
• Polycystic kidney disease and other genetic disorders. Autosomal dominant polycystic kidney disease, Alport syndrome, and many other inherited conditions.
• Tubulointerstitial and obstructive disease. Recurrent urinary infection, reflux nephropathy, renal calculi, prostatic obstruction, and retroperitoneal fibrosis.
• Drugs and toxins. Chronic use of analgesics (especially non-steroidal anti-inflammatory drugs in combination with other agents), lithium, calcineurin inhibitors, and heavy-metal or herbal toxins.
• Unknown. In a substantial minority of cases, no cause is identified, particularly in older adults.

People at higher risk of developing CKD, and who should be tested, include those with diabetes, hypertension, cardiovascular disease, previous acute kidney injury, structural renal tract disease, multisystem diseases with possible renal involvement, gout, a family history of kidney failure, and incidental haematuria or proteinuria. ^[1] Age, sex, ethnicity, and obesity without metabolic syndrome are not themselves indications for testing. ^[1]

Risk factors for faster progression once CKD is present include cardiovascular disease, proteinuria, a past episode of AKI, high blood pressure, diabetes, tobacco use, Black or South Asian family background, regular NSAID use, and untreated urinary outflow obstruction. ^[1]

The basic sequence is simple to state and important to understand. Nephrons are lost; the remaining nephrons hyperfilter to compensate; over years this compensation itself becomes damaging.

Chronic hyperglycaemia or raised intraglomerular pressure forces more plasma through fewer glomeruli. The hyperfiltering nephrons develop glomerulosclerosis, and tubulointerstitial fibrosis spreads from each damaged glomerulus into the surrounding cortex. Proteinuria both marks and worsens this process: filtered albumin is taken up by proximal tubular cells, triggering inflammation and fibrosis. Systemic hypertension and intraglomerular hypertension are not the same thing, but they travel together, and blocking the renin-angiotensin-aldosterone system lowers pressure inside the glomerulus as well as in the arm.

Several complications follow directly from the lost function rather than from the underlying cause:

• Filtration falls, so urea, creatinine, and other waste products rise slowly.
• Sodium and water handling becomes erratic, producing hypertension, oedema, and nocturia.
• Potassium excretion fails, especially once the distal nephron is affected, leading to hyperkalaemia.
• Acid excretion falls and bicarbonate is lost, leading to metabolic acidosis.
• Phosphate is retained and vitamin D activation falls, disturbing bone and parathyroid hormone.
• Erythropoietin production by peritubular fibroblasts falls, and iron handling becomes disordered, producing anaemia.

CKD is usually asymptomatic for years. When symptoms appear, they tend to be non-specific and advanced: fatigue, loss of appetite, nausea, pruritus, sleep disturbance, nocturia, ankle swelling, and breathlessness from fluid overload. Advanced disease can produce pericarditis, encephalopathy, and bleeding tendencies from uraemia.

Signs on examination depend on the cause and stage: hypertension, volume overload with elevated jugular venous pressure and peripheral oedema, pallor from anaemia, and sometimes a palpable polycystic kidney or bladder in obstruction. Retinopathy may be present in diabetic or hypertensive disease.

Proteinuria and haematuria are often the earliest detectable features. A person with CKD can feel completely well while quietly approaching kidney failure, which is the central reason for screening at-risk groups and for regular monitoring.

When kidney function is reduced, the first question is whether the fall is acute or chronic. A rising creatinine over days, with a known baseline, suggests acute kidney injury superimposed on or mistaken for CKD. The most useful separators are duration, previous results, imaging (small echogenic kidneys suggest chronic disease), and urinalysis. When proteinuria or haematuria dominates, glomerular diseases must be distinguished from urological bleeding; cystoscopy and renal imaging address the latter. Other mimics of CKD complications, such as unexplained anaemia or bone pain, should always be considered in their own right.

