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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...

Art of Medicine: Diabetic Nephropathy

The above painting shows glomeruli with nodular mesangial expansion and arterial hyalinosis, changes frequently seen in diabetic nephropathy. Diabetic nephropathy is graded by the classification system established by the Renal Pathology Society to separate lesions into varying degrees of severity. In class I diabetic glomerulopathy, there are no changes identified by light microscopy, but thickening of the glomerular basement membranes are seen on electron microscopy (see photomicrograph below). Thickened glomerular basement membranes are greater than 471 nm in women or 520 nm in men (in our lab), which represents greater than 2 standard deviations above the normal population. Glomerular basement...

Disease Week: Lupus Nephritis

Monday:  Introduction to Systemic Lupus Erythematosus and Clinical Diagnostic Criteria Answer:  C.  50%  50% of adults with SLE will develop lupus nephritis.   In children with SLE, 80% have nephritis. References: Madhok R.  Systemic lupus erythematosus: lupus nephritis.  BMJ Clinical Evidence 2015 Dec 18; pp 1123. https://www.ncbi.nlm.nih.gov/pubmed/26683208 Liu CC, Kao AH, Manzi S, Ahearn JM.  Biomarkers in systemic lupus erythematosus: challenges and prospects for the future.  Therapeutic Advances in Musculoskeletal Disease 2013; 5 (4): 210-233. https://www.ncbi.nlm.nih.gov/pubmed/23904865 In a majority of cases, renal involvement in SLE often occurs in the first year following diagnosis, but can occur at any time in the disease course. ...

Art of Medicine: Lupus Nephritis Genetics

The above painting shows an image of a sequencing gel, which are produced by DNA synthesis in the presence of sequence terminators such as dideoxyribonucleotides (that are mixed with deoxyribonucleotides used for chain elongation), with the DNA fragments run on an agarose gel. The agarose gels are then imaged using a DNA intercalator, such as ethidium bromide, that allows the DNA fragments to fluoresce in the ultraviolet spectrum. This is the basis of Sanger sequencing. Advances to Sanger sequencing included use of fluorescent labeled chain terminators, which allowed for a higher throughput readout and faster results. These could also be...