Case 3 -

IgA-Dominant Post-Infectious GN Mark Haas Johns Hopkins Medical Institutions Baltimore MD

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Click here to view (or print) handout in single page format. (1.01 MB) Note: Any slides will be printed in color. Click here to view (or print) black and white handout. (664 KB) Note: Text will be in single page format and any slides will be in 6-per-page format. Clinical History 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 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 - Figure 1 Low-power photomicrograph shows mild mesangial proliferation, as well as a moderate degree of tubular atrophy and interstitial fibrosis. (PAS, x100) Case 3 - Figure 2 Glomeruli show an increase in mesangial matrix and cellularity, more pronounced in the glomerulus near the top of the field. An interlobular artery shows marked intimal fibrosis and thickening. (PAS, x100) Case 3 - Figure 3 The two intact glomeruli in this field show only very slight mesangial prominence. One globally sclerotic glomerulus is also present. There is patchy interstitial inflammation, comprised mainly of lymphocytes, with a small number of eosinophils, the latter not apparent on this low-power photomicrograph. (PAS, x100) Case 3 - Figure 4 These 2 glomeruli are hypercellular, mainly in mesangial areas, although the glomerulus at left also shows segmental endocapillary hypercellularity. Modest numbers of mononuclear leukocytes are present in the glomeruli. (H&E, x200) Case 3 - Figure 5 This glomerulus shows an increase in mesangial matrix and cellularity. Several tubules contain heme-positive material. A preglomerular arteriole appears thickened. (H&E, x200) Case 3 - Figure 6 Direct immunofluorescence for IgA and C3, showing granular staining (2-3+, 0-4+ scale) in a primarily mesangial distribution. There was only weak mesangial staining for IgM, with no specific staining for IgG or C1q. There was approximately equivalent (1-2+) staining for kappa and lambda light chains, with a pattern and distribution similar to that for IgA. Case 3 - Figure 7 Electron microscopy. Left panel: There are mesangial electron-dense deposits as well as a large, partially resorbed subepithelial deposit located in a mesangial "notch" or "waist" region (arrow). Right panel: A higher power electron micrograph showing another subepithelial deposit in a mesangial "notch" or "waist" region. Note the membrane-like structures within the deposit, indicative of partial resorption.