Nephrology Flashcards
AKI
What causes AKI?
Causes of AKI are traditionally divided into prerenal, intrinsic and postrenal causes
Prerenal
Think of what causes big problems in other major organs. In the heart a lack of blood (ischaemia) to the myocardium causes a myocardial infarction. In a similar fashion 85% of strokes are causes be ischaemia to the brain. The same goes for the kidneys. One of the major causes of AKI is ischaemia, or lack of blood flowing to the kidneys.
Examples
hypovolaemia secondary to diarrhoea/vomiting
renal artery stenosis
Intrinsic
The second group of causes relate to intrinsic damage to the glomeruli, renal tubules or interstitium of the kidneys themselves. This may be due to toxins (drugs, contrast etc) or immune-mediated glomuleronephritis.
Examples
glomerulonephritis
acute tubular necrosis (ATN)
acute interstitial nephritis (AIN), respectively
rhabdomyolysis
tumour lysis syndrome
Postrenal
The third group relates to problems after the kidneys. This is where there is an obstruction to the urine coming from the kidneys resulting in things ‘backing-up’ and affecting the normal renal function. An example could be a unilateral ureteric stone or bilateral hydroneprosis secondary to acute urinary retention caused by benign prostatic hyperplasia.
Examples
kidney stone in ureter or bladder
benign prostatic hyperplasia
external compression of the ureter
Who is at an increased risk of AKI?
One of the keys to reducing the incidence of AKI is identifying patient who are at increased risk. NICE support this approach and have published guidelines suggesting which patients are at greater risk.
Risk factors for AKI include:
chronic kidney disease
other organ failure/chronic disease e.g. heart failure, liver disease, diabetes mellitus
history of acute kidney injury
use of drugs with nephrotoxic potential (e.g. NSAIDs, aminoglycosides, ACE inhibitors, angiotensin II receptor antagonists [ARBs] and diuretics) within the past week
use of iodinated contrast agents within the past week
age 65 years or over
oliguria (urine output less than 0.5 ml/kg/hour)
neurological or cognitive impairment or disability, which may mean limited access to fluids because of reliance on a carer
Preventing AKI
By identifying patients at increased risk of AKI (see above) it may be possible to take steps to reduce the risk. For example, patients who are at risk of AKI and who are undergoing an investigation requiring contrast are usually given IV fluids to reduce the risk. Certain drugs such as ACE inhibitors and ARBs may also be temporarily stopped.
What happens when kidneys stop working?
It’s best to work backwards and think about what kidneys actually do. The kidneys are primarily responsible for fluid balance and maintaining homeostasis. Therefore two of the key ways AKI may be detected are:
a reduced urine output. This is termed oliguria and is defined as a urine output of less than 0.5 ml/kg/hour
fluid overload
a rise in molecules that the kidney normal excretes/maintains a careful balance of. Examples include potassium, urea and creatinine
Symptoms and signs
Many patients with early AKI may experience no symptoms. However, as renal failure progresses the following may be seen:
reduced urine output
pulmonary and peripheral oedema
arrhythmias (secondary to changes in potassium and acid-base balance)
features of uraemia (for example, pericarditis or encephalopathy)
Detection
One of the most common blood tests performed on the wards is ‘urea and electrolytes’ or ‘U&Es’. This returns a number of markers, including
sodium
potassium
urea
creatinine
NICE recommend that we can use a variety of different criteria to make an official diagnosis of AKI. They state:
Detect acute kidney injury, in line with the (p)RIFLE, AKIN or KDIGO definitions, by using any of the following criteria:
a rise in serum creatinine of 26 micromol/litre or greater within 48 hours
a 50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days
a fall in urine output to less than 0.5 ml/kg/hour for more than 6 hours in adults and more than
Urinanalysis
all patients with suspected AKI should have urinanalysis
Imaging
if patients have no identifiable cause for the deterioration or are at risk of urinary tract obstruction they should have a renal ultrasound within 24 hours of assessment.
AKI Management
The management of AKI is largely supportive. This means patients require careful fluid balance to ensure that the kidneys are properly perfused but not excessively to avoid fluid overload. It is also important to review a patient’s medication list to see what treatments may either be exacerbating their renal dysfunction or may be dangerous as a consequence of renal dysfunction. The table below gives some examples of common drugs:
Should be stopped in AKI as may worsen renal function
- NSAIDs
- Aminoglycosides
- ACE inhibitors
- Angiotensin II receptor antagonists
- Diuretics
May have to be stopped in AKI as increased risk of toxicity (but doesn’t usually worsen AKI itself)
- Metformin
- Lithium
- Digoxin
Usually safe to continue in AKI
- Paracetamol
- Warfarin
- Statins
- Aspirin (at a cardioprotective dose of 75mg od)
- Clopidogrel
- Beta-blockers
Treatments which are not recommend include the routine use of loop diuretics (to artificially boost urine output) and low-dose dopamine (in an attempt to increase renal perfusion). There is however a role for loop diuretics in patients who experience significant fluid overload.
