Chronic Kidney Disease (CKD)

• RCSI Royal College of Surgeons in Ireland is also known as Coláiste Ríoga na Máinleá in Éirinn.
• Dr Carol Traynor is a Consultant Nephrologist and Renal Transplant Physician.

Learning Outcomes

• Define Chronic Kidney Disease (CKD)
• List the causes of CKD
• Explain how each cause leads to the development of CKD
• Outline common signs and symptoms in CKD
• Develop a differential diagnosis for the features of CKD
• Outline overarching principles of investigation and management in CKD

CKD Definition

• Chronic Kidney Disease is defined as abnormalities of kidney structure or function.
• These abnormalities must be present for more than 3 months.
• CKD has implications for health, as per the KIDIGO Guideline of the 2023 update.

Markers of Kidney Damage

• Albuminuria with an Albumin Creatinine Ratio (ACR) greater than 3.4mg/mmol
• Urinary sediment abnormalities
• Pathological abnormalities found via biopsy or imaging
• Kidney Transplant

Kidney Function

• Decreased kidney function is shown through GFR (glomerular filtration rate)
• Declining GFR is a hallmark of progressive kidney disease and measures overall kidney function.

Causes of CKD

• Diabetes
• Hypertension
• Glomerulonephritis
• Autosomal dominant polycystic kidney disease (ADPKD)
• Alport’s syndrome
• Chronic pyelonephritis
• Obstructive uropathy

Glomerular Damage

• All causes of CKD lead to glomerular damage.
• Glomerular damage results in a reduction in glomerular filtration rate and eventual scarring.

RAAS Activation

• Reduction in glomerular perfusion causes a response from the Renin, angiotensin aldosterone system.
• Causes for concern are reduced circulating blood volume or thickened/scarred glomeruli.
• This constriction worsens renal ischaemia.
• The overall result is salt and water retention and ultimately volume overload.
• Sustained activation worsens renal damage.

Diabetes and CKD

• Excess glucose in the blood as a result of type 1 or type 2 diabetes causes excess glucose to be excreted in the urine (glycosuria).
• Glucose interacts with proteins in the glomerular basement membrane causing it to thicken.
• Hyaline arteriolosclerosis results and causes an increase in glomerular pressure.
• The glomerulus expands and becomes more permeable.
• Mesangial cells try to regenerate, developing Kimmelstiel-Wilson nodules.
• Damaged, diffusely scarred glomeruli result and the GFR declines.

Hypertension and CKD

• Progressive replacement of the normal renal parenchyma with cysts occurs.
• Genetic mutation in collagen type IV results in poorly functioning glomerular basement membrane.
• Gradual scarring results in CKD

Alport's Syndrome and CKD

• Genetic mutation in collagen type IV results in a thin, poorly functioning glomerular basement membrane.
• Gradual scarring results in CKD.

Chronic Pyelonephritis and CKD

• Chronic infection causes scarring of the glomeruli.

Obstructive Uropathy and CKD

• Chronic backpressure on the glomeruli with progressive scarring occurs.

Symptoms of CKD

• Asymptomatic for a long time before diagnosis
• Non-specific symptoms, such as nausea, vomiting, anorexia, and uraemia
• Malaise
• Lethargy and fatigue
• Anaemia
• Palpitations
• Hyperkalaemia
• Pruritus
• Uraemia
• Disordered Sleep
• Confusion
• Uraemia

Other Symptoms of CKD

• Frothy urine (proteinuria)
• Decreased kidney output
• Lower limb swelling due to decreased oncotic pressure from albuminuria
• Orthopnoea Volume Overload (pulmonary oedema)
• Bone pain +/- fractures
• Mineral bone disease often secondary to hyperparathyroidism
• Symptoms that are aligned with the underlying causes; diabetes, hypertension, ADPKD

