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Renal Pathology
Wednesday, March 11, 2009, 7:30 PM
Convention Center 304
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Is That Your Final Answer?
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Moderator:
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ROBERT B. COLVIN
Massachusetts General Hospital
Boston, MA
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Disclosure:
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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.
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Panelists:
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LAURA BARISONI-THOMAS, New York University School of Medicine, New York, NY
SHANE MEEHAN, The University of Chicago Medical Center, Chicago, IL
TERENCE COOK, Imperial College London, Kensington, London, United Kingdom
MICHAEL MENGEL, University of Alberta, Edmonton, Alberta, Canada
CHARLES ALPERS, University of Washington Medical Center, Seattle, WA
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Clinical histories are displayed below.
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Submitted by: Laura Barisoni, Department of Pathology, New York University, NY
31 year old African-American with renal disease of unknown etiology (possibly related to malaria and/or hypertension).
December 2006: He received a cadaveric kidney transplant on December 3rd, 2006. A time zero biopsy revealed mild mesangial expansion suggestive of possible early diabetic nephropathy - donor transmitted, and arteriolar hyalinosis. There was slow graft function, and he was treated initially with thymoglobulin and then a regimen of Prograf, Cellcept, and Steroids. His creatinine plateaued at about 1.8-2.0 mg/dl.
July 2007: In July 2007, he presented with painless jaundice and workup revealed multiple masses in the head of the pancreas consistent with pancreatic cancer.
August 2007: He underwent a Whipple procedure in August of 2007. His recovery was uncomplicated. Following this procedure, he was discharged home with a creatinine of 1.4 and no edema or proteinuria. His immune regimen was reduced to low-dose tacrolimus (blood trough levels were in the 4-6 ng/mL range) and prednisone.
September 2007: In early September he had a rise in his creatinine which was treated with a bolus of steroids (500 mg) and his creatinine returned to 1.7-1.9 (prior to starting chemotherapy).
In late September 2007*, he started adjuvant chemotherapy on a regimen of Taxotere, Avastin, and Gemzar given monthly.
October 2007: On October 8th, his creatinine was 1.9 and he had 1+ edema. November 2007: Repeat labs on November 12th showed a rise in creatinine to 2.7 and 3+ pedal edema. His protein to creatinine ratio at this time was 22.0 (1399 mg protein/63.6 mg creatinine).
December 2007: His edema continued to worsen and his creatinine rose to 3.9 on December 6th. A renal biopsy was performed on December 13th to rule out rejection versus membranous glomerulopathy secondary to malignancy.
| Date | Prograf Levels | S. Creatinine | Edema & | Proteinuria |
| April 07: | 15.5 | 1.4 | - | - |
| May 07: | 18.4 | 1.4 | - | - |
| June 07: | 6.1 | 1.4 | - | - |
| July 07: | 6.1 | 1.4 | - | - |
| August 07: | 4.1 | 1.4 | - | - |
| Sept 07*: | 6.0 | 1.8 | - | - |
| Oct 07: | 4.1 | 1.9 | 1+ | 1+ |
| Nov 07: | 4.1 | 2.7 | 3+ | 3+ |
| Dec 07: | Renal biopsy | 3.9 | 3+ | 3+ |
Case 1 - Slide 1
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Submitted by: Terence Cook, Imperial College London, Kensington, London, United Kingdom
The patient was a female referred at age 7 for the investigation of asymptomatic proteinuria initially diagnosed following a history of abdominal pain. She was one of 4 children and all her siblings were well. The only family history of note was that her mother had persistent microscopic haematuria. The patient had no urinary symptoms and she had a normal renal ultrasound. On examination her height was between the 75th and 90th centile and her weight on the 75th centile for her age. Blood pressure was 106/64 mmHg. Urinalysis showed 3+ proteinuria and 3+ haematuria but no red blood cells or casts were seen on urine microsocopy. Urine protein was 2.5g/24 h. Her urinary proteinuria persisted and so she was admitted for a renal biopsy. Her laboratory results at that time were as follows:
Hb 13.6 g/dL
WBC 6 x 109 per litre
C3, C4 normal
Creatinine 56 micromol/l (0.49 mg/dL)
GFR 96 ml/min/1.6 m2
Albumin 35 g/l
ANCA negative
IgG 8.2 g/l, IgA 1.8 g/l, IgM 0.7 g/l (all normal)
Renal biopsy #1. Representative light microscopy and EM is shown in Powerpoint slides. Immunoperoxidase staining showed segmental mesangial IgM+, C1q+
She was started on enalapril. Her proteinuria persisted and at age 10 was 2.2 g/24h and so the dose of enalapril was increased. At age 11 her GFR had decreased to 74 ml/min/1.6 m2 and Renal biopsy #2 was performed
At age 13 her weight was 51.9 kg and height 163.5cm. BP 106/78 mmHg. GFR 52 ml/min/1.6 m2. Her family were very anxious that her GFR had continued to decline and concerned about the effect of her renal failure on her general health. Her mother commented that her periods had not yet started and wondered if this was due to the renal impairment and whether a special diet was needed. Renal biopsy #3 was performed.
