Medicine chapters
Chronic kidney disease (stages, causes, complications, ESRD)
Chronic kidney disease from definition and KDIGO staging to causes, presentation, the major complications (anaemia, bone disease, acidosis, cardiovascular disease), renoprotection and end-stage kidney disease.
- CKD = abnormal kidney structure or function for more than 3 months; staged by eGFR (G1–G5) and albuminuria (A1–A3); G5 (eGFR <15) is end-stage kidney disease.
- Commonest causes are diabetes and hypertension; early CKD is silent, later uraemia brings tiredness, nausea, itch, nocturia and small kidneys on ultrasound.
- Key complications: normocytic anaemia (low erythropoietin), CKD-MBD (low calcium, high phosphate, high PTH), hyperkalaemia, acidosis, fluid overload and cardiovascular disease (main cause of death); slow progression with BP control and ACE inhibitor/ARB.
On this page
Overview
Chronic kidney disease (CKD) is a long-standing (more than 3 months), usually progressive loss of kidney function or evidence of kidney damage, whatever the cause. It replaced the older term "chronic renal failure".
CKD is common (about 11–15% of adults worldwide, most at stage 3) and is mostly silent until late. Its importance lies in three things: progression to end-stage kidney disease (ESKD/ESRD), a large rise in cardiovascular risk, and many metabolic complications.
Definition and stages
CKD is present if, for more than 3 months, there is either:
- eGFR below 60 mL/min/1.73 m², or
- markers of kidney damage with any GFR: albuminuria, haematuria of renal origin, structural abnormality on imaging (e.g. polycystic kidneys), biopsy changes, or a kidney transplant.
GFR (G) categories
| Stage | eGFR (mL/min/1.73 m²) | Description |
|---|---|---|
| G1 | ≥90 | Normal GFR with other evidence of damage |
| G2 | 60–89 | Mildly reduced, with evidence of damage |
| G3a | 45–59 | Mild to moderate decrease |
| G3b | 30–44 | Moderate to severe decrease |
| G4 | 15–29 | Severe decrease |
| G5 | <15 (or on dialysis) | Kidney failure (ESKD) |
Albuminuria (A) categories (urine albumin:creatinine ratio)
| Category | ACR (mg/mmol) | Approximate albumin per day |
|---|---|---|
| A1 | <3 | <30 mg |
| A2 | 3–30 | 30–300 mg (old "microalbuminuria") |
| A3 | >30 | >300 mg |
A patient is labelled with both, e.g. G3bA3. Both a lower GFR and more albuminuria predict faster progression and more cardiovascular events.
A G2 eGFR on its own is not CKD. It needs another marker of damage (protein, blood, structural change).
eGFR equations (MDRD, CKD-EPI) assume a steady state. They are unreliable in AKI, at extremes of muscle mass, in pregnancy and in amputees. Cystatin C can refine eGFR in stage 3.
Aetiology
| Group | Causes |
|---|---|
| Diabetes mellitus | Commonest cause of CKD and ESKD |
| Hypertension and vascular | Hypertensive nephrosclerosis (common in people of African descent), renovascular disease (atherosclerotic renal artery stenosis, elderly), vasculitis |
| Glomerular | IgA nephropathy, FSGS, membranous, lupus, other GN |
| Inherited/congenital | Adult polycystic kidney disease, Alport syndrome, congenital urinary tract obstruction, cystinosis |
| Tubulointerstitial | Reflux nephropathy / chronic pyelonephritis, analgesic nephropathy and papillary necrosis, myeloma, TB, nephrocalcinosis, lithium, herbal medicines |
| Obstruction | Prostatic disease, stones, pelvic tumours, retroperitoneal fibrosis, schistosomiasis |
| Unknown | A significant proportion, presenting late with small kidneys |
Diabetes, hypertension and atherosclerosis together explain over 70% of CKD.
Why CKD keeps progressing
Surviving ("remnant") nephrons take over the work. Each one is hyperfiltered at high pressure, which is helped by angiotensin II constricting the efferent arteriole. Over time this causes glomerulosclerosis, proteinuria and interstitial fibrosis (angiotensin II drives TGF-β). Proteinuria itself injures tubules. That is why ACE inhibitors and ARBs, which lower glomerular pressure, slow progression.