Serum creatinine is the standard test, but it varies with muscle mass, diet, and acute illness, so laboratories should report an eGFR calculated with the CKD-EPI creatinine equation alongside every creatinine result. ^[1] eGFR should be read cautiously in people with extremes of muscle mass. ^[1] In an adult not previously tested, an eGFR under 60 ml/min/1.73 m2 should be confirmed by repeating the test within 2 weeks. ^[1] People should also avoid eating meat in the 12 hours before the blood test. ^[1]

Proteinuria is detected with a urine albumin:creatinine ratio (ACR), which is more sensitive than a protein:creatinine ratio at low levels. A confirmed ACR of 3 mg/mmol or more is clinically important proteinuria, and an ACR between 3 and 70 mg/mmol should be confirmed on a repeat early-morning sample. ^[1] Reagent strips are not adequate in adults unless they specifically measure albumin. ^[1]

Imaging is used selectively. Renal ultrasound is offered to adults with CKD who have accelerated progression, visible or persistent invisible haematuria, symptoms of obstruction, a family history of polycystic kidney disease (if over 20 years old), an eGFR under 30 ml/min/1.73 m2, or a nephrologist's decision that biopsy may be needed. ^[1]

Because CKD is often not progressive, the frequency of monitoring is agreed individually. As a guide, an adult with stage 3a CKD and normal albumin excretion (ACR under 3 mg/mmol) needs eGFR checked at least once a year, whereas stage 4 disease with severely increased albuminuria (ACR over 30 mg/mmol) needs checking at least three times a year, and stage 5 disease at least four times a year. ^[1] Before judging that the disease is progressing, at least three eGFR measurements spanning at least 90 days are needed. ^[1]

CKD is classified by combining the GFR category with the ACR category. The two dimensions multiply risk: a low eGFR on its own raises risk, albuminuria on its own raises risk, and the two together raise risk more than either alone. ^[1]

The same KDIGO 2024 CKD guideline uses the same CGA (cause, GFR category, albuminuria category) framework. ^[5] The thresholds are:

• G1 eGFR 90 ml/min/1.73 m2 or more
• G2 60 to 89
• G3a 45 to 59
• G3b 30 to 44
• G4 15 to 29
• G5 under 15 (kidney failure)

Everyone with CKD benefits from the same basic advice: stop smoking, take regular exercise, achieve and maintain a healthy weight, moderate salt and alcohol intake, and receive education about the condition. ^[1] Dietary advice about potassium, phosphate, calories, and salt is tailored to severity and delivered with supervision so that malnutrition does not occur. ^[1] Low-protein diets with intake below 0.6 to 0.8 g/kg/day are not offered. ^[1]

Blood pressure control is the single most established way to slow progression. The targets depend on albuminuria:

• ACR under 70 mg/mmol: clinic systolic pressure under 140 mmHg (target range 120 to 139) and diastolic under 90 mmHg. ^[1]
• ACR 70 mg/mmol or more: clinic systolic pressure under 130 mmHg (target range 120 to 129) and diastolic under 80 mmHg. ^[1]

Treatment choices for hypertension in CKD follow the same principles as the general population, with two important additions: renin-angiotensin system blockade when albuminuria is present (see below), and attention to volume status.

ACE inhibitors and angiotensin receptor blockers (ARBs) lower intraglomerular pressure as well as systemic pressure, and they reduce albuminuria. They are not given to everyone: the indications are specific.

