Arkana Advances

Over the past decade, there has been a dramatic increase in kidney biopsy inadequacy rate. Evaluation of biopsy adequacy by pathology is often not available. This study utilizes a smartphone camera to take a photograph of the biopsy at the bedside, which is then enlarged to allow for distinction between cortex and medulla. The physician performing the procedure, most often a radiologist, can then decide if additional samples are needed. In this study, there was a high agreement rate in the determination of adequacy between pathology (using a dissecting microscope) and radiology (using a smartphone). This method of determining specimen adequacy has the potential to decrease the biopsy inadequacy rate while simultaneously lowering cost and improving patient outcome.

Read the paper: https://journals.lww.com/jasn/pages/articleviewer.aspx?year=2021&issue=12000&article=00012&type=Fulltext

Membranous Nephropathy, or Membranous Glomerulopathy, is an autoimmune disease-causing nephrotic syndrome in which there is subepithelial deposition of IgG and complements along the glomerular basement membrane. Membranous Nephropathy is the second leading cause of nephrotic syndrome in adults. Following the description of the first membranous antigen PLA2R in 2009, there has been numerous antigens described and associations with different diseases. In addition to a discussion of the individual antigens, this review article covers a description of techniques for discovery of new antigens and how these techniques have changed over time.

NELL1 is a recently described antigen seen in membranous glomerulopathy, which has been associated with malignancy.  A recent study linked Lipoic Acid supplementation with membranous glomerulopathy. In this letter to the editor, medication use was examined in 115 patients with NELL1 positive membranous glomerulopathy and 200 patients with membranous glomerulopathy of other types. In the NELL1 positive group, 15 patients had active Lipoic Acid use, while no Lipoic Acid supplementation was seen in the non-NELL1 membranous group. In addition to a malignancy workup in patients diagnosed with NELL1 positive membranous glomerulopathy, patients should also be asked about Lipoic Acid supplementation.

Read the paper: https://www.kidney-international.org/article/S0085-2538(21)01140-6/fulltext

Early in the COVID-19 pandemic many wondered how COVID-19 would impact kidney function. A collaboration across multiple institutions was formed to study kidney biopsies from COVID-19 patients. This paper analyzes 284 native and transplant kidney biopsies from patients with COVID-19. Compared to a five-year pre-pandemic cohort, native kidney biopsies showed an increase in collapsing glomerulopathy, myoglobin cast nephropathy, and proliferative glomerulonephritis with monoclonal IgG deposits. Over 90% of patients with collapsing glomerulopathy had two APOL1 high-risk alleles, compared to 35% of non-collapsing glomerulopathy cases (both increased over the general population). Transplant biopsies were more likely to have transplant rejection in patients with COVID-19, with a mix of antibody mediated and T-cell mediated rejection. No direct infection of the kidney tissue by COVID-19 was detected.

Read the paper: https://www.kidney-international.org/action/showPdf?pii=S0085-2538%2821%2900734-1

A renal biopsy is an invasive procedure requiring sedation that is often necessary for appropriate patient treatment. A biopsy is "inadequate" when a complete diagnosis cannot be rendered, usually due to the lack of sufficient renal cortex within the biopsy. Over a 16 year period, a total of 123,372 native renal biopsies were received at Arkana Laboratories. The rate of inadequate kidney biopsies increased from approximately 2% in 2005 to 14% in 2020. In 2005, only 5% of biopsies were performed by radiology. This increased to 95% performed by radiology in 2018. The rate of inadequate biopsies increased over time for both radiology and nephrology but was much higher for radiology. This correlates with the diameter of needles used by radiology (18g/20g) vs nephrology (14g/16g). The rate of deep misses, where the biopsy is predominately medulla, is higher in radiology performed biopsies. We have many resources available at Arkana Labs if your institution is struggling with inadequate biopsies. If your renal biopsies are read at Arkana Labs, we can pull the miss rate for your hospital and also offer training programs incorporating different tools to assess adequacy in real-time.

Read the paper: Increasing Incidence of Inadequate Kidney Biopsy Samples Over Time: A 16-Year Retrospective Analysis From a Large National Renal Biopsy Laboratory

Approximately half of lupus patients have kidney disease, including membranous glomerulopathy. On renal biopsy, immunofluorescence shows granular capillary loop deposits, and holes are seen in the capillary loops on silver stain. Electron microscopy shows subepithelial immune complex deposits.  It is important to determine an antigen in these cases, as it can be linked to patient prognosis. The most common antigen seen in membranous lupus nephritis is EXT1/2, followed by NCAM1. This study identified a new target antigen, TGFBR3, seen in approximately 6% of membranous lupus nephritis cases. TGFBR3 was also seen in a few patients with membranous glomerulopathy and other autoimmune diseases.  Of 15 patients who were followed clinically, only 2 achieved clinical remission (average 11-month follow-up). Patients with TGFBR3 positive membranous glomerulopathy should undergo a workup for autoimmune disease.

Read the paper: https://kidney360.asnjournals.org/content/kidney360/2/8/1275.full.pdf?with-ds=yes

The association of rare autoimmune responses to vaccination is well known. This study investigates the effect of COVID-19 vaccination on the kidney. In a six-month period, 29 cases (including relapse of disease) were identified with temporal association to COVID-19 vaccination out of approximately 10,000 biopsies. The most common diagnoses were IgA Nephropathy (10 cases), minimal change disease (7 cases), and crescentic glomerulopathy with positive ANCA (6 cases). The overall frequency of these diseases was not increased compared to pre-pandemic levels. The true incidence and association with vaccination is not entirely clear in this period of mass vaccination. An NIH registry for glomerulonephritis post-COVID-19 vaccination has been created to further study this topic and is open to international patients. See the link below if you would like to register a patient.

Link to the registry (Glomerulonephritis post-COVID-19 vaccination): https://redcapsurvey.niddk.nih.gov/surveys/?s=LCDAMFD9JA

Read the paper: https://kidney360.asnjournals.org/content/kidney360/2/11/1770.full.pdf?with-ds=yes

Membranous nephropathy is a leading cause of nephrotic syndrome. On renal biopsy, immunofluorescence shows granular capillary loop deposits, and holes are seen in the capillary loops on silver stain. Electron microscopy shows subepithelial immune complex deposits. Membranous glomerulopathy can be seen in association with autoimmune diseases including lupus. The most common antigen seen in membranous lupus nephritis is EXT1/2. This study identified a new target antigen, NCAM1, which was present in 6.6% of membranous lupus nephritis cases. Few cases of NCAM1 membranous were seen in patients with non-lupus autoimmune disease. NCAM1 can also be detected in the serum of these patients. Approximately 40% of patients had neuropsychiatric disease, including seizures and cerebritis. Clinical outcomes for these patients are still unknown.

Read the paper: https://www.kidney-international.org/action/showPdf?pii=S0085-2538%2820%2931180-7

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Membranous nephropathy is a leading cause of nephrotic syndrome. On renal biopsy, immunofluorescence shows granular capillary loop deposits, and holes are seen in the capillary loops on silver stain. Electron microscopy shows subepithelial immune complex deposits. A majority of cases have autoantibodies against PLA2R and THSD7A. This study identified a new target antigen, NELL1, which was present in 1.7% of membranous cases. NELL1 can also be detected in the serum of these patients. Approximately 33% of patients with NELL1 have a known malignancy. Patients with successful treatment of the malignancy showed good responses to membranous treatment. Patients with NELL1 positive membranous nephropathy should receive age-appropriate cancer screening.

Read the paper: https://www.kidney-international.org/action/showPdf?pii=S0085-2538%2820%2930956-X

 

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