Chronic Kidney Disease (CKD) is a (1) progressive condition characterised by a gradual loss of kidney function over time; 0r (2) structural abnormality of the kidneys, with normal renal function.
It is defined by a decrease in the glomerular filtration rate (GFR) or evidence of kidney damage (e.g. proteinuria) persisting for over three months.
CKD is associated with an increased risk of cardiovascular disease, end-stage renal disease (ESRD), and other complications.
Early detection and management can slow disease progression and reduce complications.
Management focuses on controlling blood pressure, treating complications, managing comorbidities (e.g. diabetes), and lifestyle modifications.
1. Definition
Chronic Kidney Disease (CKD) is defined as the persistent (for over three months) reduction in kidney function, characterised by a glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m², or evidence of structural or functional kidney damage, such as albuminuria, electrolyte abnormalities, or imaging findings of kidney abnormalities (e.g. polycystic kidney disease, PCKD).
CKD is classified into five stages based on GFR:
Stage 1: Normal GFR (≥90 mL/min/1.73 m²) with evidence of kidney damage.
Stage 2: Mildly reduced GFR (60-89 mL/min/1.73 m²) with evidence of kidney damage.
Stage 3a: Moderately reduced GFR (45-59 mL/min/1.73 m²).
Stage 3b: Moderately to severely reduced GFR (30-44 mL/min/1.73 m²).
Stage 4: Severely reduced GFR (15-29 mL/min/1.73 m²).
Prevalence: Approximately 10-15% of adults in the UK have some degree of CKD. However, most cases are mild (Stages 1-3B), with a smaller percentage progressing to moderate-severe CKD (CKD3B-4) or ESRF (CKD5). CKD stages 1 and 2 should be considered risk factors for more significant CKD.
Age Distribution: CKD prevalence increases with age, with a significant proportion of older adults affected. It is often associated with other age-related conditions like hypertension and diabetes.
Gender: CKD is slightly more prevalent in women, but men are more likely to progress to ESRD.
Health Disparities: Higher prevalence rates are seen in populations with increased rates of diabetes, hypertension, and obesity, and in ethnic minorities, particularly individuals of South Asian, African, and Afro-Caribbean descent.
3. Risk factors
Diabetes Mellitus
Hypertension
Cardiovascular Disease: Strongly associated with CKD, both as a risk factor and a consequence.
Family History: Genetic predisposition to certain kidney diseases (e.g. PCKD) or a family history of CKD increases risk (mechsnism is unclear).
Older Age: Renal function naturally declines with age, increasing the risk of CKD.
Ethnicity: Higher rates in certain ethnic groups, including South Asians, African, and Afro-Caribbean populations.
Obesity: Associated with increased risk of diabetes, hypertension, and directly linked to CKD.
Smoking: The major risk factor for renovascular disease (see below).
4. Causes
Unknown: Commonest ’cause’ of CKD (responsible for 30% of cases). Often associated with small kidneys.
Diabetic Nephropathy: The leading cause of CKD (responsible for 20% of cases) when the cause is known. Poor glycaemic control (may) accelerate kidney damage. It is a glomerular disease.
Chronic Glomerulonephritis: Inflammation of the glomeruli; can be due to various conditions including autoimmune diseases, infections (especially viral, e,g. Hepatitis B/C and HIV) or unknown causes.
Polycystic Kidney Disease (PCKD): A genetic disorder causing cyst formation in the kidneys, leading to progressive kidney damage.
Renovascular Disease (RVD): Bilateral renal artery stenosis (RAS; or unilateral in someone with a single kidney) is a commoin cause in older people, especially smokers.
Obstructive Nephropathy: Conditions such as benign or malignant prostatic disease can obstruct urine flow, leading to kidney damage.
Chronic Tubulo-interstitial Disease (e.g. Reflux Nephropathy): Recurrent or chronic kidney infections can lead to scarring and reduced function.
Hypertensive Nephropathy: Accelerated hypertension can cause glomerulosclerosis and kidney damage. Unusual in Caucasian people.
5. Symptoms
Early stages of CKD are often asymptomatic. Symptoms typically develop as kidney function declines and may include:
Fatigue and Weakness: Due to anaemia and accumulation of waste products.
Oedema: Swelling in the legs, ankles, and around the eyes due to fluid retention.
Hypertension: Worsening or difficult-to-control high blood pressure.
Changes in Urination: Increased frequency, particularly at night (nocturia), reduced urine output, or hematuria.
Nausea, Vomiting, and Loss of Appetite: Related to uraemia in advanced CKD.
Muscle Cramps: Electrolyte imbalances, particularly low calcium and high phosphate, can lead to cramps.
Pruritus: Itchy skin, often due to buildup of urea and other toxins.
Other symptoms: Restless legs.
