What are the causes and treatment options for nephrosis in a 38-year-old adult?

Causes of Nephrosis in a 38-Year-Old Adult

The most common causes of nephrosis in a 38-year-old adult are primary focal segmental glomerulosclerosis (FSGS) and membranous nephropathy for idiopathic causes, while diabetes mellitus is the most common secondary cause.

Primary (Idiopathic) Causes

Most Common Primary Causes

• Focal Segmental Glomerulosclerosis (FSGS)

  • Most common cause of acquired nephrotic syndrome leading to end-stage renal disease in adults 1
  • Characterized by scarring in parts of the glomeruli
  • Can be steroid-resistant in >50% of adult patients 2

• Membranous Nephropathy

  • Associated with anti-phospholipase A2 receptor (PLA2R) antibodies 1
  • Higher risk of thromboembolic complications 2
  • Often responds to calcineurin inhibitors or rituximab 2

• Minimal Change Disease (MCD)

  • More common in children but can occur in adults
  • Characterized by massive proteinuria with diffuse fusion of podocytes without visible immune deposits 1
  • Generally responds well to corticosteroids 2

Secondary Causes

Most Common Secondary Causes

• Diabetes Mellitus

  • Most common secondary cause of nephrotic syndrome in adults 1, 3
  • Presents with characteristic diabetic nephropathy

• Systemic Lupus Erythematosus

  • Can present with lupus nephritis
  • May require immunosuppressive therapy based on biopsy classification 2

• Infections

  • HIV, hepatitis B, hepatitis C, syphilis 1
  • Screening for these infections is recommended in appropriate clinical contexts 2

• Medications

  • NSAIDs, gold, penicillamine, certain antibiotics
  • Suspension of causative medications may be necessary 1

• Amyloidosis

  • Deposition of abnormal protein in kidney tissue
  • May be primary or secondary to chronic inflammatory conditions

• Malignancies

  • Particularly hematologic malignancies (lymphoma, leukemia)
  • Solid tumors can also cause paraneoplastic glomerular disease

Diagnostic Approach

1. Initial Laboratory Evaluation

   • Quantification of proteinuria (>3.5 g/day defines nephrotic range)
   • Serum albumin (<3.0 g/dL in nephrotic syndrome)
   • Lipid profile (typically elevated in nephrotic syndrome)
   • Complete blood count
   • Serum creatinine and estimated GFR
   • Serological tests (ANA, complement levels, hepatitis panels, HIV) 1

2. Renal Biopsy

   • Necessary for definitive diagnosis in adults with unexplained proteinuria >3.0 g/g creatinine 1
   • Helps distinguish between primary and secondary causes
   • KDIGO guidelines recommend biopsy for accurate diagnosis and treatment planning 2

3. Genetic Testing

   • Consider in cases of:
     • Familial renal disease
     • Steroid-resistant FSGS
     • Early-onset disease
     • 11-24% of adults with steroid-resistant FSGS have causative genetic variants 1

Treatment Considerations

Treatment depends on the underlying cause:

1. Primary Glomerular Diseases

   • FSGS: High-dose corticosteroids (prednisone 1 mg/kg/day) for 4-16 weeks 2
   • Membranous Nephropathy: Rituximab, cyclophosphamide with oral prednisolone, or calcineurin inhibitors 1
   • Minimal Change Disease: Prednisone 1 mg/kg/day (maximum 80 mg) 2

2. Secondary Causes

   • Treatment of underlying condition (e.g., antiretroviral therapy for HIV, glycemic control for diabetes)
   • Immunosuppression generally not recommended for secondary FSGS 1

3. Supportive Care

   • RAS inhibition for proteinuria and blood pressure control 2
   • Anticoagulation for high-risk patients, especially with membranous nephropathy 2
   • Lipid management with statins 2
   • Sodium restriction and diuretics for edema management 1

Complications to Monitor

• Venous thromboembolism (particularly in membranous nephropathy)
• Infections due to urinary loss of immunoglobulins
• Acute kidney injury
• Cardiovascular complications from dyslipidemia and hypertension

Proper identification of the underlying cause of nephrosis is crucial for appropriate management and improving outcomes in a 38-year-old patient.