Podocyte Pathologies
This is the fundamental structural component of the glomerular filtration barrier that is primarily affected in nephrotic syndromes, leading to increased protein permeability.
What is the podocyte?
This is the classic histological finding on light microscopy in Minimal Change Disease, despite severe proteinuria.
What is normal or unremarkable glomeruli?
This is the characteristic histological lesion seen on light microscopy that defines Focal Segmental Glomerulosclerosis.
What is segmental scarring/sclerosis of some (focal) glomeruli?
On electron microscopy, this is the classic location of immune complex deposition in Membranous Nephropathy, appearing as electron-dense material on the external surface of the glomerular basement membrane.
What are subepithelial immune deposits?
This systemic autoimmune disease is a common cause of secondary nephrotic syndrome, often manifesting as Class V lupus nephritis, which has features of membranous nephropathy.
What is Systemic Lupus Erythematosus (SLE)?
Disruption of these specialized glycosaminoglycans between adjacent podocytes is a hallmark feature in many primary nephrotic diseases, leading to effacement and proteinuria.
What is heparan sulfate.
On electron microscopy, this is the characteristic ultrastructural change seen in Minimal Change Disease, correlating with the loss of permselectivity.
What is diffuse effacement of podocyte foot processes?
FSGS can be classified into primary (idiopathic) and secondary forms. Name one common secondary cause of FSGS.
What is HIV infection, heroin nephropathy, obesity, reflux nephropathy,
Immunofluorescence microscopy in primary Membranous Nephropathy typically shows a diffuse, granular pattern of which specific immunoglobulin and complement component along the glomerular capillary loops?
What are IgG and C3?
Characterized by the extracellular deposition of abnormal, insoluble protein fibrils, this systemic disorder can lead to nephrotic syndrome, with AL type being the most common form affecting the kidneys.
What is Amyloidosis?
Risk variants in this gene, particularly common in individuals of West African descent, are strongly associated with a much higher risk of developing aggressive, collapsing forms of FSGS and HIV-associated nephropathy
What is the Apolipoprotein L1 (APOL1)
While generally idiopathic, Minimal Change Disease in adults is sometimes associated with which type of malignancy?
What are lymphomas (especially Hodgkin lymphoma)?
Unlike Minimal Change Disease, FSGS often shows a poorer response to corticosteroids and has a higher rate of progression to what end-stage renal condition?
What is end-stage renal disease (ESRD)?
In approximately 70-80% of primary Membranous Nephropathy cases, circulating autoantibodies are detected against this specific podocyte surface antigen.
What is the Phospholipase A2 Receptor (PLA2R)?
A patient with nephrotic syndrome also presents with macroglossia, periorbital purpura (raccoon eyes), and restrictive cardiomyopathy. These multi-organ findings are highly suggestive of what specific systemic etiology for their kidney disease?
What is Amyloidosis?
In Minimal Change Disease, the diffuse effacement of podocyte foot processes is thought to be mediated by cytokines released from what dysfunctional immune cell type, leading to the subsequent loss of the glomerular charge barrier?
What are T-cells (or T-lymphocytes)?
A 5-year-old presents with sudden onset of periorbital edema, ascites, and frothy urine. Urinalysis reveals 4+ protein. What is the most likely initial treatment for this patient?
What are corticosteroids (e.g., prednisone)?
BONUS QUESTION: What age did Parth move to the United States.
What is 7 years old.
A 65-year-old male is newly diagnosed with Membranous Nephropathy. Before initiating immunosuppressive therapy, what specific category of secondary causes, commonly associated with MN in older adults, must be thoroughly screened for?
What are malignancies (solid tumors)?
This condition is the most common cause of end-stage renal disease (ESRD) in the United States, and its renal manifestations can include nephrotic-range proteinuria. Early histological changes include thickening of the glomerular basement membrane and mesangial expansion, eventually leading to Kimmelstiel-Wilson lesions.
What is Diabetic Nephropathy?
Name three hallmark features of nephrotic syndrome besides proteinuria.
Edema, hypoalbuminemia, and hyperlipidemia.
These result from low oncotic pressure, liver compensation, and increased lipid synthesis.
A patient with Minimal Change Disease achieves remission with steroids but relapses frequently. What is a common second-line immunosuppressive agent used to induce sustained remission and reduce steroid dependence?
What is cyclophosphamide
What are the nonspecific focal deposits for FSGS
IgM,C3,C1.
Describe the characteristic "spike and dome" appearance seen on silver stain or electron microscopy in Membranous Nephropathy, and explain what each component represents pathologically.
Domes are the subepithelial immune deposits, and "spikes" are newly synthesized glomerular basement membrane material laid down between and around these deposits
A patient with a history of long-term NSAID use for chronic pain develops nephrotic-range proteinuria. A renal biopsy shows diffuse effacement of podocyte foot processes on EM with otherwise normal light microscopy and negative immunofluorescence. This presentation is most consistent with what drug-induced glomerular pathology?
What is NSAID-induced Minimal Change Disease (or sometimes FSGS)?