What is the difference in underlying mechanisms between nephritic and nephrotic syndrome?

Differences in Underlying Mechanisms Between Nephritic and Nephrotic Syndrome

Nephritic and nephrotic syndromes differ fundamentally in their pathophysiological mechanisms, with nephritic syndrome primarily involving inflammation-mediated glomerular damage, while nephrotic syndrome results from podocyte dysfunction leading to increased glomerular permeability to proteins.

Nephrotic Syndrome Mechanisms

• Nephrotic syndrome is characterized by massive proteinuria (>3.5g/day), hypoalbuminemia (<30g/L), edema, and often hyperlipidemia 1, 2
• The primary pathophysiological mechanism involves increased glomerular permeability to proteins due to podocyte dysfunction 3
• A T-cell-driven circulating "glomerular permeability factor" that interferes with glomerular permselectivity to albumin has been proposed in minimal change disease and focal segmental glomerulosclerosis (FSGS) 4, 3
• Podocyte injury leads to disruption of the slit diaphragm structure, altering the filtration barrier 5
• In membranous nephropathy, there is unequivocal proof of an autoimmune mechanism with pathogenic autoantibodies targeting podocyte antigens 4, 3
• The loss of albumin leads to decreased oncotic pressure, causing fluid to shift from intravascular to interstitial spaces, resulting in edema 6
• Hyperlipidemia in nephrotic syndrome occurs as a compensatory mechanism for the loss of plasma proteins 4

Nephritic Syndrome Mechanisms

• Nephritic syndrome is characterized by hematuria, proteinuria (usually non-nephrotic range), abnormal kidney function, and hypertension 7
• The primary pathophysiological mechanism involves inflammation-mediated glomerular damage 7
• Immune complex deposition in the glomeruli activates complement and inflammatory cells 4
• Neutrophils, macrophages, and other inflammatory cells infiltrate the glomeruli, causing damage to the basement membrane 5
• In post-infectious glomerulonephritis, antibodies form against streptococcal antigens and deposit in glomeruli 7
• In IgA nephropathy, IgA immune complexes deposit in the mesangium, activating complement and triggering inflammation 7
• In ANCA-associated vasculitis, antibodies target neutrophil components, leading to neutrophil activation and vascular damage 4

Key Differences in Clinical Manifestations

• Nephrotic syndrome presents with massive proteinuria, hypoalbuminemia, and edema, while nephritic syndrome presents with hematuria, moderate proteinuria, and hypertension 7
• Nephrotic syndrome is associated with higher risk of thromboembolism (29% for renal vein thrombosis, 17-28% for pulmonary embolism) due to loss of anticoagulant proteins 4, 6
• Nephritic syndrome typically has a more rapid decline in kidney function due to inflammatory damage 7
• Nephrotic syndrome has a higher association with hyperlipidemia and increased cardiovascular risk 4
• Patients with nephrotic-range proteinuria >3.8g/day have a 35% risk of end-stage renal disease within 2 years 4, 3

Histopathological Differences

• Common causes of nephrotic syndrome include minimal change disease, FSGS, and membranous nephropathy 3, 1
• Common causes of nephritic syndrome include post-infectious glomerulonephritis, IgA nephropathy, and lupus nephritis 7
• Nephrotic lesions typically show podocyte foot process effacement on electron microscopy 4
• Nephritic lesions typically show endocapillary proliferation, neutrophil infiltration, and sometimes crescent formation 7
• FSGS with diffuse foot process effacement is associated with nephrotic syndrome, while segmental foot process effacement is seen in non-nephrotic presentations 4

Treatment Implications Based on Mechanisms

• Treatment of nephrotic syndrome often targets immune mechanisms, particularly T-cell dysfunction, using calcineurin inhibitors like cyclosporin 4
• Cyclosporin inhibits cytokine production from T-helper cells and has an inhibitory effect on antigen-presenting cells, addressing the proposed immune mechanisms in nephrotic syndrome 4
• Treatment of nephritic syndrome focuses on controlling inflammation and immune complex formation 7
• Both syndromes require supportive care, including management of hypertension and proteinuria with RAAS inhibitors 4
• Thromboprophylaxis is more commonly needed in nephrotic syndrome due to the higher risk of thromboembolism 4, 6