Nephrotic and Nephritic Syndromes: Definitions and Key Distinctions
Nephrotic Syndrome
Nephrotic syndrome is a glomerular disorder characterized by the triad of heavy proteinuria (≥3.5 g/day in adults or ≥1.0 g/m²/day in children), hypoalbuminemia (<3.0 g/dL in adults or <2.5 g/dL in children), and peripheral edema, typically accompanied by hyperlipidemia. 1, 2, 3
Pathophysiology
The primary mechanism involves increased glomerular permeability to proteins due to podocyte dysfunction, which disrupts the glomerular filtration barrier 1
Loss of albumin decreases oncotic pressure, causing fluid shift from intravascular to interstitial spaces, resulting in the characteristic edema 1
Hyperlipidemia occurs as a compensatory hepatic response to plasma protein loss 1
In minimal change disease and focal segmental glomerulosclerosis (FSGS), a T-cell-driven circulating "glomerular permeability factor" interferes with glomerular permselectivity to albumin 1
Clinical Presentation
Patients typically present with periorbital edema (most noticeable in the morning) or dependent pitting edema (more common later in the day) 3
Fatigue is common, without evidence of heart failure or severe liver disease 2
Proteinuria should be documented quantitatively using urine protein:creatinine ratio (PCR > 300-350 mg/mmol indicates nephrotic range) or albumin:creatinine ratio 3
Common Causes
In children: Minimal change disease is the predominant cause, characterized by normal-appearing glomeruli on light microscopy but diffuse foot process effacement on electron microscopy 1, 4
In white adults: Membranous nephropathy is most frequent, with proven autoimmune mechanism involving pathogenic autoantibodies targeting podocyte antigens 1, 3
In populations of African ancestry: Focal segmental glomerulosclerosis (FSGS) is the most common cause 3
Secondary causes: Diabetic nephropathy is the most common multisystem disease causing nephrotic syndrome 3
Major Complications
Thromboembolism is a critical complication with 29% risk for renal vein thrombosis and 17-28% risk for pulmonary embolism due to loss of anticoagulant proteins 1
Infections occur due to loss of immunoglobulins and complement factors in urine 1
Patients with nephrotic-range proteinuria >3.8 g/day have a 35% risk of end-stage renal disease within 2 years 1
Acute kidney injury can occur, though spontaneous acute kidney injury from nephrotic syndrome alone is rare 2
Nephritic Syndrome
Nephritic syndrome is characterized by hematuria, proteinuria (typically sub-nephrotic range), hypertension, and abnormal kidney function with a generally poorer prognosis than nephrotic syndrome. 4
Key Distinguishing Features
Hematuria is the hallmark feature that distinguishes nephritic from nephrotic syndrome 4
Proteinuria is present but typically less than 3.5 g/day (sub-nephrotic range) 4
Hypertension is typically present and prominent 4
Progressive decline in kidney function is more common and occurs more rapidly than in nephrotic syndrome 4
Common Causes
Post-infectious glomerulonephritis is a predominant cause 4
IgA nephropathy is among the most common causes 4
Lupus nephritis frequently presents with nephritic features 4
Management Principles
Nephrotic Syndrome Management
Supportive care includes sodium restriction, fluid restriction when feasible (especially with hyponatremia and severe edema), and loop diuretics (furosemide 0.5-2 mg/kg per dose) for patients with fluid overload and preserved kidney function 5, 2
Avoid diuretics in patients with evidence of intravascular hypovolemia 5
Albumin infusions should be administered only when clinically indicated (oliguria, acute kidney injury, prolonged capillary refill time, tachycardia, hypotension), not based on serum albumin levels alone 6, 5
Renin-angiotensin system (RAS) blockade with ACE inhibitors or angiotensin receptor blockers for proteinuria management 6
Immunosuppressive therapy varies by cause: For FSGS, prednisone 1 mg/kg/day (maximum 80 mg) for minimum 4 weeks up to 16 weeks as tolerated or until complete remission, then taper slowly over 6 months 6, 1, 7
Genetic testing should be considered in early-onset cases, family history, or congenital nephrotic syndrome 5, 1
Thromboprophylaxis should be considered, especially with significant hypoalbuminemia and central venous access 6, 5
Nephritic Syndrome Management
Corticosteroids are often first-line therapy for many forms of nephritic syndrome 8
For steroid-resistant cases, calcineurin inhibitors (cyclosporine, tacrolimus), mycophenolate mofetil, rituximab, or cyclophosphamide may be considered depending on underlying cause 8
Hypertension control and proteinuria management with RAAS inhibitors are essential 1
Monitoring for kidney function decline is critical given the poorer prognosis 4
Critical Pitfalls to Avoid
Do not use immunosuppressive agents for genetic forms of nephrotic syndrome as they are unlikely to respond 5, 8
Avoid excessive diuretic dosing (>6 mg/kg per day for >1 week) which can lead to intravascular volume depletion 6, 5
Do not perform routine early nephrectomies in congenital nephrotic syndrome; a stepwise approach with prolonged conservative management is preferred 6, 5
Renal biopsy is often recommended to establish the specific glomerular disease and guide management, particularly when systemic lupus erythematosus or other renal disorders are suspected 2, 3