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Archive: Teaching Points

Membranous Glomerulopathy Subtyping

The diagnosis of membranous glomerulopathy has evolved rapidly in the past 10 years since the identification of PLA2R as the major target antigen in primary membranous glomerulopathy. Today, rather than subtyping into vague categories such as 'primary' and 'secondary', we have tools available to name the specific type of disease present in most cases. Arkana Laboratories offers diagnostic testing for membranous glomerulopathy including immunohistochemical stains for tissue typing of PLA2R, THSD7A, EXT1/2, and NELL1 membranous and serum testing to monitor disease in patients with PLA2R and THSD7A-associated membranous glomerulopathy.  

Endocarditis-Associated Glomerulonephritis

The patient is a 45-year-old IV drug user who presents with fevers, chills, hematuria, and fatigue. On laboratory testing, he was found to have a creatinine of 4.8. Complement levels are depressed and blood cultures are positive. A transesophageal echocardiogram confirmed the presence of endocarditis. A kidney biopsy was obtained due to hematuria. Image 1 and Image 3 shows circumferential cellular crescents with fibrinoid necrosis (many intracapillary neutrophils are seen in image 3). Figure 2 shows severe interstitial fibrosis. Images 4 and 5 show immunofluorescence staining with IgM and C3, respectively. This is a case of endocarditis-associated glomerulonephritis with diffuse...

ALECT2 Amyloidosis

The patient is a 75-year-old Hispanic male who presents with progressively worsening kidney function and a creatinine of 1.6 mg/dl (baseline 1.0 mg/dl). His physician called for a biopsy due to a slowly "creeping" creatinine over the last 8 months. Images 1 & 2 show "apple-green birefringence" on a Congo red stain under polarized light within the interstitium. Image 3 shows mild interstitial fibrosis. Image 4 shows a normal glomerulus on PAS stain and Image 5 shows positive immunohistochemical staining with Lect2. Leukocyte cell-derived chemotaxin 2 (ALECT2) amyloidosis preferentially affects Hispanics (particularly Mexicans) as well as Punjabis, First Nations people...

Resolving Membranous Nephropathy

A 40-year-old white male presents with 3 grams/24 hr of proteinuria and swelling around his ankles. He reports that he has had foamy urine over the last 4 months, but was unable to go to a doctor till now because of lack of insurance. Image 1 and image 2 shows irregularly thickened glomerular basement membranes with lamellation. Image 3 shows numerous "holes" on silver stain. Images 4, 5, and 6 show weak staining for IgG, kappa, and lambda, respectively. Membranous nephropathy in a resolving phase can be a tricky diagnosis since the immunofluorescence staining may be extremely weak or negative....

Nucleated Red Blood Cells in Circulation

The patient is a 70-year-old male who presents with a creatinine of 5 mg/dl and a history of primary myelofibrosis. The biopsy shows a kidney with severe glomerular and tubulointerstitial chronicity, approaching end-stage kidney disease from arterionephrosclerosis. Interestingly, circulating nucleated red blood cells were identified in the arteries and peritubular capillaries. Although not representing a specific kidney disease, the presence of nucleated red blood cells within the circulation points toward premature release of erythroid precursors from the bone marrow. This finding is has been reported in the setting of a space-occupying lesion in the bone marrow from metastases or in...

HIVICK

The patient is a 24 year-old African American male who has recently been diagnosed with HIV infection. He has not received HAART therapy and presents to the hospital with 1.2 g/g of proteinuria and a creatinine of 2.9 mg/dL. Figure 1 shows segmental sclerosis. Figure 2 shows tubular atrophy and interstitial inflammation. Figure 3 shows "hole" formation in glomerular basement membranes. Figures 4, 5, and 6 shows IgG, kappa, and lambda, respectively. Figure 7 shows mesangial and capillary wall electron dense deposits. This is a case of HIV immune complex disease of the kidney (HIVICK). HIV immune complex disease of...

Methotrexate-Induced Crystal Nephropathy

The patient is a 50-year-old male who presents with a creatinine of 4.2 mg/dL (baseline 1.0 mg/dL). He has been receiving high dose methotrexate for treatment of osteosarcoma. Image 1 shows a normal glomerulus. Image 2 shows moderate interstitial fibrosis. Image 3, 4, and 5 shows polarizable silver-positive crystals within the tubular lumens. This is a case of methotrexate-induced crystal nephropathy. Methotrexate-induced crystal nephropathy is characterized by acute tubular injury with scattered intratubular and interstitial needle-shaped, golden-brown crystals which are frequently arranged in annular structures. The crystals show birefringence under polarized light and are methenamine silver positive.  Methotrexate-induced crystal nephropathy...

BK Nephritis

The patient is a 45-year-old male with a past medical history significant for ESKD secondary to IgA nephropathy S/P renal transplant (3 years ago). He has been in his normal state of health but presented with an abnormal creatinine of 2.5 mg/dL on routine examination. His BK viral load was elevated at 25,000 copies in the serum. Figure 1 shows a normal glomerulus, figure 2 shows severe interstitial inflammation, figures 3 & 4 show marked tubulitis, and figure 5 shows a SV40 positive stain. This is a case of BK nephritis. BK virions are non-enveloped double-stranded DNA viruses. In immunohistochemistry,...

Type 1 Cryoglobulinemic Glomerulonephritis

The patient is a 75 year-old female who presents with proteinuria, a necrotic skin lesion on her lower extremity, and a creatinine of 5.5 mg/dL. Her serum complement levels (C3/C4) are low.  Serologies for ANA, dsDNA, rheumatoid factor, c-ANCA, p-ANCA, anti-GBM, and ASO are negative. Her cryoglobulins are positive. Image 1 shows hyaline thrombi and image 2 shows mild interstitial fibrosis. Images 3, 4, 5, and 6 are IgG, IgM, kappa, and lambda, respectively. This is a case of Type 1 cryoglobulinemia. Type 1 cryoglobulins are composed of a single monoclonal immunoglobulin that reversibly participates at low temperature (<37C).  Type...

Waldenström’s Macroglobulinemia

A 57-year-old white male presents with fatigue, mild proteinuria, and a creatinine of 1.5 mg/dL. He was diagnosed with lymphoplasmacytic lymphoma 6 months ago, but refused treatment. Figures 1 & 2 show prominent pseudothrombi and a membranoproliferative pattern of glomerular injury. Image 3 shows moderate interstitial fibrosis. Image 4, 5, 6, & 7 show IgG, IgM, kappa, and lambda, respectively. This is a case of cryoglobulinemic glomerulonephritis secondary to lymphoplasmacytic lymphoma (Waldenström's macroglobulinemia). Waldenström's macroglobulinemia is a rare B-cell lymphoma characterized by lymphoplasmacytic cell infiltration in the bone marrow and other organs and the presence of a monoclonal immunoglobulin M...