Renal (General, AKI and CKD) Flashcards
Drugs that are usually safe in acute kidney injury (AKI)
Some common drugs that are usually safe in AKI are:
- Paracetamol
- Aspirin (at a cardioprotective dose)
- Clopidogrel
- Warfarin
- Statins
- Beta-blockers
Drugs that should be stopped in AKI
These drugs should be stopped as they may worsen an AKI:
- NSAIDs (except low-dose cardioprotective aspirin)
- ACE inhibitors
- Angiotensin II receptor blockers (ARBs)
- Aminoglycosides (e.g. gentamicin)
- Diuretics
Drugs with an increased risk of toxicity in AKI
Drugs that may be stopped as an AKI can increase toxicity, but they do not usually worsen the AKI itself:
- Metformin – due to increased risk of lactic acidosis
- Lithium – due to increased risk of lithium toxicity
- Digoxin – due to increased risk of digoxin toxicity
Drugs causing pre-renal damage
Any drug that causes volume depletion or reduced renal perfusion may cause pre-renal damage. Some examples are:
- NSAIDs
- ACE inhibitors
- ARBs
Drugs causing intrarenal damage
These drugs may be directly nephrotoxic or lead to hypersensitivity reactions:
Drugs that may cause glomerulonephritis:
- Rifampicin
- Sulfonamides
- Penicillamine
Drugs that may cause acute interstitial nephritis:
- Antibiotics – generally penicillins and cephalosporins
- Sulfonamides
- Thiazide diuretics
Drugs that are directly nephrotoxic and may cause acute tubular necrosis:
- Aminoglycosides (e.g. gentamicin)
- Amphotericin
- Ciclosporin
Drugs causing post-renal damage
These drugs may lead to urinary tract obstruction:
- Anticholinergic drugs (e.g. tricyclic antidepressants) may cause acute urinary retention
- Acetazolamide, methotrexate, and sulfonamides can cause crystalluria which can lead to obstruction
Acute kidney injury (AKI)
describes a spectrum of disorders leading to reduced kidney function over hours to days. An AKI can lead to a failure to maintain fluid, electrolyte, or acid-base homeostasis.
An AKI may occur in patients with previously intact renal function or in patients with pre-existing renal disease (known as acute-on-chronic kidney disease).
causes of AKI can be split into
pre-renal
renal
post-renal
Pre-renal causes
- include causes that decrease blood flow to the kidney such as*
- Hypovolaemia (e.g. dehydration), decreased cardiac output (e.g. heart failure)
- Drugs that cause renal hypoperfusion (e.g. ACE inhibitors, angiotensin II receptor blockers and diuretics)
Renal (intrinsic) causes
Toxins and drugs:
- Antibiotics (e.g. aminoglycosides such as gentamicin)
- Radiocontrast media, particularly iodinated contrast
- Chemotherapy drugs (e.g. tacrolimus)
Vascular disease:
- Vasculitis (usually anti-neutrophil cytoplasmic antibody- (ANCA-) associated)
- Thrombotic microangiopathies (e.g. haemolytic uraemic syndrome or thrombotic thrombocytopenic purpura)
- Renal artery stenosis
- Renal vein thrombosis
- Malignant hypertension
Tubular disease:
- Acute tubular necrosis
- Rhabdomyolysis
- Multiple myeloma
- Interstitial disease:
- Acute interstitial nephritis
- Lymphoma infiltration
Glomerular diseases:
- Glomerulonephritis (e.g. anti-glomerular basement membrane disease, IgA nephropathy, post-infectious glomerulonephritis etc.)
