Renal

Question 1

Acute Kidney Injury

Answer 1

Acute kidney injury (AKI) is defined as an acute drop in kidney function. It is diagnosed by measuring the serum creatinine.

Question 2

NICE criteria for AKI

Answer 2

Rise in creatinine of ≥ 25 micromol/L in 48 hours
Rise in creatinine of ≥ 50% in 7 days
Urine output of < 0.5ml/kg/hour for > 6 hours

Question 3

Risk factors for AKI

Answer 3

Consider the possibility of an acute kidney injury in patients that are suffering with an acute illness such as infection or having a surgical operation. Risk factors that would predispose them to developing acute kidney injury include:

Chronic kidney disease
Heart failure
Diabetes
Liver disease
Older age (above 65 years)
Cognitive impairment
Nephrotoxic medications such as NSAIDS and ACE inhibitors
Use of a contrast medium such as during CT scans

Question 4

Pre-renal causes of AKI

Answer 4

Pre-renal pathology is the most common cause of acute kidney injury. It is due to inadequate blood supply to kidneys reducing the filtration of blood. Inadequate blood supply may be due to:

Dehydration
Hypotension (shock)
Heart failure

Question 5

Renal causes of AKI

Answer 5

This is where intrinsic disease in the kidney is leading to reduced filtration of blood. It may be due to:

Glomerulonephritis
Interstitial nephritis
Acute tubular necrosis

Question 6

Post-renal causes of AKI

Answer 6

Post renal acute kidney injury is caused by obstruction to the outflow of urine from the kidney, causing back-pressure into the kidney and reduced kidney function. This is called an obstructive uropathy. Obstruction may be caused by:

Kidney stones
Masses such as cancer in the abdomen or pelvis
Ureter or uretral strictures
Enlarged prostate or prostate cancer

Question 7

Investigating AKI

Answer 7

Urinalysis for protein, blood, leucocytes, nitrites and glucose.

Leucocytes and nitrites suggest infection
Protein and blood suggest acute nephritis (but can be positive in infection)
Glucose suggests diabetes

Ultrasound of the urinary tract is used to look for obstruction. It is not necessary if an alternative cause is found for the AKI.

Question 8

Managing AKI

Answer 8

Prevention of acute kidney injury is important. This is achieved by avoiding nephrotoxic medications where possible and ensuring adequate fluid input in unwell patients, including IV fluids if they are not taking enough orally.

The first step to treating an acute kidney injury is to correct the underlying cause:

Fluid rehydration with IV fluids in pre-renal AKI
Stop nephrotoxic medications such as NSAIDS and antihypertensives that reduce the filtration pressure (i.e. ACE inhibitors)
Relieve obstruction in a post-renal AKI, for example insert a catheter for a patient in retention from an enlarged prostate

In a severe acute kidney injury or where there is doubt about the cause or complications, input from a renal specialist is required. They may need dialysis.

Question 9

Complications of AKI

Answer 9

Hyperkalaemia
Fluid overload, heart failure and pulmonary oedema
Metabolic acidosis
Uraemia (high urea) can lead to encephalopathy or pericarditis

Question 10

Chronic kidney disease

Answer 10

Chronic kidney disease describes a chronic reduction in kidney function. This reduction in kidney function tends to be permanent and progressive.

Question 11

Causes of CKD

Answer 11

Diabetes
Hypertension
Age-related decline
Glomerulonephritis
Polycystic kidney disease
Medications such as NSAIDS, proton pump inhibitors and lithium

Question 12

Risk factors of CKD

Answer 12

Older age
Hypertension
Diabetes
Smoking
Use of medications that affect the kidneys

Question 13

Presentation of CKD

Answer 13

Usually chronic kidney disease is asymptomatic and diagnosed on routine testing. A number of signs and symptoms might suggest chronic kidney disease:

Pruritus (itching)
Loss of appetite
Nausea
Oedema
Muscle cramps
Peripheral neuropathy
Pallor
Hypertension

Question 14

Investigating CKD

Answer 14

Estimated glomerular filtration rate (eGFR) can be checked using a U&E blood test. Two tests are required 3 months apart to confirm a diagnosis of chronic kidney disease.

Proteinuria can be checked using a urine albumin:creatinine ratio (ACR). A result of ≥ 3mg/mmol is significant.

Haematuria can be checked using a urine dipstick. A significant result is 1+ of blood. Haematuria should prompt investigation for malignancy (i.e. bladder cancer).