Worse prognosis with: high blood pressure, heavy proteinuria, interstitial scarring on biopsy, smoking, diabetes with poor control, and repeated AKI.
Presentation
Early (G1–G3)
- Usually no symptoms. Found on routine blood tests, urine dipstick, or during check-ups for diabetes and hypertension.
- Nocturia and polyuria from loss of concentrating ability.
- Hypertension.
Advanced (G4–G5): the uraemic syndrome
Symptoms usually appear when urea is very high (often above about 40 mmol/L), though many feel unwell earlier.
| System | Features |
|---|---|
| General | Tiredness, malaise, weight loss, loss of appetite |
| GI | Nausea, vomiting, hiccups, metallic taste, uraemic breath (fetor), gastritis and GI bleeding |
| Skin | Pruritus, pallor, sallow ("lemon-yellow") tinge, bruising, uraemic frost (very late) |
| Blood | Anaemia (breathlessness, fatigue), bleeding from platelet dysfunction |
| CVS | Hypertension, fluid overload, pericarditis (rub), heart failure |
| Respiratory | Kussmaul breathing (acidosis), pulmonary oedema |
| Nervous | Restless legs, peripheral neuropathy, asterixis, confusion, fits, coma |
| Musculoskeletal | Bone pain, fractures, myopathy |
| Endocrine/sexual | Amenorrhoea, erectile dysfunction, low libido; impaired growth in children |
Investigations
- Urea, creatinine, eGFR; serial values show the trend.
- Electrolytes: high potassium, low bicarbonate, high phosphate, low calcium, high urate.
- PTH (raised), alkaline phosphatase, vitamin D.
- Full blood count: normocytic normochromic anaemia; iron studies (ferritin, transferrin saturation), B12, folate.
- Urine: dipstick, ACR or PCR, microscopy.
- Ultrasound: kidney size and symmetry, cortical thickness, obstruction, cysts. Small, echogenic kidneys mean chronic disease. Kidneys may be normal or large in diabetes, amyloidosis, polycystic disease, myeloma and HIV nephropathy. Asymmetric kidneys suggest renovascular disease or reflux.
- Cause-specific tests: HbA1c, autoimmune screen, electrophoresis, hepatitis serology; biopsy if kidneys are normal-sized and the cause is unclear.
The most useful single test to separate CKD from AKI is kidney size on ultrasound. Anaemia, renal bone disease and raised PTH also point to chronicity.
Complications and their management
Anaemia
- Normocytic, normochromic. Main cause: erythropoietin deficiency. Also iron deficiency (blood loss, poor absorption due to hepcidin), shortened red cell survival, marrow suppression by uraemic toxins or hyperparathyroid fibrosis, B12/folate deficiency, ACE inhibitors.
- Treatment:
1. Check and correct iron first: oral or IV iron (IV works better in CKD). 2. Erythropoiesis-stimulating agents (ESAs): epoetin alfa or beta, darbepoetin (longer acting), given SC or IV. 3. Target Hb 100–120 g/L. Aiming higher raises the risk of stroke, hypertension and thrombosis without benefit.
- ESA side-effects: hypertension (common), access thrombosis, seizures, rarely pure red cell aplasia from anti-erythropoietin antibodies.
- Poor ESA response: look for iron deficiency, bleeding, infection, inflammation, hyperparathyroidism, malignancy, under-dialysis.
- Avoiding transfusion protects against HLA sensitisation before a future transplant.
Iron deficiency is the commonest reason for a poor response to erythropoietin, so check ferritin and transferrin saturation before blaming the drug.
CKD–mineral and bone disorder (CKD-MBD, renal osteodystrophy)
Sequence:
- Falling GFR → phosphate retention → bone cells release FGF23 (makes the kidney excrete phosphate and suppresses 1α-hydroxylase).
- Less 1α-hydroxylase → less calcitriol (1,25-dihydroxyvitamin D) → less calcium absorbed from gut → low calcium.
- Low calcium, high phosphate and low calcitriol all drive PTH up → secondary hyperparathyroidism.