Hyperkalaemia also needs prompt treatment to avoid arrhythmias which may potentially be life-threatening. The table below categorises the different treatments for hyperkalaemia:
Stabilisation of the cardiac membrane
- Short-term shift in potassium from extracellular to intracellular fluid compartment
- Removal of potassium from the body
- Intravenous calcium gluconate
- Combined insulin/dextrose infusion
- Nebulised salbutamol
- Calcium resonium (orally or enema)
- Loop diuretics
- Dialysis
Specialist input from a nephrologist is required for cases where the cause is not known or where the AKI is severe.
All patients with suspected AKI secondary to urinary obstruction require prompt review by a urologist.
Renal replacement therapy (e.g. haemodialysis) is used when a patient is not responding to medical treatment of complications, for example hyperkalaemia, acidosis or uraemia.
ADPKD
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively
ADPKD type 1
85% of cases
Chromosome 16
ADPKD type 2
15% of cases
Chromosome 4
Presents with renal failure earlier
The screening investigation for relatives is abdominal ultrasound:
Ultrasound diagnostic criteria (in patients with positive family history)
two cysts, unilateral or bilateral, if aged < 30 years
two cysts in both kidneys if aged 30-59 years
four cysts in both kidneys if aged > 60 years
Management
For select patients, tolvaptan (vasopressin receptor 2 antagonist) may be an option. NICE recommended it as an option for treating ADPKD in adults to slow the progression of cyst development and renal insufficiency only if:
they have chronic kidney disease stage 2 or 3 at the start of treatment
there is evidence of rapidly progressing disease and
the company provides it with the discount agreed in the patient access scheme.
Chronic kidney disease
Chronic kidney disease: causesCommon causes of chronic kidney disease
diabetic nephropathy
chronic glomerulonephritis
chronic pyelonephritis
hypertension
adult polycystic kidney disease
Chronic kidney disease eGFR and classification
Serum creatinine may not provide an accurate estimate of renal function due to differences in muscle. For this reason formulas were develop to help estimate the glomerular filtration rate (estimated GFR or eGFR). The most commonly used formula is the Modification of Diet in Renal Disease (MDRD) equation, which uses the following variables:
serum creatinine
age
gender
ethnicity
Factors which may affect the result
pregnancy
muscle mass (e.g. amputees, body-builders)
eating red meat 12 hours prior to the sample being taken
CKD may be classified according to GFR:
CKD stage
GFR range
1
Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests* are normal, there is no CKD)
2
60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no CKD)
3a
45-59 ml/min, a moderate reduction in kidney function
3b
30-44 ml/min, a moderate reduction in kidney function
4
15-29 ml/min, a severe reduction in kidney function
5
Less than 15 ml/min, established kidney failure - dialysis or a kidney transplant may be needed
*i.e. normal U&Es and no proteinuria
Chronic kidney disease hypertension
The majority of patients with chronic kidney disease (CKD) will require more than two drugs to treat hypertension. ACE inhibitors are first line and are particularly helpful in proteinuric renal disease (e.g. diabetic nephropathy). As these drugs tend to reduce filtration pressure a small fall in glomerular filtration pressure (GFR) and rise in creatinine can be expected. NICE suggest that a decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable, although any rise should prompt careful monitoring and exclusion of other causes (e.g. NSAIDs). A rise greater than this may indicate underlying renovascular disease.
Furosemide is useful as a anti-hypertensive in patients with CKD, particularly when the GFR falls to below 45 ml/min*. It has the added benefit of lowering serum potassium. High doses are usually required. If the patient becomes at risk of dehydration (e.g. Gastroenteritis) then consideration should be given to temporarily stopping the drug
*the NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min
Haematuria
The management of patients with haematuria is often difficult due to the absence of widely followed guidelines. It is sometimes unclear whether patients are best managed in primary care, by urologists or by nephrologists.
The terminology surrounding haematuria is changing. Microscopic or dipstick positive haematuria is increasingly termed non-visible haematuria whilst macroscopic haematuria is termed visible haematuria. Non-visible haematuria is found in around 2.5% of the population.
Causes of transient or spurious non-visible haematuria
urinary tract infection
menstruation
vigorous exercise (this normally settles after around 3 days)
sexual intercourse
Causes of persistent non-visible haematuria
cancer (bladder, renal, prostate)
stones
benign prostatic hyperplasia
prostatitis
urethritis e.g. Chlamydia
renal causes: IgA nephropathy, thin basement membrane disease
Spurious causes - red/orange urine, where blood is not present on dipstick
foods: beetroot, rhubarb
drugs: rifampicin, doxorubicin
Management
Current evidence does not support screening for haematuria. The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the general population hence these patients should also be investigated.
