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Nephrology (Long) > Renal transplant > Flashcards

Renal transplant Flashcards

1
Q

CKD/Transplant History (PRICMCP)

A

Take Hx with CKD+Transplant together.

P:

  • Primary kidney disease, disease duration, initial symptoms
  • Duration of dialysis prior to transplant
  • Transplant date, type (i.e. pancreas), indication, matching (HLA/ABO), the donor (CMV/decreased/live)

R: FH of primary kidney disease, secondary causes (e.g. HTN, DM, GN, analgesia, reflux, PCKD…etc)

I: renal biopsy if so when, why, what showed. Does the patient know the eGFR/Cr?

C:

  • CKD: Anaemia, Bone disease, HTN, CVD/PVD/CVA, PN/RLS, electrolytes, fluid overload, dialysis-related complications
  • Operation/Transplant: did you have to go back to theatre? ICU? duration of hospital stay? any complications you know of? Rejection? if so how soon after? Recurrence? Retransplanted?
  • Drugs: (MMMINS)
    • infection**
    • Metabolic - diabetes, OP, HTN, dyslipidemia, AVN
    • Malignancy - lymphoma, solid tumours, skin Ca
    • Macrovascular disease - IHD, Stroke, PVD (risk remains higher)
    • Nephrotoxicity
    • Specifics: Hirsuitism/Gingival [Cyclosporin], BM/GI [MMF], wound healing [mTOR].

M:

  • Dialysis: type, access, where - keep brief, unless currently on dialysis again.
  • Disease: depending on the primary disease
  • CKD complications:
    • A: EPO, iron supplements/infusion
    • B: ACEi, antihypertensives, Bone: Calcium/Vit D
    • C: diuretics, salt/fluid restriction
    • DE: resonium, phosphate binders, lyrica…etc.
  • Transplant: current regime, previous regime, any recent changes? (e.g. dose reduced due to BK virus…etc). Surveillance: malignancy, OP, vaccines

C: current GFR/Cr, symptoms of overload (weight gain) & uraemia (itchy, lethargy, anorexia/weight loss, chest pain, encephalopathy). Are they compliant?

P: insights into the complexity of transplant care - do they understand signs of rejection? if not, probable poor health-literacy, coping/managing?

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2
Q

Renal transplant - examination (7)

A

SCC/BCCs / Cushingoids

AVF - function. Will there be problems finding sites for access for further dialysis?

Old Vascath scars

Volume status

Mouth - candida / gum hypertrophy (CsA)

Allograft site & tenderness / bruits

Gouty tophy

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3
Q

What are the risk factors for long-term allograft failure? (8)

A

Categorise into pre, peri, post transplant factors.

•Pre-transplant factors

  1. Live or deceased
  2. Degree of HLA mismatch
  3. CMV serostatus

•Peri-operative factors

  1. Long cold-ischaemia time
  2. Episode of acute rejection

•Long term factors

  1. Recurrence of primary disease
  2. HTN, hyperlipidaemia, proteinuria
  3. Poor compliance
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4
Q

What are the complications of Tacrolimus? 5

A

•Mainly metabolic

  • HTN
  • Diabetes / NODAT (new onset diabetes after transplantation)
  • Hypercholesterolaemia
  • Nephrotoxicity
  • Pure Red Cell Aplasia
  • Poor wound healing
  • Prolonged QTc
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5
Q

5 side effects of Cyclosporin?

A

•Metabolic

  1. HTN
  2. Dyslipidaemia
  • Nephrotoxicity
  • Neuropathy
  • Hirsuitism
  • Gingival hyperplasia
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6
Q

What are the main complications of MMF? (2)

A
  • GI upset – diarrhoea, dyspepsia
  • BM failure – leukopaenia, anaemia
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7
Q

Main complications of mTOR inhibitors (5)?

A

•Metabolic

  • Diabetes / NODAT
  • HTN
  • Hyperlipidaemia
  • Nephrotoxicity
  • GI: diarrhoea
  • Poor wound healing: must be stopped before surgery
  • Pneumonitis
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8
Q

What are the absolute contraindications for kidney transplant? - General 6. Specific 3.

