Case Presentation

1. Case Presentation Lorraine C. Racusen MD FASN The Johns Hopkins University School of Medicine

2. Case History – Pre-transplant • 52 y/o white female • H/O obesity, HTN, Hashimoto’s thyroiditis, multiple drug allergies • Diagnosed with CNS sarcoidosis in 2004, with pulmonary and renal involvement • Developed Stage IV CKD

3. Case History - Transplant • Pre-emptive compatible live donor transplant June 2009 • Highly sensitized – husband donated to a paired kidney exchange program to ensure an optimally matched donor • Post-transplant- creatinine decreased to 1.2 mg/dl at discharge

4. Case History – Post-transplant • Problems with urinary retention, UTIs – renal function remained excellent • In August 2010 – presented with a large incisional hernia and left adnexal cyst • Meds: Tacrolimus, MMF, prednisone, Exatimibe, metoprolol, oxycodone, Prilosec • In January 2011- admitted for hernia repair with mesh placement • “Incidental biopsy done during surgery

12. Pathology Findings • Glomeruli – focal ischemia only • Tubulointerstitium – intensely inflamed in 50%, mildly inflamed elsewhere- lympho- plasmacytic with focal eosinophils and numerous non-caseating granulomas with giant cells; early evolving fibrosis • Stains for fungi, AFB- negative • IP stain for PPV (SV40 large T antigen) negative

13. Pathology Diagnoses • Granulomatous interstitial nephritis consistent with recurrent sarcoidosis – R/O infection, R/O drug reaction • Lymphocytic tubulitis – cannot rule out cell-mediated rejection • Evolving interstitial fibrosis and tubular atrophy, moderate

14. Granulomatous IN - causes • Infection – bacterial (brucellosis, AFB), fungal • Drugs- antibiotics, allopurinol, furosemide, HCTZ, omeprazole, NSAIDs, bisphosphonates, carbamazepine, oxycodone • Tubulointerstitial nephritis with uveitis (TINU) • Oxalosis • Gout • Sarcoidosis • Idiopathic

15. Follow-up studies • Infection Stains for AFB, fungi negative Urine culture for fungi and AFB- negative Brucellosis titers- negative • Drugs Prilosec/omeprazole – IN may be very indolent clinically Oxycodone – reported in drug abuse cases using drug from suppositories – probably due to adulterant • TINU, oxalosis, gout- no relevant findings for these • Sarcoidosis – major possibility given the history

16. Recurrence of Sarcoidosis in Transplants • Described in lung allografts (eg Milman et al, Eur Resp J, 2005) • Described in hepatic allografts (eg Hunt J et al, 1999; Cezig C et al 2005, Abraham SC et al 2008) • A few cases in renal allografts (Shea SY et al 1986; Kakura S et al 2004, Brown JH et al 1992, Vargas F et al 2010 • Incidence of recurrence unknown – some cases are associated with organ dysfunction +/- hypercalcemia, but SOME DETECTED IN STABLE GRAFTS, as in this case

17. Recurrent sarcoidosis - Kidney • Some cases detected on protocol biopsy • Lymphocytic tubulitis common • In one case (Shea SY et al)- there was granulomatous uveitis and arteritis, and positive tuberculin skin test- ?!? • Treatment with steroids usually efficacious- must rule out infection

18. Case – Follow-up • After evaluation for infection, begun on high-dose steroid therapy with plan to re-biopsy after 8 weeks; also begun on Fluconazole for Candida esophagitis; discharge creatinine 1.2 • Readmitted for acute arterial clot- placed on Coumadin • In mid-February, admitted for HSV esophagitis- begun on Acyclovir; creatinine 3.3 improved to 2.7 • By April 2011 – creatinine 1.7 • In July 2011- creatinine 1.6; still on Coumadin- no kidney re-biopsy performed

19. THANK YOU