Chronic Kidney Disease (CKD)
Summary
Chronic Kidney Disease (CKD) is defined as kidney damage or reduced kidney function (GFR <60 mL/min/1.73m²) persisting for ≥3 months. It is staged by GFR (G1-G5) and albuminuria (A1-A3), which together determine prognosis and management. The most common causes are diabetes and hypertension. Management focuses on slowing progression (ACE inhibitors/ARBs, SGLT2 inhibitors), managing cardiovascular risk, and treating complications (anaemia, bone disease, hyperkalaemia). SGLT2 inhibitors have revolutionised CKD management, providing kidney and cardiovascular protection. End-stage kidney disease (ESKD, G5) requires renal replacement therapy (dialysis or transplantation).
Key Facts
- Definition: Kidney damage or GFR <60 mL/min/1.73m² for ≥3 months
- Prevalence: ~10% of population; increases with age
- Main Causes: Diabetes (~40%), Hypertension (~25%)
- Staging: KDIGO GFR (G1-G5) + Albuminuria (A1-A3)
- Key Protective Drugs: ACE-I/ARB + SGLT2 inhibitor
- Target BP: <130/80 mmHg (especially with albuminuria)
Clinical Pearls
"SGLT2 Inhibitors for Everyone with CKD": DAPA-CKD and EMPA-KIDNEY trials showed SGLT2 inhibitors slow CKD progression regardless of diabetes status. Consider in all patients with CKD (GFR >20-25) and albuminuria.
Don't Stop ACE-I/ARB for Small Creatinine Rise: A rise in creatinine of up to 30% after starting ACE-I/ARB is acceptable and expected. Only stop if rise >30% or K>6.0.
eGFR Decline Predicts Risk: Rate of eGFR decline is as important as absolute level. A decline of >5 mL/min/year is rapid and warrants investigation and intensified management.
Why This Matters Clinically
CKD is extremely common and a major risk factor for cardiovascular death (more patients die of CVD than reach dialysis). Early identification (albuminuria screening in at-risk groups), appropriate pharmacotherapy, and cardiovascular risk management improve outcomes.
Incidence & Prevalence
- Global Prevalence: ~10-15% of adults
- CKD G3-G5: ~5-7%
- Trend: Increasing (due to diabetes, hypertension, ageing population)
- ESKD on RRT (UK): ~65,000 patients
Demographics
| Factor | Details |
|---|---|
| Age | Prevalence increases markedly with age |
| Sex | Similar overall; ESKD more common in men |
| Ethnicity | Higher risk in Black and South Asian populations |
| Socioeconomic | Higher prevalence in lower SES |
Causes
| Cause | Proportion |
|---|---|
| Diabetic Nephropathy | ~40% |
| Hypertensive Nephrosclerosis | ~25% |
| Glomerulonephritis (various) | ~10-15% |
| Polycystic Kidney Disease | ~5-10% |
| Other | Tubulointerstitial, obstructive, renovascular |
Mechanism
Step 1: Initial Injury
- Diabetes: Hyperglycaemia → glomerular hypertension, hyperfiltration
- Hypertension: Arteriolosclerosis, nephrosclerosis
- Glomerulonephritis: Immune-mediated glomerular injury
Step 2: Nephron Loss & Maladaptive Response
- Nephron loss → remaining nephrons hyperfiltrate
- Increased intraglomerular pressure
- Proteinuria → tubular damage → further nephron loss
- Vicious cycle of progression
Step 3: Loss of Kidney Functions
- Excretion: Accumulation of uraemic toxins, potassium, acid
- Endocrine: Reduced EPO (anaemia), reduced 1,25-OH vitamin D activation (bone disease)
- Fluid balance: Oedema, hypertension
Step 4: Complications
- Anaemia, CKD-MBD, acidosis, hyperkalaemia, CVD
KDIGO Risk Stratification (Heat Map)
Risk is determined by GFR stage (G1-G5) and albuminuria stage (A1-A3):
- Low risk: G1-G2 + A1
- Moderate risk: G1-G2 + A2; G3a + A1
- High risk: G1-G2 + A3; G3a + A2; G3b + A1
- Very high risk: G3a + A3; G3b + A2-A3; G4-G5
Symptoms
Early CKD (Often Asymptomatic):
Advanced CKD (G4-G5):
Signs
Red Flags
[!CAUTION] Red Flags Requiring Urgent Action:
- Hyperkalaemia (K+ >6.5 or ECG changes) — emergency
- Severe acidosis (HCO3 <15)
- Pulmonary oedema (fluid overload)
- Uraemic pericarditis (chest pain, rub)
- Uraemic encephalopathy (confusion, asterixis)
- Rapidly declining GFR (>5 mL/min in 3 months — AKI on CKD?)
