—  SPECIALTY CONFERENCE  — Renal Pathology Sunday, March 18, 2012, 7:30 PM Convention Centre 205-207 Click the button above to add this event to your Itinerary Planner... Yes, We Still Need Electron Microscopy Moderator: MARK HAAS Cedars-Sinai Med Ctr 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: Sherry L. Werner, University of Texas Health Sciences Center, San Antonio, TX David N. Howell, Duke Univ Med Ctr, Durham, NC Kensuke Joh, Sendai Shakaihoken Hospital, Sendai City, Miyagiken, Japan Megan L. Troxell, Oregon Health & Science Univ, Portland, OR Guillermo A. Herrera, Bostwick Lab/Nephrocor, Orlando, FL 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: Sherry L. Werner - University of Texas Health Sciences Center, San Antonio, TX Clinical Summary: A 56 year-old man underwent left lung transplantation for idiopathic pulmonary fibrosis. Initial immunosuppression included anti-thymocyte globulin followed by tacrolimus, mycophenolate mofetil and prednisone. Early post-op course was complicated by cellular rejection with a humoral component which was treated with steroids and rituximab. The patient had a history of hypertension and worked as a cattle rancher with herding dogs. Five to six months after transplantation, he was admitted to the hospital twice with episodic fever, weight loss, persistent cough, fluctuating altered mental status, diarrhea and renal insufficiency. Serum creatinine increased from a baseline of 0.8 mg/dl to 1.2 mg/dl. Chest CT scans showed small ground glass infiltrates in the upper lobe of the transplanted lung. The patient underwent an extensive evaluation for fever including two transbronchial biopsies that showed no significant histologic changes. MRI of the brain was unrevealing. Colonoscopy and stool cultures were negative. Blood, urine, sputum and CSF cultures were negative for bacteria and fungi. Despite an extensive evaluation for fever over a four week period and empiric therapy with multiple antimicrobial agents including Vancomycin and Cefepine as well as Acyclovir, the fever persisted and the renal function worsened. Tacrolimus blood levels were high (11- 23 ng/ml) and renal function transiently improved with decreased tacrolimus doses. However, the patient developed acute renal failure with a peak serum creatinine of 4.3 mg/dl requiring dialysis. Urinalysis demonstrated sterile pyuria, pleomorphic rod-shaped organisms and tubular epithelial cells with inclusions. A renal biopsy established the diagnosis on electron microscopic studies and the patient was immediately begun on the appropriate therapy. Pertinent Laboratory Data: Other labs: PCR tests for HIV, CMV, EBV, HSV, BK and JC virus DNA were negative. Serum studies were negative for: Hepatitis B and C, coccidiomycosis/histoplasma antibody, cryptococcal antigen, C. difficile fecal toxin, ANA and ANCA. Case 1 - Figure 1 urine Case 1 - Figure 2 H&E Case 1 - Figure 3 H&E Case 1 - Figure 4 H&E Case 1 - Figure 5 H&E Case 1 - Figure 6 H&E Case 1 - Figure 7 Gram Case 1 - Figure 8 EM Case 1 - Figure 9 EM Case 1 - Figure 10 Case 1 - Figure 11 Case 1 - Figure 12 Case 2 Submitted by: David N. Howell - Duke Univ Med Ctr, Durham, NC Clinical Summary: A 68-year-old Caucasian woman presented to an outside medical center with a two-month history of nausea and vomiting that had worsened over the past week. There was no associated abdominal pain, diarrhea, melena, hematemesis, or hematochezia. The patient had experienced a cough with subjective fever a few days previously, but denied hemoptysis. Her past medical history was notable for anemia, hypertension, breast cancer (status post lumpectomy), chronic kidney disease stage II, and hematuria of unclear duration. Urinalysis showed 3+ blood and 3+ protein; microscopic examination of the urine revealed numerous red and white blood cells as well as abundant bacteria and a moderate number of yeasts. The patient was felt to have a urinary tract infection, and was admitted to the hospital for hydration and therapy with antibiotic and antifungal agents. Her serum creatinine level increased from 2.4 mg/dL on admission to 3.9 mg/dL one week later, after which it trended downward. Hematuria and proteinuria persisted, however, and a percutaneous renal biopsy was performed to assess the cause. Pertinent Laboratory Data: Peripheral and cytoplasmic anti-neutrophil cytoplasmic antibody (pANCA and cANCA), anti-nuclear antibody (ANA), and anti-double-stranded DNA (dsDNA) all undetectable. No monoclonal protein detected by serum or urine protein electrophoresis. Serum complement levels (C3 and C4) within normal limits. No other serologic results available at the time of biopsy. Case 2 - Figure 1 albumin IF, 20x objective Case 2 - Figure 2 EM #1 Case 2 - Figure 3 EM #2 Case 2 - Figure 4 H&E #1, 4x objective Case 2 - Figure 5 H&E #2, 20x objective Case 2 - Figure 6 H&E #3, 20x objective Case 2 - Figure 7 IgG IF #1, 20x objective Case 2 - Figure 8 iGg IF #2, 20x objective Case 2 - Figure 9 Masson, 20x objective Case 2 - Figure 10 PAMS, 40x objective Case 3 Submitted by: Kensuke Joh - Sendai Shakaihoken Hospital, Sendai City, Miyagiken, Japan Clinical Summary: 57 yrs old male has been treated with medication against hypertension, hyperlipidemia, and hyperuricemia in a clinics from 1994 (40 yrs old). 