—  SPECIALTY CONFERENCE  — Renal Pathology Tuesday, March 23, 7:30 PM Maryland Click the button above to add this event to your Itinerary Planner... Challenging Renal Transplant Biopsies Moderator: MARK HAAS Cedars-Sinai Medical Center Los Angeles, CA Disclosure: In accordance with ACCME guidelines regarding disclosure, the USCAP policy requires that faculty members who have a significant financial or other relationship with a commercial company, entity, or service (which will be discussed in this Symposium) must disclose this to attendees. The Academy also requires that speakers disclose any products that are not labeled for the use under discussion. The speakers listed below have indicated they have nothing to disclose. Panelists: IAN W. GIBSON, University of Manitoba, Winnipeg, Manitoba, Canada INGEBORG BAJEMA, Leiden University Medical Center, Leiden, Netherlands CYNTHIA C. NAST, Cedars-Sinai Medical Center, Los Angeles, CA SERENA M. BAGNASCO, Johns Hopkins University School of Medicine, Baltimore, MD LILLIAN W. GABER, The Methodist Hospital, Houston, TX Clinical histories are displayed below. For the fastest viewing of virtual slides, click: under each thumbnail image below. You must have Aperio ImageScope installed on your PC. If you do not already have Aperio ImageScope, Windows users with administrator privileges may download and install a free version in order to view USCAP Virtual Slides. Click the icon on the right to get your free copy:   Or, click on slide thumbnail images to view each slide in a Web-based slide viewer, which is somewhat slower. If you have any difficulties viewing these slides, email or call George Clay at +1.724.449.1137. Case 1 Submitted by: Cynthia C. Nast, Cedars-Sinai Medical Center, Los Angeles, CA Clinical Summary: History of Present Illness: 53 year old Filipino female with end stage renal disease thought to be secondary to long standing severe hypertension. She underwent a deceased donor transplant (39 hours cold ischemia time) and induction therapy included steroids, thymoglobulin and mycophenolate. On POD #6 she was steroid-free, and tacrolimus was begun on POD#10, with subtherapeutic levels until POD#15 at which time the serum creatinine declined from a peak of 5.2 mg/dl to 1.8 mg/dl. Five days later the serum creatinine increased to 2.7 mg/dl at which time she also experienced hypotension and had a urinary tract infection for which IV vancomycin was administered. Past Medical History: Severe hypertension as noted above with coronary artery disease. Remote history of tuberculosis. Medications: mycophenolate, tacrolimus, septra nightly, cipro, vancomycin, valcyte, sporanox, magnesium oxide, labetolol, diltiazem, catapres, minoxidil, hydralazine, Review of Systems: Noncontributory. Physical Exam: BP: 130/63 T: 97.8 HR: 62 RR: 16 Chest: clear Heart: regular rate, loud murmur Abd: nontender, well-healed incision, no herniation. Ext: 1-2+ bilateral lower extremity edema. Foley catheter draining clear urine Neuro: Alert and oriented Case 1 - Figure 1 PAS Case 1 - Figure 2 Jones Stain Case 1 - Figure 3 Jones Stain Case 1 - Figure 4 Jones Stain Case 1 - Figure 5 PAS Case 1 - Figure 6 PAS Case 1 - Figure 7 Jones Case 1 - Figure 8 IgM Case 1 - Figure 9 Glomerulus Case 1 - Figure 10 Peritubular capillary Case 1 - Figure 11 C4d Case 2 Submitted by: Serena M. Bagnasco, Johns Hopkins University School of Medicine, Baltimore, MD Clinical Summary: At the time of biopsy the patient was a 72 year old white male with past medical history of hypertension, and achalasia, found to have renal failure with serum creatinine 9 mg/dl, during hospitalization for chest pain. A native kidney biopsy showed “Necrotizing crescentic GN, c/w anti-GBM disease” with positive anti-GBM titer: 7.7 U/ml (NV:<3 U/ml). He underwent transplant from deceased donor followed by DGF with slow serum creatinine stabilization to baseline ~1.3 mg/dl. The post transplant course included: Repair of anterior wall hernia, and recurrent esophageal stricture. 2.7 years post transplant: a severe stenosis of right and left coronary arteries was diagnosed, and was followed by CABG x3. 