Renal ultrasound can be used to investigate patients with accelerated CKD, haematuria, family history of polycystic kidney disease or evidence of obstruction.

Question 15

Stages of CKD

Answer 15

The G score is based on the eGFR:

G1 = eGFR >90
G2 = eGFR 60-89
G3a = eGFR 45-59
G3b = eGFR 30-44
G4 = eGFR 15-29
G5 = eGFR <15 (known as “end-stage renal failure”)
The A score is based on the albumin:creatinine ratio:

A1 = < 3mg/mmol
A2 = 3 – 30mg/mmol
A3 = > 30mg/mmol
The patient does not have CKD if they have a score of A1 combined with G1 or G2. They need at least an eGFR of < 60 or proteinuria for a diagnosis of CKD.

Question 16

Complications of CKD

Answer 16

Anaemia
Renal bone disease
Cardiovascular disease
Peripheral neuropathy
Dialysis related problems

Question 17

When to refer CKD

Answer 17

NICE suggest referral to a specialist when there is:

eGFR < 30
ACR ≥ 70 mg/mmol
Accelerated progression defined as a decrease in eGFR of 15 or 25% or 15 ml/min in 1 year
Uncontrolled hypertension despite ≥ 4 antihypertensives

Question 18

Managing CKD

Answer 18

Aims of management

Slow the progression of the disease
Reduce the risk of cardiovascular disease
Reduce the risk of complications
Treating complications

Slowing the progression of the disease

Optimise diabetic control
Optimise hypertensive control
Treat glomerulonephritis

Reducing the risk of complications

Exercise, maintain a healthy weight and stop smoking
Special dietary advice about phosphate, sodium, potassium and water intake
Offer atorvastatin 20mg for primary prevention of cardiovascular disease

Treating complications

Oral sodium bicarbonate to treat metabolic acidosis
Iron supplementation and erythropoietin to treat anaemia
Vitamin D to treat renal bone disease
Dialysis in end stage renal failure
Renal transplant in end stage renal failure

Question 19

Treating hypertension in CDK

Answer 19

ACE inhibitors are the first line in patients with chronic kidney disease. These are offered to all patients with:

Diabetes plus ACR > 3mg/mmol
Hypertension plus ACR > 30mg/mmol
All patients with ACR > 70mg/mmol
Aim to keep blood pressure <140/90 (or < 130/80 if ACR > 70mg/mmol).

Serum potassium needs to be monitored as chronic kidney disease and ACE inhibitors both cause hyperkalaemia.

Question 20

Anaemia of CKD

Answer 20

Healthy kidney cells produced erythropoietin. Erythropoietin is the hormone that stimulates production of red blood cells. Damaged kidney cells in CKD cause a drop in erythropoietin. Therefore there is a drop in red blood cells and a subsequent anaemia.

Anaemia can be treated with erythropoiesis stimulating agents such as exogenous erythropoeitin. Blood transfusions should be limited as they can sensitise the immune system (“allosensitisation”) so that transplanted organs are more likely to be rejected.

Iron deficiency should be treated before offering erythropoetin. Intravenous iron is usually given, particularly in dialysis patients. Oral iron is an alternative.

Question 21

Renal bone disease

Answer 21

Renal bone disease is also known as chronic kidney disease-mineral and bone disorder (CKD-MBD).

Features

Osteomalacia (softening of bones)
Osteoporosis (brittle bones)
Osteosclerosis (hardening of bones)

Xray Changes

Spine xray shows sclerosis of both ends of the vertebra (denser white) and osteomalacia in the centre of the vertebra (less white). This is classically known as “rugger jersey” spine after the stripes found on a rugby shirt.

Question 22

Pathophysiology of renal bone disease

Answer 22

High serum phosphate occurs due to reduced phosphate excretion. Low active vitamin D because the kidney is essential in metabolising vitamin D to its active form. Active vitamin D is essential in calcium absorption from the intestines and kidneys. Vitamin D also regulates bone turnover.

Secondary hyperparathyroidism occurs because the parathyroid glands react to the low serum calcium and high serum phosphate by excreting more parathyroid hormone. This leads to increased osteoclast activity. Osteoclast activity lead to the absorption of calcium from bone.

Osteomalacia occurs due to increased turnover of bones without adequate calcium supply.

Osteosclerosis occurs when the osteoblasts respond by increasing their activity to match the osteoclasts by creating new tissue in the bone, however due to the low calcium level this new tissue is not properly mineralised.

