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Renal Pathology
Sunday, March 25, 2007, 7:30 PM
Elizabeth HDrug-Induced Renal Disease
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Moderator:
ROBERT B. COLVIN
Massachusetts General Hospital
Boston, MA
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Submitted by: Stephen Bonsib - LSU Health Sciences Center, Shreveport, LA
The patient is a 19-year old white female. She was first seen by her family physician because of acute onset of peripheral edema with swelling of feet and lower extremities. Two days before the patient received vaccinations (hepatitis B and meningococcal) in preparation for college. She was treated with a prednisone Dosepak pack with transient resolution of the edema. The edema recurred 1 week later and was still present at a follow up visit 1 month later. 3+ proteinuria was detected and she was referred to a nephrologist.
The initial nephrology evaluation occurred 2 months after the first onset of edema. By that time she had gained 8 kg. Physical examination was essentially unremarkable aside from significant edema. She was afebrile, with blood pressure of 110/60 mm Hg, and weight of 72.4 kg.
Family history: No family history of renal disease.
Past medical history: Recurrent upper respiratory infections characterized by tonsillitis
Laboratory findings:
Creatitine - 0.5 mg/dl
Urinalysis:
4+ proteinuria
No rbcs or cellular casts
24-hr urine protein - 6.5 gm
Serum albumin - 2.4 gm/dl
Cholesterol - 280 mg/dl / Triglycerides - 216 mg/dl
C3/C4 - normal
ANA - negative
Case 1 - Slide 1 - H&E
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Case 1 - Slide 2 - PAS
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Submitted by: Arthur H. Cohen - Cedars-Sinai Medical Center, Los Angeles, CA
A 58 year old Caucasian man with 22 year history of HIV infection developed heavy proteinuria (6.4 grams/24 hr) with renal insufficiency (creatinine clearance 78 ml/min with serum creatinine 1.6 mg/dl) one year prior to renal biopsy. Kidneys were of normal size by ultrasound (11.2 and 11.0 cm). He was started on an aggressive regimen of antiretroviral therapy; this led to a decrease in viral count to 50 and a dramatic reduction in protein excretion to 836 mg/24 hrs. The serum creatinine remained at 1.6 mg/dl. Two months prior to biopsy, renal function began to deteriorate and Scr was 2.0 mg/dl and clearance 59 ml/min. In addition, hypouricemia, hypophosphatemia and increased urinary acid excretion were noted. Protein excretion also increased. He was normotensive; urine analysis was "bland." Because of these developments he was referred to a nephrologist for renal biopsy.
Past medical history was pertinent for HIV infection and hepatitis B infection. Liver biopsy in the past disclosed increased iron stores and no evidence of cirrhosis. Recent CD4 - 260/ cu mm, and HIV RNA by PCR was 73 copies/ml. He was hypertensive for two years.
Medications included kaletra (lopinavir, ritonivir), epivir (lavimudine), viread (tenofovir), among many.
Physical exam disclosed a chronically ill appearing man of stated age and in no distress and with BP 120/70. There were no abnormal findings.
Laboratory data on admission:
Hgb/Hct - 17.4 gm/50.5; WBC 5,900 with normal differential; platelets 173,000.
Na 139; K 5.4; Cl 101; CO2 23.
BUN/Cr - 223/2.3.
Urine analysis protein 2+; 0 rbc; 26 granular casts.
A biopsy was performed.
Case 2 - Slide 1 - Jones
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Case 2 - Slide 2 - PAS
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Case 2 - Slide 3 - Trichrome
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Case 2 - Slide 4
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Submitted by: Agnes Fogo - Vanderbilt University Medical Center, Nashville, TN
This 64-year-old white retired man with a kidney transplant for end-stage renal disease (ESRD) secondary to diabetes, presented in August 2006 for evaluation of recent weakness, muscle pain and diarrhea. He had received a living non-related 0 antigen match kidney in June 2005, and had been in stable health, with controlled glucose and moderately controlled blood pressure, but persistent hyperlipidemia. He had one episode of acute cellular rejection, biopsy proven, in January 2006. Serum creatinine stabilized after this at 2.6-2.7 mg/dl. His medications included mycophenolate, cyclosporine, diuretics, prednisone, aspirin, simvastatin and insulin. His prescription for an angiotensin receptor-blocker (ARB) had not been filled as it was not on his hospital's formulary. An ARB was added to his medications in mid-July 2006, when he presented with edema and increased weight of 8-10lbs. His dose of diuretic was also increased. Serum creatinine remained stable at this time. Approximately one month later, he had muscle aches and weakness that started in the lower legs and then involved the anterior thigh and calf. The pain rendered him unable to walk. He also had diarrhea for three days, and noticed red/brown urine, but maintained normal urine output.
