Chronic Kidney Disease — Causes, Stages, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function — persistent for more than 3 months — with implications for health. The two key markers are reduced glomerular filtration rate (eGFR below 60 mL/min/1.73 m²) and/or elevated urinary albumin-to-creatinine ratio (ACR above 3 mg/mmol — albuminuria). CKD is staged by the KDIGO (Kidney Disease Improving Global Outcomes) classification: eGFR stages G1 (above 90, normal with kidney damage), G2 (60-89, mildly reduced), G3a (45-59), G3b (30-44), G4 (15-29, severely reduced), G5 (below 15 — kidney failure); combined with albuminuria stages A1, A2, A3. CKD affects approximately 850 million people worldwide — 10% of the global population — and is the 8th leading cause of mortality. CKD is predominantly caused by diabetic nephropathy and hypertensive nephropathy in high-income countries. CKD increases cardiovascular mortality dramatically — patients with CKD G3-G4 are far more likely to die of cardiovascular disease than reach dialysis. With appropriate management, progression can be substantially slowed.

The two most common causes globally: diabetic nephropathy (diabetic kidney disease — DKD, accounts for 25-40% of CKD — chronic hyperglycaemia causes glomerular hypertension, hyperfiltration, basement membrane thickening, mesangial expansion, and ultimately glomerulosclerosis; hallmark: microalbuminuria progressing to macroalbuminuria); hypertensive nephropathy (chronic hypertension causes arteriolar nephrosclerosis — accounts for 25-30% of CKD). Other causes: IgA nephropathy (most common primary glomerulonephritis worldwide — presents with haematuria and proteinuria); focal segmental glomerulosclerosis (FSGS); membranous nephropathy; autosomal dominant polycystic kidney disease (ADPKD — PKD1/PKD2 mutations, most common inherited kidney disease); lupus nephritis; vasculitis (ANCA-associated); renovascular disease (renal artery stenosis from atherosclerosis); reflux nephropathy (from childhood VUR and recurrent UTIs); and obstructive uropathy. Risk factors for CKD progression: poorly controlled diabetes (HbA1c above 7%); hypertension (BP above 130/80 mmHg); proteinuria (higher ACR = faster progression); smoking; NSAIDs and nephrotoxic medications; obesity; and acute kidney injury episodes.

Early CKD (G1-G3): usually asymptomatic — detected only by blood tests (elevated creatinine, reduced eGFR) and urine tests (albuminuria, haematuria). Symptoms develop progressively with advanced CKD: uraemia (accumulation of urea and metabolic waste products) in G4-G5 — fatigue, malaise, nausea and vomiting (uraemic gastroenteropathy), anorexia and weight loss, itch (pruritus — from uraemic toxins and secondary hyperparathyroidism), metallic taste, and uraemic fetor (breath smell). CKD-related complications: anaemia (normochromic normocytic — reduced erythropoietin production; target haemoglobin 100-120 g/L with ESA); renal osteodystrophy (CKD-MBD — mineral bone disorder: elevated PTH, hyperphosphataemia, hypocalcaemia, reduced vitamin D activation — bone pain, fractures, vascular calcification); fluid overload (oedema, hypertension, pulmonary oedema in severe CKD); metabolic acidosis (bicarbonate below 22 mmol/L — accelerates muscle wasting and CKD progression); hyperkalaemia (especially in G4-G5 — risk of fatal arrhythmia); and significantly elevated cardiovascular disease risk (MI, stroke, heart failure). End-stage kidney disease (ESKD, G5): requires renal replacement therapy (RRT) — haemodialysis (HD), peritoneal dialysis (PD), or kidney transplantation.

CKD diagnosis requires two measurements more than 90 days apart showing abnormal eGFR or albuminuria (to exclude acute kidney injury, which resolves). Serum creatinine and eGFR (CKD-EPI equation 2021): best single marker of kidney filtration function — eGFR is calculated from creatinine, age, and sex. NICE recommends monitoring eGFR frequency by stage: annually for G1-G2; biannually for G3a; three-monthly for G3b-G4. Urine albumin-to-creatinine ratio (ACR) on early morning urine specimen: A1 (below 3 mg/mmol — normal); A2 (3-30 mg/mmol — moderately increased/microalbuminuria); A3 (above 30 mg/mmol — severely increased/macroalbuminuria). Combined eGFR + ACR determines risk of progression (heat map in KDIGO guidelines). Additional tests: FBC (anaemia), bicarbonate (acidosis), potassium (hyperkalaemia), phosphate, PTH, vitamin D, lipid profile, HbA1c (if diabetic). Renal ultrasound: assess kidney size and echogenicity, exclude obstruction and ADPKD (bilateral enlarged cysts). Renal biopsy: for unexplained CKD with proteinuria or haematuria — determines histological cause and guides specific treatment. 24-hour ambulatory blood pressure monitoring (ABPM) for hypertension assessment.

