Chronic Kidney Disease (CKD): Causes, Symptoms, Treatment 

Chronic Kidney Disease (CKD): Causes, Symptoms, Treatment 

In this article, we will describe 10 facts about CKD. It is primarily for health professionals

Key Points

1. Chronic Kidney Disease (CKD) is defined as a
   • Gradual loss of kidney function over time, or ..
   • Structural abnormality of the kidneys, with normal renal function.
2. CKD is not a diagnosis. It is a syndrome with a cause(s) – you need to find out what is causing it
3. CKD affects approximately 10% of adults in the UK to some degree. However, most cases are mild (Stages 1-3B) and age-related
4. CKD is associated with an increased risk of cardiovascular disease and hypertension, and can cause end-stage renal failure (ESRF; i.e. need for dialysis or a kidney transplant) in 1% of cases (rare). This equates to 1 in 1000 of the population
5. Early detection and management can slow disease progression and reduce complications.

1. Definition

• Chronic Kidney Disease (CKD) is defined as the persistent (for over three months) abnormal kidney function or structure, characterised by:
  • Glomerular filtration rate (GFR): of less than 60 mL/min/1.73 m², or
  • Structural or (other) functional kidney damage: such as albuminuria, electrolyte abnormalities, or imaging findings of kidney abnormalities (e.g. polycystic kidney disease, PKD).

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)
• Stage 5: End-Stage Renal Failure (ESRF) or kidney failure (GFR <15 mL/min/1.73 m²).

Note. CKD stages 1 and 2 should be considered risk factors for more significant CKD.

2. Epidemiology

• Prevalence: CKD affects approximately 10% of adults in the UK to some degree. However, most cases are mild (Stages 1-3B) and age-related; with a smaller percentage progressing to moderate-severe CKD (CKD3B-4) or ESRF (CKD5)
• 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 ESRF
• 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. gene defect, e.g. PKD) or a family history of CKD increases risk (mechanism is unclear)
• Age: Renal function (probably) naturally declines with age, increasing the risk of CKD
• Ethnicity: There are 5x 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

These are 7 groups of 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 (PKD): A genetic disorder causing cyst formation in the kidneys, leading to ESRF in 50% of people by age 60 years
• Renovascular disease (RVD): Bilateral renal artery stenosis (RAS; or unilateral in someone with a single kidney) is a common 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 (TID; e.g. reflux nephropathy): Recurrent or chronic kidney infections can lead to scarring and reduced function. Also caused by autoimmune disease and drugs.

Other causes

• 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 (occasioanlly), or haematuria
• Nausea, vomiting, and loss of appetite: Related to uraemia in advanced CKD
• Muscle cramps: Electrolyte imbalance can lead to cramps
• Pruritus: Itchy skin, perhaps related to buildup of urea and other toxins
• Other symptoms: Deep cold, pain and restless legs.

Note. Macroscopic haematuria (blood that you can see in the urine) should not be attributed to CKD. Surgical causes (e.g. cancer, stones) in the urinary tract should be excluded.

6. Diagnosis

Diagnostic criteria

• Glomerular filtration rate (eGFR): A calculated measure based on blood creatinine level, age, gender, and ethnicity, used to estimate kidney function. A consistent GFR <60 mL/min/1.73 m² for over three months confirms CKD.

Investigation

• Serum creatinine and GFR: Key tests for assessing kidney function
• Urinalysis: Tests for proteinuria and haematuria
• MSU: Looking for infection, haematuria and casts
• Urine albumin-to-creatinine ratio (ACR): Used to estimate protein levels in urine, which is 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
• Kidney (and bladder) ultrasound: To detect structural abnormalities, cysts, or evidence of chronic damage (e.g. obstructed or small kidneys, or PKD)
• 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 patients usually look well
• Benign prostatic hyperplasia (BPH)
• Chronic heart failure (and other causes of fluid overload): Fluid retention can mimic symptoms of CKD; distinguish by cardiac function assessment
• Nephrotic syndrome: Patients may have CKD and nephrotic syndrome.

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. If proteinuric, add SGLT2i
• Glycaemic control in diabetes: Target HbA1c <42 mmol/mol (may prevent or slow CKD progression)
• Dietary modification: 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 dyslipidaemia 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). Manage 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 failure (Stage 5 CKD): Renal replacement therapy (RRT) options include haemodialysis, peritoneal dialysis, or kidney transplantation (deceased donor or living), or kidney-pancreas transplantation (in patients with DM1).

Which patients with CKD should be referred to a nephrologist?

1. CKD1-3A: manage in GP and community
2. CKD3B: discuss with nephrologist
3. CKD4 (or concern re structural renal disease, e.g. PCKD): should be seen by a nephrologist soon (less than 2 months)
4. CKD5 (or nephrotic syndrome): Ring nearest renal unit today.

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 (RBD): 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 ESRF: Without intervention, many patients with more severe CKD (Stage 4) will progress to ESRF 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 and smoking
• Prevention
  • Early detection and monitoring: Regular screening for kidney function in high-risk groups – e.g. people with diabetes or hypertension. Black/Asian people over 30 years should have yearly CKD/DM/BP screening
  • Renoprotection: Use ACE/ARBs and SGLT2is to protect kidney function in patients with proteinuria, even if normotensive.

Summary

We have described 10 facts about CKD. We hope it has been helpful.

Other resource

MyHSN CKD podcast (8 min)

Top Tip – CKD

CKD is not a diagnosis. It is a syndrome with a cause(s). You need to find the cause(s).