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Art of Medicine: Covid-19 Associated Nephropathy (COVAN)

SARS-CoV-2, COVAN, Covid-19, collapsing Myoglobin cast, renal pathology
Development of acute kidney injury (AKI) in the setting of COVID-19 substantially worsens outcomes, with increased morbidity and mortality, and has been a recent area of investigation.  The painting shown above includes two common disease manifestations in the setting of Coronavirus Disease-2019 (COVID19), which include collapsing glomerulopathy and myoglobin cast nephropathy.   Histologic images of each of these entities are shown below. Collapsing glomerulopathy, also known as COVID-19-associated nephropathy (COVAN), is one of the most common causes of acute kidney injury (as well as nephrotic syndrome) in patients with COVID-19.   COVAN results from SARS-CoV-2 acting as a 'second hit' to individuals...

Disease Week: MGMID

MGMID
Tuesday: Let's start with a poll. You have a 25-year-old female patient with a positive ANA and proteinuria.  On a kidney biopsy, light microscopy looks fairly unremarkable - a little mesangial expansion and mildly prominent capillary loops.  IF is also nearly unremarkable, but with 2+ C3 staining.  On EM, you have this finding. What do you do next? Stain the biopsy with PLA2R Perform IgG subclasses Do paraffin immunofluorescence There has to be a mix-up - check with the lab Answer - Paraffin Immunofluorescence   What do you expect to find by paraffin immunofluorescence? Strong C3 staining to confirm C3...

Art of Medicine: Segmental Membranous Glomerulopathy

segmental membranous nephropathy (MN) Art of Medicine painting
The painting depicts a silver stain of a glomerulus, showing thickened capillary loops with segmental ‘holes’, consistent with a segmental membranous nephropathy (MN). An IgG immunofluorescence image and an electron photomicrograph showing segmental immune deposits are shown below.    IgG staining in a segmental distribution within a glomerulus, note capillary loop sparing.   Ultrastructural evaluation of a glomerulus shows capillary loops with and without subepithelial electron-dense deposits.   The majority of MN cases show diffuse and global IgG staining, with segmental subepithelial immune deposits seen in only 2.5% of all MN biopsies.  In a recent case series, of all cases...

Art of Medicine: Proliferative Glomerulonephriits with Monoclonal Immunoglobulin Deposits

monoclonal gammopathies , arkana laboratories, art of medicine, kidney art
The above painting shows normal bone marrow, containing erythroid and myeloid precursors at various stages of maturation and normal trabeculae.   Bone marrow biopsies may be performed to evaluate for a lymphoid or plasma cell clone in patients with monoclonal gammopathies of undetermined significance and in work-up of patients found to have a monoclonal gammopathy of renal significance (MRGS).  Monoclonal gammopathies of renal significance occur when light chain restriction within a kidney biopsy is thought to be responsible for the patient's renal dysfunction, which is usually acute kidney injury or proteinuria.  This includes a broad spectrum of findings, which includes but...

Art of Medicine: Alport Syndrome- A Review of Ultrastructural Abnormalities

The above painting depicts electron microscopy of a case of Alport syndrome.   Alport syndrome is a type of hereditary nephritis due to mutations in the alpha 3, alpha 4, or alpha 5 chains of collagen type IV.   As a result, the typical alpha 3-4-5 meshwork of type IV collagen in the GBM is replaced by an alpha 1-2 meshwork, which has less tensile strength and has susceptibility to proteolysis by matrix metalloproteinases (Zeisberg et al, 2006). Patients with Alport syndrome present with hematuria and progressive renal failure, and males are disproportionately affected.  Deafness and visual problems can also occur.  Kidney...

Art of Medicine: Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits

Monoclonal Immunoglobulin Deposits
Small destructive B cell or plasma cell clones may be responsible for disease development. The above painting shows normal bone marrow, containing erythroid and myeloid precursors at various stages of maturation and normal trabeculae.   Bone marrow biopsies may be performed to evaluate for a lymphoid or plasma cell clone in patients with monoclonal gammopathies of undetermined significance (MGUS) and in work-up of patients found to have a monoclonal gammopathy of renal significance (MRGS).  Monoclonal gammopathies of renal significance occur when light chain restriction within a kidney biopsy is thought to be responsible for the patient's renal dysfunction, which is usually...

Art of Medicine: Proliferative Glomerulonephritis

Proliferative Glomerulonephritis
The above painting shows endocapillary hypercellularity with mononuclear cells and neutrophils, as well as hyaline deposits within glomeruli.  Red blood cell casts are seen within focal tubular lumens, and the tubules are widely spaced due to interstitial edema and inflammation.  These findings can be seen within acute proliferative glomerulonephritis.  Other proliferative changes within glomeruli seen in acute proliferative glomerulonephritis include mesangial hypercellularity and crescent formation. The differential diagnosis for proliferative glomerulonephritis is broad and includes infection-associated glomerulonephritis including post-streptococcal glomerulonephritis, focal or diffuse lupus nephritis, shunt nephritis, cryoglobulinemic glomerulonephritis, hepatitis-associated glomerulonephritis, and IgA nephropathy (or Henoch-Schonlein purpura nephritis).   Other considerations...

Art of Medicine: Thrombotic Microangiopathy

Thrombotic Microangiopathy
The above painting shows a glomerulus containing capillary loop fibrin thrombi, an arteriole with onion-skinning, and acute tubular injury, findings that can be seen in thrombotic microangiopathy.  Morphologic findings of thrombotic microangiopathy that can be seen on a renal biopsy include arteriolar or capillary loop fibrin or platelet thrombi, red blood cell fragmentation within glomerular capillary loops or within arteries, mesangiolysis, endothelial cell swelling,  glomerular basement membrane duplication, mucoid intimal edema of arteries, and a myointimal proliferation surrounding arterioles (onion-skinning like reaction). Thrombotic microangiopathy (TMA) has a wide clinical differential diagnosis, which can have substantial morphologic overlap on a kidney...

Art of Medicine: Monoclonal Gammopathies of Renal Significance

Monoclonal Gammopathies of Renal Significance
The above painting is of a bone marrow biopsy showing replacement of the hematopoietic elements with plasma cells, including atypical plasma cells (Mott cells and plasma cells with Dutcher bodies shown).  This can be seen in plasma cell myeloma. Multiple myeloma can be diagnosed with the presence of a plasma cell myeloma (>10% clonal bone marrow plasma cells), and one or more myeloma-defining events.  These include hypercalcemia, renal insufficiency, anemia, or lytic lesions within bones.   On a kidney biopsy, light chain cast nephropathy is a myeloma defining event and is a paraprotein-associated renal disease.  Other renal manifestations that can occur...

Art of Medicine: Plasma Cell Rich Interstitial Nephritis

Plasma Cell Rich Interstitial Nephritis
The above painting shows plasma cell rich interstitial inflammation with lymphocytic and plasma cell tubulitis, findings that can be seen in plasma cell rich interstitial nephritis.  Acute interstitial nephritis can have an inflammatory infiltrate with lymphocytes, plasma cells, eosinophils, neutrophils, and/or histiocytes.  Greater than 10 percent plasma cells would be considered “plasma cell rich”.  An H & E stained section of a plasma cell rich infiltrate is shown below. The differential diagnosis for a plasma cell rich interstitial nephritis in native kidney biopsies includes drug reactions, Sjögren's syndrome, chronic pyelonephritis, and IgG4-related kidney disease.  IgG4-related kidney disease is characterized by...