2 weeks post CABG he developed internal jugular vein thrombosis (started on anticoagulant), pleural effusions, had an episode of altered mental status, and his serum creatinine increased up to 2.6-3 mg/dl. ~1.5 months post CABG his creatinine had reached 7 mg/dl, he was hospitalized, and underwent bladder decompression with incomplete recovery of renal function, and serum creatinine of 4.9 mg/ml at discharge. ~2.9 years post transplant , due to persistence of elevated serum creatinine a graft biopsy was performed. Laboratory tests at time of biopsy, serology was pending: Na 134 mEq/L K 5.4 mEq/L CO2 20 mEq/L Glucose 104 mg/dl BUN 70 mg/dl Creat 5.3 mg/dl Ca 8.8 mg/dl Tot Prot 5.3 g/dl Albumin 2.8 g/dl Total Bilirubin 0.3 mg/dl Alk. Phosp. 36 U/L Asp. Amino Transf. 8 U/L Ala. Amino Transf. 9 U/L AnionGap 14 U/L WBC 13,100 c/cu mm RBC 3.47 M/cu mm Ht 29.9 % Platelet 491 K/cu mm ESR 58 mm/hr IgA 236 mg/dl C-R Prot 6.4 mg/dl Tacrolimus 9.8 ng/dl Medications at time of biopsy: Prednisone 5 mg/day, Tacrolimus 3 mg/day, Zocor 10 mg/day, Darbepoetin alpha 25 mcg/7 days, Myfortic 360 mg x3/day, Norvasc 5 mg/day, Tamsulosin 0.8 mg/day Case 2 - Figure 1 Case 2 - Figure 2 Case 2 - Figure 3 Case 2 - Figure 4 Case 2 - Figure 5 Case 2 - Figure 6 Case 2 - Figure 7 Case 2 - Figure 8 Case 2 - Figure 9 Case 2 - Figure 10 Case 2 - Figure 11 Case 2 - Figure 12 Case 3 Submitted by: Ingeborg Bajema, Leiden University Medical Center, Leiden, Netherlands Clinical Summary: This 60-year-old male was diagnosed with Wegener's Granulomatosis 8 years ago. A native renal biopsy at that time showed a pauci-immune crescentic glomerulonephritis. There were 20 glomeruli, one was globally sclerosed. All other glomeruli were affected by extracapillary proliferation, some contained fibrinoid necrosis. There was a moderate interstitial infiltrate. There was no extensive interstitial fibrosis or tubular atrophy. Despite extensive treatment with immunosuppressive therapy, the patient gradually developed renal insufficiency. Six years after the initial diagnosis, he received a postmortal renal transplant. The procedure was without complications. Because the patient was entered into a clinical trial, a protocolized renal transplant biopsy was taken 12 days after transplantation. This showed 13 glomeruli of which one was globally sclerosed, the others were without histopathological abnormalities. Tubuli showed signs of recovered ATN. There was minimal intimal fibrosis of large arteries. In three years time, his renal function slightly deteriorated (serum creatinine levels rose from 170 to 220 micromol/l). A renal biopsy was performed. The main clinical question was: Chronic allograft nephropathy? Pertinent Laboratory Data: At the time of his second renal transplant biopsy, 3 years after transplantion, the following laboratory data were available for the renal pathologist: MDRD 25 Proteinuria: 0.7 grams/24 hours Edema: 1+ Urine sediment: no abnormalities Serum cholesterol: 4.93 Case 3 - Figure 1 BK virus Case 3 - Figure 2 C4d Case 3 - Figure 3 giantcell Case 3 - Figure 4 thrombus Case 3 - Figure 5 C4d Case 3 - Figure 6 hyalinosis Case 3 - Figure 7 IFTA Case 4 Submitted by: Ian W. Gibson, University of Manitoba, Winnipeg, Manitoba, Canada Clinical Summary: A 54-year old male undergoing peritoneal dialysis for end-stage renal disease due to hereditary nephritis, received a kidney transplant from a living unrelated donor. The donor was a 2-antigen match (1A, 1DR) and the crossmatch was negative using flow cytometry. Both donor and recipient were CMV positive. The recipient was treated with prednisone, mycophenolate (1 g bid), and tacrolimus, with the last of these being started one week prior to transplantation; he did not receive induction/anti-lymphocyte antibody therapy. The transplant surgery was uncomplicated, and renal function was immediate; no dialysis was required post-transplant, and the patient's serum creatinine dropped to 156 umol/L (1.76 mg/dl) at one week. Early post-transplant, the patient complained of odynophagia, and he