Nephrotic Syndrome Pathology Study Guide

Nephrotic Syndrome Pathology Video

Nephrotic Syndrome

Nephrotic syndrome is characterized by proteinuria and glomerular disorders leading to hypoalbuminemia-pitting edema.

Nephrotic syndromes include:

Minimal change disease
Focal segmental glomerulosclerosis (FSGS)
Membranous nephropathy
Membranoproliferative glomerulonephritis (MPGN)
Diabetes mellitus
Systemic amyloidosis

Complications of nephrotic syndrome includes:

Hypogammaglobulinemia increases the risk of infection
Hypercoagulable state because of loss of antithrombin I (fibrin)
Hyperlipidemia
Hypercholesterolemia

Nephrotic Syndrome. Urinalysis will be able to detect high levels of proteins and occasionally microscopic haematuria. - Not altered. CC BY 2.5
Nephrotic Syndrome. Usually accompanied by retention of water and sodium. The degree to which this occurs can vary between slight edema in the eyelids that decreases during the day, to affecting the lower limbs, to generalized swelling, to full blown anasarca.[5] CharlesPicavet - Own work Facial edema selfportrait Not altered. Public Domain
Nephrotic Syndrome. Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. H&E stain. No machine-readable author provided. KGH assumed (based on copyright claims). Not altered. CC BY-SA 3.0
Nephrotic Syndrome. Ultrasound of a kidney with nephrotic syndrome. There is a hyperechoic kidney without demarcation of the cortex and medulla.[30] Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - Not altered. CC BY 4.0
Nephrotic Syndrome. Diabetic glomerulonephritis in a person with nephrotic syndrome. No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims). Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. PAM stain. Not altered. CC BY-SA 3.0
Nephrotic Syndrome. Histological image of a normal kidney glomerulus. It is possible to see a glomerulus in the centre of the image surrounded by kidney tubules. KGH Not altered. Copyrighted free use
Nephrotic Syndrome Pathology. Ultrasound of a kidney with nephrotic syndrome. There is a hyperechoic kidney without demarcation of the cortex and medulla.[30] Kristoffer Lindskov Hansen, Michael Bachmann Nielsen and Caroline Ewertsen - (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics 6 (1): 2. DOI:10.3390/diagnostics6010002. ISSN 2075-4418. Not altered. CC-BY 4.0
A: Focal segmental glomerulosclerosis with glomerular capillary wall collapse, balloon adhesion, and fibrous small new moon body form. Surrounding the open capillary lumen, the mesangial area has no obvious proliferation. (silver staining, 400x). B: Segmental glomerular sclerosis, capillary bundle segmental collapse, balloon adhesion, and cell sex small new moon body form. (PAS staining, 400x). C: HBcAg immunohistochemistry staining: HBcAg along the glomerular capillary wall and mesangial area; stage positive. (400x). D: Immunofluorescence: The glomerulus and mesangial area along the grain; sample fluorescence distribution: LgG-, LgA-, LgM++, C3-, F-, C1q-. HBV reactivation in an occult HBV infection patient treated with prednisone for nephrotic syndrome: case report and literature review: Du W, Zheng Z, Han S, Ma S, Chen S - BMC infectious diseases (2013). Not altered. CC.
Increased BASP1 expression in tubular cells in human nephrotic syndrome. BASP1 immunohistochemistry. (a) Minimal tubular BASP1 staining was observed in control kidney tubules. (b) BASP1-positive tubular cells were observed in human nephrotic syndrome. Original magnification × 20. Albumin-induced apoptosis of tubular cells is modulated by BASP1: Sanchez-Niño MD, Fernandez-Fernandez B, Perez-Gomez MV, Poveda J, Sanz AB, Cannata-Ortiz P, Ruiz-Ortega M, Egido J, Selgas R, Ortiz A - Cell death & disease (2015). Not altered. CC.

Minimal Change Disease

Minimal change disease is the most prevalent cause of nephrotic syndrome in children.

Minimal change disease is typically idiopathic.

Minimal change disease can be linked to Hodgkin lymphoma.

The kidney histology looks normal in minimal change disease (“minimal change” disease).

Electron microscopy is needed to see the pathology of minimal change disease.

Electron microscopy of minimal change disease shows podocyte foot effacement.

Selective proteinuria may be present because loss of albumin, but not immunoglobulin.

Minimal change disease is treated with steroids.