Other:
* Eclampsia
Post-renal causes
include causes of obstruction to urine outflow such as:
- Renal stones
- Prostatic hyperplasia/cancer
- Urinary retention, which may be secondary to drugs (e.g. tricyclic antidepressants)
- Blocked catheter
investigations for AKI
- U&Es
- Urea:creatinine ratio
- Urinalysis
- Renal US
Others
- FBC
- Blood cultures if sepsis suspected
- liver function tests (hepatorenal syndrome)
- CK (rhabdomyolysis)
- CRP or ESR
- Virology tests
- Kidney biopsy
UEs in AKI
- Urea, creatinine, and potassium may be elevated
- Creatinine tends to rise around 24 hours following the start of an AKI
Urea:creatine ratio AKI
Urea:creatinine ratio – can help determine if the cause is pre-renal, renal, or post-renal:
Calculated by dividing urea by creatinine, ensuring the units are the same
1) A ratio of >110:1 suggests a pre-renal cause
- A disproportionate increase in urea suggests hypoperfusion
2) A ratio of <40:1 suggests a renal cause
- Suggests decreased urea absorption due to intrinsic renal damage
3) A ratio of 40-110:1 suggests a normal result or post-renal cause
- This suggests urea reabsorption is within normal limits
urinalysis in AKI
dipstick testing for blood, protein, leukocytes, nitrites, and glucose should be performed in all patients with AKI
Renal ultrasound and AKI
- If there is an AKI with no identifiable cause or those at risk of urinary tract obstruction
- Performed within 24 hours of assessment
An AKI can be diagnosed if any of the following apply:
- A rise in creatinine of ≥26 µmol/L in 48 hours or
- A ≥50% rise in creatinine over 7 days or
- A fall in urine output to <0.5 mL/kg/hr for >6 hours in adults or 8 hours in children or
- A ≥25% fall in the estimated glomerular filtration rate (eGFR) in both children and young people over 7 days
AKI staging
Stage 1 AKI:
- An increase in creatinine to 1.5-1.9 times the baseline or
- A reduction in urine output to <0.5 mL/kg/hr for ≥6 hours
Stage 2 AKI:
- An increase in creatinine to 2.0-2.9 times the baseline or
- A reduction in urine output to <0.5 mL/kg/hr for ≥12 hours
Stage 3 AKI:
- An increase in creatinine to ≥3.0 times the baseline or
- A reduction in urine output to <0.5 mL/kg/hr for ≥24 hours
AKI vs. CKD
Features supporting CKD:
- Anaemia – due to anaemia of chronic disease and reduced erythropoietin release from the kidneys
- Hypocalcaemia – due to reduced activation of vitamin D, which takes place in the kidneys
- Increased phosphate also leads to the deposition of calcium in calcium phosphate, which is insoluble, and therefore removed from the circulation
- Hyperphosphataemia – dysfunction of the kidneys leads to decreased phosphate excretion
- Small kidneys on ultrasound – this may not always be seen:
- E.g. in polycystic kidney disease, a cause of CKD, the kidneys may be enlarged
Features supporting AKI:
- Acutely unwell patients or hypovolaemia make CKD less likely and AKI more likely.