Osteoporosis can exist alongside the renal bone disease due to other risk factors such as age and use of steroids.

Question 23

Managing renal bone disease

Answer 23

Management involves a combination of:

Active forms of vitamin D (alfacalcidol and calcitriol)
Low phosphate diet
Bisphosphonates can be used to treat osteoporosis

Question 24

Renal dialysis

Answer 24

Dialysis is a method for performing the filtration tasks of the kidneys artificially in patients with end stage renal failure or complications of renal failure. It involves removing excess fluid, solutes and waste products.

Question 25

Indications for acute dialysis

Answer 25

The mnemonic is AEIOU can be used to remember the indications for acute dialysis in patients with a severe AKI: A – Acidosis (severe and not responding to treatment) E – Electrolyte abnormalities (severe and unresponsive hyperkalaemia) I – Intoxication (overdose of certain medications) O – Oedema (severe and unresponsive pulmonary oedema) U – Uraemia symptoms such as seizures or reduced consciousness

Question 26

Indications for long term dialysis

Answer 26

End stage renal failure (CKD stage 5) Any of the acute indications continuing long term

Question 27

Options for maintenance dialysis

Answer 27

There are three main options for dialysis in patients requiring it long term: Continuous Ambulatory Peritoneal Dialysis Automated Peritoneal Dialysis Haemodialysis The decision about which form to use is based on: Patient preference Lifestyle factors Co-morbidities Individual differences regarding risks

Question 28

Peritoneal dialysis

Answer 28

Peritoneal dialysis uses the peritoneal membrane as the filtration membrane. A special dialysis solution containing dextrose is added to peritoneal cavity. Ultrafiltration occurs from the blood, across the peritoneal membrane, in to the dialysis solution. The dialysis solution is then replaced, taking away the waste products that have filtered out of the blood into the solution. Peritoneal dialysis involves a Tenckhoff catheter. This is a plastic tube that is inserted into the peritoneal cavity with one end on the outside. It allows access to peritoneal cavity. This is used for inserting and removing the dialysis solution. Continuous Ambulatory Peritoneal Dialysis This is where the dialysis solution is in the peritoneum at all times. There are various regimes for changing the solution. One example is where 2 litres of fluid is inserted into the peritoneum and changed four times a day. Automated Dialysis This involves peritoneal dialysis occurring overnight. A machine continuously replaces dialysis fluid in the abdomen overnight to optimise ultrafiltration. It takes 8-10 hours.

Question 29

Complications of peritoneal dialysis

Answer 29

Bacterial peritonitis. Infusions of glucose solution make the peritoneum a great place for bacterial growth. Bacterial infection is a common and potentially serious complication of peritoneal dialysis. Peritoneal sclerosis involves thickening and scarring of the peritoneal membrane. Ultrafiltration failure can develop. This occurs when the patient starts to absorb the dextrose in the filtration solution. This reduces the filtration gradient making ultrafiltration less effective. This becomes more prominent over time. Weight gain can occur as they absorb the carbohydrates in the dextrose solution. Psychosocial effects. There are huge social and psychological effects of having to change dialysis solution and sleep with a machine every night.

Question 30

Haemodialysis

Answer 30

With haemodialysis, patients have their blood filtered by a haemodialysis machine. Regimes can vary but a typical regime might be 4 hours a day for 3 days a week. They need good access to an abundant blood supply. The options for this are: Tunnelled cuffed catheter Arterio-venous fistula

Question 31

Tunnelled Cuffed Catheter

Answer 31

A tunnelled cuffed catheter is a tube inserted into the subclavian or jugular vein with a tip that sits in the superior vena cava or right atrium. It has two lumens, one where blood exits the body (red) and one where blood enters the body (blue). There is a ring called a “Dacron cuff” that surrounds of the catheter. It promotes healing and adhesion of tissue to the cuff, making the catheter more permanent and providing a barrier to bacterial infection. These can stay in long term and be used for regular haemodialysis. The main complications are infection and blood clots within the catheter.