Minimal Change Disease. A schematic of the changes seen under the electron microscope of minimal change disease. M Komorniczak. Not altered. CC BY-SA 3.0
Minimal Change Disease. Periorbital edema that can be seen in minimal change disease Not altered. CC BY-SA 3.0
Immunohistochemical staining of PLA2R in glomerular deposits (ALP ×400). (A) In patients with minimal change disease, there is a very weak expression of PLA2R on the glomerular podocytes and it is recognized as a negative result in this study. (B) In patients with PMN, there is strongly stained PLA2R distributed along the glomerular capillary walls in a fine granular pattern. Retrospective Study of Phospholipase A2 Receptor and IgG Subclasses in Glomerular Deposits in Chinese Patients with Membranous Nephropathy: Dong HR, Wang YY, Cheng XH, Wang GQ, Sun LJ, Cheng H, Chen YP - PloS one (2016). Not altered. CC.

Focal Segmental Glomerulosclerosis (FSGS)

Focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome.

Ethnicities at risk of focal segmental glomerulosclerosis (FSGS) include:

Hispanics
Americans of African descent

Focal segmental glomerulosclerosis (FSGS) can be linked to HIV infection, heroin use, and sickle cell disease.

Histology of focal segmental glomerulosclerosis (FSGS) shows segmental (some glomeruli) and focal (part of effected glomeruli) fibrosis and sclerosis.

There are no immune complex deposits associated with focal segmental glomerulosclerosis (FSGS).

Treatment of focal segmental glomerulosclerosis (FSGS) is steroids.

If focal segmental glomerulosclerosis (FSGS) does not respond to steroid treatment that portends to a worse diagnosis.

Chronic renal failure is a complication of focal segmental glomerulosclerosis (FSGS).

Focal Segmental Glomerulosclerosis. High magnification micrograph of focal segmental glomerulosclerosis, hilar variant. Focal segmental glomerulosclerosis is commonly abbreviated FSGS. PAS stain. Kidney biopsy. It presents as a nephrotic syndrome. Related images Intermed. mag. High mag. Very high mag. Nephron - Not altered. CC BY-SA 3.0
Focal Segmental Glomerulosclerosis. Micrograph of the collapsing variant of FSGS (collapsing glomerulopathy). A collapsed glomerulus is seen at the top, right-of-centre. PAS stain. Kidney biopsy. Nephron. Not altered. CC BY-SA 3.0
Renal biopsy showing the collapsing variant of focal segmental glomerulosclerosis. Arrows indicate widened and effaced podocyte foot process. (A: Periodic acid-Schiff staining, ×400; B: electron microscopy image, ×2,500). Bilateral iliac and popliteal arterial thrombosis in a child with focal segmental glomerulosclerosis: Han KH, Park JY, Min SK, Ha IS, Cheong HI, Kang HG - Korean journal of pediatrics (2016). Not altered. CC.

Membranous Nephropathy

Membranous nephropathy is the most common cause of nephrotic syndrome in Caucasian adults.

Membranous nephropathy is normally idiopathic.

Known causes of membranous nephropathy include:

Hepatitis B
Hepatitis C
Cancer
Systemic lupus erythematous (SLE)
Non-steroidal anti-inflammatory drugs (NSAIDs)
Penicillamine
Systemic lupus erythematous

Histology of membranous nephropathy shows glomerular basement membrane thickening.

A periodic acid Schiff (PAS) stain may highlight the thickened basement membrane dark pink.

Electron microscopy of membranous nephropathy shows subepithelial deposits with spike and dome appearance due to immune complex deposition.

Chronic renal failure may develop as a complication of membranous nephropathy.

