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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!  

Twitter Poll (November 15, 2018)

ANSWER: A The number of nephrons in the normal kidney is important because they may play a role in the development of hypertension and progression of chronic renal disease. Nephron number is influenced by many factors that affect renal development. References: 1. Luyckx VA, Brenner BM. The clinical importance of nephron mass. J Am Soc Nephrolo 2010;21:898-910. 2. Bertram JF, Douglas-Denton R, et al. Human nephron

IgA nephropathy with something extra…

The biopsy is from a 61-year-old man with a history of intermittent microscopic hematuria for many years who presents with recent 18-pound weight loss and nephrotic syndrome.  His creatinine is mildly elevated at 1.3 mg/dL.  He has 12.5 g of proteinuria and his serum albumin is 2.6 mg/dL.  The biopsy shows diffuse mild mesangial matrix expansion with no necrosis or proliferative lesions (Fig. 1).  Immunofluorescence microscopy shows extensive granular mesangial IgA deposits (3+) (Fig. 2), compatible with IgA nephropathy.  Interestingly, the Jones methenamine silver stain also shows argyrophilic spikes involving capillary loops, which are most suggestive of spicular amyloid deposits...

DNAJB9 helps uncover dual pathology…

This case illustrates the utility of immunohistochemical staining for DNAJB9, a recently described biomarker for fibrillary glomerulopathy (see reference).  The renal biopsy is taken from a 68-year-old man with a history of cirrhosis (cause unknown) who presents with mild microscopic hematuria, non-nephrotic range proteinuria, and chronic renal failure.  Glomeruli show diffuse mild mesangial matrix expansion.  Immunofluorescence shows granular mesangial IgA (2+) and smudgy mesangial and capillary wall IgG (2+) staining.  Electron microscopy (not shown) shows both immune complex-type and fibrillary deposits involving glomerular capillary basement membranes and mesangium.  Immunohistochemical staining for DNAJB9 shows mesangial staining.  Although IgA immunofluorescence staining may...

Not Quite Nodular

This biopsy came from a 70-year-old gentleman with acute renal failure. He had a known history of diabetes, hypertension, and chronic kidney disease.  His baseline serum creatinine is between 1.7 mg/dl and 1.9 mg/dl and was found to be elevated up to 2.9 mg/dl. Proteinuria was quantified as 0.2 g/g on urine protein to creatinine ratio.  Urinalysis showed trace blood and protein.  While processing the clinical information, one has to admit that this clinical presentation is not an unusual one.  A fair number of patients will have a decline in renal function that reflects the reality of an already struggling...

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...

Twitter Post (August 30, 2018)

ANSWER: B Type II (mixed) cryoglobulinemia is characterized by immune-complexes containing a monoclonal Ig (usually IgM) that have an RF activity and polyclonal Ig (usually IgG). It’s most commonly caused by HCV, with some cases caused by lymphoproliferative or autoimmune disorders. References: Zaidan M, et al. Spectrum and prognosis of noninfectious renal mixed cryoglobulinemic GN. J Am Soc Nephrol 2016; 27:1-12. Fabrizi F, et al. Hepatitis C virus infection, mixed cryoglobulinemia, and kidney disease. Am J Kidney Dis 2013; 61(4): 623-637.  

Differential Diagnosis of Kidney Injury in CLL/SLL Patients

There are many causes of decreased kidney function in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and a renal biopsy may provide a definitive diagnosis. Prerenal etiologies include poor oral intake, sepsis, and heart failure.  Intrarenal causes include diseases of the glomeruli (e.g. minimal change disease, MPGN pattern glomerulopathy, membranous glomerulopathy), tubules (e.g. toxic or ischemic tubular injury/necrosis, light chain cast nephropathy), interstitium (e.g. acute interstitial nephritis caused by infection or drugs), and vasculature (e.g. TMA).  The biopsy shown in this image illustrates infiltration of the kidney parenchyma by the lymphoid neoplasm (characteristic immunophenotypic studies not shown).  Postrenal causes...

Proliferative Glomerulonephritis with Monoclonal IgG Deposits

This biopsy was performed on a 58-year-old female who presented with mild proteinuria. The glomeruli show diffuse and global endocapillary hypercellularity with segmental double contour formation of the capillary loops on the silver stain (Fig 1). Immunofluorescence shows mesangial and segmental capillary wall deposits positive for IgG (3+, Fig 2), C3 (3+, not shown), C1q (1+, not shown) and lambda light chain (3+, Figure 4). Staining for kappa light chain is negative in glomeruli (Fig 3). Further immunofluorescence staining for IgG subclasses proves the deposits to be IgG3 restricted. Electron microscopy shows mesangial and segmental subendothelial immune-complex type deposits. The...

One little, two little, three little findings…

This biopsy came to us for evaluation of nephrotic syndrome. The patient is a Hispanic gentleman in his late 80s, with CKD stage IV and a history of arthritis, diabetes mellitus, coronary artery disease, and hypertension.  He had 4.9 g/g of proteinuria.  He had negative ANA, hepatitis B, and C serologies. C3 and C4 were within normal limits. Clinically, the differential diagnosis included membranous glomerulopathy and FSGS. The biopsy was a very good sample, consisting of long cores of renal tissue, mostly from cortex.  More than 20 glomeruli were present.  The glomeruli had clear features of diabetic nephropathy, as expected...