Renal III Flashcards
Renal biopsy, or trauma, is a risk factor for subsequent development of a []
Name two presentations that the above answer may present with [2]
Renal biopsy may cause renal arteriovenous malformations (AVMs)
most common presentation is with hypertension and haematuria
Describe the two immunological compatibility issues when it comes to transplantation [2]
Blood groups
HLA
Which type of GN is associated with renal transplants? [1]
Focal sclerosis glomerulosclerosis
What are two mechanisms that acute rejection occurs? [2]
(probably don’t learn that much)
Acute rejection can be either via:
Acute Cellular Rejection (ACR)
- Cytotoxic T lymphocyte response
- Macrophage response
OR
Acute Antibody Mediated Response (AMR)
- B lymphocyte response making antibodies (agaisnt MHC Class 1 /2 antigens or ABO blood group antigens)
Describe the features of acute graft failure:
- Why does it usually occur? [2]
- How does it present? [3]
- Prognosis? [2]
- usually due to mismatched HLA; also caused by CMV infection
- usually asymptomatic and is picked up a rising creatinine, pyuria and proteinuria
- potentially reversbile with steroid and immunosuppressant
What are the sites of action used for immunosuppressive drugs? [3] and what drugs used? [5]
Calcineurin inhibitors:
* Calcineurin is an enzyme that activates T-cells of the immune system.
* E.g. Cyclosporin and tacrolimus
Anti-proliferative drugs:
* (target nucleus at end stage of T cell activation)
* e.g. Azathioprine and Mycophenolic acid
Prevent cytokine (IL-2) gene activation
* Use cortiosteroids
* e.g. Prednisolone
Rapamycin: stops clonal expansion of T cells
Explain how can you prevent acute rejection of transplants? [2]
HLA matching (make sure that not positive for match)
Minimising ischaemia-reperfusion injury:
* Ischaemia causes upregulation of adhesion molecules, which increases adhesion of leukocytes when blood is reperfused.
* More leukocytes increases chance of rejection, SO try and limit ischaemia time.
* Cold ischaemia time: 12 hrs
* Warm ishaemia time: 1 hour
Describe the features of hyperacute rejection [3]
- Happens within minutes to hours of transplant
- Occurs due to pre-exisiting antibodies agaisnt ABO or HLA antigens (that have already been pre-activated)
- Leads to neutrophil inifiltration, intravascular coagulation and cortical necrosis
What is delayed graft function (DGF)? [1]
What does the risk of DGF increaese with? [1]
Delayed graft function (DGF) is defined by the need for dialysis in the first week after transplantation.
Risk increases with prolonged WITs and CITs (therefore is relatively rare with living donor grafts). Whilst most DGF kidneys eventually function, there is a recognised association with increased rejection rates and decreased graft survival rates.
Describe the AEs of the following drugs used in kidney transplantation:
- Immunosuppressants [2]
- Tacrolimus [1]
- Cyclosporine [1]
- Steroids [1]
- 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
Two doses of which drug are given after a transplant to prevent acute rejection [1]
Basiliximab is a monoclonal antibody targeting the interleukin-2 receptor on T-cells.
What increases the chance of having better kidney transplant outcomes?
Patient and donor kidneys are matched based on the human leukocyte antigen (HLA) type A, B and C.
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.
