Renal Flashcards
What is AKI?
What are the risk factors?
What are the causes?
Acute kidney injury (AKI) refers to a rapid drop in kidney function, diagnosed by measuring the serum creatinine. Acute kidney injury is most common in acutely unwell patients (e.g., infections or following surgery).
The NICE guidelines (2019) criteria for diagnosing an acute kidney injury are:
Rise in creatinine of more than 25 micromol/L in 48 hours
Rise in creatinine of more than 50% in 7 days
Urine output of less than 0.5 ml/kg/hour over at least 6 hours
Risk Factors
Risk factors that would predispose to developing acute kidney injury include:
- Older age (e.g., above 65 years)
- Sepsis
- Chronic kidney disease
- Heart failure
- Diabetes
- Liver disease
- Cognitive impairment (leading to reduced fluid intake)
- Medications (e.g., NSAIDs, gentamicin, diuretics and ACE inhibitors)
- Radiocontrast agents (e.g., used during CT scans)
Causes
Pre-renal causes are the most common. Insufficient blood supply (hypoperfusion) to kidneys reduces the filtration of blood. This may be due to:
- Dehydration
- Shock (e.g., sepsis or acute blood loss)
- Heart failure
Renal causes are due to intrinsic disease in the kidney. This may be due to:
- Acute tubular necrosis
- Glomerulonephritis
- Acute interstitial nephritis
- Haemolytic uraemic syndrome
- Rhabdomyolysis
Post-renal causes involve obstruction to the outflow of urine away 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
Tumours (e.g., retroperitoneal, bladder or prostate)
Strictures of the ureters or urethra
Benign prostatic hyperplasia (benign enlarged prostate)
Neurogenic bladder
What is the management for AKI?
Management
Acute kidney injury is often preventable by:
Avoiding nephrotoxic medications where appropriate
Ensuring adequate fluid intake (including IV fluids if oral intake is inadequate)
Additional fluids before and after radiocontrast agents
Treating an acute kidney injury involves reversing the underlying cause and supportive management, for example:
IV fluids for dehydration and hypovolaemia
Withhold medications that may worsen the condition (e.g., NSAIDs and ACE inhibitors)
Withhold/adjust medications that may accumulate with reduced renal function (e.g., metformin and opiates)
Relieve the obstruction in a post-renal AKI (e.g., insert a catheter in a patient with prostatic hyperplasia)
Dialysis may be required in severe cases
Input from a renal specialist is required where there is severe AKI, doubt about the cause or complications.
What is CKD and what are the causes?
Chronic kidney disease (CKD) describes a chronic reduction in kidney function sustained over three months. It tends to be permanent and progressive.
Causes
Kidney function naturally declines with age. Factors that can speed up the decline and cause CKD include:
- Diabetes
- Hypertension
- Medications (e.g., NSAIDs or lithium)
- Glomerulonephritis
- Polycystic kidney disease
What investigations would you if suspected CKD?
How do you classify CKD?
Investigations
The estimated glomerular filtration rate (eGFR) is based on the serum creatinine, age and gender. It estimates the glomerular filtration rate (the rate at which fluid is filtered from the blood into Bowman’s capsule).
Proteinuria (protein in the urine) is quantified with a urine albumin:creatinine ratio (ACR).
Haematuria (blood in the urine) can be assessed with a urine dipstick or microscopy. Microscopic haematuria is when blood is identified on testing but not visible on inspection. Macroscopic haematuria refers to visible blood in the urine. Haematuria can indicate infection, malignancy (e.g., bladder cancer), glomerulonephritis or kidney stones.
Renal ultrasound helps identify obstructions (e.g., kidney stones or tumours) and polycystic kidney disease.
Other investigations are necessary to identify risk factors, including:
Blood pressure (for hypertension)
HbA1c (for diabetes)
Lipid profile (for hypercholesterolaemia)
Classification
A diagnosis can be made when there are consistent results over three months of either:
Estimated glomerular filtration rate (eGFR) is sustained below 60 mL/min/1.73 m2
Urine albumin:creatinine ratio (ACR) is sustained above 3 mg/mmol
Accelerated progression is a sustained decline in the eGFR within one year of either 25% or 15 mL/min/1.73 m2.
What are complications of CKD?
What is the managemnt?
Complications
* Anaemia
* Renal bone disease
* Cardiovascular disease
* Peripheral neuropathy
* End-stage kidney disease
* Dialysis-related complications
Management
The Kidney Failure Risk Equation can be used to estimate the 5-year risk of kidney failure requiring dialysis.