A

Active infection

Active cancer (2 years of remission - considered)

Active substance abuse

Adherence - documented non-adherence

Uncontrolled psychiatric disease

Significantly shortenend life-expectancy

Specific to renal transplant

Severe ischaemic heart disease

Active vasculitis or anti-GBM disease

Occlusive aorto-iliac disease

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9
Q

What is the general recommended trough level for tacrolimus

A

7-10 ng/ml for 1st month, then 3-7 thereafter

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10
Q

What side effects of medications would you ask for in renal transplant patients? (6, except for steroid complications)

A

MMMINS

  • Infection**
  • Metabolic - diabetes, OP, HTN, dyslipidemia, AVN
  • Malignancy - lymphoma, solid tumours, skin Ca
  • Macrovascular disease - IHD, Stroke, PVD (risk remains higher)
  • Nephrotoxicity
  • Specifics: Hirsuitism/Gingival [Cyclosporin], BM/GI [MMF], wound healing [mTOR]
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11
Q

What are the differentials of weight loss in transplant patients (5) – what’s your approach?

A

Malignancy, Malabsorption, Intentional (to minimise metabolic complications of drugs), CMV colitis, drugs (MTX) - remember 4 M’s.

Work-up

Clarify in history - any previous MTX use, intentional weight loss? depression?

Bloods: FBC (anaemia), iron studies (IDA), B12 (pernicious anaemia), folate (raised in SIBO). LDH, beta-2 microglobulin, blood film (haematological malig). EBV viral load (PTLD), CMV serology/VL, TTG/IgA (coeliac). Big 6 initial test for mal-absorption (iron studies, coags, CMP, lipids, carotine, Sudan stain for stool fat). Consider tumour markers.

Imaging: AXR (blinded loops of bowel - SIBO, pancreatic calcification), CT-CAP and GIT endoscopy (looking for malignancy).

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12
Q

What is your approach to worsening GFR in kidney transplant patients? Start by listing differential diagnosis (including 5 causes specific to renal transplant)

A

DDx can be divided into transplant specific vs. general pre/intrinsic/post-renal causes.

Transplant specific causes include…

  • Rejection / graft failure
  • Recurrence of original disease
  • CNI toxicity
  • BK nephropathy
  • CMV nephritis

General causes include…

  • Pre-renal: RAS, any cause of hypovolaemia - sepsis, cardiac failure, bleeding…etc.
  • Intra-renal: GN, infection (pyelonephritis), AIN (drug induced)
  • Post-renal: obstructive uropathy

Work-up

  • Routine bloods: FBC (anaemia, infection), EUC (trend), LFT, CRP (infection)
  • Special bloods: Drug levels e.g. tacrolimus troph, cyclosporin levels, Virology: BK PCR, CMV serology & PCR. Disease bloods - e.g. C3/4, dsDNA for lupus
  • Urine: ACR, PCR looking for proteinuria, wcc/rbc casts/blood (nephritis), decoy cells (BK)
  • Imagings: USS + doppler (obstruction, RAS), CTKUB
  • Kidney Biopsy
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13
Q

How would you balance the risk of immunosuppression and infection?

A

Key principles - initial spiel.

  • Aknowledge that this is a difficult management issue, because at one side you have a risk of significant end-organ damage (or threaten an allograft) but on the other side there is a significant risk of morbidity/mortality of infection.
  • The most important thing is to establish/quantify the risk associated with each variables of the equation
  • Always discuss with the patient the risk and benefit

Firstly I would assess he risks posed by infection - I would ask myself…

  • How acute & severe is he infection? - are there marker of organ dysfunction? - e.g if graft funtion is immediately being thretenened but infection is mild, can we increase the immSx? → manage the rejection first whilst watching carefully for signs of worsening infection?
  • Can infection be treated without decreasing ImmSx? (for some it is harder, such as BK virus)

Secondly I would assess he risk posed by decreasing immunosuppression

  • Is the graft functin stable or deteriorating? is there an active need for immunosuppression?
  • If so, how severe is it? or has been severe in the past? (predictive of severe phenotype on reducing immSx)
  • Are there other alternative drugs?