Testing
urine dipstick is the test of choice for detecting haematuria
persistent non-visible haematuria is often defined as blood being present in 2 out of 3 samples tested 2-3 weeks apart
renal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood pressure should also be checked
urine microscopy may be used but time to analysis significantly affects the number of red blood cells detected
NICE urgent cancer referral guidelines were updated in 2015.
Haemolytic uraemic syndrome
Haemolytic uraemic syndrome is generally seen in young children and produces a triad of:
acute kidney injury
microangiopathic haemolytic anaemia
thrombocytopenia
Most cases are secondary (termed ‘typical HUS’):
classically Shiga toxin-producing Escherichia coli (STEC) 0157:H7 (‘verotoxigenic’, ‘enterohaemorrhagic’). This is the most common cause in children, accounting for over 90% of cases
pneumococcal infection
HIV
rare: systemic lupus erythematosus, drugs, cancer
Primary HUS (‘atypical’) is due to complement dysregulation.
Investigations
full blood count: anaemia, thrombocytopaenia, fragmented blood film
U&E: acute kidney injury
stool culture
Management
treatment is supportive e.g. Fluids, blood transfusion and dialysis if required
there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients
the indications for plasma exchange in HUS are complicated. As a general rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea
eculizumab (a C5 inhibitor monoclonal antibody) has evidence of greater efficiency than plasma exchange alone in the treatment of adult atypical HUS
Henoch-Schonlein purpura
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Berger’s disease). HSP is usually seen in children following an infection.
Features
palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs
abdominal pain
polyarthritis
features of IgA nephropathy may occur e.g. haematuria, renal failure
Treatment
analgesia for arthralgia
treatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressants
Prognosis
usually excellent, HSP is a self-limiting condition, especially in children without renal involvement
around 1/3rd of patients have a relapse
Hyperkalaemia: management
Untreated hyperkalaemia may cause life-threatening arrhythmias. Precipitating factors should be addressed (e.g. acute renal failure) and aggravating drugs stopped (e.g. ACE inhibitors).
Hyperkalaemic and has associated ECG changes (peaked T waves in the anterior leads and bradycardia). Bradycardia in such patients is a worrying sign as asystole may occur. The first priority in this patient is to stabilise the myocardium with intravenous calcium gluconate.
Management may be categorised by the aims of treatment
Stabilisation of the cardiac membrane
intravenous calcium gluconate
+ does NOT lower serum potassium levels
Short-term shift in potassium from extracellular to intracellular fluid compartment
combined insulin/dextrose infusion
nebulised salbutamol
Removal of potassium from the body
calcium resonium (orally or enema)
enemas are more effective than oral as potassium is secreted by the rectum
loop diuretics
dialysis
haemofiltration/haemodialysis should be considered for patients with AKI with persistent hyperkalaemia
Hypokalaemia
This gentleman has severe hypokalaemia, defined as a serum potassium < 2.5mmol/l. Mild to moderate hypokalaemia can be asymptomatic but the more severe the electrolyte derangement the more likely that symptoms will develop. Symptoms include weakness, leg cramps, palpitations secondary to cardiac arrhythmias and ascending paralysis.
Causes can be secondary to:
1.) Increased potassium loss:
Drugs: thiazides, loop diuretics, laxatives, glucocorticoids, antibiotics
GI losses: diarrhoea, vomiting, ileostomy
Renal causes: dialysis
Endocrine disorders: hyperaldosteronism, Cushing’s syndrome
2.) Trans-cellular shift
Insulin/glucose therapy
Salbutamol
Theophylline
Metabolic alkalosis
- ) Decreased potassium intake
- ) Magnesium depletion (associated with increased potassium loss)
ECG changes seen in hypokalaemia include:
U waves
T wave flattening
ST segment changes
Treatment of hypokalaemia depends on severity. Any causative agents should be removed. Gradual replacement of potassium via the oral route is preferred if possible.
Mild to moderate hypokalaemia 2.5 - 3.4 mmol/l can be treated with oral potassium provided the patient is not symptomatic and there are no ECG changes.
Severe hypokalaemia (<2.5mmol/l) or symptomatic hypokalaemia should be managed with IV replacement. The patient should be managed in an area where cardiac monitoring can take place. If there are no contraindications to fluid therapy (e.g. volume overload, heart failure) potassium should be diluted to low concentrations as higher concentrations can be phlebitic. The infusion rate should not exceed 20mmol/hr. In this case, 3 bags of 0.9% Saline with 40mmol KCL is the correct answer.