Question 32

A-V Fistula

Answer 32

An A-V fistula is an artificial connection between an artery to a vein. It bypasses the capillary system and allows blood to flow under high pressure from the artery directly into the vein. This provides a permanent, large, easy access blood vessel with high pressure arterial blood flow. Creating an A-V fistula requires a surgical operation and a 4 week to 4 month maturation period without use. They are typically formed between an artery and vein in the patient’s forearm: Radio-cephalic Brachio-cephalic Brachio-basilic (less common and more complex operation)

Question 33

Examining an A-V fistula

Answer 33

Skin integrity Aneurysms Palpable thrill (a fine vibration felt over the anastomosis) Stereotypical “machinery murmur” on auscultation

Question 34

A-V fistula complications

Answer 34

Aneurysm Infection Thrombosis Stenosis STEAL syndrome High output heart failure STEAL Syndrome STEAL syndrome is where there is inadequate blood flow to the limb distal to the AV fistula. The AV fistula “steals” blood from the distal limb. The blood is diverted away from where is was supposed to supply and flows straight into the venous system. This causes distal ischaemia. High output heart failure Where there is an A-V fistula blood is flowing very quickly from the arterial to the venous system through the fistula. This means there is rapid return of blood to the heart. This increases the pre-load in the heart (how full the heart is before it pumps). This leads to hypertrophy of the heart muscle and heart failure. TOM TIP: NEVER take blood from a fistula! This is a lifeline for the patient to allow them access to dialysis. If it gets damaged it will set them back and you will be in big trouble.

Question 35

Renal transplant

Answer 35

A renal transplant is where a kidney is transplanted into a patient with end-stage renal failure. It typically adds ten years to life compared to just using dialysis and significantly improves quality of life.

Question 36

Donor matching in renal transplant

Answer 36

Patient and donor kidneys are matched based on the human leukocyte antigen (HLA) type A, B and C on chromosome 6. They do not have to match fully, but the closer the match, the less likely there is organ rejection and the better the outcomes. Recipients can receive treatment to desensitise them to the donor HLA in preparation for a transplant from a living donor.

Question 37

Renal transplant procedure

Answer 37

The patient’s kidneys are left in place. The donor kidney blood vessels are connected (anastomosed) with the pelvic vessels, usually the external iliac vessels. The ureter of the donor kidney is anastomosed directly with the bladder. The donor kidney is placed anteriorly in the abdomen and can usually be palpated in the iliac fossa area. A “hockey stick” incision is typically used, and there will be a “hockey stick” scar.

Question 38

After a renal transplant

Answer 38

The new kidney will function immediately. Basiliximab is a monoclonal antibody targeting the interleukin-2 receptor on T-cells. Two doses are given after surgery to prevent acute rejection. Patients require life-long immunosuppression to reduce the risk of transplant rejection. There are various options and combinations of: Tacrolimus Mycophenolate Ciclosporin Azathioprine Prednisolone TOM TIP: When examining a patient with a renal transplant, you can look particularly clever by looking for the side effects of particular immunosuppressant medications. Immunosuppressants cause seborrhoeic warts and skin cancers (look for scars from skin cancer removal) Tacrolimus causes a tremor Cyclosporine causes gum hypertrophy Steroids cause features of Cushing’s syndrome

Question 39

Complications of renal transplant

Answer 39

Complications relating to the transplant: Transplant rejection (hyperacute, acute or chronic) Transplant failure Electrolyte imbalances

Question 40

Complications related to immunosuppressants

Answer 40

Ischaemic heart disease Type 2 diabetes (steroids) Infections are more likely, more severe and may involve unusual pathogens Non-Hodgkin lymphoma Skin cancer (particularly squamous cell carcinoma)

Question 41

Unusual infections can occur secondary to immunosuppressant medication, such as

Answer 41

Pneumocystis jiroveci pneumonia (PCP/PJP) Cytomegalovirus (CMV) Tuberculosis (TB)

Question 42

Glomerulonephritis

Answer 42

Glomerulonephritis refers to inflammation of the glomeruli in the kidneys. The glomerulus is the first part of the nephron. It filters fluid out of the capillaries and into the renal tubule. Glomerulonephritis describes the pathology that occurs in various diseases rather than being a disease. Treatment is targeted at the underlying cause and often involves supportive care and immunosuppression (e.g., corticosteroids).

Question 43

Nephritis

Answer 43

Nephritis is a very generic term for inflammation in the kidneys. It is a descriptive term and is not a diagnosis.

