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

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

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

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

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

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

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

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

16. Recurrence of Sarcoidosis in Transplants u Described in lung allografts (eg Milman et al, Eur Resp J, 2005) u Described in hepatic allografts (eg Hunt J et al, 1999; Cezig C et al 2005, Abraham SC et al 2008) u 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 u 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 u Some cases detected on protocol biopsy u Lymphocytic tubulitis common u In one case (Shea SY et al)- there was granulomatous uveitis and arteritis, and positive tuberculin skin test- ?!? u Treatment with steroids usually efficacious- must rule out infection

18. Case – Follow-up u 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 u Readmitted for acute arterial clot- placed on Coumadin u In mid-February, admitted for HSV esophagitis- begun on Acyclovir; creatinine 3.3 improved to 2.7 u By April 2011 – creatinine 1.7 u In July 2011- creatinine 1.6; still on Coumadin- no kidney re-biopsy performed

19. u THANK YOU