Sethi et. al have reported new markers Exostocin 1 & Exostocin 2, which are particularly useful for diagnosing PLA2R/THSD7A negative cases of Membranous nephropathy. In approximately 70%–80% of cases of primary membranous nephropathy (MN), phospholipase A2 receptor (PLA2R)/Thrombospondin Type-1 Domain–Containing 7A (THSD7A) and anti-PLA2R/THSD7A antibodies form immune complexes along the glomerular basement membrane (GBM) that characterize the condition. In other cases of primary MN and all secondary MN, the target antigen is unknown. Using proteomics and immunohistochemistry, Sethi et. al detected two proteins, exostosin 1 (EXT1) and exostosin 2 (EXT2), in the GBM of PLA2R-negative MN. EXT1 and EXT2 were absent in all cases of PLA2R-associated MN and controls. Clinical and biopsy findings showed features of autoimmune disease, including membranous lupus nephritis, in 81% of the 26 EXT1/EXT2-associated MN cases the authors identified. These findings suggest that EXT1/EXT2-associated MN represents a distinct subtype of MN, most commonly associated with autoimmune diseases (secondary MN).
Jean Berger (1930-2011)
On September 27–29, 2018, the International Symposium on IgA Nephropathy, organized by the International IgA Nephropathy Network, was held in Buenos Aires, Argentina, celebrating the 50th anniversary of the first description of IgA nephropathy by Berger and Hinglais in 1968. The meeting was attended by over 200 scientists and clinicians from 26 different countries across the globe. We report some key insights drawn from the meeting–including the molecular pathogenesis, genetics, pathology, and therapeutics of IgA nephropathy.
An excellent overview of this conference also describing the current state of knowledge and exciting new developments related to this enigmatic disease is published in April 2019 issue of Kidney International. This article is a must read for everyone as it provides a birds eye view of all the burning issues pertaining to IgA nephropathy.
Current issue of Kidney International features the largest series of renal biopsy findings in patients with morbid obsesity.This study includes analysis of 248 biopsies in patients with morbid obesity and brings forth some interesting facts. Morbid obesity is defined as BMI > 40kg/m2& is a recognized risk factor for chronic kidney disease (CKD). Among 3263 native kidney biopsies interpreted at Columbia University in 2017, authors encountered 248 biopsies from morbidly obese patients. Diabetes and hypertension were present in 47% and 81% of patients, respectively. Median estimated glomerular filtration rate (eGFR) was 30 ml/min/1.73 m2, and most patients had nephrotic range proteinuria. Obesity related glomerulopathy (ORG), defined as focal segmental glomerulosclerosis with glomerulomegaly or glomerulomegaly alone, was detected in 73 patients, including 29 with ORG alone and 44 with ORG plus another kidney disease. In contrast, 167 patients had other kidney diseases alone, without ORG, most commonly (in descending order) diabetic nephropathy, acute tubular necrosis, hypertensive nephrosclerosis, IgA nephropathy, membranous nephropathy, and lupus nephritis. In 49% of patients, kidney biopsy yielded a diagnosis predicted to change patient management. The strongest predictor of non-ORG lesions was eGFR <30 ml/min per 1.73 m2, and presentation with nephrotic syndrome or acute kidney injury (with or without background CKD) was more common in non-ORG than ORG. The findings reveal an unexpectedly broad spectrum of kidney pathology beyond metabolic syndrome-associated disorders and highlight the importance of kidney biopsy to guide management and prognosis in the morbidly obese population.
Few other studies on this topic can be read by clicking on links below:
Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment
Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis.
The Renal Pathology of Obesity.
An interesting study was published in recent issue of American Journal of Transplantation which looks at the way current Banff classification of Antibody Mediated Rejection (ABMR) is interpreted by Nephrologists and Renal Pathologists and its eventual implications.
The aim of this study was to determine how the Banff antibody‐mediated rejection (ABMR) classification for kidney transplantation is interpreted in practice and affects therapy. The Banff Antibody‐Mediated Injury Workgroup electronically surveyed clinicians and pathologists worldwide regarding diagnosis and treatment for 6 casebased scenarios. The participants’ (95 clinicians and 72 renal pathologists) assigned diagnoses were compared to the Banff intended diagnoses (reference standard). The assigned diagnoses and reference standard differed by 26.1% (SD 28.1%) for pathologists and 34.5% (SD 23.3%) for clinicians. The greatest discordance between the reference standard and clinicians’ diagnosis was when histologic features of ABMR were present but donor‐specific antibody was undetected (49.4% [43/87]). For pathologists, the greatest discordance was in the case of acute/active ABMR C4d staining negative in a positive crossmatch transplant recipient (33.8% [23/68]).
Treatment approaches were heterogeneous but linked to the assigned diagnosis. When acute/active ABMR was diagnosed by the clinician, treatment was recommended 95.3% (SD 18.4%) of the time vs only 77.7% (SD 39.2%) of the time when chronic active ABMR was diagnosed (P < .0001). In conclusion, the Banff ABMR classification
is vulnerable to misinterpretation, which potentially has patient management implications. Continued efforts are needed to improve the understanding and standardized application of ABMR classification in the transplant community.
What are your thoughts on this? Do we as Pathologists or Nephrologists face similar difficulties when dealing with ABMR and what is the best way to approach this issue?
Welcome to the official blog page of ISRTP. We will keep posting here about topics of interest in the realm of renal and transplantation pathology and welcome your active participation in the discussions. Let us make this a platform for active and constructive interactions and a learning tool for all concerned...