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 levelsRenal 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

Further Resources

September 2022
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