Case 2 - Slide 1
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Case 2 - Slide 2
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Case 2 - Slide 3
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Case 2 - Slide 4
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Submitted by: Shane Meehan, The University of Chicago Medical Center, Chicago, IL
A 58 year old female developed end stage renal disease due to hypertensive nephrosclerosis and received chronic peritoneal dialysis for 4 years. Her past medical history was notable for hypertension, left cerebrovascular accident, asthma, avascular necrosis of the left hip treated by total hip replacement and superior vena cava syndrome related to a central line. She underwent cadaveric renal transplantation in May 2008. The transplant kidney was from a previously well 28 year old donor after cardiac death. The cause of donor death was blunt head trauma from a motorcycle accident. This was the recipient's first kidney transplant, with a six HLA antigen mismatch. Standard and flow cytometric pre-transplant cross matches were negative. Donor warm ischemia time was 13 minutes. Pulsatile cold (4°C) perfusion with University of Wisconsin perfusate was used for 17 hours and 17 minutes. Total cold ischemia time was 24 hours and 29 minutes. Subsequent warm ischemia time at implantation was 56 minutes. At reperfusion the kidney became immediately homogenously pink. Within minutes a mottled blue discoloration developed. At this time the renal artery had a regular strong pulse and the renal vein was soft. The discoloration persisted and a needle biopsy was obtained at approximately 45 minutes and sections are submitted (3A, H&E). Indirect immunofluorescence for C4d on a frozen core was negative. Over the next 24 hours the patient developed oliguria and then anuria. Ultrasound revealed no flow in the renal vein and systolic flow in the renal artery. At this time, the white cell count was 7.1 K/ µl (3.5-11), red cell count 4.2 M/ µl (3.9-5.3), hemoglobin 11.4 g/dl (11.5-15.5), MCV 81.2 fL (81-99), MCHC 33.8 g/dl (32-35), hematocrit 33.8% (36-47), RDW 16.5% (<15% in females) and platelets were 288 K/µl (150-450). The serum creatinine was 12.1 mg/dl (0.5-1.4). The patient had commenced Thymoglobulin induction. On re-exploration the allograft was dark purple and had a palpable thrombus in the renal vein. Allograft nephrectomy was performed. On gross examination the kidney was 290 gm and had firm thrombus filling the arcuate, interlobar and renal vein branches. The cut surface was mottled red-purple. A representative section of the parenchyma is submitted (3B, H&E).
Case 3 - Slide 1
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Case 3 - Slide 2
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Submitted by: Michael Mengel, University of Alberta, Edmonton, Canada
A 32-years old male patient received in November 1998 his first renal transplant from a diseased donor (35 years, female). Failure of his own kidneys was accounted to IgA nephropathy but never confirmed by biopsy. Prior to transplantation T cell PRA peaked at 17% and B cell PRA at 42%, but at transplantation the patient was PRA and cross match negative. The allograft showed slow initial graft function with a reduction of the serum creatinine between day 0 and day 11 from 800 to 185 µmol/L. Initial immunosuppression comprised Cyclosporin, Steroids, and Sirolimus, no antibody induction therapy was done.