Presentation of AKI
The presentation depends on the underlying cause. Many patients may not experience clear symptoms, however, as urea and electrolytes become more deranged in AKI, symptoms may emerge such as:
- Decreasing urine output with or without increasing serum creatinine
- Nausea and vomiting
- Arrhythmia – if hyperkalaemia develops
- Dehydration
- Confusion
- Features of Uraemia
management of AKI
STOP
- Sepsis – screen for sepsis and treat
- Toxins – stop and identify any nephrotoxic drugs/agents
- Optimise blood pressure – correct hypovolaemia, withhold drugs that contribute to AKI, consider critical care escalation for vasopressors if patients are still hypotensive despite fluid resuscitation
- Prevent harm – identify and treat reversible causes, treat complications, and review medications
May need haemodialysis
Indications for haemodialysis
Remembered with AEIOU:
- Acidosis
- Electrolytes (hyperkalaemia)
- Ingestion or overdose of medications/drugs
- Overload of fluid causing heart failure and pulmonary oedema
- Uraemia leading to pericarditis or encephalopathy
complications of AKI
Hyperkalaemia
Acidosis
Pulmonary oedema
Uraemic encephalopathy or pericarditis
management of mild hyperkalaemia (5.5-5.9 mmol/L)
- Identify and treat underlying cause
- Consider cation exchange resin to remove K+ from body (e.g. calcium resonium)
management of moderate hyperkalaemia (K+ of 6.0-6.4 mmol/L)
- Perform ECG. If changes are present, treat as severe hyperkalaemia
- If no ECG changes present: IV insulin and glucose infusion – moves potassium intracellularly
- Consider adjunct nebulised salbutamol – avoid if tachyarrhythmia present
management of severe hyperkalaemia (K+ ≥6.5 mmol/L):
- Seek advice from nephrology/intensive care and monitor in a high-dependency area
- Immediate IV calcium gluconate or IV calcium chloride – for cardioprotection and prevents arrhythmia
- Seek senior advice if the ECG does not normalise after one dose
Pulmonary oedema
This may occur due to the underlying cause of AKI (e.g. heart failure, renal artery stenosis) or due to excessive IV fluid resuscitation
- Sit the patient upright – allows for better gas exchange as fluids settle in the lung bases
- Give high-flow oxygen at 15 L/min via a reservoir mask
- Consider IV glyceryl trinitrate if systolic blood pressure is >90 mmHg and there is no valvular heart disease
- Loop diuretics may be considered by specialists if the patient is haemodynamically stable and not dehydrated
Seek senior support
Refer for renal replacement therapy
acidosis
- IV sodium bicarbonate may be needed due to the risk of volueme overload or hypernatraemia (pH <7.20)
- refer for renal replacement therapy
Uraemic encephalopathy or pericarditis
Refer for renal replacement therapy
Chronic kidney disease (CKD)
is defined as a reduction in kidney function, structural damage, or both for more than 3 months with associated health implications.
CKD can lead to fluid and electrolyte imbalance, and protein and/or blood leakage into the urine, causing proteinuria and haematuria.
2 main causes of CKD
- Diabetic nephropathy ( most common )
- Hypetensive nephorpathy (second)
causes of CKD
- Diabetic nephropathy – the most common cause
- Hypertensive nephropathy – the second most common cause
- Hypertension can cause CKD and CKD can cause hypertension
- Glomerulonephritis
- Current or previous acute kidney injury (AKI)
- Nephrotoxic drugs
- Causes of obstructive uropathy (e.g. recurrent renal stones)
- Systemic disorders that may involve the kidneys (e.g. systemic lupus erythematosus, vasculitis, multiple myeloma)
- Polycystic kidney disease
- Alport’s syndrome
- Cardiovascular disease
- Obesity with metabolic syndrome (obesity alone is not a risk factor)
- Gout
- Solitary functioning kidney
presentation of CKD
CKD is often asymptomatic, and it is often detected on routine blood tests. As kidney function decreases, symptoms may emerge including:
- Uraemia – accumulation of urea due to failure of renal clearance:
- Reduced appetite
- Nausea with or without vomiting
- Pruritus
- Restless legs
- If severe, patients may have seizures or coma
- Reduced urine output– may lead to fluid overload which may present with:
- Peripheral oedema
- Weight gain
- Orthopnoea
- Pulmonary oedema
-
Anaemia – due to reduced anaemia of chronic disease (AOCD) secondary to erythropoietin (EPO) deficiency:
* Fatigue
* Shortness of breath
* Headache - Foamy urine – due to proteinuria
- Dark urine – due to haematuria
investigations for CKD
- UEs and calcium
- Creatinine
- eGFR
- Urinary albumin: creatinine ration (ACR)
- Urine dipstick
CKD: Urea and electrolytes (U&Es) and calcium
– may identify initial abnormalities:
Urea is not a reliable marker of renal function as it varies with diet and hydration
CKD and creatinine
Creatinine – important for the estimated glomerular filtration rate
- May be falsely low/high (e.g. falsely elevated in those with high muscle mass)
- It may remain normal despite losing over 50% of renal function.