- After years, the glands become autonomous → tertiary hyperparathyroidism with high calcium.
| Type of bone disease | Features |
|---|---|
| Osteitis fibrosa cystica (high turnover, hyperparathyroid) | Bone pain, subperiosteal erosions of phalanges, "pepperpot" skull, brown tumours; high PTH and ALP |
| Osteosclerosis | "Rugger jersey" spine (bands of dense and porotic bone) |
| Osteomalacia | Calcitriol deficiency (and, in the past, aluminium); Looser's zones |
| Adynamic bone disease (low turnover) | Over-suppressed PTH (too much vitamin D, parathyroidectomy), aluminium, diabetes; low PTH, normal ALP, hypercalcaemia risk |
| Osteoporosis | After transplant and steroids |
Also vascular calcification (stiff arteries, LVH) and calciphylaxis (painful skin necrosis from calcified small vessels; risk with high phosphate, hyperparathyroidism, obesity and warfarin).
Management:
- Lower phosphate: dietary restriction; phosphate binders with meals (calcium carbonate or acetate, sevelamer, lanthanum; aluminium binders are cheap but risk bone disease and dementia).
- Active vitamin D: alfacalcidol or calcitriol to correct calcium and suppress PTH.
- Calcimimetics (cinacalcet): make the parathyroid "think" calcium is high, lowering PTH.
- Parathyroidectomy for refractory or tertiary hyperparathyroidism.
- Check calcium, phosphate and PTH regularly (about every 3 months in advanced CKD).
Secondary hyperparathyroidism in CKD = "low calcium, high phosphate, high PTH"; tertiary = "high calcium, very high PTH" (the glands have gone their own way).
Plain vitamin D (cholecalciferol) cannot correct the problem fully in advanced CKD, because the kidney cannot carry out 1α-hydroxylation. Give already 1α-hydroxylated forms (alfacalcidol, calcitriol).
Fluid, electrolyte and acid–base problems
- Hyperkalaemia: dietary potassium restriction; stop potassium-sparing drugs and salt substitutes; correct acidosis; potassium binders (patiromer, sodium zirconium cyclosilicate). Emergency: calcium gluconate, insulin–glucose, dialysis.
- Metabolic acidosis (reduced ammonium excretion and acid retention; often high anion gap late): oral sodium bicarbonate; it also slows decline and reduces muscle wasting.
- Fluid overload and hypertension: salt restriction, loop diuretics, antihypertensives.
- Hyponatraemia if water intake is excessive; inability to concentrate or dilute urine.
Cardiovascular disease
- The commonest cause of death in CKD; risk rises as GFR falls and proteinuria increases.
- Mechanisms: hypertension, diabetes, dyslipidaemia, LVH, vascular calcification, anaemia, inflammation.
- Treat with BP control, statin (ezetimibe–simvastatin lowered vascular events in CKD), smoking cessation, glycaemic control.
- Uraemic pericarditis in severe or under-dialysed uraemia: may be haemorrhagic, risk of tamponade; treated by (intensified) dialysis; caution with anticoagulants.
Other complications
- Pruritus: uraemia, high calcium × phosphate product, hyperparathyroidism, iron deficiency; improves with adequate dialysis.
- Neurological: peripheral neuropathy, restless legs, carpal tunnel syndrome (dialysis amyloid), encephalopathy.
- Endocrine: hyperprolactinaemia, low testosterone, menstrual disturbance, falling insulin requirement (the kidney clears insulin), altered thyroid tests.
- Gout (urate retention).
- Bleeding tendency (platelet dysfunction).
- Infections (impaired immunity).
- Nephrogenic systemic fibrosis after gadolinium MRI contrast in eGFR <30: avoid gadolinium.
Management of CKD
General measures
- Find and treat the cause, especially reversible ones: relieve obstruction, treat renal artery stenosis, control accelerated hypertension, immunosuppress active GN or vasculitis.
- Avoid further injury: no NSAIDs, avoid dehydration, care with contrast, adjust drug doses.
- Cardiovascular risk reduction: stop smoking, exercise, lose weight, statin.
- Regular monitoring of eGFR and ACR; frequency depends on stage.
Renoprotection (slowing progression)
- Blood pressure below 130/80 mmHg (lower targets when proteinuria is heavy).
- ACE inhibitor or ARB (at maximum tolerated dose) for anyone with proteinuria or diabetes; recheck potassium and creatinine soon after starting (a small rise in creatinine is acceptable).