Question 44

Nephritic syndrome

Answer 44

Nephritic syndrome refers to a group of features that occur with nephritis: Haematuria (blood in the urine), which can be microscopic (not visible) or macroscopic (visible) Oliguria (significantly reduced urine output) Proteinuria (protein in the urine), but less than 3g per 24 hours (higher protein suggests nephrotic syndrome) Fluid retention

Question 45

Nephrotic syndrome

Answer 45

Nephrotic syndrome occurs when the basement membrane in the glomerulus becomes highly permeable, resulting in significant proteinuria. It refers to a group of features without specifying the underlying cause. It involves: Proteinuria (more than 3g per 24 hours) Low serum albumin (less than 25g per litre) Peripheral oedema Hypercholesterolaemia Nephrotic syndrome presents with oedema. Patients might notice frothy urine due to the high protein content. Nephrotic syndrome predisposes patients to thrombosis, hypertension and high cholesterol.

Question 46

The most common cause of nephrotic syndrome in children

Answer 46

The most common cause of nephrotic syndrome in children is minimal change disease. This is usually: Idiopathic (no identified cause) Treated successfully with steroids

Question 47

The top causes of nephrotic syndrome in adults are:

Answer 47

Membranous nephropathy Focal segmental glomerulosclerosis

Question 48

Other causes of nephrotic syndrome include:

Answer 48

Membranoproliferative glomerulonephritis Henoch-Schönlein purpura (HSP) Diabetes Infection (e.g., HIV)

Question 49

IgA nephropathy

Answer 49

IgA nephropathy (or Berger’s disease) is the most common cause of primary glomerulonephritis. The exact cause is unclear. The typical patient is in their 20s presenting with haematuria. Histology shows IgA deposits and mesangial proliferation. The mesangial cells are found in the centre of the glomerulus and help support the capillaries (as well as performing other functions).

Question 50

Membranous nephropathy

Answer 50

Membranous nephropathy involves deposits of immune complexes in the glomerular basement membrane, causing thickening and malfunctioning of the membrane and proteinuria. Histology shows IgG and complement deposits on the basement membrane. It is a key cause of nephrotic syndrome in adults. The majority (around 70%) are idiopathic. It can be secondary to malignancy, systemic lupus erythematosus or drugs (e.g. NSAIDs).

Question 51

Membranoproliferative glomerulonephritis

Answer 51

Membranoproliferative glomerulonephritis (or mesangiocapillary glomerulonephritis) typically affects patients under 30. It involves immune complex deposits and mesangial proliferation.

Question 52

Post-streptococcal glomerulonephritis

Answer 52

Post-streptococcal glomerulonephritis tends to affect patients under 30. It presents 1-3 weeks after a streptococcal infection (e.g., tonsillitis or impetigo). Patients usually make a full recovery.

Question 53

Rapidly progressive glomerulonephritis

Answer 53

Rapidly progressive glomerulonephritis (or crescentic glomerulonephritis) presents with an acute severe illness but tends to respond well to treatment. Histology shows glomerular crescents.

Question 54

Goodpasture syndrome

Answer 54

Goodpasture syndrome is also known as anti-glomerular basement membrane (anti-GBM) disease. Anti-GBM (glomerular basement membrane) antibodies attack the glomerulus and pulmonary basement membranes. It causes glomerulonephritis and pulmonary haemorrhage. The typical presentation is a patient in their 20s or 60s with acute kidney failure and haemoptysis (coughing up blood).

Question 55

Systemic diseases that can cause glomerulonephritis include:

Answer 55

Henoch-Schönlein purpura (HSP) Vasculitis (e.g., microscopic polyangiitis or granulomatosis with polyangiitis) Lupus nephritis (associated with systemic lupus erythematosus)

Question 56

TOM TIP: If you come across a patient in your exams with significant acute kidney injury and haemoptysis, the top conditions to consider can be differentiated based on the antibodies:

Answer 56

Anti-GBM antibodies – Goodpasture syndrome p-ANCA (or MPO antibodies) – microscopic polyangiitis c-ANCA (or PR3 antibodies) – granulomatosis with polyangiitis

Question 57

Managing glomerulonephritis

Answer 57

Diagnosis may require a renal biopsy for histology. A renal specialist will guide treatment, which depends on the underlying cause. It may involve: Supportive care (e.g., hypertension management and dialysis in severe disease) Immunosuppression (e.g., corticosteroids)

Question 58

Renal tubular acidosis

Answer 58

Renal tubular acidosis (RTA) involves metabolic acidosis due to pathology in the tubules of the kidneys. The tubules balance hydrogen (H+) and bicarbonate ions (HCO3–) between the blood and urine to maintain a normal pH. There are four types of renal tubular acidosis, with different pathophysiology. RTA Pathology Urinary pH Serum Potassium Type 1 Distal tubule cannot excrete hydrogen ions High Low Type 2 Proximal tubule cannot reabsorb bicarbonate High Low Type 4 Low aldosterone or impaired aldosterone function Low High TOM TIP: Remembering types 1 and 4 for your exams (type 4 is the most common). Both involve inadequate hydrogen excretion in the distal tubules. In type 1, there is hypokalaemia. In type 4, there is hyperkalaemia.