On admission, his blood pressure was 152/78 mmHg, he was afebrile, pulse was 88 beats/min and weight 259 lbs. He had tenderness of the posterior calves and anterior thighs and 1+ edema of the lower extremities, but otherwise normal neurological and musculoskeletal exam. Admission laboratories showed sodium 130 mmol/L, potassium 7.0 mmol/L, chloride 95 mmol/L, CO2 19 mmol/L, serum creatinine 8.3 mg/dl, glucose 242 mg/dl, phosphorus 8.8 mg/dl, AST 503 U/L, ALT 204 U/L, alkaline phosphatase 80 U/L, total bilirubin 0.6 mg/dl, direct bilirubin 0.4 mg/dl. His CBC showed a decreased hematocrit at 31.5%, with platelets 209,000/mm3, white blood cells 8,900/mm3, with lymphocytes 5.3%, PMNs 88.5%, monocytes 5.6%, eosinophils 0.5%, and basophil 0.1%. PT and PTT were normal. CPK was 16,393 U/L, with CPK-MB 123.9 ng/mL (normal 0-3.6). Urinalysis showed positive dipstick for protein, large blood and urobilinogen, with negative glucose and bilirubin.
He had a smoking history of 60-70 pack yrs, but had quit five years ago. He did not use alcohol. His past history was significant for coronary artery disease with four vessel bypass in 2000, ICD placement in March 2005 and elective cholecystectomy in 2005.
He was treated with fluids, and cyclosporin, ARB and simvastatin were discontinued, and the patient was given Imuran. On day four, with creatinine remaining high, a renal biopsy was performed.
Case 3 - Slide 1
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Submitted by: Glen S. Markowitz - Columbia Presbyterian Medical Center, New York, NY
A 64-year-old Caucasian female presented with unexplained renal failure, a creatinine of 2.6 mg/dl, malaise, and weight loss. Four months prior, the patient had a creatinine of 0.9 mg/dl. Past medical history was significant for hypertension for 6 months and a remote history of chronic urethritis and cystitis requiring urethrotomy (40 years prior). At the time of evaluation the patient's medications included amlodipine, metoprolol, and esomeprazole (as needed), although she had recently been switched from lisinopril to amlodipine and metoprolol due to poor blood pressure control. Physical examination revealed a blood pressure of 194/74 and no edema. Urinalysis revealed rare WBC's, no RBC's, and no proteinuria. There was no evidence of a monoclonal serum spike. The patient had an albumin of 4.3 g/dl, calcium 9.9 mg/dl, hematocrit 27.3%, platelet count 301,000, normal C3 and C4, negative ANCA, and negative anti-GBM antibody. The kidneys measured 9.5 and 8.8 cm in length by ultrasound. During the following 2 months the patient's creatinine declined to 2.3 mg/dl, at which time renal biopsy was performed.
Biopsy materials:
Single glass slide (stained with H&E)
Immunofluorescence: negative
Electron microscopy: not provided (no significant glomerular abnormalities noted)
Case 4 - Slide 1
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Submitted by: Helmut Rennke - Brigham & Women's Hospital, Boston, MA
61-year-old man was diagnosed Stage IIIB non-small-cell carcinoma of the lung (T2, N3) in 2002. He received carboplatin and Taxol chemotherapy followed by concurrent chemoradiotherapy. In April 2003 a right supraclavicular node was noted and treated with radiation. At the time he had received Taxotere with ZD6474, Iressa, Navelbine, and beginning February 2004, gemcitabine was started. He tolerated the treatment well, and on 2 subsequent scans he showed improvement.
On July 5, 2004 he was admitted to Brigham and Women’s Hospital with increasing dyspnea, edema, pleural effusions, which showed no malignant cells. He was discharged, the edema got worse, and he developed systemic hypertension. He was re-admitted to the renal service. His PE remained unchanged with marked edema, his UA showed 4+ protein, and a 24-hour collection revealed 10 g of protein. The sediment was bland. His serum creatinine was 1.6 mg/dl.
Biopsy materials: Images of LM, IF, and EM
Case 5 - Slide 1 - H&E
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Case 5 - Slide 2 - Jones
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Case 5 - Slide 3 - PAS
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Case 5 - Slide 4
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During the meeting the slides and protocols will be available for study in the microscope
room in the Manchester Grand Hyatt (Betsy A-C) for participants who wish to review them prior to the
evening session.
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. However, we will provide a booklet at the
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for the important "take home messages".
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