6. Diagnosis
Diagnostic criteria
Estimated Glomerular Filtration Rate (eGFR): A calculated measure based on serum creatinine, age, gender, and ethnicity, used to estimate kidney function. A consistent eGFR <60 mL/min/1.73 m² for over three months confirms CKD.
Investigation
Serum Creatinine and eGFR: Key tests for assessing kidney function.
Urinalysis: Tests for proteinuria, haematuria, and presence of casts.
Urine Albumin-to-Creatinine Ratio (ACR): A marker for kidney damage; higher levels indicate worsening disease.
Blood Tests
Full blood count (FBC) – for anaemia
U&Es – for metabolic imbalances (e.g. hyperkalemia and metabolic acidosis)
Bone biochemistry – calcium, phosphate, alkaline phosphatase, vitamin D and parathyroid hormone (PTH)
Renal immunology profile:
Anti-nuclear antibody (ANA). Positive in systemic lupus erythematosus (SLE, lupus). In most CKD patients, it will be negative
Anti-neutrophil cytoplasmic antibody (ANCA; and PR3 and MPO subtypes). Positive in some types of vasculitis. In most, negative.
Complement C3/4. Low in SLE. In most, negative.
Double-stranded DNA (DsDNA). Positive in SLE. In most, negative.
Immunoglobulins (IgG, A and M). IgA high in 50% people with IgA nephropathy. In most, negative.
Serum electrophoresis. Done looking for an abnormal protein suggestive of myeloma (and other blood disorders). In most, negative.
Serum free light chains (SFL). Done looking for myeloma (and other blood disorders). In most, negative.
Kidney Ultrasound: To detect structural abnormalities, cysts, or evidence of chronic damage (e.g. small kidneys).
Renal Biopsy: Occasionally indicated if the cause of CKD is unclear or for specific conditions like glomerulonephritis.
Differential diagnosis
Acute Kidney Injury (AKI): Rapid onset of kidney dysfunction, usually reversible with treatment; distinguished from CKD by history, rapid changes in serum creatinine, and kidney size on imaging. AKI patients look unwell; CKD ones often look well.
Benign Prostatic Hyperplasia (BPH)
Congestive Heart Failure: Fluid retention can mimic symptoms of CKD; distinguish by cardiac function assessment.
7. Treatment
General
Blood Pressure Control: Aim for <130/80 mmHg (120/70 if has diabetes), usually with ACE inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) as first-line treatment, particularly in patients with proteinuria.
Glycaemic Control in Diabetes: Target HbA1c <42 mmol/mol (may prevent or slow CKD progression).
Dietary Modifications: Low salt intake, restricted protein intake to reduce renal workload, and careful management of potassium and phosphate levels.
Smoking Cessation: Reduces cardiovascular risk, which is high in CKD patients.
Statins: Indicated for managing dyslipidemia and reducing cardiovascular risk.
Stage-specific
Early Stages (CKD1-3): Focus on monitoring kidney function, managing comorbidities (diabetes, hypertension), and slowing progression.
Later Stages (CKD4-5): Prepare for renal replacement therapy (RRT; dialysis or transplantation) or supportive care (in frail elderly). Management of symptoms such as fluid overload (loop diuretics and/or fluid restriction), anaemia (erythropoiesis-stimulating agents< ESAs), hyperphosphataemia (phosphate binders), and acidosis (sodium bicarbonate).
End-Stage Renal Disease (Stage 5): Renal replacement therapy (RRT) options include haemodialysis, peritoneal dialysis, or kidney transplantation (deceased donor or living), or kidney-pancreas transplantation (in patients with DM1)
8. Complications
Hypertension: Cause and consequence of CKD.
Fluid Overload
Cardiovascular Disease: Leading cause of mortality in CKD patients; includes heart failure, myocardial infarction, and stroke.
Hyperkalaemia: Can cause cardiac arrhythmias.
Anaemia: Due to reduced erythropoietin production by the kidneys.
Renal Bone Disease: Imbalance of calcium, phosphate, and parathyroid hormone (PTH) can lead to bone pain and fractures.
Uraemia: Accumulation of toxins can cause encephalopathy, pericarditis, and other systemic symptoms.
9. Prognosis
Early-Stage CKD: Disease progression can be slowed with appropriate management of risk factors.
Progression to ESRD: Without intervention, many patients with severe CKD (Stages 4-5) will progress to ESRD requiring dialysis or transplantation.
Cardiovascular Outcomes: Patients with CKD are at significantly higher risk of cardiovascular events, which impacts overall prognosis.
10. Prevention
Primary
Control risk factors: Regular screening and effective management of hypertension, diabetes, and other comorbid conditions.
Public health strategies: Promote lifestyle changes to reduce obesity, smoking, and alcohol use.
Prevention
Early detection and monitoring: Regular screening for kidney function in high-risk groups (e.g. people with diabetes or hypertension).
Renoprotection: Use of ACEIs or ARBs to protect kidney function in patients with proteinuria, even if normotensive.