- Serum sodium may be normal or low
- Serum potassium may be elevated
- Serum calcium may be low, normal, or high
CKD: Estimated glomerular filtration rate (eGFR)
– assesses kidney function:
Since creatinine is not reliable on its own, eGFR may be used, which is a formula based on serum creatinine, age, gender, and ethnicity
Patients should avoid eating meat for at least 12 hours before collecting creatinine measurements
AKI Urinary albumin:creatinine ratio (ACR)
To assess proteinuria:
- This test avoids the need to collect urine over 24 hours to quantify proteinuria
- Ideally should be performed with an early morning sample for a more accurate result
Results
- <3 mg/mmol – no proteinuria, no action needed
- 3-70 mg/mmol – clinically significant proteinuria, repeat within 3 months
- ≥70 mg/mol – significant proteinuria
CKD and urine dipstick
- Urine dipstick – to check for haematuria:
- ≥1+ blood: arrange mid-stream urine (MSU) sample to rule out a urinary tract infection (UTI)
- Isolated persistent haematuria (2/3 dipsticks show ≥1+ blood and no decrease in eGFR and proteinuria): rule out urological malignancy
CKD diasnosis
Diagnose CKD if eGFR is persistently <60 mL/min/1.73 m2 and/or proteinuria (ACR >3 mg/mmol) is present for at least 3 months.
CKD can be excluded if eGFR is persistently >60 mL/min/1.73 m2 and/or no proteinuria (ACR <3 mg/mmol) and no markers of kidney damage.
CKD classification
major cause of death in CKD patients is
cardiovascular disease
management of CVD in CKD
- statins
- antihypertensives (ACEi or ARB)
- diabetic control
what immunisations should patients with CKD receive
- CKD stage 3, 4, or 5: offer annual influenza vaccination
- CKD stage 4 or 5: offer 5-yearly pneumococcal vaccine
complications of CKD
- Anaemia
- ]Minerala nd bone disorders
- Metabolic acidosis
- End-stage renal disease
others
- hyperkalaemia
- peripheral neuropathy and myopathy
- increased risk of malignancy
why does anaemia occur in CKD
ANaemia occurs once eGFR is <60
- due to reduced EPO secretion
management of anaemia in CKD
- optimise iron status
- Erythropoietic-stimulating agents e.g. EPO
Mineral and bone disorders and CKD
Pathophysiology
Activation of vitamin D normally happens in the kidneys, however, in CKD this is reduced, leading to low vitamin D. The kidneys also normally excrete phosphate, therefore in CKD, more is retained, leading to hyperphosphataemia.
Low vitamin D leads to reduced calcium absorption and hypocalcaemia. Hyperphosphataemia removes calcium ions from the circulation and deposits them in the insoluble salt calcium phosphate, worsening hypocalcaemia.
Results in:Hypocalcaemia, low vitamin D, and hyperphosphataemia then cause secondary hyperparathyroidism (HPT).
This generally happens at CKD G3 and can lead to osteomalacia, osteopenia, osteoporosis, and osteosclerosis.
Management of mineral and bone disorders includes:
- 1st-line: reduce dietary phosphate intake
- Phosphate binders (e.g. calcium acetate)
- Vitamin D supplements (e.g. alfacalcidol, calcitriol)
Metabolic acidosis and CKD
This may occur as the kidneys are responsible for excreting excess H+. Oral sodium bicarbonate may be considered if eGFR is <30 mL/min/1.73 m2 (G4 or G5) and serum bicarbonate is <20 mmol/L.
management of End-stage renal disease
People with CKD stages 4-5 may need renal replacement therapy (RRT). This is either haemodialysis or a kidney transplant.