• CKD with diabetes: offer an ACE inhibitor or ARB, titrated to the highest licensed dose the person can tolerate, if the ACR is 3 mg/mmol or more. ^[1]
• CKD without diabetes: refer for nephrology assessment and offer an ACE inhibitor or ARB if the ACR is 70 mg/mmol or more; monitor closely if the ACR is above 30 but below 70 mg/mmol. ^[1]
• CKD with hypertension and ACR above 30 mg/mmol: offer an ACE inhibitor or ARB. ^[1]

Two (or more) renin-angiotensin system antagonists must never be combined in CKD. ^[1]

Safety checks are essential and are often mishandled:

• Measure serum potassium and estimate GFR before starting, and repeat them 1 to 2 weeks after starting or after each dose increase. ^[1]
• Do not start if pretreatment potassium is above 5.0 mmol/litre. ^[1]
• Stop the drug if potassium rises to 6.0 mmol/litre or more (after removing other promoting medicines) and reassess. ^[1]
• A fall in eGFR of less than 25% or a creatinine rise of less than 30% from baseline is acceptable and does not need a dose change; repeat the test in 1 to 2 weeks. ^[1]
• A fall of 25% or more, or a creatinine rise of 30% or more, needs investigation for other causes such as volume depletion or NSAIDs; if none is found, stop or reduce to the last tolerated dose. ^[1]

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have become a standard additional therapy. They reduce hyperfiltration and provide cardiovascular and kidney protection across a range of eGFR values. NICE recommends them as an option in adults with CKD on top of maximally tolerated ACE inhibitor or ARB (unless unsuitable), if the eGFR is:

• 20 to under 45 ml/min/1.73 m2, or
• 45 to 90 ml/min/1.73 m2 where the urine albumin-to-creatinine ratio is at least 22.6 mg/mmol, or the patient has type 2 diabetes. ^[1]

The named products are dapagliflozin (NICE technology appraisal TA1075, 2025) and empagliflozin (NICE technology appraisal TA942, 2023). ^[1] Finerenone is additionally recommended for stage 3 or 4 CKD with ACR of 3 mg/mmol or more and type 2 diabetes, as an add-on to optimised ACE inhibitor or ARB and SGLT2 inhibitor, if the eGFR is 25 ml/min/1.73 m2 or more. ^[1]

Anaemia develops mainly from reduced erythropoietin production and disordered iron metabolism, worsened by uraemic inhibition of marrow and blood loss, often occult gastrointestinal bleeding. NICE suggests investigating and managing anaemia when the haemoglobin is 110 g/litre or less, or when symptoms attributable to anaemia are present. ^[1] The extent of investigation depends on the eGFR:

• eGFR above 60 ml/min/1.73 m2: anaemia is unlikely to be due to CKD; investigate other causes. ^[1]
• eGFR 30 to 60: other causes should still be sought, but the anaemia may be from CKD. ^[1]
• eGFR below 30: anaemia is often caused by CKD, although other causes should still be considered. ^[1]

Iron status is monitored every 3 months, using percentage of hypochromic red cells if processing is rapid; otherwise reticulocyte haemoglobin content; or, if these are unavailable, a combination of transferrin saturation (under 20%) and serum ferritin (under 100 micrograms/litre). ^[1] Absolute iron deficiency should be treated before starting erythropoiesis-stimulating agents (ESAs), whose pros and cons should be discussed with the person. ^[1] Serum ferritin should not exceed 800 micrograms/litre during iron therapy, with review of the dose at 500 micrograms/litre. ^[1] ESA therapy is not started when comorbidity or prognosis makes benefit unlikely, and hypoxia-inducible factor prolyl-hydroxylase inhibitors (roxadustat, vadadustat in selected groups) are options in some patients. ^[1]

Secondary hyperparathyroidism should be treated, because it worsens anaemia. ^[1]

As GFR falls, phosphate is retained, vitamin D activation in the kidney falls, and calcium absorption drops. The parathyroid glands respond with secondary hyperparathyroidism, producing high-turnover bone disease, and low-turnover (adynamic) bone disease also occurs. Fractures, vascular calcification, and cardiovascular risk all rise.

Management begins with dietary discussion and dialysis optimisation where applicable, followed by phosphate binders in stage 4 or 5 disease with hyperphosphataemia. NICE recommends calcium acetate as the first binder for adults, with sevelamer carbonate if calcium acetate is unsuitable or not tolerated, and reserved alternatives thereafter. ^[1] Calcium and phosphate levels should be kept from exceeding the upper end of their age-adjusted normal range, and the person's preferences matter because binders are unpleasant and must be taken with food. ^[1] Vitamin D deficiency is corrected; active vitamin D sterols and calcimimetics are used for refractory hyperparathyroidism under specialist care.

