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Intro
- You’re at Sinai – and your patient is a renal transplant patient. Classic. What do you do?
- “Don’t you just call renal transplant?” – Amy Ahn.
- Yes, you should definitely call them. But there’s other things to consider – see below for today’s TR pearls
Tl;Dr – (<5 minutes)
- Most commonly transplanted organs: Kidney >> liver >> heart > lung > pancreas
- Most patients are on LIFE-LONG immunosuppression and on some variant of 3 medications: Calcineurin inhibitor (ie, Prograf) + Antimetabolite (ie, Cellcept) + Steroids (+/- antimicrobial prophylaxis)
- Transplanted kidneys are often in the abdomen, the R>L iliac fossa – so abdominal tenderness (not flank tenderness) can be a problem with the transplanted organ
- Fever is the most common sign/symptom of infection; 50% of patients, especially those on mycophenolate (Cellcept) & azathioprine (Azazan) will not have a fever!
- Studies in transplant patients show incidence of 15-28% ESBL UTIs – Ceftriaxone as single agent has zero Enterococcus/ESBL coverage, and vanc/zosyn doesn’t cover all ESBL organisms! Carbapenems such ass meropenem or imipenem are the gold standard therapy if you’re worried about ESBL/severe infection
- Limited, small studies have not shown benefit in treating asymptomatic bacteriuria in renal transplant patients (in the form of reduced UTI risk or maintenance of renal function)
- If you see a nonspecific rash = think possible graft-v-host reaction
- For renal transplant patients – consider UA/UCx (note – sterile pyuria may be a sign of rejection); Cr, Tacrolimus/Cyclosporine levels, Renal US with doppler
Extended Pearls – (>5 minutes)
- Most commonly transplanted organs: Kidney >> liver >> heart > lung > pancreas
Important Parts of the H&P:
- When was the transplant and reason for transplant? – ESRD 2/2 to DM w/HTN is the most common reason for transplant (75%), but others include: glomerulonephritis, sickle cell, polycystic kidney disease
- Graft source? Cadaveric vs living donation – living donor kidneys often function better and function immediately, while 30% of cadaver transplants undergo delayed graft function
- Any rejection hx? & changes in meds & compliance – to see if rejection should be higher on your ddx, as well as medication side effects
- Most patients are on LIFE LONG immunosuppression and on some variant of 3 medications: Calcineurin inhibitor + Antimetabolite + Steroids +/- prophylaxis. This is often times Prograf, Cellcept, and Prednisone
- Calcineurin inhibitors: Tacrolimus aka Prograf AKA FK506; Cyclosporine AKA Neoral; or Sirolimus aka Rapamune – Tacrolimus is often the standard of care for most patients, and is DOSED by level & fairly toxic with lots of systematic effects including nephrotoxicity, so check the level.
- Antimetabolites: Mycophenolate Modefinl aka Cellcept; Azathioprine aka Imuran – these are often NOT dosed by level but can also cause toxicity
- Systemic steroids (prednisolone): first are given in high doses, then tapered
- Do they have any chronic infections (CMV, EBV, Hepatitis B/C, etc) and take pphx antibiotics?
- Some patients are on antimicrobial prophylaxis short-term to prevent infection; ie Bactrim (UTI/PCP prophylaxis); Acyclovir or valganciclovir (HSV/CMV prophylaxis)
- Physical Exam
- Remember renal transplant patients have their kidneys in their abdomen, usually the R>L iliac fossa & have their ureter sutured to side of the bladder -> this can distort anatomy and cause complications!
- Fun fact: Routine for the transplanted ureter to be stented – the stent stays in for the first 6 weeks and then is removed!
Consider these possibly life threatening transplant complications:
1 – Transplant infection – most frequent complication!
- Fever is the most common sign/symptom of infection; but 50% of patients will not have a fever! Especially those on Mycophenolate (Cellcept) & Azathioprine (Azazan)
- Not all fever is an infection! Consider rejection, malignancy, GVHD, as well as drug effects/toxicity
- Timeline of transplant is important!