Membranous Nephropathy. Very high magnification micrograph of membranous nephropathy, abbreviated MN. MN may also be referred to as membranous glomerulonephritis, abbreviated MGN. Kidney biopsy. Jones stain. The characteristic feature on light microscopy is basement membrane thickening/spike formation, which is best seen with silver stains. On electron microscopy, subepithelial deposits are seen. Related images Intermed. mag. MPAS. High mag. MPAS. Very high mag. MPAS. Very high mag. MPAS. Very high mag. MPAS. (cropped) High mag. HE. Very high mag. HE. Very high mag. PAS. Nephron. Not altered.CC BY-SA 3.0
IgG4-related membranous glomerulonephropathy. a Periodic acid-Schiff (PAS) stain of a case of clinically confirmed IgG4-related kidney disease (IgG4-RKD, same patient as in Fig. 1), showing a membranous pattern of glomerulonephropathy with occasional plasma cells in the mesangium. b IgG4 immunohistochemistry confirming several IgG4 expressing plasma cells in the glomerulus. c Electron microscopy demonstrating subepithelial electron-dense deposits, consistent with membranous glomerulonephropathy. Recognizing IgG4-related tubulointerstitial nephritis: Mann S, Seidman MA, Barbour SJ, Levin A, Carruthers M, Chen LY - Canadian journal of kidney health and disease (2016). Not altered. CC.
Immunohistochemical analysis for thrombospondin type-1 domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R).Immunostaining for THSD7A (a, c, e) and PLA2R (b, d, f) in patients with idiopathic membranous nephropathy (a–d) and secondary membranous nephropathy (e, f). Original magnification: ×400. Inset, enhanced granular expression of THSD7A (a) and PLA2R (d) shown at a higher magnification (arrows). Abbreviations: THSD7A, Thrombospondin type-1 domain-containing 7A; PLA2R, M-type phospholipase A2 receptor; MN, membranous nephropathy. Prevalence of Enhanced Granular Expression of Thrombospondin Type-1 Domain-Containing 7A in the Glomeruli of Japanese Patients with Idiopathic Membranous Nephropathy: Iwakura T, Ohashi N, Kato A, Baba S, Yasuda H - PloS one (2015). Not altered. CC.

Membranoproliferative Glomerulonephritis (MPGN)

Membranoproliferative glomerulonephritis (MPGN) classically shows a thick glomerular basement membrane on H&E that looks like a “tram-track.”

The tram track appearance of membranoproliferative glomerulonephritis (MPGN) is present because immune complex deposition.

Immunofluorescence of membranoproliferative glomerulonephritis (MPGN) shows immune complex deposition.

The immune complex deposition of membranoproliferative glomerulonephritis (MPGN) is classified into two types based on the location of deposits:

Type 1 subendothelial (associated with HBV and HCV)
Type 2 dense deposit disease (which is intramembranous associated with C3 nephritic factor)

Membranoproliferative glomerulonephritis (MPGN) may progress to chronic renal failure.

Membranoproliferative Glomerulonephritis. Very high magnification micrograph of membranoproliferative glomerulonephritis, abbreviated MPGN. PAS stain. Kidney biopsy. The most common cause of MPGN is hepatitis C. Related images Intermed. mag. High mag. Very high mag. Nephron. Not altered. CC BY-SA 3.0
Membranoproliferative Glomerulonephritis. Renal corpuscle. Membranoproliferative glomerulonephritis involves deposits at the intraglomerular mesangium which leads to "splitting" of the glomerular basement membrane. M Komorniczak Not altered. CC BY-SA 4.0
a Periodic acid–Schiff stain, 100× magnification, showing features of membranoproliferative glomerulonephritis type 1. b Methenamine silver stain, 200× magnification, highlighting double contour formation in capillary loops. Mesangial proliferation and segmental endocapillary proliferation can also be seen. An association between membranoproliferative glomerulonephritis and metastatic colorectal carcinoma: a case report: Chan S, Oliver KA, Gray NA - Journal of medical case reports (2016). Not altered. CC.

Diabetes Mellitus

High serum glucose levels in patients with diabetes mellitus causes the vascular basement membrane to be glycosylated non-enzymatically, which results in hyaline arteriolosclerosis.

The glomerular efferent arteriole is more impacted than afferent arteriole, resulting in increased glomerular filtration pressure.

Hyperfiltration injury may result in microalbuminuria and nephrotic syndrome.

Diabetes mellitus causes cirrhosis of the mesangium with formation of Kimmelstiel-Wilson nodules.

Diabetes mellitus induced hyaline arteriolosclerosis is treated with angiotensin converting enzyme (ACE) inhibitors.

Diabetes Mellitus. Retinopathy, nephropathy, and neuropathy are potential complications of diabetes. Complications of Diabetes (from LtoR): Retinopathy, Nephropathy and Neuropathy. Not altered. CC BY-SA 4.0

Systemic Amyloidosis

The kidney is the organ that is most often involved by systemic amyloidosis.

Systemic amyloidosis is characterized by deposits in the mesangium which can cause nephrotic syndrome.

Systemic Amyloidosis. Amyloidosis, dystrophic calcification Ed Uthman, MD. Not altered. CC BY-SA 2.0
Systemic Amyloidosis. Small bowel duodenum with amyloid deposition 20X Michael Feldman, MD. Not altered. CC BY 2.0