Clinical data at time of biopsy
Dec 2004 (6 years post transplant)
Indication for the biopsy was an acute deterioration of renal graft function two weeks before biopsy. The serum creatinine increased from 175 µmol/L to 212 µmol/L. However, the patient was unable to come for biopsy at this time. The serum creatinine dropped without anti-rejection therapy from 212 µmol/L to 163 µmol/L at the day of biopsy. PRAs were negative and no BK in urine was detectable at the day of biopsy. Maintenance immunosuppression comprised Tacrolimus (Tac level: 8.5), Steroids,and MMF (2g/d).
Case 4 - Slide 1
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Case 4 - Slide 2
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Submitted by: Charles Alpers, University of Washington Medical Center, Seattle, WA
A 56 year-old Native American woman with a long history of symmetric polyarthritis presented with progressive proteinuria and mild renal insufficiency. Twelve years previously, the patient presented to a rheumatologist with arthralgias involving the hands, knees and ankles. At that time, serologic testing for rheumatoid factor was negative, but circulating anti-nuclear antibodies (ANA) were detected at a titer of 1:80. The patient was treated with non-steroidal anti-inflammatory medications. She presented a short time later to a different rheumatologist with similar symptoms, and was diagnosed with "inflammatory arthritis". Over the next 10 years, she was treated intermittently with steroids, gold therapy, hydroxychloroquine, and methotrexate. The patient's medical history included hypertension, impaired glucose tolerance, and fibromyalgia. A brain magnetic resonance imaging (MRI) scan performed approximately 4 years before the biopsy showed changes consistent with a remote stroke in the left occipital lobe.
A review of symptoms was significant for transient "pins and needles" sensations involving the legs and hands, and joint pain involving the knees, wrists and hands. She had no symptoms of Sicca (Sjogren's) syndrome and no additional signs or symptoms of lupus. The patient had no significant family history of renal disease. She had two healthy sons.
Physical Examination revealed normal blood pressure (120/70 mmHg), heart rate (70 bpm) and respiratory rate (16 rpm). Ophthalmologic exam revealed bilateral cataracts. Cardiac, respiratory and abdominal exams were within normal limits. Neurological exam was normal, with the patient demonstrating normal sensation of the hands and feet. Dermatologic examination showed no lesions. Examination of the hands revealed degenerative changes and bony hypertrophy of the distal and proximal interphalangeal joints.
Laboratory Data: 2+ proteinuria by dipstick analysis was first detected 6 years prior to the current presentation. Over the next several years, she had trace to absent urinary protein by dipstick. One year prior to the current presentation, she again demonstrated 2+ urinary protein on dipstick analysis. A 24-hour urine collection performed 5 months prior to biopsy showed 1260 mg of protein, a creatinine clearance of 67.2 mL/minute and a serum creatinine level of 1.1 mg/dL (97 µmol/dl). A subsequent 24-hour urine collection performed closer to the time of biopsy demonstrated 3384 mg protein, a creatinine clearance of 73.1 mL/minute and a serum creatinine level of 1.3 mg/dL (115 µmol/dl). The urinary sediment was inactive. The patient had a long history of mildly elevated level of circulating antinuclear antibodies, with titers fluctuating between 1:80 and 1:320 (homogeneous pattern). Additional serologic studies revealed circulating SS-A autoantibodies, but showed no evidence of SS-B, anti-double-stranded DNA, synovial membrane (SM), or ribonucleoprotein (RNP) antibodies, or circulating rheumatoid factor. Serum complement levels were within normal limits. The kidneys were of normal size by ultrasound. A biopsy of our favored organ was performed.
Case 5 - Slide 1
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