Metabolic acidosis
Metabolic acidosis is commonly classified according to the anion gap. This can be calculated by: (Na+ + K+) - (Cl- + HCO-3). If a question supplies the chloride level then this is often a clue that the anion gap should be calculated. The normal range = 10-18 mmol/L
Normal anion gap ( = hyperchloraemic metabolic acidosis)
gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula
renal tubular acidosis
drugs: e.g. acetazolamide
ammonium chloride injection
Addison’s disease
Raised anion gap
lactate: shock, sepsis, hypoxia
ketones: diabetic ketoacidosis, alcohol
urate: renal failure
acid poisoning: salicylates, methanol
Metabolic acidosis secondary to high lactate levels may be subdivided into two types:
lactic acidosis type A: sepsis, shock, hypoxia, burns
lactic acidosis type B: metformin
Minimal change disease
Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults.
The majority of cases are idiopathic, but in around 10-20% a cause is found:
drugs: NSAIDs, rifampicin
Hodgkin’s lymphoma, thymoma
infectious mononucleosis
Pathophysiology
T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss
the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin
Features
nephrotic syndrome
normotension - hypertension is rare
highly selective proteinuria
only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus
renal biopsy
normal glomeruli on light microscopy
electron microscopy shows fusion of podocytes and effacement of foot processes
Management
majority of cases (80%) are steroid-responsive
cyclophosphamide is the next step for steroid-resistant cases
Prognosis is overall good, although relapse is common. Roughly:
1/3 have just one episode
1/3 have infrequent relapses
1/3 have frequent relapses which stop before adulthood
Nephrotoxicity due to contrast media
Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within 3 days of the intravascular administration of contrast media.
Risk factors include
known renal impairment (especially diabetic nephropathy)
age > 70 years
dehydration
cardiac failure
the use of nephrotoxic drugs such as NSAIDs
Contrast-induced nephropathy occurs 2 -5 days after administration.
Prevention
the evidence base currently supports the use of intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure. There is also evidence to support the use of isotonic sodium bicarbonate
N-acetylcysteine has been given in the past but recent evidence suggests it is not effective*
* Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med. 2018;378(7):603
Renal transplant immunosuppression
Example regime
initial: ciclosporin/tacrolimus with a monoclonal antibody
maintenance: ciclosporin/tacrolimus with MMF or sirolimus
add steroids if more than one steroid responsive acute rejection episode
Ciclosporin
inhibits calcineurin, a phosphotase involved in T cell activation
Tacrolimus
lower incidence of acute rejection compared to ciclosporin
also less hypertension and hyperlipidaemia
however, high incidence of impaired glucose tolerance and diabetes
Mycophenolate mofetil (MMF)
blocks purine synthesis by inhibition of IMPDH
therefore inhibits proliferation of B and T cells
side-effects: GI and marrow suppression
Sirolimus (rapamycin)
blocks T cell proliferation by blocking the IL-2 receptor
can cause hyperlipidaemia
Monoclonal antibodies
selective inhibitors of IL-2 receptor
daclizumab
basilximab
Monitoring
Patients on long-term immunosuppression for organ transplantation require regular monitoring for complications such as:
Cardiovascular disease - tacrolimus and ciclosporin can cause hypertension and hyperglycaemia. Tacrolimus can also cause hyperlipidaemia. Patients must be monitored for accelerated cardiovascular disease.
Renal failure - due to nephrotoxic effects of tacrolimus and ciclosporin/graft rejection/recurrence of original disease in transplanted kidney
Malignancy - patients should be educated about minimising sun exposure to reduce the risk of squamous cell carcinomas and basal cell carcinomas
Rhabdomyolysis
Rhabdomyolysis will typically feature in the exam as a patient who has had a fall or prolonged epileptic seizure and is found to have an acute kidney injury on admission.
Features
acute kidney injury with disproportionately raised creatinine
elevated creatine kinase (CK)
myoglobinuria
hypocalcaemia (myoglobin binds calcium)
elevated phosphate (released from myocytes)
hyperkalaemia (may develop before renal failure)
metabolic acidosis
Causes
seizure
collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)
ecstasy
crush injury
McArdle’s syndrome
drugs: statins (especially if co-prescribed with clarithromycin)
Management
IV fluids to maintain good urine output
urinary alkalinization is sometimes used
Spironolactone
Spironolactone is an aldosterone antagonist which acts in the cortical collecting duct.
Indications
ascites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often used
hypertension: used in some patients as a NICE ‘step 4’ treatment
heart failure (see RALES study below)
nephrotic syndrome
Conn’s syndrome
Adverse effects
hyperkalaemia
gynaecomastia: less common with eplerenone
RALES
NYHA III + IV, patients already taking ACE inhibitor
low dose spironolactone reduces all cause mortality