Question 59

Type 1 Renal Tubular Acidosis

Answer 59

Type 1 RTA (or distal RTA) occurs when the distal tubule cannot excrete hydrogen ions. This results in: High urinary pH (above 6) due to the absence of hydrogen ions Metabolic acidosis, due to retained hydrogen ions in the blood Hypokalaemia, due to failure of the hydrogen and potassium exchange (H+/K+ ATPase)

Question 60

Type 1 renal tubular acidosis causes

Answer 60

Many conditions can cause this pathology in the distal tubule: Genetic (there are both autosomal dominant and autosomal recessive forms) Systemic lupus erythematosus Sjögren’s syndrome Primary biliary cholangitis Hyperthyroidism Sickle cell anaemia Marfan’s syndrome

Question 61

Presentation of type 1 renal tubular acidosis

Answer 61

It presents with: Failure to thrive in children Recurrent UTIs (due to alkaline urine) Bone disease (rickets or osteomalacia) Muscle weakness Arrhythmias (due to hypokalaemia)

Question 62

Treating type 1 renal tubular acidosis

Answer 62

Treatment is with oral bicarbonate, which corrects the acidosis and electrolyte imbalances.

Question 63

Type 2 renal tubular acidosis

Answer 63

Type 2 RTA (or proximal RTA) occurs when the proximal tubule cannot reabsorb bicarbonate from the urine to the blood, with excessive bicarbonate excreted in the urine. This results in: High urinary pH (above 6) due to the excess bicarbonate in the urine Metabolic acidosis, due to inadequate bicarbonate in the blood Hypokalaemia, due to urinary loss of potassium along with bicarbonate

Question 64

Type 2 renal tubular acidosis causes

Answer 64

Key causes are inherited (autosomal dominant or recessive), multiple myeloma and Fanconi’s syndrome.

Question 65

Treating type 2 renal tubular acidosis

Answer 65

Treatment is with oral bicarbonate.

Question 66

Type 3 renal tubular acidosis

Answer 66

Type 3 RTA (or mixed RTA) is a combination of type 1 and 2, with pathology in the proximal and distal tubules. It is rare and unlikely to appear in exams.

Question 67

Type 4 renal tubular acidosis

Answer 67

Type 4 RTA (or hyperkalaemic RTA) is caused by reduced aldosterone. Aldosterone stimulates sodium reabsorption and potassium and hydrogen ion excretion in the distal tubules. Low aldosterone or impaired aldosterone function leads to insufficient potassium and hydrogen ion excretion. Normally, ammonia is produced in the distal tubules to balance the excretion of hydrogen ions. Ammonia is a base and buffers the hydrogen ions, preventing the urine from becoming too acidotic. Hyperkalaemia suppresses ammonia production, so the urine becomes acidotic. The results are: Metabolic acidosis, due to retained hydrogen ions in the blood Hyperkalaemia, due to retained potassium in the blood Low urinary pH due to reduced ammonia production in response to hyperkalaemia

Question 68

Low aldosterone or low aldosterone activity can be due to:

Answer 68

Adrenal insufficiency Diabetic nephropathy Medications (e.g., ACE inhibitors, spironolactone or eplerenone)

Question 69

Managing type 4 renal tubular acidosis

Answer 69

Management is targeted at the underlying cause. Fludrocortisone (a mineralocorticoid steroid) may be used in aldosterone deficiency. Oral bicarbonate and treatment of hyperkalaemia may also be required.