Signs of CKD

• Tachypnoea / accessory muscle use
• Pulmonary oedema
• Yellow discoloration to the skin
• Cushingoid appearance due to chronic steroid use
• Capillary glucose testing marks
• Palmar crease pallor Anaemia
• Thin skin from chronic steroid use
• Asterixis
• AV fistula due to haemodialysis
• Hypertension risk factor and consequence of CKD
• Risk of skin cancer on immunosuppressants (post-transplant)
• Conjunctival Pallor
• Previous central lines for haemodialysis
• Tunnelled line for haemodialysis
• Volume overload and resulting ascites; can also be associated with peritoneal dialysis
• Tenckhoff catheter
• Ballotable kidneys (ADPKD)
• Hepatomegaly due to cystic liver in ADPKD
• Evidence of kidney transplant

Signs During Kidney Transplant

• Mass in the RIF (May be in the LIF or both in cases of two transplants)
• “Hockey stick” or Rutherford-Morison scar

More Signs of CKD

• Peripheral oedema caused by volume overload or nephrotic syndrome
• Bibasal crepitations caused by volume overload
• Pericardial rub due to uraemia
• Rash (vasculitis)

Differential Diagnosis - Volume Overload

• Congestive cardiac failure
• Liver disease
• Pleural Effusion
• Exacerbation of Pre-existing Chronic lung disease
• Protein-losing enteropathy
• Lymphoedema
• Oedema

Differential Diagnosis - Uraemic Encephalopathy

• Acute liver failure/Hepatic encephalopathy
• Sepsis
• Hypertensive encephalopathy
• Metabolic encephalopathy i.e Diabetic ketoacidosis/Hyperosmolar coma
• Hypoglycaemia
• Fluid and electrolyte disturbances, such as hyponatremia and hypermagnesemia
• Drug toxicity
• Wernicke-Korsakoff encephalopathy

Investigations for Diagnosing CKD

Blood Tests

• Urea and Electrolytes
• eGFR (estimated glomerular filtration rate)

Urine Tests

• Blood, protein, nitrites, ketones via dipstick
• RBCs, WBCs, casts, crystals via microscopy
• Albumin / Creatinine ratio for detecting microalbuminuria

Imaging

• Renal Ultrasound
• CT-KUB

Other

• Renal biopsy when diagnosis is unclear

Investigations for Determining Cause of CKD

• Fasting glucose and HbA1c to rule out Diabetes
• Blood or protein to rule out Globulernephritis
• Protein found in nephrotic syndrome
• Nitrites or leukocyte esterase to rule out infection
• Ketones to rule out diabetes
• 24-hour ambulatory BP monitor to check for HTN Dx

Investigations for Complications of CKD

• Progressively worsening eGFR, uraemia, hyperkalaemia due to U&E
• Calcium abnormalities, raised phosphate, low albumin due to bone profile changes
• Raised PTH in response to low Ca2+
• Anaemia due to Reduced EPO production FBC
• Metabolic acidosis via ABG
• Hyperkalaemia ECG changes
• Tall tented t-waves
• Pulmonary oedema discovered through CXR imaging

Management of CKD

• Aim to slow decline in eGFR by managing risk factors.
• Good diabetes control
• Blood pressure management
• ACEi or ARB treatments
• Smoking cessation
• Avoid nephrotoxins
• Annual flu and pneumococcal vaccines

Management of Complications

• Recombinant human EPO
  • Anaemia
• Iron transfusion
• B12/Folate replacement
• Restrict dietary phosphate -Mineral bone disease
• Calcium supplements
• Vitamin D analogues
• Diuresis -Fluid balance
• Bicarbonate -Metabolic acidosis
• Calcium gluconate, Insulin + Dextrose -Hyperkalaemia
• Calcium resonium
• Diuretics
• Aspirin
• Statin -Reduce CVD risk

Renal Replacement Therapy

• Replaces the non-endocrine function of the kidneys, removes fluid and clears solutes when the native kidneys stop functioning.
• RRT Includes kidney transplant, Haemodialysis and Peritoneal Dialysis.