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Renal Pathology
Sunday, March 2, 2008, 7:30 PM
CC 201/203 Mad About Deposits (MAD)
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Moderator:
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ROBERT COLVIN
Massachusetts General Hospital
Boston, MA
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Clinical histories are displayed below.
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Submitted by: Vivette D'Agati - Columbia University, New York, NY
The patient is a 74 year-old Caucasian female with longstanding hypothyroidism and depression and a 3-year history of hypertension. In March, 2003 she underwent a workup for chronic headaches, which led to discovery of a cerebellar mass and successful surgical resection of a cerebellar hemangioblastoma. In February, 2006 she developed asymptomatic microhematuria, and urologic work up (including cystoscopy and renal ultrasound) was negative. In July, 2006 she was noted on routine urinalysis to have 3+ proteinuria, 0-3 rbc/hpf, and 6-10 wbc/hpf. In December, 2006 she developed edema and was referred to a nephrologist for investigation of nephrotic syndrome. Medications at that time included Avalide, Zoloft, Singulair, Allegra, Toprol and Synthroid.
On nephrologic work-up in January, 2007 the patient was found to have BP 138/80 and 2+ lower extremity edema. The patient denied history of diabetes, fever, rash, arthralgias, or gross hematuria. Laboratory studies included serum creatinine 1.3 mg/dL, BUN 43 mg/dL, 24 hour urine protein 5.119 grams, serum albumin 3.3 g/dL, Hct 31.4%, WBC 7.2K, platelets 340K, and normal serum electrolytes (Na, K, Cl, CO2, Ca). Urinalysis revealed 3+ protein and microhematuria, without rbc casts. Serologies included negative ANA, ANCA, hepatitis B surface Ag, HCV, HIV and rheumatoid factor. Serum complements (C3 and C4) were within the normal range. Serum protein electrophoresis revealed reduced albumin 3.0 (normal 3.6-4.7 g/dL) and reduced gamma globulins 0.4 (normal 0.6-1.6 g/dL). Kidney size by ultrasound was 10.4 and 10.3 cm.
A renal biopsy was performed in January, 2007.
Case 1 - Slide 1
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Case 1 - Slide 2
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Case 1 - Slide 3
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Submitted by: Lynn D. Cornell - Mayo Clinic, Rochester MN
A 68-year-old woman underwent an abdominal CT scan to evaluate a previously detected liver mass and was found to have bilateral renal masses. On follow-up scans, the renal masses had become larger, prompting three renal biopsies over one year's time. The patient's creatinine at the time of the third biopsy was 0.9 mg/dl. Over several months following the third renal biopsy, the creatinine had slowly increased and ranged from 1.1 to 1.6 mg/dl. The patient's medical history was significant for hypertension, hyperlipidemia, type II diabetes mellitus, Crohn's disease, sclerosing cholangitis, and bilateral orbital inflammatory lesions. The patient had intermittent pancreatic insufficiency, and an endoscopic ultrasound done three years previously showed sclerosing pancreatitis.
On physical examination, the patient weighed 99 pounds, her blood pressure was 160/60, the lungs were clear, she had normal cardiac sounds, and she had a benign abdominal examination without palpable masses. She did not have edema. Medications were alendronate, pravastatin, hydrochlorothiazide, lisinopril, atenolol, ursodiol, insulin, iron, calcium carbonate (TUMS), a multivitamin, and Ensure. Other laboratory values included serum albumin 3.2 g/dL, hemoglobin 11.4 g/dL, hematocrit 35.2%, white blood cell count 6x109/L, and platelet count 234,000/L. She had a positive anti-nuclear antibody with a titer of 1:80, and normal serum C3 and decreased serum C4 levels. She did not have significant proteinuria or hematuria.
The two previous renal biopsies showed arteriosclerosis and scant areas of inflammation consisting of mononuclear cells, plasma cells, and eosinophils; these specimens were considered nondiagnostic.
Case 2 - Slide 1
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Case 2 - Slide 2
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Submitted by: Mark Haas - Johns Hopkins Medical Institutions, Baltimore MD
The patient is a 65 year old white male with a history of coronary artery disease, s/p bypass graft several years ago, and hypertension, controlled by medication. Approximately 2 years ago, he underwent resection of an extradural schwannoma in the region of the lumbar spine, with L3-L5 laminectomy and placement of 3 metal screws at L3, L4, and L5. At that time, the patient's serum creatinine was 0.9 mg/dl, with urinalysis negative for protein, RBCs and WBCs.