Question 70

Haemolytic uraemic syndrome

Answer 70

Haemolytic uraemic syndrome (HUS) involves thrombosis in small blood vessels throughout the body, usually triggered by Shiga toxins from either E. coli O157 or Shigella. It most often affects children following an episode of gastroenteritis. Antibiotics and anti-motility medication (e.g., loperamide) used to treat gastroenteritis caused by E. coli O157 or Shigella increase the risk of HUS. HUS leads to the classic triad of: Microangiopathic haemolytic anaemia Acute kidney injury Thrombocytopenia (low platelets) The formation of blood clots consumes platelets, leading to thrombocytopenia. The blood flow through the kidney is affected by thrombi and damaged red blood cells, leading to acute kidney injury. Microangiopathic haemolytic anaemia (MAHA) involves the destruction of red blood cells (haemolysis) due to pathology in the small vessels (microangiopathy). Tiny blood clots (thrombi) partially obstruct the small blood vessels and churn the red blood cells as they pass through, causing them to rupture.

Question 71

Presentation of haemolytic uraemic syndrome

Answer 71

E. coli O157 and Shigella cause gastroenteritis. Diarrhoea is the first symptom, which turns bloody within 3 days. Around a week after the onset of diarrhoea, the features of HUS develop: Fever Abdominal pain Lethargy Pallor Reduced urine output (oliguria) Haematuria Hypertension Bruising Jaundice (due to haemolysis) Confusion

Question 72

Managing haemolytic uraemic syndrome

Answer 72

Stool culture is used to establish the causative organism. HUS is a medical emergency and requires hospital admission and supportive management with treatment of: Hypovolaemia (e.g., IV fluids) Hypertension Severe anaemia (e.g., blood transfusions) Severe renal failure (e.g., haemodialysis) It is self-limiting, and most patients fully recover with good supportive care.

Question 73

Rhabdomyolysis

Answer 73

Rhabdomyolysis involves skeletal muscle breaking down and releasing various chemicals into the blood. Muscle cells (myocytes) undergo cell death (apoptosis), releasing: Myoglobin Potassium Phosphate Creatine kinase Potassium is the most immediately dangerous breakdown product. Hyperkalaemia can cause cardiac arrhythmias and cardiac arrest. These breakdown products can cause acute kidney injury. Myoglobin, in particular, is toxic in high concentrations. Impaired renal function results in further accumulation of these substances in the blood. Other complications include compartment syndrome and disseminated intravascular coagulation.

Question 74

Causes of rhabdomyolysis

Answer 74

Anything that causes significant damage to muscle cells can cause rhabdomyolysis. For example: Prolonged immobility, particularly frail patients who fall and spend time on the floor before being found Extremely rigorous exercise beyond the person’s fitness level (e.g., endurance events or CrossFit) Crush injuries Seizures Statins

Question 75

Signs and symptoms of rhabdomyolysis

Answer 75

Muscle pain Muscle weakness Muscle swelling Reduced urine output (oliguria) Red-brown urine (myoglobinuria) Fatigue Nausea and vomiting Confusion (particularly in frail patients)

Question 76

Investigating rhabdomyolysis

Answer 76

Creatine kinase (CK) is the crucial diagnostic blood test for rhabdomyolysis. It is normally less than around 150 U/L. In rhabdomyolysis, it can be 1,000-100,000 U/L. It typically rises in the first 12 hours, then remains elevated for 1-3 days, then gradually falls. The higher the CK, the greater the risk of kidney injury. Myoglobinuria refers to myoglobin in the urine. It gives urine a red-brown colour. A urine dipstick will be positive for blood. Urea and electrolytes (U&E) are required for acute kidney injury and hyperkalaemia. ECGs are used to assess and monitor the heart’s response to hyperkalaemia.

Question 77

Investigating rhabdomyolysis

Answer 77

Intravenous fluids are the mainstay of treatment to correct hypovolaemia and encourage filtration of the breakdown products. Treatment of complications, particularly hyperkalaemia, is also essential. Additional options that are debatable and have associated risks include: Intravenous sodium bicarbonate (to increase urinary pH and reduce the toxic effects of myoglobinuria) Intravenous mannitol (to increase urine output and reduce oedema)

Question 78

Hyperkalaemia

Answer 78

Hyperkalaemia refers to a raised serum potassium. The main complication of hyperkalaemia is cardiac arrhythmias, such as ventricular fibrillation, which can lead to cardiac arrest. Serum Potassium (mmol/L) Normal 3.5 – 5.3 Mild Hyperkalaemia 5.4 – 6 Moderate Hyperkalaemia 6 – 6.5 Severe Hyperkalaemia Over 6.5

Question 79

Hyperkalaemia causes

Answer 79

Conditions that can cause hyperkalaemia include: Acute kidney injury Chronic kidney disease (stage 4 or 5) Rhabdomyolysis Adrenal insufficiency Tumour lysis syndrome Medications that can cause hyperkalaemia include: Aldosterone antagonists (e.g., spironolactone and eplerenone) ACE inhibitors (e.g., ramipril) Angiotensin II receptor blockers (e.g., candesartan) NSAIDs (e.g., naproxen) Haemolysis (rupture of blood cells) during sampling can create a falsely elevated potassium (pseudohyperkalaemia). The lab might indicate that they have noticed some haemolysis and recommend a repeat sample.