The NICE clinical knowledge summaries (May 2023) suggest referral to a renal specialist when:
eGFR less than 30 mL/min/1.73 m2
Urine ACR more than 70 mg/mmol
Accelerated progression (a decrease in eGFR of 25% or 15 mL/min/1.73 m2 within 12 months)
5-year risk of requiring dialysis over 5%
Uncontrolled hypertension despite four or more antihypertensives
Treating the underlying cause involves:
- Optimising diabetic control
- Optimising hypertension control
- Reducing or avoiding nephrotoxic drugs (where appropriate)
- Treating glomerulonephritis (where this is the cause)
The blood pressure target is less than 130/80 in patients under 80 with CKD and an ACR above 70 mg/mmol.
Medications that help slow the disease progression are:
ACE inhibitors (or angiotensin II receptor blockers)
SGLT-2 inhibitors (specifically dapagliflozin)
Reducing the risk of complications involves:
Exercise, maintain a healthy weight and avoid smoking
Atorvastatin 20mg for primary prevention of cardiovascular disease (in all patients with CKD)
Management of complications involves:
Oral sodium bicarbonate to treat metabolic acidosis
Iron and erythropoietin to treat anaemia
Vitamin D, low phosphate diet and phosphate binders to treat renal bone disease
Management of end-stage renal disease involves:
Special dietary advice
Dialysis
Renal transplant
What is glomerulonephritis?
What is nephritic and nephrotic syndrome?
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).
Nephritic Syndrome
Nephritis is a very generic term for inflammation in the kidneys. It is a descriptive term and is not a diagnosis.
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
Nephrotic Syndrome
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.
The most common cause of nephrotic syndrome in children is minimal change disease. This is usually:
Idiopathic (no identified cause)
Treated successfully with steroids
The top causes of nephrotic syndrome in adults are:
Membranous nephropathy
Focal segmental glomerulosclerosis
Other causes of nephrotic syndrome include:
Membranoproliferative glomerulonephritis
Henoch-Schönlein purpura (HSP)
Diabetes
Infection (e.g., HIV)
What is type 1 and 4 renal tubular acidosis and how do you manage them?
Type 1 Renal Tubular Acidosis
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)
Type 4 Renal Tubular Acidosis
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
Low aldosterone or low aldosterone activity can be due to:
Adrenal insufficiency
Diabetic nephropathy
Medications (e.g., ACE inhibitors, spironolactone or eplerenone)
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.
What is rhabdomyolisis?
what are the causes and symptoms?
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.
What investigations would you do if suspected rhabdomyolosis?
What is the management?
Investigations
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.
Management
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)
what can cause hyperkalaemia?
What is the management for hyperkalaemia?
Causes
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)
**Management **
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
What is polycystic kidney disease?
What is the managemnt?
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.
Management
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
What is haemolytic uraemic syndrome?
How does it present?
What is the management?
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.
**Presentation **
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
Management
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)**
What is a lower urinary tract infection?
How does it present?
Lower urinary tract infections (UTIs) involve infection in the bladder, causing cystitis (inflammation of the bladder).
Pyelonephritis refers to inflammation of the kidney resulting from bacterial infection. The inflammation affects the kidney tissue (parenchyma) and the renal pelvis (where the ureter joins the kidney).
Urinary tract infections are far more common in women, where the urethra is much shorter, making it easier for bacteria to get into the bladder.
The primary source of bacteria for urinary tract infections is faeces. Normal intestinal bacteria, such as E. coli, can easily journey to the urethral opening from the anus. Sexual activity is a crucial method for spreading bacteria around the perineum. Incontinence or poor hygiene can also contribute to the development of UTIs.
Urinary catheters are a possible source of infection, and catheter-associated urinary tract infections tend to be more serious and challenging to treat.
Presentation
Lower urinary tract infections present with:
- Dysuria (pain, stinging or burning when passing urine)
- Suprapubic pain or discomfort
- Frequency
- Urgency
- Incontinence
- Haematuria
- Cloudy or foul-smelling urine
- Confusion is commonly the only symptom in older and frail patients
Pyelonephritis has a similar presentation to lower urinary tract infections plus the additional triad of symptoms:
Fever
Loin or back pain (bilateral or unilateral)
Nausea or vomiting
Patients with pyelonephritis may also have:
- Systemic illness
- Loss of appetite
- Haematuria
- Renal angle tenderness on examination
TOM TIP: It is essential to distinguish between lower urinary tract infections and pyelonephritis. Pyelonephritis is a more severe condition with significant complications, including sepsis and kidney scarring. Suspect pyelonephritis in patients with:
- Fever
- Loin or back pain
- Nausea or vomiting
- Renal angle tenderness on examination
What investigation would you do for UTI and what findings would you expect?