Structured Approach
General:
- Nutritional status
- Pallor (anaemia)
- Oedema
Cardiovascular:
- Blood pressure
- JVP (fluid status)
- Heart sounds (pericardial rub — uraemic pericarditis)
Respiratory:
- Signs of pulmonary oedema
Abdominal:
- Palpable kidneys (polycystic kidney disease)
- Bladder (urinary retention)
Peripheral:
- Oedema
- Arteriovenous fistula (if on haemodialysis)
- Scratch marks
Key Findings
| Finding | Significance |
|---|---|
| Hypertension | Both cause and consequence of CKD |
| Pallor | CKD anaemia |
| Palpable kidneys | ADPKD |
| Pericardial rub | Uraemic pericarditis (urgent) |
| Oedema | Fluid overload |
First-Line
| Test | Purpose |
|---|---|
| eGFR (Creatinine-based) | Stage CKD; repeated to confirm chronicity |
| Urine ACR (Albumin/Creatinine Ratio) | Quantify albuminuria; stage CKD |
| Urine Dipstick | Blood (haematuria → workup), protein |
| U&E | Potassium, creatinine, urea |
| FBC | Anaemia (normocytic) |
| Bone Profile (Ca, PO4, ALP) | CKD-MBD |
| HCO3 (or venous blood gas) | Metabolic acidosis |
Further Investigations
| Test | When |
|---|---|
| PTH | G4-G5 (secondary hyperparathyroidism) |
| Iron Studies (Ferritin, TSAT) | If anaemia; guide iron therapy |
| Vitamin D (25-OH) | G3-G5 |
| Hepatitis B/C serology | Pre-dialysis workup |
| Renal USS | All new CKD (size, obstruction, structure) |
| Immunology (ANA, ANCA, C3/4) | If suspected glomerulonephritis |
| Renal Biopsy | If cause unclear and would change management |
Pharmacological
Core Therapies:
| Drug Class | Indication | Notes |
|---|---|---|
| ACE-I or ARB | Albuminuria (ACR ≥3); Hypertension | Renoprotective; reduce intraglomerular pressure |
| SGLT2 Inhibitor | CKD (with or without diabetes); eGFR ≥20-25 | DAPA-CKD/EMPA-KIDNEY evidence; first-line add-on |
| Statin | All CKD (high CV risk) | Atorvastatin 20mg |
Blood Pressure:
- Target <130/80 mmHg (lower if heavy proteinuria)
- ACE-I/ARB first-line if albuminuria
- Add diuretic, CCB as needed
Glycaemic Control (Diabetes):
- SGLT2 inhibitor (renal protection + glucose control)
- GLP-1 agonist (CVOT benefit)
- Avoid excess hypoglycaemia
Complications Management
| Complication | Management |
|---|---|
| Anaemia | IV iron if deficient; ESA (erythropoietin) if Hb <100 and iron-replete |
| CKD-MBD | Phosphate binders; active vitamin D (alfacalcidol); manage PTH |
| Acidosis | Sodium bicarbonate (target HCO3 >22) |
| Hyperkalaemia | Dietary potassium restriction; potassium binders (patiromer, SZC) |
| Fluid Overload | Loop diuretics (furosemide); fluid restriction |
Renal Replacement Therapy (RRT)
Indications for Dialysis (G5 / Uraemia):
- Refractory hyperkalaemia
- Refractory pulmonary oedema
- Uraemic symptoms (pericarditis, encephalopathy)
- Severe acidosis
Options:
- Haemodialysis (in-centre or home)
- Peritoneal dialysis
- Kidney transplant (preferred if suitable)
- Conservative management (if dialysis declined)
CKD Complications
| Complication | Mechanism |
|---|---|
| Anaemia | Reduced EPO production; iron deficiency |
| CKD-MBD | Phosphate retention, low active vitamin D, secondary hyperparathyroidism |
| Hyperkalaemia | Reduced potassium excretion |
| Metabolic Acidosis | Reduced acid excretion |
| Cardiovascular Disease | Accelerated atherosclerosis, hypertension, calcification |
| Fluid Overload | Reduced sodium and water excretion |
| Uraemia | Accumulation of toxins (pericarditis, encephalopathy) |
| Malnutrition | Anorexia, catabolism |
Treatment-Related
| Treatment | Complication |
|---|---|
| ACE-I/ARB | Hyperkalaemia; creatinine rise; AKI (volume depletion) |
| SGLT2 Inhibitors | Genital infections; euglycaemic ketoacidosis (rare) |
| ESAs | Hypertension; thrombosis |
| Dialysis | Access complications; infection; heart failure |
Natural History
CKD is usually progressive, though rate varies. Diabetes and heavy proteinuria are associated with faster progression. Many CKD patients die from cardiovascular disease before reaching ESKD.