role of renal replacement therapy
- Clear metabolic toxins
- Normalise serum electrolytes
- Correct volume deficit
2 types of renal replacement therapy
intermittent therapy e.g:
- haemodialysis
- Peritoneal dialysis
Permanent
- Renal transplant
how haemodialysis work
The dialysis machine pumps blood from the patient, through disposable tubing, through a dialyser, or artificial kidney, and back into the patient. Waste solute, salt and excess fluid is removed from the blood as it passes through the dialyser.
advantages and disadvantages of haemodialysis
Advantages
- Efficient form of dialysis
- Unit-based – plenty of support from staff
Disadvantages/Complications
- Dialysis access needs to be secured
- Infection/Bacteraemia
- Haemodynamic instability
- Reactions to dialysers
- Haematomas/risk of bleeding
- Muscle cramps
- Anaemia due to clotted lines/Haemolysis
- AVF steal syndrome
- SVCO from central lines
types of haemodialysis
Types
Home HD– offer training at home for more frequent HD
Nocturnal HD– Overnight slow, long HD
CRRT – continuous renal replacement therapy mainly used in acute setting (ITU/HDU)
Peritoneal dialysis
How it works
- Home based therapy
- Reliant on the patients’ own peritoneal membrane acting as the dialysis membrane.
- Solutes (electrolytes, urea, creatinine) move from the patient’s blood, across the peritoneal membrane, down the concentration gradient into the dialysate fluid.
- Osmotic gradient is created by high concentration of glucose (occasionally amino acid or glucose polymer solutions are used) in the dialysate fluid, which removes water from the patient.
advantages and disadvantages of peritoneal dialysis
Advantages
* Quality of life
* It is often an excellent first choice for patients starting dialysis, particularly when they still have some residual native renal function
* PD regimes are designed on a much more individualised basis than patients on HD.
Disadvantages
* Patients need to be able to manage technical aspects of dialysis
* Unsuitable in patients with stoma/previous surgery
* Risk of infection (PD peritonitis)
* Complications – drainage problems, malposition, leaks, herniae, hydrothorax, long term use associated with encapsulating peritoneal sclerosis
types of PD
Types
Automated PD
- Carried out with an automated cycler machine performed at night.
- 10-12L usually exchanged, over 8-10 hours.
- Lifestyle advantages – Leaves the daytime free
Continuous Ambulatory PD
- Usually consisting of 4-5 dialysis exchanges per day (usually 2 litres each)
- Exchanges are performed at regular intervals throughout the day, with a long overnight dwell.
Assisted Automated PD
Trained healthcare assistants visit the patient’s home to help with setting up APD.
Getting blood out of a patient for dialysis
1) Creating a venous fistula for haemodialysis
2) Central venous line
Creating a venous fistula for haemodialysis
Process
- Take radial artery and join it up with cephalic vein and overtime the cephalic vein becomes arterialised
- This can them be used to cannulate x3 times per week
- Will be able to feel a thrill and hear a bruit
2) Central venous line
Blood can be taken a t a flow rate of 200ml/minute from the superior vena cava.
- High risk of infection from skinendocarditis
advantages and disadvantages of renal transplant
Advantages
* Near normal lifestyle
* Better mortality/morbidity
Disadvantages
* Criteria to meet suitability to safely undergo operation
* Compliance with medication lifelong
* Risk of rejection
* Risk of malignancies over time
* Risk of infection (on immunosuppression)
o CMV, hepatitis B, herpes, varicella zoster, EBV, aspergillus, pneumocystis jiroverccii, listeria, MTB
* Long waiting times for cadaveric organ
* New onset diaebetes
types of donor
Living related donor
- Best
- Good compatibility
- Time to transplantation can happen in months
Living unrelated
4 forms:
- Live-donor paired exchange,
- Live- donor/deceased-donor exchange,
- Live-donor chain,
- Altruistic donation
- Usually have comparable outcomes to live-related donors
- Time to transplantation can happen in months
Deceased donor
Approximately 60% of the transplants in the UK fall into this category
Patients receive a kidney (or two from the same donor) with little time for preparation, so transplant protocols are important to keep updated regularly
Time to transplantation happen in years
Survival of kidney allograft and patients are significantly low compared to live donor transplantation.
