Kidney Transplant Medicine

Trey Richardson

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Introduction

• The goal of this section is to serve as a guide for tackling the most common transplant complications as well as offer a few tips for managing immunosuppression while kidney transplant patients are admitted to the hospital

Alphabet soup

• PRA: panel reactive antibodies

• DSA: donor specific antibodies

• CMV (-/+): indicates the CMV status of both the recipient and the donor

• FK506 or FK: another name for tacrolimus

• KDPI: Kidney donor profile index used to “grade” the quality of the donated organ

• X/6 MM: indicates the number of HLA subtypes that are mismatched between donor and recipient

Infections in Kidney Transplant Recipients

Background

• Infections in a kidney transplant recipient can be divided into 3 phases:

• \<1-month post-transplant

  • Surgical site infections, nosocomial infections (e.g. C. Diff, CAUTIs, and CLABSIs), and donor-derived infections/reactivation of latent recipient infections predominate

• 1-6 months post-transplant

  • Depleted immune-system regenerates increased risk for disseminated fungal (e.g. PJP, histo/blasto) and viral infections (HSV, adenovirus)

• >6 months post-transplant

  • Risk for atypical infections persists, but common community acquired syndromes should still be on the differential

• This section will focus on the most common infection in kidney transplant recipients- infections of the urinary tract

Evaluation

• UA with culture 

• Examine the native kidneys (CVA tenderness) AND the allograft (almost always in RLQ, denervated so the graft itself will not be tender, but the surrounding soft-tissue may)

• Renal U/S (of both allograft and native kidneys) or CT AP if:

  • Early post-op (1 month)

  • Recurrent (2+ episodes in year)

  • History of nephrolithiasis or if sepsis/bacteremia

• Blood cultures if systemic signs/symptoms

• Consider testing for C. urealyticum, and sending fungal and AFB urine cultures if UA is recurrently positive but culture negative

Management

• Remove or replace indwelling catheters

• Review prior culture susceptibilities (if available)

• Empiric antibiotic regimens:

  • Asymptomatic bacteriuria: treat with FQ or beta lactam for 5-7 days if \<3 mos post-transplant

  • Simple cystitis: Fluoroquinolones (ciprofloxacin 250 BID or Levaquin 500 mg daily), Augmentin (500 mg BID), 3^rd gen cephalosporin (cefpodoxime 100 mg BID or cefixime 400 mg daily) or nitrofurantoin 100 mg BID (if GFR>30, only treats cystitis since drug only concentrates in the urine)

    • \< 6 mos post-transplant: treat for 10-14 days

    • >6 mos post-transplant: treat for 5-7 days

  • Complicated UTI/Pyelonephritis (cover Pseudomonas, gram negatives and Enterococcus): Ceftriaxone 2g daily (preferred), Cefepime 2g q8hrs (add Vancomycin when using cephalosporin if suspicious for enterococcus) or Pip-tazo 3.75g q6hrs, can also use meropenem 1g q8h (need ID approval)

    • Treat for 14-21 days

    • For stable pts with mild complicated UTI, can consider giving more narrow empiric antibiotics: Augmentin 875 mg BID or ciprofloxacin 500 mg q12h

  • MDR UTI: Consult transplant ID

    • Options: meropenem-vaborbactam, ceftolozone-tazobactam, ceftazidime-avibactam

  • In pts w/PCKD, include lipophilic antibiotic (such as ciprofloxacin) to penetrate cysts

Prevention

• Bactrim used for PJP prophylaxis during first 6 mos post-transplant also prevents UTIs

• Basic infection prevention measures for all comers (e.g. hydration, frequent voiding, wiping front to back, voiding after sexual intercourse)

Rejection - See Kidney Transplant Rejection section

AKI - See AKI of Kidney Transplant Section

Kidney Transplant Immunosuppression

Background

• Most patients with kidney transplants are on triple therapy with an anti-metabolite (azathioprine or mycophenolate compound) or mTOR inhibitor + calcineurin inhibitor + prednisone

• You may also come across patients who are on monthly infusions with belatacept, a selective T-cell co-stimulation blocker

Calcineurin inhibitors

• Tacrolimus (FK), cyclosporine (CsA)

• Envarsus XR is a once a day long acting formulation of tacrolimus

  • Common side-effects

    • Worsening kidney function: mediated by vasoconstriction to the afferent arterioles

    • Hypertension- treat with CCBs

    • Diabetes

    • Hand tremors, headache, nausea

    • Thrombotic microangiopathy

    • T4 RTA- hyperkalemia

    • Gingival hyperplasia

mTOR Inhibitors

• Sirolimus, everolimus

  • Major side effects: Poor wound healing, rarely pneumonitis

Anti-metabolites

• Azathioprine

• Mycophenolate preparations: Mycophenolate mofetil (Cellcept, MMF), Mycophenolic acid (Myfortic)

• Side effects: Bone marrow suppression- hold for lymphopenia; GI upset- hold for diarrhea

Additional Information for Overnight Admits:

• Do not change immunosuppression

  • Exception: If pt has severe diarrhea, can hold night tacro dose and inform the day team

• Daily tacrolimus or cyclosporine level (order qam at 5:00). Always order tacrolimus or cyclosporine dose at 6:00 am and 6:00 pm (regardless of what time patient takes at home, lab can only run am tacro levels at a certain time in batches)

  • EXCEPTION: If late afternoon admission, consider paging the fellow (since its early) and ask if they want the evening dose held until the am level comes back

• Transplant patients with normal kidney function can have regular diet