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Zebrafish: How Can They Help Us?

I have enjoyed working with laboratory zebrafish since 2003.  Zebrafish have become a very well accepted model organism for human disease due to rapid breeding, fast development, transparent embryos, and conservation of 70% of human genes.  Several human diseases have been successfully modeled using zebrafish such as acute lymphoblastic leukemia, melanoma, and Duchenne muscular dystrophy. The majority of my time with zebrafish was spent in the Vanderbilt University system where I was involved in diverse research areas such as gastrulation, fetal alcohol syndrome, holoprosencephaly, Menkes Disease, and obesity. I discovered that I like contributing to the discovery or development of...

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...

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...

Membranous Lupus Nephritis

The patient is a 19-year-old female who presents with hematuria, nephrotic range proteinuria, and a creatinine of 1.2 mg/dL. She has a recent diagnosis of systemic lupus erythematosus. Figure 1 shows a normal glomerulus without "spikes" and "holes" of the glomerular basement membranes. Figure 2 shows no significant interstitial fibrosis. Figures 3, 4, 5, & 6 shows IgG, kappa, lambda, and C1q respectively. Image 7 and 8 shows subepithelial deposits. This is a case of membranous lupus nephritis (ISN/RPS Class V). By definition, no proliferative changes (crescents, fibrinoid necrosis, endocapillary hypercellularity) are seen within the glomeruli in a pure class...

Twitter Poll (July 10, 2019)

Answer: True About 5-10% of the patients with monoclonal gammopathy and findings consistent with C3GN by standard IF (on frozen tissue) will actually have a Membranoproliferative GN with masked monoclonal deposits. These patients require additional IF studies to be performed on protease-digested, paraffin-embedded tissue for identification of the monoclonal immunoglobulin in the deposits. References: Leung N, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol 2019; 15(1): 45-59. Larsen CP, et al. Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits. Kidney Int 2015; 88(4): 867-873....

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...

Disease Week: Monoclonal Gammopathy of Renal Significance

Disease Week: Monoclonal Gammopathy of Renal Significance   Summary: Renal disease caused by parenchymal deposition of circulating monoclonal immunoglobulins (mIg) is a well established phenomenon. Light chain cast nephropathy, light chain deposition disease and AL amyloidosis are probably the best known entities; nevertheless, the list also includes a number of less common and recently described entities, some of which are still poorly understood.  These disorders may be seen in the setting of either a B-cell or plasma cell proliferative disorder with production of a mIg. When these proliferative disorders represent an overtly malignant disease (e.g. multiple myeloma, Waldenström macroglobulinemia, high-grade...

Kidney Pillow

How cute is this kidney pillow?!  Dr. Caza and Dr. Dvanajscak had two of these pillows commissioned by Heather Weathers at sewoddity.com for Dr. Larsen and Dr. Walker. Be sure to go check out her work.  She creates anatomical and science-based art in her home studio and everything is super cute.     

Diagnose This (July 1, 2019)

What is your diagnosis?       ​ ​   ​   ​ ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​ ​   ​ ​   ​ ​   ​ ​     ​   ​   ​ ​...