underwent an upper GI endoscopy on post-transplant day 6, which revealed a ring of discrete ulcers in the lower esophagus, suggestive of viral esophagitis. Biopsies were taken, and the patient was started on valganciclovir 450 mg bid, following which his symptoms quickly improved. The esophageal biopsy showed ulcerated squamous mucosa with regenerative changes, negative for viral inclusions and fungal organisms. Viral cultures and immunocytochemical stains for HSV and CMV of the esophageal biopsy were both ultimately negative. The patient was maintained on valganciclovir at the same dose, in addition to his immunosuppression. He was noted to have viral cytopathic changes (“decoy cells”) in his urine on routine monitoring at 12 days post-transplant, and these changes persisted. Weekly serum PCR for BK and JC viruses were negative throughout the post-transplant course. Serum for donor-specific antibodies was negative. An ultrasound of his allograft, performed 2 weeks post-transplant due to persistently high serum creatinine (around 150-170 umol/L), was suggestive of renal artery stenosis. A conventional renal angiogram was then performed, which showed no stenosis. Serum creatinine steadily increased to 190 umol/L (2.15 mg/dl). The patient was clinically well, and repeat ultrasound of the allograft was normal. Acute rejection was suspected, and the patient was given an oral dose of 200 mg of prednisone, followed by a taper. A renal allograft biopsy was performed three days later, at six weeks post-transplant (biopsy 1, Slide 1, Figures 1 - 10). One week later, serum creatinine had risen to 283 umol/L (3.2 mg/dl), and a repeat renal allograft biopsy was performed at seven weeks post-transplant (biopsy 2, Slide 2, Figures 11 - 17). Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4 - Slide 2 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4 - Figure 1 Case 4 - Figure 2 Case 4 - Figure 3 Case 4 - Figure 4 Case 4 - Figure 5 Case 4 - Figure 6 Case 4 - Figure 7 Case 4 - Figure 8 Case 4 - Figure 9 Case 4 - Figure 10 Case 4 - Figure 11 Case 4 - Figure 12 Case 4 - Figure 13 Case 4 - Figure 14 Case 4 - Figure 15 Case 4 - Figure 16 Case 4 - Figure 17 Case 5 Submitted by: Lillian W. Gaber, The Methodist Hospital, Houston, TX Clinical Summary: A 63-year-old female, with past medical history of arthritis, elevated uric acid, anemia, HTN, anxiety and panic attacks was first seen in 1987, at age 40 for renal dysfunction ( Scr 1.7mg/dl), Proteinuria (700 mg/24 hr), and hematuria. The patient had slow progression to end stage kidney disease. At the time when transplant work up was initiated in 2002 her 24 hour urine collection had 7.0 gm of protein. She underwent a kidney transplant from a living unrelated donor in 2002. Post transplant Immune suppression consisted of prednisone, Cellcept and Neoral, which was later switched to Prograf in 2003. Post transplant renal function was generally stable (baseline serum creatinine around 1.3 mg/dl). She had fluctuations in renal function attributed to calcineurin nephrotoxicity that responded to adjustments of immune suppression medications. Proteinuria (urine protein/creatinine ratio of 1) was first detected in 2002, and slowly progressed over the following 7 years to nephrotic range proteinuria. The patient refused to undergo diagnostic renal biopsy. Finally, the patient consented to a kidney biopsy to investigate nephrotic range proteinuria in 2009. The enal allograft biopsy was entirely submitted for light microscopy. Pertinent Laboratory Data: Serum creatinine: 1.8 mg/dl Creatinine clearance: 27.8 ml/min U p/c ration: 3.5 Serum albumin: 4.0 gm/dl Serum Cholesterol: 184 mg/dl Case 5 - Figure 1 Case 5 - Figure 2 Case 5 - Figure 3 Case 5 - Figure 4 Case 5 - Figure 5 Case 5 - Figure 6 Case 5 - Figure 7 Case 5 - Figure 8 Case 5 - Figure 9 Case 5 - Figure 10 Case 5 - Figure 11 Handouts for all Specialty Conferences will be accessible via the "Educational Materials" section on the homepage the morning after each respective conference. Printed copies of the handout will not be available at the meeting.