- Aim to reduce proteinuria below 0.3 g/day.
- SGLT2 inhibitors (dapagliflozin, empagliflozin) protect kidneys and heart in diabetic kidney disease.
- Add a diuretic, then a calcium channel blocker, if targets are not met.
- Normal protein diet (about 0.8–1 g/kg/day), salt restriction.
- Diabetes: HbA1c around 7% (53 mmol/mol).
- Correct acidosis with sodium bicarbonate.
Drugs in CKD
| Avoid or use with great care | Reduce dose or monitor |
|---|---|
| NSAIDs, tetracyclines (except doxycycline), potassium-sparing diuretics (spironolactone, amiloride) and potassium salt substitutes, metformin at low eGFR, gadolinium | Gentamicin and other aminoglycosides (levels), vancomycin, digoxin, opioids (accumulate, especially morphine), insulin and sulphonylureas, lithium, low molecular weight heparin, DOACs, many antibiotics and antivirals |
Gentamicin needs the biggest dose adjustment of the common antibiotics in CKD (it is cleared almost entirely by the kidney and is nephrotoxic). Doxycycline is the tetracycline that is safe.
End-stage kidney disease (ESKD/ESRD)
- G5: eGFR <15 mL/min/1.73 m² or on dialysis. Without RRT, uraemia is fatal.
- Preparation starts early: when eGFR falls towards 20, a dedicated team discusses diet, drugs, and choice of treatment: haemodialysis, peritoneal dialysis, transplantation (pre-emptive living donor transplant is the best option where possible), or conservative (supportive) care, which some frail patients choose.
- An arteriovenous fistula is created months ahead (for example when creatinine reaches about 400–500 µmol/L in non-diabetics, earlier in diabetics), because it needs several weeks to mature. Protect the non-dominant arm veins: no cannulas or blood tests there.
- Dialysis is usually started for symptoms or complications, typically around eGFR 10; starting early has not improved survival.
Details of dialysis and transplantation are in the dialysis chapter.
Expect: KDIGO G and A stages with cut-offs; commonest cause (diabetes); separating CKD from AKI by kidney size and its exceptions; the mechanism and treatment of renal anaemia (EPO, iron first, Hb target 100–120 g/L); the biochemistry of secondary and tertiary hyperparathyroidism and renal bone X-ray signs; why alfacalcidol is used; phosphate binders and cinacalcet; acidosis from reduced ammonium excretion; cardiovascular disease as the main cause of death; renoprotection with ACE inhibitors and BP targets; drugs to avoid or reduce (gentamicin, NSAIDs, tetracyclines, potassium-sparing diuretics, metformin, gadolinium); and when to plan a fistula.
Quick revision
- CKD: damage or eGFR <60 for >3 months; G1–G5 plus A1–A3.
- G3a 45–59, G3b 30–44, G4 15–29, G5 <15.
- Diabetes > hypertension as causes; often silent until late.
- Small kidneys = chronic (except diabetes, amyloid, PKD, myeloma).
- Anaemia: EPO deficiency; give iron then ESA; Hb 100–120 g/L.
- CKD-MBD: low Ca, high PO4, high PTH, high ALP; binders, alfacalcidol, cinacalcet.
- Death mostly cardiovascular.
- Renoprotection: BP <130/80, ACE inhibitor/ARB, SGLT2 inhibitor, stop smoking.
- ESKD: plan fistula early; dialysis around eGFR 10 or for symptoms; transplant is best.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
Why is the anaemia of CKD normocytic?
It is caused mainly by too little erythropoietin, so the marrow makes fewer red cells of normal size; iron deficiency can coexist and must be corrected first.
Why are alfacalcidol or calcitriol used instead of ordinary vitamin D?
The failing kidney cannot carry out 1α-hydroxylation, so it cannot activate ordinary vitamin D; these drugs are already hydroxylated at the 1α position.
What usually kills patients with CKD?
Cardiovascular disease, such as myocardial infarction, heart failure, stroke and sudden death, rather than kidney failure itself.
Can CKD be reversed?
Sometimes, if the cause is treatable, such as obstruction, renal artery stenosis, accelerated hypertension or active glomerulonephritis; otherwise treatment aims to slow progression.