Which infections can occur secondary to immunosuppressant medication? [3]
Pneumocystis jiroveci pneumonia (PCP/PJP)
Cytomegalovirus (CMV)
Tuberculosis (TB)
State complications related to immunosuppressants w/ kidney transplants [5]
Ischaemic heart disease
Type 2 diabetes (steroids)
Infections are more likely, more severe and may involve unusual pathogens:
- Viral, e.g. cmv and warts (CMV affects 8-10% of all transplant recipients
- Bacterial infection especially of the urine (40-50% of female transplant recipients)
- Fungal infections such as pneumocystis
Non-Hodgkin lymphoma
Skin cancer (particularly squamous cell carcinoma)
When HLA matching for a renal transplant the relative importance of the HLA antigens are as follows []
When HLA matching for a renal transplant the relative importance of the HLA antigens are as follows DR > B > A
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Where do you find HLA Class I and HLA Class II cells? [2]
Describe the role of HLAs
HLA Class I is present on most cells in the body
HLA Class II is expressed on APCs and B cells, or some cells which are activated or injured
Role:
* HLA is responsible for presenting antigens to T cell receptor
* The T cell ‘sees’ the antigen sat in the groove of the HLA protein
State the two classes of HLA [2]
HLA Class I:
- HLA A
- HLA B
HLA Class II
- HLA DR
Name two monoclonal antibodies used as immunosuppressants in kidney transplant [2]
What is their MoA? [1]
Basilixumab
Daclizumab
Selectively block T cells via CD-25
Basilixumab
Daclizumab
Are two monoclonal antibodies used in kidney transplants. When are they administered? [1]
Given immediately after transplant: ‘induction’
Which drug class of immunosuppressants are at risk of creating NODAT (new-onset diabetes after transplantation)? [1]
Calcineurin inhibitors (tacrolimus & ciclosporin)
What is the first choice treatment for acute rejection of transplant? [1]
Prednisolone
To decrease infection risk, prophylaxis drugs for which two pathogens are given? [2]
CMV
Pneumocysitis jirovecii
What impact does kidney transplant have on CVD? [2]
3-5 increasae if premature CVD compared to general pop (but 80% less that dialysis
NODAT
BP increase
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What is the difference in organs implicated between lower UTI and upper UTIs? [3]
Lower: cystitis; prostatitis
Upper: pyelonephritis (kidney / renal pelvis)
What is abacterial cystitis / urethral syndrome? [1]
A diagnosis of exclusion with dysuria and frequency, without demonstrable infection
State 4 categoriesand examples of risk factors for UTIs
Increase in bacterial innoculation:
* sexual activity
* urinary incontinence
* faecal incontinence
Increased binding of uropathogenic bacteria:
- spermicide use
- decreased oestrogen
- menopause
Decreased urine flow
Increased bacterial growth:
- DM
- I/S
- Stones
- Obstruction
- Pregnancy
Pyelonephritis has a similar presentation to lower urinary tract infections plus the additional triad of symptoms [3]
Fever
Loin or back pain (bilateral or unilateral)
Nausea or vomiting
Renal angle tenderness on examination
If vaginal discharge is present, what is your most likely differential? [1]
PID
Which pathogen is the most common cause of UTI? [1]
Name two other causes
E. coli
Staph. saprophyticus
Klebsiella pneumoniae
How do you manage UTIs in non-pregnant women? [2]
If 3+ symptoms of cystitis and no vaginal discharge:
- 3 day course of trimethoprim or nitrofurantoin
- If fails, take a MSU and send for culture
How do you manage UTIs in pregnant women? [1]
Which drugs should be avoided [3] and in which semesters? [3]
Get expert help: associated with pre-term babies
Avoid:
* trimethoprim & ciprofloxacin in trimester 1
* nitrofurantoin in 3rd trimester
How do you manage UTIs in men:
- If lower UTI [2]
- If suspected prostatic involvement [1]
If lower UTI:
* 7 day course of trimethoprim or nitrofurantoin
If suspected prostatic involvement:
- Ciprofloxacin
- Cefalexin (the typical choice)
The typical duration of antibiotics is:
[] days of antibiotics for simple lower urinary tract infections in women
[] days of antibiotics for immunosuppressed women, abnormal anatomy or impaired kidney function
[] days of antibiotics for men, pregnant women or catheter-related UTIs
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
What risk does giving nitrofurantoin in 3rd trimester risk? [1]
Nitrofurantoin should be avoided in the third trimester as there is a risk of neonatal haemolysis (destruction of the neonatal red blood cells).
What risk does giving trimethoprim in 1st trimester risk? [1]
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.
UTIs:
Two things to keep in mind with patients that have significant symptoms or do not respond well to treatment are? [2]
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
NICE guidelines (2018) recommend which first-line antibiotics for 7-10 days when treating pyelonephritis in the community? [4]
Cefalexin
Co-amoxiclav (if culture results are available)
Trimethoprim (if culture results are available)
Ciprofloxacin (keep tendon damage and lower seizure threshold in mind)