- If EARLY <1 month post transplant, think nosocomial infections, SSI, UTI, donor infections
- If intermediate, 1-6 months – think: opportunistic infections & reactivation of dormant host infections – ie. Herpesviruses (CMV, HSV, VZV), PCP, HEP B/C, etc
- PCP: Subacute dyspnea, hypoxemia, fevers – Txt: Bactrim (15-20 mg/kg/day q6h)
- CMV: fever, leukopenia, flu-like generalized infection with end organ disease. Pneumonitis is the most common presentation, but can also see hepatitis, pancreatitis, colitis with diarrhea – Txt: Valganciclovir vs IV ganciclovir (C/s ID)
- EBV: asymptomatic viremia to a mononucleosis-like syndrome that includes fever, malaise, lymphadenopathy, and even hepatosplenomegaly
- Late >6+ months – think community acquired infections, as well & opportunistic infections – CAP, UTI, viral, JC/PML, EBV, CMV, etc
- UTI is the most common source of bacteremia in renal transplant patients – this occurs in up to 20% of renal transplant patients at 1 year & frequent UTIs can lead to decreased graft survival
- Order cultures and guide your treatment based on it, as studies in transplant patients show incidence of 15-28% ESBL UTIs
- Ceftriaxone as a single agent has zero Enterococcus/ESBL coverage, and vanc/zosyn doesn’t cover all ESBL organisms! Carbapenems such ass meropenem or imipenem are the gold standard therapy for ESBL/severe infections.
- Limited, small studies have not shown benefit in treating asymptomatic bacteriuria in renal transplant patients (in the form of reduced UTI risk or maintenance of renal function)
- BK Virus: Nephritis with AKI, urethral stenosis, hemorrhagic cystitis – txt: decrease immunosuppressant
2 – Medication side effects & toxicity
- Calcineurin inhibitors: Tacrolimus aka Prograf AKA FK506; Cyclosporine AKA Neoral; or Sirolimus aka Rapamune = lots of side effects including hyperkalemia/nephrotoxicity, headache/seizure, hypertensive crisis/PRES, tremors
- Antimetabolites: Mycophenolate Modefinl aka Cellcept; Azathioprine aka Imuran = anemia, thrombocytopenia, n/v, GI issues
- NSAIDs – try to avoid, as these can worsen kidney injury!
- Fun fact: immunosuppressants along with corticosteroids can cause de novo diabetes in 5-20% of renal transplant recipients!
3 – Rejection/Graft failure –
- Most common presentation is hypertension and falling urine output, but can also see rise in Cr – this is defined as a 20% rise from their baseline, not 50% in non transplant patients
- Renal U/S with doppler will reveal increased graft size & high resistive indices (Normal transplant kidneys have an average resistive indices of 0.71 vs 0.77 in rejection)
- You can have nonspecific complaints as well such as graft pain, but 10-20% of patients are otherwise asymptomatic!
4 – Graft vs. Host Disease (GVHD)
- This is when donated T cells attack antigens on host cells! While extremely rare in solid transplants (~1%), these have high 75-100% mortality
- These can be acute or chronic!
- If you see a nonspecific rash = think graft-v-host
- Transfusion-associated GVHD is rare, but a fatal complication of blood transfusions!
- This is when immunocompetent T cells from the transfused blood are not eliminated by the recipient’s immune system, and then proliferate and attack organs. This can be fatal!
- While not all renal transplants patients need irradiated blood, those who are further immunocompromised/at risk – ie, taking purine analogs, have hx of stem cell transplant/leukemia/lymphoma – should receive irradiated blood components indefinitely to avoid this
5 – Post operative complications
- Post transplant lymphoproliferative disorder – most common post transplant cancer, lymphoma/mass ANYWHERE – neck, lungs, etc. If you see a new mass on imaging – think about this!
- Vascular complications – renal artery stenosis/thrombosis first month after transplant (12%), graft hematoma, allograft infarction, AV fistulas
- A renal transplant recipient in the first week post transplant with ARF may have occlusion of the transplant renal artery
- Non vascular complications – urethral obstruction, urine leak, fluid collections
- Urinary leak usually in the first transplant month, from disruption of the ureteric anastomosis to the bladder > extravasation of urine > acute renal failure
Workup and Mgmt considerations: In addition to your typical workup…
- For most patients – consider: UA/UCx (note – sterile pyuria may be a sign of rejection); BMP with Cr, as Cr can help you look for for rejection vs infection, Tacrolimus/Cyclosporine levels, Renal US with doppler, +/- BKV PCR
- For AMS/HA: Consider PRES (0.5%–5% of transplant recipients, mostly seen with tacrolimus), steroid psychosis, HSV/Listeria/Cryptococcal meningitis – CTH, +/- LP (CSF studies, HSV PCr, Crypto Ag)
- For SOB: Consider PCP – CXR +/- CT Chest, possible induced sputum, Legionella urine Ag, viral resp. Panel
- For Diarrhea: consider C. diff, other colitis including CMV – Stool Cx, O&P, C. diff PCR, CMV PCR
- For Leukopenia: consider: CMV PCR, EBV PCR, tick-borne w/u
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