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Art of Medicine: Proliferative Glomerulonephritis with 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

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

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

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

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...

Art of Medicine: Anti-Brush Border Antibody Disease

The above painting shows massive tubular basement membrane (electron dense on EM) deposits along proximal tubules with sparing of the distal tubules.  This is a finding that can be seen by electron microscopy in anti-brush border antibody disease (ABBA).   Tubular basement membrane deposits are also seen in lupus nephritis (all classes), IgG4-associated kidney disease, idiopathic hypocomplementemic interstitial nephritis, polyomavirus nephritis (BK virus or JC virus), or in response to certain medications (eculizumab, NSAIDS, and others).   Interstitial inflammation is not prominent in ABBA disease, as it is with other pathologies with tubular basement membrane deposits (such as IgG4-associated disease, drug reactions,...

Art of Medicine: IgA Nephropathy

The above painting shows glomeruli with mesangial hypercellularity, endocapillary hypercellularity, and crescent formation.  These findings can be seen in IgA nephropathy, and other active glomerulonephritides.  These lesions shown in the painting above are represented in the Oxford Classification for IgA nephropathy.  The Oxford classification is a scoring system on kidney biopsies that  includes mesangial hypercellularity (M0 = <50%, M1 = >50%), endocapillary hypercellularity (E0 = none, E1 = present), segmental sclerosis (S0 = absent, S1 = present), tubular atrophy / interstitial fibrosis (T0 = <25%, T1 25-50%, T2 >50%), and crescents (C0 = absent, C1 = up to 25%, C2...

Art of Medicine: Membranous Lupus Nephritis

The above painting depicts electron microscopy of two glomerular capillary loops and a mesangial region from a case of membranous lupus nephritis, showing intramembranous and mesangial electron-dense deposits.  An electron photomicrograph from a patient with membranous lupus nephritis, showing the same features, is also shown below. Pure membranous lupus nephritis (classified under the International Society of Nephrology / Renal Pathology Society system as class V), without an associated focal or diffuse (proliferative) lupus nephritis, occurs in approximately 15 percent of all patients with renal involvement by systemic lupus erythematosus (SLE).   This percentage is higher in African Americans with SLE.   While...

Art of Medicine: The Pre-Implantation Kidney Biopsy

The painting above shows normal glomeruli, tubulointerstitium, and a normal artery from a pre-implantation wedge biopsy. Pre-implantation wedge biopsies, also known as donor biopsies, procurement biopsies, or harvest biopsies, are performed for extended criteria donor kidneys, high risk recovered donor kidneys, or at the request of the transplant surgeon, to evaluate for suitability for transplantation. Over 40% of procured kidneys are discarded prior to transplantation. The use of preimplantation kidney biopsies, performed as frozen sections at transplant centers, may reduce the discard rate by accepting kidneys that are histopathologically acceptable, as well as to avoid transplantation of sub-optimal organs. “Extended...

Art of Medicine: Collapsing Glomerulopathy

The above painting shows a glomerulus with capillary tuft collapse, visceral epithelial cell hyperplasia, and numerous protein resorption droplets within Bowman’s space; findings that can be seen in collapsing glomerulopathy.  A PAS stain from a case of collapsing glomerulopathy is also shown in the photomicrograph below.  Initially, collapsing glomerulopathy was considered a severe form of focal segmental glomerulosclerosis and placed into the Columbia classification. According to the Columbia classification, collapse of at least one capillary loop with obliteration of the lumen and proliferation and hypertrophy of overlying podocytes is sufficient for a diagnosis of the collapsing glomerulopathy.  Tubulointerstitial damage is...