What is the managemnt?
Urine Dipstick
Nitrites on a dipstick test suggest bacteria in the urine. Gram-negative bacteria (e.g., E. coli) break down nitrates (a normal waste product in urine) into nitrites.
Leukocytes are white blood cells. It is normal to have a small number of leukocytes in the urine, but a significant rise can result from an infection or other cause of inflammation. Leukocyte esterase (a product of leukocytes) is tested on a urine dipstick, indicating the number of leukocytes in the urine.
Red blood cells in the urine indicate bleeding. Microscopic haematuria is where blood is seen on a urine dipstick but not seen when looking at the sample. Macroscopic haematuria is where blood is visible in the urine. Haematuria is a common sign of infection but can also be present with other causes, such as bladder cancer or nephritis.
Nitrites are a better indication of infection than leukocytes. The NICE clinical knowledge summaries (June 2023) suggest that nitrites or leukocytes plus red blood cells indicate that the patient will likely have a UTI. The dipstick result is less reliable in catheterised patients or women over 65.
Where only nitrites are present, it is worth treating as a UTI. Where only leukocytes are present, a sample should be sent to the lab for further testing. Antibiotics may be considered where there is clinical evidence of a UTI.
A midstream urine (MSU) sample sent for microscopy, culture and sensitivity testing will determine the infective organism and the antibiotics that will be effective in treatment. Not all patients with an uncomplicated UTI require an MSU. An MSU is important in:
Pregnant patients
Patients with recurrent UTIs
Atypical symptoms
When symptoms do not improve with antibiotics
Management of Lower Urinary Tract Infections
Follow local guidelines. An appropriate initial antibiotic in the community would be:
Nitrofurantoin (avoided in patients with an eGFR <45)
Trimethoprim (often associated with high rates of bacterial resistance)
Alternatives:
Pivmecillinam
Amoxicillin
Cefalexin
The typical duration of antibiotics is:
3 days of antibiotics for simple lower urinary tract infections in women
5-10 days of antibiotics for immunosuppressed women, abnormal anatomy or impaired kidney function
7 days of antibiotics for men, pregnant women or catheter-related UTIs
It is worth noting that NICE recommend changing the catheter when someone is diagnosed with a catheter-related urinary tract infection.
Management of Pyelonephritis
Referral to hospital is required if there are features of sepsis or if it is unsafe to manage them in the community.
NICE guidelines (2018) recommend the following first-line antibiotics for 7-10 days when treating pyelonephritis in the community:
Cefalexin
Co-amoxiclav (if culture results are available)
Trimethoprim (if culture results are available)
Ciprofloxacin (keep tendon damage and lower seizure threshold in mind)
Patients admitted to hospital with sepsis require the sepsis six, which includes a serum lactate, blood cultures, urine output monitoring, oxygen, empirical broad-spectrum antibiotics and IV fluids.
Two things to keep in mind with patients that have significant symptoms or do not respond well to treatment are:
Renal abscess
Kidney stone obstructing the ureter, causing pyelonephritis
Pregnancy
Urinary tract infections in pregnancy increase the risk of pyelonephritis, premature rupture of membranes and pre-term labour.
Management in Pregnancy
Urinary tract infection in pregnancy requires 7 days of antibiotics. All women should have an MSU for microscopy, culture and sensitivity testing.
The antibiotic options are:
Nitrofurantoin (avoided in the third trimester)
Amoxicillin (only after sensitivities are known)
Cefalexin (the typical choice)
Nitrofurantoin should be avoided in the third trimester as there is a risk of neonatal haemolysis (destruction of the neonatal red blood cells).
Trimethoprim should be avoided in the first trimester as it works as a folate antagonist. Folate is essential in early pregnancy for the normal development of the fetus. Trimethoprim in early pregnancy can cause congenital malformations, particularly neural tube defects (e.g., spina bifida). It is not known to be harmful later in pregnancy but is generally avoided unless necessary.