Thirdly I wold address modifiable risk factors

  • Prophylactic anti-microbials if immSx would be increased
  • _Exclude contributary/secondary cause_s - e.g. HIV, secondary hypogamma → screen for Ig deficiency and IVIG
  • Ensure vaccinations upto date
  • Avoid contact, hand/food hygiene
  • Smoking cessation (contributes to immSx)
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14
Q

What are the causes of leukopaenia/bi/pancytopaenia in renal transplant patient (5)?

A
  • Immunosuppressants: MMF, Azathioprine, Cyclophosphamide (not CNIs)
  • _Bactrim, Valganciclovir**_
  • Infection / Sepsis
  • Malignancies - BM infiltration (e.g. MM, infiltrating malignancies)
  • Chronic Liver Disease: can cause pancytopaenia
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15
Q

How should you approach pretransplant cardiac assessment for renal transplant recipients?

A
  • Risk stratify using traditional risk factors
  • Low-risk patients need no stress testing
  • Medium or high-risk patients should undergo stress testing with stress echo or MPS (stress ECG should be avoided in dialysis patients)
  • Positive stress tests should prompt ‘consideration’ of coronary angiography
  • Revascularisation should be considered on a case-by-case basis
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16
Q

What qualifies a patient with ESRF as low cardiovascular risk? (5)

A

Age < 50

No angina

No heart failure

No diabetes

Normal ECG

17
Q

Why are guidelines about revascularising Pts with ESRF before transplant so equivocal? (i.e. ‘consider’ treatment)

A
  1. Because there is no solid evidence that revascularising patients with significant coronary artery disease improves their outcome post-transplant
  2. Because risks of PCI and CABG are higher in people with ESRF
  3. The decision should be based on the perioperative risk of an ischaemic event (based on anatomy) vs. bleeding (if on DAPT)
18
Q

A Pt with ESRF due to diabetes is being listed for transplant. How should diabetes factor into your management? – i.e. what are the key Mx problems? (5)

A
  • Cardiovascular risk assessment
  • Pancreas – renal transplant (if TIDM)
  • Control of DM once transplanted (in context of drugs that worsens BSL control)
  • Elevation of infection risk post-transplant
  • Diabetic nephropathy – high chance of recurring & hence requires aggressive Mx strategy
19
Q

What criteria need to be met for HIV patients to be eligible for renal transplant?

A

Adherence to a highly active antiretroviral therapy (HAART) treatment protocol

  • Although Pts with persistent negative viral load off treatment may be considered (rare)

no recent change to anti-retrovirals within 3 months

Undetectable viral load for at least 3 months

CD4 count >200/μL for at least 6 months

20
Q

What is your approach to managing HBV and HCV infection in ESRF patient being listed for renal transplant?

A

Refer to hepatologist early.

  • Look for complications – cirrhosis, HCC
  • Treat HBV as per usual standards – if evidence of chronic hepatitis but no decompensation; treatment can be continued post-transplant
  • Treat HCV with DAAs prior to transplant if possible
  • Consider liver-kidney transplant in patients with decompensated cirrhosis
21
Q

How should you approach malignancy risk in patients awaiting transplant who DON’T have a previous diagnosis of cancer?

A

•Age and gender-appropriate screening prior to transplant only

(no need to scope your 40yo!)

22
Q

How should you approach obesity in a patient being considered for renal transplant? Would you support transplant in this patient?

A
  • Not an absolute contraindication, but reduces patient and graft survival compared with non-obese patients
  • Presents a higher perioperative risk
  • No advantage to transplant over dialysis for BMI > 40
  • CV risk assessment and investigation as indicated
23
Q

How would you diagnose acute rejection and how wuld you manage it depending on its type (2)?

