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KDIGO Connections: Membranous Glomerulopathy

Welcome to the first post in our new series KDIGO Connections, a series in which we are asking our nephrologist colleagues to educate us in real-world experiences treating kidney disease. In this series, Dr. David Bourne will be kicking it off with KDIGO guidelines for a kidney disease in visual abstract form. Our hope is that these posts will foster discussion regarding these diseases and how different providers approach them. Please share any points, pearls, questions, caveats, thoughts, or experience you have on the presented disease letting us all learn from your experience!  

Membranous Glomerulopathy in Obesity-Related Glomerulopathy

The patient is a 57-year-old female, with a history of morbid obesity and persistent mild proteinuria (approximately 1 gm), who now presents with nephrotic syndrome and a UPCR of 10.5 g/g. Renal function is normal with a serum creatinine of 0.5 mg/dl. The biopsy shows marked glomerulomegaly with focal areas of perihilar segmental glomerulosclerosis (Fig 1 and 2). Additionally, the capillary loops appear mildly thickened, with frequent subepithelial fuchsinophilic deposits on trichrome stain and diffuse and global holes and spikes seen on silver stain (Fig 3). Immunofluorescence shows global capillary loop granular staining for IgG, C3, kappa, and lambda (Fig...

Diabetic Glomerulosclerosis with Superimposed Diseases

Diabetic glomerulosclerosis is one of the most common causes of nephrotic range proteinuria in adults. When the clinical course of these patients is atypical, a renal biopsy is of utmost importance to rule out superimposed or other concomitant diseases. Figure 1 (PAS stain) shows a representative glomerulus from a renal biopsy performed on a 65 year old Caucasian female with longstanding history of type 2 diabetes mellitus, who experienced a sudden increase in proteinuria from a baseline UPCR of 1.2 g/g to 7.5 g/g. The glomerulus shows severe mesangial matrix expansion with frequent large nodule formation, characteristic of diabetic glomerulosclerosis....

Diagnose This (June 25, 2018)

What immunofluorescence stain is shown here, what is the immune complex deposition pattern and what disease does it represent?   ​   ​ ​   ​   ​ ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​ ​   ​...

Membranous with FSGS

Some patients with membranous glomerulopathy also have associated focal segmental glomerulosclerosis (FSGS) lesions. The glomerulus in this biopsy image, for example, shows a prominent area of segmental sclerosis surrounded by mildly thickened capillary loops which have granular IgG deposits by immunofluorescence (see inset). As in other renal diseases, studies have linked the presence of FSGS lesions in patients with membranous glomerulopathy to more severe disease (e.g. higher levels of proteinuria). Dumoulin A, Hill GS, Montseny JJ, Meyrier A. Clinical and morphological prognostic factors in membranous nephropathy: significance of focal segmental glomerulosclerosis. Am J Kidney Dis. 2003 Jan;41(1):38-48. PMID: 12500220.

PLA2R Tutorial

The diagnosis of membranous glomerulopathy has been transformed in the past 10 years with the discovery of PLA2R. PLA2R is the most common target antigen in cases of primary membranous glomerulopathy. Immunohistochemical staining for PLA2R (shown here) can detect the PLA2R type of membranous with high sensitivity and specificity. Recent studies have shown that serum testing for PLA2R antibodies can serve as a useful biomarker for monitoring the clinical activity of this disease. 

Resolving Membranous Glomerulopathy

A renal biopsy was performed on this 55-year-old female with a history of biopsy-proven membranous glomerulopathy status post immunosuppressive therapy, with a partial clinical response. The patient is currently being worked up for persistent subnephrotic proteinuria. This representative electron micrograph shows globally thickened capillary loops by a combination of intramembranous electron dense deposits completely surrounded by neomembrane (Ehrenreich and Churg stage III, blue arrow) and intramembranous electron lucent deposits with glomerular basement membrane remodeling (Ehrenreich and Churg stage IV, red arrow). These findings are compatible with a resolving membranous glomerulopathy. In light of these electron microscopy findings, the presence of...

Diagnose This! (February 5, 2018)

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