Acid retention is a predictable consequence of reduced nephron mass. Metabolic acidosis is common in CKD and becomes more frequent as eGFR falls; one study found it in 79% of patients in stages G4 and G5 when the criterion is a serum bicarbonate under 22 mmol/l. ^[4]

Guidelines disagree on when to treat, which reflects genuinely mixed evidence. The KDIGO 2024 CKD guideline lowered the treatment threshold to a serum bicarbonate under 18 mmol/l, aiming to prevent severe acidosis only. ^[4] NICE 2021 suggests considering oral sodium bicarbonate when the eGFR is under 30 ml/min and the serum bicarbonate is under 20 mmol/l. ^[2] UK Kidney guidance and KDOQI use a threshold under 22 mmol/l, with caution about overcorrection above about 26 mmol/l because of the risk of hypertension, oedema and heart failure. ^{[2] [4]} Fruit- and vegetable-based diets that produce alkali are an alternative that may control bicarbonate as well as sodium bicarbonate. ^[2]

Potassium accumulates as distal nephron function declines and this is worsened by ACE inhibitors, ARBs, potassium-sparing diuretics, and NSAIDs. A high serum potassium is one of the commonest reasons to modify or stop renin-angiotensin system blockade.

Community measures include avoiding high-potassium salt substitutes and high-potassium foods, reviewing culprit drugs, and correcting acidosis. Sodium bicarbonate can help shift potassium intracellularly. Persistent hyperkalaemia in stages G3b to G5 CKD may be treated with potassium binders (sodium zirconium cyclosilicate or patiromer) as recommended by NICE and the UK Kidney Association. ^{[1] [2]} Acute, severe or ECG-changing hyperkalaemia is a medical emergency requiring calcium to stabilise the myocardium, insulin with glucose, and urgent dialysis if needed; those details are covered in hyperkalaemia guidelines.

Progression in CKD is often not linear; episodes of acute illness can cause stepwise drops. Accelerated progression is defined, in adults, as either a sustained decrease in GFR of 25% or more with a change of GFR category within 12 months, or a sustained decrease of 15 ml/min/1.73 m2 per year. ^[1] A person meeting either criterion, or with an eGFR fall of 15 ml/min/1.73 m2 or more over 12 months, is at increased risk of reaching kidney failure. ^[1]

To estimate the rate reliably, obtain at least three GFR measurements over at least 90 days and repeat within 2 weeks after any new finding of reduced GFR to exclude acute kidney injury. ^[1] The Kidney Failure Risk Equation estimates 5-year risk of needing renal replacement therapy and should be discussed with the person using plain language. ^[1]

The levers that genuinely slow progression are well established: blood pressure control, renin-angiotensin system blockade in albuminuric disease, SGLT2 inhibitors, glycaemic control in diabetes, smoking cessation, and correction of metabolic acidosis. ^{[1] [2] [4]}

Refer adults with CKD for specialist assessment if any of the following apply:

• a 5-year risk of needing renal replacement therapy above 5%
• ACR 70 mg/mmol or more (unless known to be diabetic and already treated) ^[1]
• ACR above 30 mg/mmol together with haematuria
• sustained eGFR fall of 25% or more with change of category within 12 months
• sustained eGFR fall of 15 ml/min/1.73 m2 or more per year
• hypertension poorly controlled despite at least four antihypertensive drugs at therapeutic doses ^[1]
• known or suspected rare or genetic causes
• suspected renal artery stenosis. ^[1]

Children and young people should be referred if they have an ACR of 3 mg/mmol or more, haematuria, any fall in eGFR, hypertension, known or suspected genetic cause, suspected renal artery stenosis, or renal outflow obstruction. ^[1]

