Most patients are on LIFE-LONG immunosuppression and on some variant of 3 medications: Calcineurin inhibitor (ie, Prograf) + Antimetabolite (ie, Cellcept) + Steroids (+/- antimicrobial prophylaxis)
Transplantedkidneys 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
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
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
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 alsosee 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