Contraindications for kidney transplantation
- Active infection or malignancy
- Severe heart disease not suitable for correction
- Severe lung disease
- Reversible renal disease
- Uncontrolled substance abuse, psychiatric illness
- On-going treatment non-adherence
- Short life expectancy
induction for transplant
Immunosuppressive drugs to create tolerance of the graft
- Methylprednisolone with any of the following:
- Basiliximab
- Thymoglobulin
Maintenance : Prevent acute rejection
- Steroids: prednisolone
- Calcineurin inhibitors (CNI): tacrolimus, cyclosporine, voclosporin
- Antimetabolite medications: mycophenolate, azathioprine
- T cell regulation: belatacept and belimumab
long term care renal transplant
- Regular follow ups
o GFR
CNI levels
o Proteinuria
o Calcium, phosphate and PTH
o Lipids
o Glucose - Screen for infections
- Vaccination (except live or live attenuated)
- Monitor and control CVD
- Screen for malignancies
- Contraception obligatory in first yes and counsel about pregnancy one year after
transplant mortality related to
- Cardiovascular disease
- Infections
- Malignancy
indication for haemodialysis
Acute indications
Acute indications for haemodialysis include complications of a severe acute kidney injury (AKI). These indications can be remembered using the mnemonic AEIOU:
- Acidosis that is severe and unresponsive to initial treatment
- Electrolyte abnormalities – hyperkalaemia that is severe and unresponsive to initial treatment
- Intoxication – overdose of certain drugs (such as aspirin, methanol, and ethylene glycol)
- Oedema – severe pulmonary oedema that is unresponsive to initial treatment
- Uraemia and its complications – uraemic pericarditis or uraemic encephalopathy
Chronic indications
NICE recommends considering starting dialysis if any of the following apply:
- The symptoms of uraemia affect activities of daily living
- Uncontrollable fluid overload
- Uncontrollable biochemical measures (e.g. electrolytes)
- Estimated glomerular filtration rate (eGFR) is around 5-7 mL/min/1.73 m2 if there are no symptoms
Renal transplant rejection
describes immune-mediated inflammation in a transplanted kidney due to the recipient’s immune system recognising the graft as non-self. It can be divided into different types based on the immunological mechanism:
- Hyperacute rejection (within minutes to hours)
- Acute graft failure (<6 months)
- Chronic graft failure (>6 months)
HLA, MHC, and matching
Renal transplant matching is done using the human leukocyte antigen (HLA) system (also known as major histocompatibility complex, MHC), which is encoded on chromosome 6. There are two classes of HLA (MHC), both with different roles and antigens:
- HLA (MHC) class I – has -A, -B, and -C antigens
- HLA (MHC) class II – has -DR, -DP, and -DQ antigens
- When matching for renal transplants, the HLA-DR antigens are most important, followed by HLA-B, and HLA-A.
Hyperacute rejection
occurs due to pre-existing antibodies in the recipient’s blood against the donor antigen (usually ABO blood group or HLA antigens). This leads to a type II hypersensitivity reaction causing polymorphonuclear cell infiltration, thrombosis, and necrosis of renal tissue.
Hyperacute rejection generally happens within minutes to hours following the transplant and no treatment is possible. The graft must be removed.
Acute graft failure
Acute graft failure occurs within 6 months of the transplant and describes T-cell mediated rejection of the graft.
It is usually asymptomatic and characterised by:
- Deranged urea and electrolytes
- Proteinuria
- Pyuria – white cells present in the urine
- Acute graft failure may be reversible with immunosuppressants.
Chronic graft failure
Chronic graft failure may occur due to both immune and non-immune-mediated factors. Causes include:
- Non-compliance with immunosuppressive medication
- Recurrence of the original disease (e.g. IgA nephropathy and focal segmental glomerulosclerosis)