People with renal outflow obstruction go to urology unless urgent treatment is needed for hyperkalaemia, severe uraemia, acidosis, or fluid overload. ^[1] Where concerns exist but formal referral is not needed, discuss management with a specialist by letter, email, telephone or virtual meeting. ^[1]

After referral, agree a documented, dated care plan and consider whether routine follow-up can occur in primary care with clear re-referral criteria. ^[1]

Pregnancy. CKD in pregnancy increases the risk of pre-eclampsia, fetal growth restriction, and preterm delivery, and the eGFR changes throughout pregnancy; ACE inhibitors and ARBs must be stopped before conception or as soon as pregnancy is recognised. Management is shared between obstetrics, nephrology, and primary care.

Children and young people. Use age-appropriate creatinine reference ranges; test risk groups such as those with a previous acute kidney injury or a solitary functioning kidney; an ACE inhibitor or ARB is offered if the ACR is 3 mg/mmol or more with diabetes, or 70 mg/mmol or more without diabetes. ^[1]

Older adults. Older age alone is not grounds for withholding treatment, but frailty, comorbidity, and medicine burden require individualised targets and careful monitoring, particularly of potassium. ^[1]

• CKD is often diagnosed late. A simple dipstick for albumin, a serum creatinine with eGFR, and a blood pressure measurement are the core of detection and are available in most settings.
• If ACR is unavailable, a protein:creatinine ratio can be used at higher concentrations, though it is less sensitive at low levels. ^[1]
• Control of blood pressure with whatever effective agents are available, and avoidance of NSAIDs, deliver most of the benefit.
• Where SGLT2 inhibitors are unavailable, blood pressure control and renin-angiotensin system blockade where affordable still slow progression.
• Anaemia management may have to rely on oral iron and nutrition, with intravenous iron and ESAs where funded.
• Phosphate binders, vitamin D, and calcimimetics are costly; calcium-based binders and dietary phosphate restriction are the fallback.
• Plan referral early, because kidney replacement therapy is often far away or unaffordable.

• CKD is a sustained abnormality of kidney structure or function for more than 3 months, often silent.
• Stage using eGFR and ACR together; the two dimensions multiply risk.
• Diabetes and hypertension are the leading causes; many other diseases matter.
• Anaemia, CKD-mineral and bone disorder, metabolic acidosis, and hyperkalaemia are the key complications and should be anticipated.
• Blood pressure targets are under 140/90 mmHg if the ACR is under 70 mg/mmol, and under 130/80 mmHg if it is 70 mg/mmol or more.
• ACE inhibitors or ARBs are indicated with diabetes and ACR of 3 mg/mmol or more, and without diabetes with ACR of 70 mg/mmol or more, and must never be combined with each other.
• Start renin-angiotensin blockade with potassium and creatinine checks at baseline and at 1 to 2 weeks, and stop if potassium reaches 6.0 mmol/litre.
• SGLT2 inhibitors are recommended when the eGFR is 20 to under 45, or 45 to 90 when the urine albumin-to-creatinine ratio is at least 22.6 mg/mmol or there is type 2 diabetes, on top of tolerated ACE inhibitor or ARB. ^[1]
• Hyperphosphataemia in stage 4 or 5 disease is treated with calcium acetate first, with sevelamer carbonate as the common alternative.
• Acidosis treatment thresholds differ between guidelines, from serum bicarbonate under 18 mmol/l (KDIGO 2024) to under 22 mmol/l (KDOQI), which reflects the limited trial evidence.
• Use the Kidney Failure Risk Equation, the nephrology referral criteria, and individualised monitoring frequencies; refer early when progression is accelerated.

Chronic renal failure; glomerulonephritis; diabetic kidney disease; hypertension; acute kidney injury; hyperkalaemia; mineral and bone disorder; anaemia of chronic disease; dialysis; kidney transplantation.