A

T-cell mediated (more common) or Ab-mediated

Diagnosis by Biopsy

Cellular rejection: methylprednisolone 250mg-1g x 3-5 days (reverses 90%) - if steroid resistant, use anti-T cell Abs (ATG or OKT3)

This reverse 75% of steroid resisant rejection → if still refractory, use high dose Tacrolimus and Mycophenolate.

Ab-rejection: IVIG / Plasmaphresis

24
Q

What is the prognosis of kidney transplant?

A

50% 15-year graft survival

25
Q

What are the symptoms of alograft rejection in renal transplant? (5)

A

Fever

Tenderness + swelling over the graft

Reduction of urine volume

HTN

Pyuria/proteinuria

Patient shuld be awaer of al these signs.

26
Q

What are the typical immunosuppressive regime post transplant?

A

Most common combination is Prednisolone, MMF and Tacrolimus.

mTOR are increasingly being used - check if CNI was ceased and why (especially renotoxicity)

Usually induction = Triple therapy + Basiliximab (IL2R ab)

Maintenance = Triple or Dual therapy

27
Q

This patient is on Sirolimus or Everolimus. If surgery is planned in future, what would be the concern hence how would you approach it?

A

mTORs are associated with poor wound healing.

I would consider replacing these with alternative agent such as tacrolimus and aim to restart mTOR 1-3 months later.

28
Q

What is the usual prophylaxis antimicrobial regime post transplant? (3)

A

Valganciclovir for 1st 6 months

Trimethoprim-sulfamethoxazole indefinitely

Consider Fluconazole

29
Q

What is the general Mx for opportunistic infections in transplant patient?

A

Infections must be aggressively diagnosed (e.g. blood culture and biopsy) and treated.

If infection is severe/life-thretening, immSx should be ceased, except for Steroids.

30
Q

How would you manage acute rejection?

A

Biopsy would show T-cell infiltrate

Usually occurs days to months after transplant

Mx = pulse steroids, if refractory - ATG +/- increased MMF or CNI

31
Q

What are 2 main advantages of combined kidney-pancreas transplant over kidney transplant? (3)

A
  • Free of insulin & dialysis – much more freedom & QOL
  • Decrease in risk of recurrent diabetic nephropathy
  • Stabilization & improvement in neuropathy & retinopathy
32
Q

How would you monitor for failing simultaneous pancreas-kidney transplant? (4)

A
  • Absence of C-peptide
  • Elevated HbA1C
  • Lipase (pancreatitis)?
  • Recipient’s insulin use ≥0.5 units/kg/day (i.e. for 70kg man, more than 35 units per day) – not perfect as this could be due to medications or weight gain post-transplant (e.g. tacrolimus, steroids)
  • All are difficult and unreliable
33
Q

How would you approach pre-transplant evaluation for this patient? (5 domain)

A

Tissue typing - ABO compatibility. Incompatibility obviously affects graft survival, HLA A, B, DR

Cardiorespiratory: intermediate risk → stress test (dobutamine ECHO, stress MIBI), high risk → coronary angiogram, ABG, pulmonary function tests

Nutritional status: SGA

Infection/ malignancy status, screening for absolute contraindications

  • active/ disseminated malignancy
  • uncontrolled/ untreated infection
  • chronic infection
  • unacceptable anaesthetic risk

Psychosocial:

  • adherence/ compliance
  • insight
  • MH comorbidities
  • Social support
34
Q

What are the long-term complications specific to pancreas-kidney transplant? (1) so what medication do they need chronically?

A

Metabolic acidosis

  • SPK with bladder exocrine drainage → loses HCO3- rich pancreatic secretions into urine → NAGMA + hyponatraemia (due to volume depletion → ADH → replacement of solute rich secretion with free water) → they need chronic Sodibic therapy
  • Problem greatly reduced with enteric exocrine drainage
35
Q

BK nephropathy Mx?