Outcomes
| Variable | Outcome |
|---|---|
| CVD mortality | Leading cause of death in CKD |
| Progression to ESKD | Depends on cause, albuminuria, BP control, treatment |
| 5-year survival on dialysis | ~50-60% |
| Transplant | Best outcomes; near-normalisation of life expectancy |
Prognostic Factors
Worse Prognosis:
- Heavy albuminuria
- Low GFR
- Rapid GFR decline
- Diabetes
- Cardiovascular disease
- High blood pressure
- Failure to use renoprotective therapies
Key Guidelines
-
KDIGO CKD Guideline 2024 — Diagnosis, evaluation, management.
-
NICE CKD Guideline (NG203) — UK-specific, including SGLT2i recommendations.
Landmark Trials
DAPA-CKD (2020) — Dapagliflozin in CKD
- RCT: Dapagliflozin vs placebo in CKD (with or without diabetes)
- Key finding: 39% reduction in kidney failure, CV death, or sustained decline
- Clinical Impact: SGLT2i now standard of care in CKD
EMPA-KIDNEY (2023) — Empagliflozin in CKD
- RCT: Empagliflozin vs placebo
- Key finding: 28% reduction in kidney disease progression or CV death
- Clinical Impact: Extended evidence to lower eGFR
FIDELIO-DKD (2020) — Finerenone in DKD
- RCT: Non-steroidal MRA in T2DM + CKD
- Key finding: 18% reduction in kidney outcomes
- Clinical Impact: Finerenone added to management options
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| ACE-I/ARB | 1a | Multiple RCTs, meta-analyses |
| SGLT2 Inhibitors | 1a | DAPA-CKD, EMPA-KIDNEY |
| Finerenone | 1b | FIDELIO-DKD |
| ESAs | 1a | RCTs; target Hb 100-120 |
What is Chronic Kidney Disease?
Chronic Kidney Disease (CKD) means your kidneys don't work as well as they should, and this has been present for at least 3 months. Your kidneys filter waste from your blood and help control blood pressure, fluid balance, and produce hormones for blood and bones.
Why does it matter?
CKD often has no symptoms until quite advanced. It increases the risk of heart disease and stroke. If severe, it can lead to kidney failure needing dialysis or a transplant. The good news is that treatment can slow it down and reduce complications.
What causes CKD?
The most common causes are:
- Diabetes
- High blood pressure
- Other conditions like kidney infections, inherited diseases, or inflammation
How is it treated?
-
Blood pressure control: Target <130/80. ACE inhibitors or ARBs are preferred.
-
SGLT2 inhibitors (dapagliflozin, empagliflozin): These tablets protect the kidneys and heart.
-
Managing diabetes and cholesterol
-
Treating complications (anaemia, bone disease, potassium problems)
-
Dialysis or transplant if kidneys fail completely
What to expect
- You'll have regular blood and urine tests to monitor kidney function
- Take your medications as prescribed
- Attend appointments — early detection of changes is important
- Lifestyle changes (healthy diet, exercise, quit smoking) help slow progression
When to seek help
Contact your doctor if:
- You're feeling unusually tired or unwell
- You have swelling in your legs or face
- You're breathless
- You notice blood in your urine
- You feel nauseous or have no appetite
Primary Guidelines
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314. PMID: 38432728
Key Trials
-
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease (DAPA-CKD). N Engl J Med. 2020;383(15):1436-1446. PMID: 32970396
-
The EMPA-KIDNEY Collaborative Group. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. PMID: 36331190
-
Bakris GL, Agarwal R, Anker SD, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes (FIDELIO-DKD). N Engl J Med. 2020;383(23):2219-2229. PMID: 33264825
Further Resources
- Kidney Care UK: kidneycareuk.org
- NICE CKD Guideline: nice.org.uk/guidance/ng203
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate guidelines and specialists for patient care.