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Archive: Art of Medicine

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...

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...

Art of Medicine: Polyomavirus Nephritis

The painting above shows acute tubular injury, reactive changes in tubular epithelial cells, tubulitis, inclusions within tubular epithelium, and interstitial inflammation.  These are morphologic changes that can be seen in polyomavirus nephritis.  BK virus is the most common etiology of polyomavirus nephritis, while JC virus and simian virus 40 (SV40) are less common etiologies.  All are DNA viruses that are non-enveloped and show tropism for the genitourinary tract, especially urothelium (Lusco et al, 2016).  Polyomavirus nephritis is a serious complication affecting approximately 5 to 6 percent of kidney transplants, often as a result of over-immunosuppression.  The prevalence is higher in...

Art of Medicine: Minimal Change Disease

The above painting shows podocytes with foot processes extending along the glomerular basement membrane of neighboring capillary loops.  Effacement of podocyte foot processes occurs in primary podocytopathies, including minimal change disease (see electron photomicrograph below). Minimal change disease is the most common etiology of idiopathic nephrotic syndrome in children and is the third most common cause in adults, after focal segmental glomerulosclerosis and membranous glomerulopathy.  A majority of cases are “primary”, require no additional workup, and are due to a circulating permeability factor.   Several possible secondary causes have also been identified.  Although these are rare, these should be considered in...

Art of Medicine: Lysozyme Nephropathy

The painting above shows acute tubular injury with numerous intracytoplasmic inclusions within proximal tubular epithelium, which can be seen in lysozyme-associated nephropathy.  Lysozyme-induced nephropathy is a rare cause of acute tubular injury seen in patients with hematologic malignancies, most commonly with chronic myelomonocytic leukemia (CMML) and acute monocytic leukemia (Santoriello et al, 2017).   Malignancy associated overproduction of lysozyme can lead to acute kidney injury and proteinuria.  Lysozyme is freely filtered by the glomerulus and reabsorbed by the proximal tubular epithelium.  While this happens at a low level physiologically, over-reabsorption of lysozyme induces toxic acute tubular injury. Lysozyme-induced nephropathy is one...

Art of Medicine: Fanconi Syndrome

This painting shows the transition between a proximal tubule and the thick descending limb of the loop of Henle.  The proximal tubule has numerous functions, including transport of sodium chloride, bicarbonate, glucose, amino acids, organic cations, organic anions, and phosphate.  Disruption of proximal tubule function manifests clinically as Fanconi syndrome.   Development of polyuria, osteomalacia, muscle weakness, and growth failure can result if it is unrecognized and untreated. Fanconi syndrome can be diagnosed by clinical chemistry tests, including urine sodium, potassium, calcium, phosphate, glucose, amino acids, and uric acid levels, as well as urine pH.   In Fanconi syndrome, there is glycosuria...