Slow CKD progression and reduce cardiovascular risk: BP target below 120/80 mmHg (systolic below 120 if tolerated). ACE inhibitors (ramipril, enalapril) or ARBs (losartan, irbesartan, candesartan): first-line reno- and cardioprotective medications — reduce glomerular capillary pressure and proteinuria; mandatory for CKD with albuminuria (ACR above 3 mg/mmol) regardless of blood pressure; monitor potassium and creatinine (10-15% rise acceptable). SGLT2 inhibitors (dapagliflozin 10 mg — DAPA-CKD trial 2020; canagliflozin — CREDENCE trial): revolutionary disease-modifying agents for CKD with albuminuria; reduce composite kidney endpoint by 39% (DAPA-CKD); NICE recommends dapagliflozin for CKD ACR above 22.6 mg/mmol regardless of diabetes status. Finerenone (non-steroidal MRA): reduces CKD progression and cardiovascular events in diabetic CKD on ACEi/ARB; NICE approved 2023. Glycaemic control: HbA1c target 53-58 mmol/mol (7-7.5%) in diabetic CKD. Anaemia management: iron supplementation (IV iron preferred for CKD G4-G5) + ESAs (darbepoetin alfa, epoetin beta) — target Hb 100-120 g/L; daprodustat (HIF-PH inhibitor, oral) — NICE approved. CKD-MBD: dietary phosphate restriction; phosphate binders (sevelamer, lanthanum carbonate); activated vitamin D analogues (alfacalcidol, calcitriol); cinacalcet for secondary hyperparathyroidism. Hyperkalaemia management: sodium zirconium cyclosilicate (Lokelma) or patiromer — potassium binders enabling continuation of ACEi/ARB. Dietary advice: sodium restriction below 2.3 g/day; protein intake 0.8 g/kg/day. Renal replacement therapy for ESKD: haemodialysis (HD — 3x weekly, 4 hours per session); peritoneal dialysis (PD — home-based); kidney transplantation (best outcome — 5-year survival above 90% with living donor).

Cardiovascular disease is the most common cause of death in CKD — risk is 10-20 times higher than the general population; CKD accelerates atherosclerosis through chronic inflammation, vascular calcification, dyslipidaemia, and fluid overload. CKD-mineral and bone disorder (CKD-MBD): hyperphosphataemia, secondary hyperparathyroidism, impaired vitamin D activation, bone pain, pathological fractures, and vascular and soft tissue calcification. Renal anaemia (normochromic normocytic anaemia from reduced erythropoietin production) causes fatigue, breathlessness, and cognitive impairment. Metabolic acidosis (low bicarbonate below 22 mmol/L) accelerates muscle wasting and CKD progression. Hyperkalaemia (potassium above 6.0 mmol/L) risks cardiac arrhythmia and arrest, particularly in CKD G4-G5 on RAAS blockade. Fluid overload causes hypertension, peripheral oedema, and pulmonary oedema. Impaired immune function increases susceptibility to bacterial infections. Progression to ESKD (eGFR below 15) requiring dialysis or transplantation — highest risk in patients with G4-G5 CKD and significant albuminuria.

Prevention of CKD onset: optimal diabetes management (HbA1c below 53 mmol/mol); blood pressure control; maintain healthy weight; avoid chronic NSAIDs (ibuprofen, diclofenac, naproxen) — nephrotoxic; avoid dehydration; attend regular GP review if diabetic or hypertensive. Prevention of CKD progression: ACEi/ARB for proteinuric CKD; SGLT2 inhibitor for ACR above 22.6 mg/mmol; smoking cessation (independent risk factor for CKD progression and cardiovascular mortality); avoid contrast-induced nephropathy — adequate hydration before contrast CT or angiography; hold metformin and nephrotoxics before contrast procedures. Medication review: many drugs require dose adjustment or are contraindicated in reduced eGFR (metformin contraindicated below eGFR 30; NSAIDs avoided; gadolinium contrast risk — nephrogenic systemic fibrosis). Immunisations: influenza annually; pneumococcal vaccine; hepatitis B vaccine; COVID-19 vaccine (CKD patients are high-risk group).

Attend Emergency Department immediately for: severely reduced urine output (oliguria — less than 400 mL/day or complete cessation of urine) — acute-on-chronic kidney injury; severe fluid overload with severe shortness of breath from pulmonary oedema; hyperkalaemia symptoms — palpitations, muscle weakness, paralysis (ECG changes: peaked T-waves, wide QRS, sine wave pattern are emergencies requiring urgent IV calcium and insulin/dextrose); uraemic pericarditis (chest pain worse lying flat) — emergency dialysis indication; altered consciousness or seizures in known CKD — uraemic encephalopathy. Contact GP or renal team urgently for: rapidly rising creatinine or rapidly falling eGFR (more than 5 mL/min/1.73 m² in 1 year); new or worsening proteinuria; recurrent or persistent haematuria; significant anaemia (Hb below 80 g/L); planning surgery requiring general anaesthesia — renal team needs to be involved. All patients with CKD G3b-G5 should be under nephrology review.