Question 80

Hyperkalaemia ECG

Answer 80

Tall peaked T-waves Flattening or absence of P waves Prolonged PR interval Broad QRS complexes

Question 81

Managing hyperkalaemia

Answer 81

Each hospital will have a policy and protocol to follow for hyperkalaemia. There should be input from experienced seniors, including the intensive care team for severe hyperkalaemia and renal physicians for renal impairment. Management of serum potassium below 6.5 mmol/L without ECG changes is aimed at the underlying cause, for example, treating acute kidney injury and stopping medications (e.g., spironolactone or ACE inhibitors). Patients require urgent treatment for hyperkalaemia if they have either: ECG changes Serum potassium above 6.5 mmol/L The mainstay of treatment is with an insulin and dextrose infusion and IV calcium gluconate: Insulin drives potassium from the extracellular space to the intracellular space Dextrose is required to prevent hypoglycaemia while on insulin Calcium gluconate stabilises the cardiac muscle cells and reduces the risk of arrhythmias Other options for lowering the serum potassium are: Nebulised salbutamol temporarily drives potassium into cells Oral calcium resonium reduces potassium absorption in the GI tract (this is slow and causes constipation) Sodium bicarbonate (in acidotic patients on renal advice) drives potassium into cells as it corrects the acidosis Haemodialysis may be required in severe or persistent cases

Question 82

Polycystic kidney disease

Answer 82

Polycystic kidney disease is a genetic condition where the healthy kidney tissue is replaced with many fluid-filled cysts. The enlarged kidneys may be palpable on examination of the abdomen. It leads to renal failure. There is an autosomal dominant and an autosomal recessive type. The autosomal dominant type is more common.

Question 83

Autosomal Dominant Polycystic Kidney Disease

Answer 83

The affected genes in autosomal dominant polycystic kidney disease (ADPKD) are: PKD1 gene on chromosome 16 (85% of cases) PKD2 gene on chromosome 4 (15% of cases) Extra-renal manifestations include: Cerebral aneurysms Hepatic, splenic, pancreatic, ovarian and prostatic cysts Mitral regurgitation Colonic diverticula Complications include: Chronic loin/flank pain Hypertension Gross haematuria can occur with cyst rupture (usually resolves within a few days) Recurrent urinary tract infections Renal stones End-stage renal failure occurs at a mean age of 50 years

Question 84

Autosomal Recessive Polycystic Kidney Disease

Answer 84

Autosomal recessive polycystic kidney disease (ARPKD) is caused by a mutation in the polycystic kidney and hepatic disease 1 (PKHD1) gene on chromosome 6. It is more rare and severe than ADPKD. It is often picked up on antenatal scans with oligohydramnios (reduced amniotic fluid volume due to reduced urine output). Oligohydramnios leads to underdevelopment of the fetal lungs (pulmonary hypoplasia) and respiratory failure shortly after birth. Patients may require haemodialysis within the first few days of life. They may have dysmorphic features, such as underdeveloped ear cartilage, low-set ears and a flat nasal bridge. End-stage renal failure usually occurs before reaching adulthood.

Question 85

Managing polycystic kidney disease

Answer 85

Ultrasound and genetic testing are used for diagnosis. Tolvaptan (a vasopressin receptor antagonist) can slow the development of cysts and the progression of renal failure in autosomal dominant polycystic kidney disease. This requires specific criteria and specialist monitoring. Management may involve: Antihypertensives for hypertension (e.g., ACE inhibitors) Analgesia for acute pain Antibiotics for infections (e.g., UTIs or cyst infections) Drainage of symptomatic can be performed by aspiration or surgery Dialysis for end-stage renal failure Renal transplant for end-stage renal failure Other management steps include: Genetic counselling Avoiding contact sports due to the risk of cyst rupture Avoiding NSAIDs and anticoagulants MR angiography (MRA) can be used to screen for cerebral aneurysms