Approximately 1½ years later, the patient developed severe back pain, and was found to have an epidural abscess in the region of L2-3. On admission, the patient had a serum creatinine of 1.0 mg/dl, with urine protein/creatinine ratio of 0.2. Culture of the abscess grew only methicillin-sensitive S. aureus. The infected area was debrided and drained, and the patient was treated with an 8-week course of antibiotics, initially vancomycin and later oxacillin. He slowly recovered from the infection, however during this recovery he developed an episode of gross hematuria, with 2+ lower extremity edema and hypertension (as high as 170/100). He was subsequently found to have a serum creatinine of 3.2 mg/dl (later peaking at 3.5 mg/dl), and proteinuria of 4.6 grams/24 hours. Serum albumin was also low at 3.1 g/dl.
Serologic work-up revealed negative ANA, ANCA, HIV, hepatitis B, and hepatitis C, and normal serum C3 and C4, although some of these tests were not completed until a month or more after the episode of gross hematuria. Serum protein electrophoresis showed a monoclonal kappa spike, as well as polyclonal hypergammaglobulinemia with elevated IgG and IgA levels. Medications included furosemide, atorvastatin, hydralazine, metoprolol, linezolid, and isosorbide dinitrate. A renal biopsy was performed. At the time of the biopsy, urinalysis continued to show protein >300 mg/dl, with 20-50 RBCs and 5-10 WBCs per high power field, but no casts or bacteria. Serum creatinine was 2.5 mg/dl. Urine culture was negative.
Case 3 - Slide 1
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Case 3 - Slide 2
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Case 3 - Figure 6 - Immunofluorescence (IF) stain for IgA and Immunofluorescence (IF) stain for C3
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Case 3 - Figure 7 - Electron microscopy (EM) of a representative glomerulus / EM of another area / Higher power EM image
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Submitted by: Maria M. Picken
A 55-year-old Caucasian female presented with transient peri-orbital and ankle edema and weight gain.
Past medical history: She has had no recent routine medical care but she states that she has been in overall good health. Except for urinary tract infections in the past, there was no evidence of chronic inflammatory disease. She denies systemic symptoms such as fever, chills, nausea, vomiting, joint pains, rash or redness upon sun exposure. She denies frequency, urgency or pain on urination. She noticed that her urine became foamy but did not notice blood in her urine. She has not traveled, and has no pets or recent insect bites. She had never smoked tobacco and did not drink alcohol.
Medication: none on admission
Family history: Northern European ancestry, both parents are deceased. Her mother died in her forties of breast cancer, her father died of lung cancer in his sixties. Her younger sister and two children are alive and well. There is no known family history of kidney disease.
Physical examination revealed: weight 155 lb, blood pressure of 165/95mm Hg, mild peri-orbital and ankle edema, heart rate of 72 bpm, regular sinus rhythm, no cardiac murmurs.
ROS: negative except for the above.
Laboratory findings:
Serum creatinine - 2.1 mg/dl, glucose 109 mg/dl
Urinalysis: 4+ proteinuria, 5-10 RBC, no RBC or cellular casts
24-hr urine protein 5.3 gm, serum albumin 2.4 gm/dl, cholesterol 260 mg/dl, triglycerides 240 mg/dl, hemoglobin 10.4 g/dL, moderately decreased creatinine clearance (62.0 mL/min/1.73 m2). C3/C4 - normal, ANA - negative, ANCA - negative, anti-GBM antibody - negative. Liver function tests were normal, Hepatitis B and C, HIV were all negative. Serum immunoelectrophoresis with immunofixation showed monoclonal immunoglobulin (IgG-kappa).
Cardiac ECHO showed mild to moderate left ventricular hypertrophy. US - normal size kidneys without hydronephrosis or stones. Kidney biopsy was performed.
Despite supportive treatment, the patient developed renal failure within 2 years post kidney biopsy. Subsequently, she underwent a combined liver and kidney transplant. Currently, 2 years post-transplant, the patient is well and has normal kidney function.
Case 4 - Slide 1
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Case 4 - Slide 2
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Submitted by: J. Charles Jennette - University of North Carolina, Chapel Hill NC
The patient was a 19 year-old Caucasian female with nephrotic range proteinuria. Laboratory data included blood pressure 110/80 mmHg, trace peripheral edema, no skin lesions, no hematuria, 4 to 5 grams of proteinuria per 24-hours, serum creatinine 0.6 mg/dl, creatinine clearance 90-110 ml/min, normal serum C3 and C4, negative ANA, and negative HBV serology.
Light microscopy and electron microscopy images are available to evaluate. Immunofluorescence microscopy demonstrated slight granular mesangial and capillary wall staining for C3 but no staining for IgG, IgA, IgM, kappa light chains, lambda light chains, C1q or fibrin.
Case 5 - Slide 1
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Case 5 - Slide 2
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Case 5 - Slide 3
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