2003: proteinuria (-) , 2004: proteinuria (+/-), 2005: proteinuria(+), 2007~2008 proteinuria (+), 2009 April: proteinuria(3+) , August : Hypoalbuminemia Blood pressure120-140/90mmHg, sCr1.0~1.2 mg/dL 2010 January: leg edema, October: Hypertension >200mmHg. Systolic Blood pressure 170mmHg after antihypertensive drug He was introduced to our hospital with edema and hypertension for further investigation and treatment. Blood pressure 197/108mmHg? Body weight 79.5kg edema(+) Followed up with 150-170/80-90mmHg in out patient clinic of the University hospital. .Diuretic drug (Lasix) was administered in December against edema Case 3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 3 - Slide 2 Click to view with ImageScope Click to view with a Web-Based Viewer Case 3 - Slide 3 Click to view with ImageScope Click to view with a Web-Based Viewer Case 3 - Slide 4 Click to view with ImageScope Click to view with a Web-Based Viewer Case 3 - Figure 1 Case 3 - Figure 2 Case 3 - Figure 3 Case 3 - Figure 4 Case 3 - Figure 5 Case 3 - Figure 6 Case 3 - Figure 7 Case 3 - Figure 8 Case 4 Submitted by: Megan L. Troxell - Oregon Health & Science Univ, Portland, OR Clinical Summary: A 40 year old Caucasian man received a living related renal allograft from his sister. Past medical history included ESRD due to FSGS, on dialysis for the past 2 years. The donor was a one haplotype-match, ABO-compatible, with negative cross-match studies prior to transplantation, including cytotoxic crossmatches (standard, anti-globulin, and B-cell), as well as flow T-cell and B-cell cross matches. The patient’s history was also significant for hypertension (controlled on one medication), hyperlipidemia (on a statin), obesity (BMI-34.5), anemia, tinea cruris, and history of small bowel perforation. Both donor and recipient were CMV-negative; the recipient was HIV, Hepatitis B, C, and HSV negative, but EBV-positive, with a history of chicken pox. The donor’s left kidney was removed in a laparoscopic operation without complications. The kidney was transplanted into the recipient’s right iliac fossa, also an uncomplicated procedure, though slightly long given the recipient’s obesity. The recipient received basiliximab induction, along with prednisone, MMF and Tacrolimus. The kidney made urine immediately in the OR, and urine output was 2 L in the first 12 hours, with creatinine decreasing gradually. Urine output slowed POD1-2, with increasing creatinine, despite fluid boluses (1.6 L UOP). Renal allograft ultrasound showed no hydronephrosis or peri-renal fluid collection, with normal Doppler arterial waveforms. MAG-3 scan demonstrated a pattern consistent with renal tubular stasis. Thymoglobulin was given, along with prednisone and MMF (tacrolimus was discontinued). Dialysis was initiated on POD3, in the setting of no urine output. An allograft biopsy was performed on POD4 (Images 1-2). C4d immunofluorescence studies were negative (not shown). A portion of the specimen submitted in glutaraldehyde was processed for electron microscopy, but did not contain glomeruli. At the time of the first biopsy, DSA studies were again negative. The patient was treated conservatively, but kidney function did not improve. A second allograft biopsy was performed on POD 11 (Images 3-7). Again, the C4d studies were negative. The electron microscopy specimen contained 9 glomeruli, seen in Images 8-10. 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 5 Submitted by: Guillermo A. Herrera - Bostwick Lab/Nephrocor, Orlando, FL Clinical Summary: 55 y/o diabetic white female who had a history of a previous prolonged admission for acute renal failure in 2001. The acute renal failure resolved but the details of this admission are not available. Her second admission was in 2003 with renal failure after gallbladder surgery. Serum creatinine at the time of this second admission was 2.7 mg/dl and increased to 4 mg/dl prior during the first week of hospitalization. At the time, complement levels were in the lower range of normal. Serological markers for connective tissue disease were all negative. Rheumatoid factor was negative. A renal biopsy was performed (first renal biopsy) which is provided for your evaluation. Patient responded well to plasmapheresis treatment and her acute renal failure improved with her serum creatinine decreasing to 1.1 mg/dl at the time of discharge. She was again admitted to the hospital 7 years later (2010) presenting with a rash, fever, and purpuric lesions which had become progressively more pronounced over a period of 2 weeks prior to admission and had extended from her extremities to her trunk and acute renal failure and renal failure. Her serum creatinine had increased to 2.68 mg/dl and the patient reported decreased urine output. Complement levels were low, especially C4 which was undetectable. Rheumatoid factor was now positive. CBC showed no anemia, leukocytosis, or thrombocytopenia. She had an elevated alkaline phosphatase- 131 with the normal range being 20-87. All other chemistries were normal. U/A showed 0-2 WBCs, 0-2 RBCs, and rare bacteria. A second renal biopsy was then performed because the diagnosed rendered in the first renal biopsy did not correlate with this patient’s clinical behavior. This second biopsy will be discussed together with the first biopsy made available to you. Case 5 - Figure 1 Case 5 - Figure 2 Case 5 - Figure 3 Case 5 - Figure 4 Case 5 - Figure 5 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.