A

Decrease immunosuppression

36
Q

Which 3 types of GN recur most often following transplant?

A

IgA, membranoproliferative and Anti-GBM.

37
Q

Diarrhoea in renal transplant - specific DDx?

A

CMV

MMF side effects

and other usual causes for diarrhoea (infection, malabsorption…etc).

38
Q

What is your approach to preserving renal transplant graft and follow-up? What is your approach to managing this patient with renal transplant?

A

This is a complex management problem that require continued education, encouragement and support.

Goals: prevent rejection, slow progression of disease, prevent complications of CKD and immSx

Confirm dx: primary CKD (biopsy), transplant details (DBD/Living, ABO, HLA, CMV.), current renal function (EUC/trend, UACR/UPCR).

A: identify & treat secondary causes & contributary/exacerbating factors

  • Compliance, r/o depression
  • Reversible causes: infection, HF, hypovolaemia, remove nephrotoxins, obstruction, hyper-Ca, hyper-Urate
  • Consider investigating for other secondary causes (AI, infection, myeloma, RAS)

Screen/investigate for complications

  • CKD: ABCDEF (anaemia, acidosis, bone, cardiac, neuro/RLS, electrolytes, fluid overload)
  • ImmSx: MMMINS

T: Non-pharm

  • Education: importance of adherence, infection risk & how to avoid them, signs of rejection, Cr/GFR, steroid complications
  • Avoid unnecessary NSAIDs & contrast, prevent hyperuricemia
  • CV risk factor Mx: weight loss, smoking cessation, exercise
  • Diet [aim Alb >35]: low Na (<6g/d)/K/Phosphate diet, minimize purine-rich food/beer that worsens hyper-uricaemia. Nephro supplement.
  • Infection prevention: vaccinations, avoiding contacts, hand/food hygiene
  • Discuss and provide written steroid plan
  • Transplant support groups

T: Pharm

  • Transplant
    • Optimise CV risks: lipid & BP control, statins, ACEi/BB/MRA…etc
    • Infection prophylaxis: indefinite Bactrim, consider Valganciclovir, fluconazole
    • Osteoporosis prophylaxis: Vitamin D, Calcium supplements, Denosumab
  • CKD
    • A: EPO, iron supplements (target Hb 100, ferritin >100, tSAT >20%), sodium Bicarbonate (titrate to Bicarb >22), watch fluid status
    • B: Ca/Vit D replacement, Calcitriol, phosphate binders to maintain Ca/phos at normal level tx OP, parathyroidectomy (if PTH >800-1000 persistently)
    • D: ensure iron replete, dopamine agonist for RLS (pramipexole, rotigotine)
    • E: phosphate binders, resonium [aim K < 6]
    • F: cautious use of diuretics based on fluid balance

Regular F/U and screen for complications

  • History and exam for CVD and malignancy (skin/LN/Solid organs)
  • ECG (IHD), urine MCS, ACR/PCR (infection, proteinuria)
  • Bloods: FBC (PTLD, BM failure), EUC (monitor graft function), LFT (MMF), CMP (hypercalcaemia), PTH/VitD, fasting lipids/glucose/HBA1C, drug levels, gamma globulins (MMF can cause it)
  • Imagings: DEXA, USS renal/doppler
  • Consider biopsy if signs of rejection
39
Q

What things would you need to review during a follow-up of patient with renal transplant?

A

Go from Hx, exam, bed-side, bloods, imagings, biopsy.

History and exam → skin Ca, volume overload, infection, BP, ensure patient is up to date with age-appropriate cancer screening

Bed-side → ECG (IHD), urine MCS, ACR/PCR, BSLs

Bloods → FBC (PTLD, BM failure), EUC (monitor graft function), LFT (MMF), CMP (hypercalcaemia), PTH/VitD, fasting lipids/glucose/HBA1C, drug levels, gamma globulins (MMF can cause it)

Imagings → DEXA, USS renal/doppler

Consider biopsy if signs of rejection

Nephrology (Long) (5 decks)

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