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Disease Week: Lupus Nephritis (Summary)

New SLE diagnostic criteria increase sensitivity for lupus nephritis diagnosis, and novel biomarkers could prove helpful to compensate for reduced specificity. Under the new criteria established by the Systemic Lupus International Collaborating Clinic as a joint effort from the American College of Rheumatology and European League Against Rheumatism, a diagnosis of lupus nephritis can now be made with a positive antinuclear antibody and class III or IV lupus nephritis alone. This increased the sensitivity of diagnosis but reduced specificity, when compared to the 1997 revision of the 1982 American College of Rheumatology SLE diagnostic criteria (Rijnink et al, 2018). With...

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...

International Society of Nephrology / Renal Pathology Society Classification of Lupus Nephritis

How do we classify lupus nephritis on a renal biopsy?  SLE patients with an active urinary sediment or proteinuria may undergo a kidney biopsy to evaluate for nephritis.  The International Society of Nephrology (ISN) and Renal Pathology Society (RPS) created a lupus nephritis classification system based on morphologic findings on kidney biopsies.  A simplified view of the classification algorithm is based on the sites of immune deposits within glomeruli.  A flow-chart demonstrating that algorithm is shown below.   Mesangial immune deposits can be present in all classes. A summary in tabular format is shown below.   While a majority of SLE patients...

Introduction to Systemic Lupus Erythematosus and Clinical Diagnostic Criteria

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which affects over 5 million people worldwide, and manifests as tissue damage within multiple organ systems.  It has a complex etiology, involving a combination of multiple genetic and environmental factors.  Women are disproportionately affected, with a 9:1 female-to-male ratio. The diagnostic criteria are determined by the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR).  In the 1997 revision of the 1982 ACR diagnostic criteria for diagnosis of SLE, 4 of 11 disease manifestations are required (Hochberg, 1997).  These are shown below: Notice that “renal disorder” is one...

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...

Art of Medicine: Borderline Changes for TCMR Painting

The painting above of a kidney transplant biopsy shows mild interstitial inflammation and tubulitis.   If this field is representative, these changes would be consistent with borderline changes suspicious for T cell-mediated rejection (TCMR).   A diagnosis for borderline changes suspicious for TCMR can be made with mild interstitial inflammation (i1; 10-25% of cortex) with any degree of tubulitis (i1t1 with 0-4 lymphocytes/tubular profile, i1t2 with 4-10 lymphocytes per tubular profile, i1t3 with >10 lymphocytes per tubular profile or tubular basement membrane rupture), by moderate interstitial inflammation (25-50% of cortex) with mild tubulitis (i2t1), or with isolated tubulitis without interstitial...

Art of Medicine: Light Chain Proximal Tubulopathy

The painting above shows light chain proximal tubulopathy with crystals, which is one type of a monoclonal gammopathy of renal significance (MGRS).  MGRS, as defined by the International Kidney and Monoclonal Gammopathy Research Group, is a “clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin” (Leung N et al, 2019), and indicates end-organ damage resulting from a monoclonal gammopathy.   The most common MGRS manifestations include AL amyloidosis, monoclonal immunoglobulin deposition disease, light chain cast nephropathy, and light chain proximal tubulopathy.   In light chain proximal tubulopathy, a nephrotoxic monoclonal light chain induces acute tubular injury or proximal tubular dysfunction.  Proximal tubular...